1. Furosemid 1.1 Theo duoc thu: Furosemid l thuc li tiu dn cht sulfonamide, c xp vo nhm thuc li tiu quai.

C ch tc dng ch yu ca furosemid l c ch h thng ng vn chuyn Na+, K+, 2Cl - , on dy ca nhnh ln quai Henle, lm tng thi tr nhng cht in gii ny km theo tng bi xut nc. Cng c s tng o thi Ca++ v Mg++. Tc dng li tiu ca thuc mnh, do ko theo tc dng h huyt p, nhng thng yu. Dc ng hc Furosemid hp thu tt qua ng ung, tc dng li tiu xut hin nhanh sau 1/2 gi, t nng ti a sau 1 - 2 gi v duy tr tc dng t 4 - 6 gi. Tc dng chng tng huyt p ko di hn.. Vi ngi bnh ph nng, kh dng sinh hc ca thuc gim, c th do nh hng trc tip ca vic gim hp thu ng tiu ha. S hp thu ca furosemid c th ko di v c th gim bi thc n. Mt phn ba lng thuc hp thu c thi tr qua thn, phn cn li thi tr qua nc tiu, ch yu di dng khng chuyn ha, thuc thi tr hon ton trong 24 gi. Ch nh Ph phi cp; ph do tim, gan, thn v cc loi ph khc; tng huyt p khi c tn thng thn; tng calci huyt. Liu lng v cch dng

iu tr ph: Liu ung bt u thng dng l 40 mg/ngy. iu chnh liu nu thy cn thit ty theo p ng. Trng hp ph nh c th dng liu 20 mg/ngy hoc 40 mg cch nht. Mt vi trng hp c th tng liu ln 80 mg hoc hn na, chia lm 1 hoc 2 ln trong ngy. Trng hp nng, c th phi d liu tng dn ln ti 600 mg/ngy. Trong trng hp cp cu, hoc khi khng dng c ng ung, c th tim bp hoc tnh mch chm 20 - 40 mg hoc cn thit c th cao hn. Nu liu ln hn 50 mg th nn tim truyn tnh mch chm. cha ph phi, liu tim tnh mch chm ban u l 40 mg. Nu p ng cha tho ng trong vng mt gi, liu c th tng ln 80 mg, tim tnh mch chm. iu tr tng huyt p: Furosemid khng phi l thuc chnh iu tr bnh tng huyt p v c th phi hp vi cc thuc chng tng huyt p khc iu tr tng huyt p ngi c tn thng thn. Liu dng ng ung l 40 - 80 mg/ngy, dng n c hoc phi hp vi cc thuc h huyt p khc. 1.2 Theo tgn tc thuc v ch khi ch nh Tng tc thuc: Thn trng mc 2: Suy gan cc thuc li niu thi kali c th khi pht hn m gan, lm tng nhim kim chuyn ha, lm tng NH3. Khng c tng tc vi cc thuc trong n 1.3 Theo MARTINDALE Adverse Effects Most adverse effects of furosemide occur with high doses, and serious effects are uncommon. The most common adverse effect is fluid and electrolyte imbalance including hyponatraemia, hypokalaemia, and hypochloraemic alkalosis, particularly after large

doses or prolonged use. Signs of electrolyte imbalance include headache, hypotension, muscle cramps, dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, oliguria, cardiac arrhythmias, and gastrointestinal disturbances. Hypovolaemia and dehydration may occur, especially in the elderly. Because of their shorter duration of action, the risk of hypokalaemia may be less with loop diuretics such as furosemide than with thiazide diuretics. Unlike the thiazides, furosemide increases the urinary excretion of calcium and nephrocalcinosis has been reported in preterm infants. Furosemide may cause hyperuricaemia and precipitate gout in some patients. It may provoke hyperglycaemia and glycosuria, but probably to a lesser extent than the thiazide diuretics. Pancreatitis and cholestatic jaundice seem to occur more often than with the thiazides. Other adverse effects include blurred vision, yellow vision, dizziness, headache, and orthostatic hypotension. Other adverse effects occur rarely. Skin rashes and photosensitivity reactions may be severe; hypersensitivity reactions include interstitial nephritis and vasculitis; fever has also been reported. Bone marrow depression may occur: there have been reports of agranulocytosis, thrombocytopenia, and leucopenia. Tinnitus and deafness may occur, in particular during rapid high-dose parenteral furosemide. Deafness may be permanent, especially in patients taking other ototoxic drugs. Hiu ng bt li Hu ht cc tc dng ph ca furosemide xy ra vi liu lng cao, v nh hng nghim trng l khng ph bin. Cc tc dng ph thng gp nht l s mt cn bng cht lng v cht in phn trong c hyponatraemia, h kali mu, v nhim kim hypochloraemic, c bit sau khi dng liu ln hoc dng ko di. Du hiu ca s mt cn bng in gii bao gm nhc u, h huyt p, au c bp, kh ming, kht nc, yu km, th , bun ng, bn chn, thiu niu, ri lon nhp tim, v ri lon tiu ha. Hypovolaemia v mt nc c th xy ra, c bit l ngi cao tui. Do thi gian ngn hn ca h v hnh ng, nguy c h kali mu c th t vi thuc li tiu nh furosemide vng hn vi thuc li tiu thiazide. Khng ging nh thiazide, furosemide lm tng bi tit canxi niu v nephrocalcinosis c bo co tr sinh non thng. Furosemide c th gy ra hyperuricaemia v kt ta trong mt s bnh nhn gout. N c

th gy tng glucose huyt v niu, nhng c l n mt mc thp hn so vi cc thuc li tiu thiazide. Vim ty v vng da mt dng nh xy ra thng xuyn hn vi cc thiazide. Cc hiu ng bt li bao gm m mt, th lc mu vng, chng mt, nhc u, h huyt p t th ng v. Cc hiu ng bt li xy ra rt t. Pht ban da v nhng phn ng nhy c th nng; phn ng qu mn bao gm vim thn k v vim mch, st cng c bo co. Ty xng trm cm c th xy ra: c bo co v mt bch cu ht, gim tiu cu, gim bch cu v. tai v ic c th xy ra, c bit trong thi gian nhanh chng nui furosemide liu cao. ic c th l vnh vin, c bit l bnh nhn dng thuc c tai. Incidence of adverse effects In a survey of 553 hospital inpatients1 receiving furosemide 220 patients (40%) had 480 adverse reactions. Electrolyte disturbances occurred in 130 (23.5%) patients and extracellular volume depletion in 50 (9%). Adverse reactions were more common in those with liver disease, and hepatic coma occurred in 20 patients with hepatic cirrhosis. A similar survey in 585 hospital inpatients2 revealed 177 adverse effects in 123 (21%). These included volume depletion in 85 patients (14.5%), hypokalaemia in 21 (3.6%), and hyponatraemia in 6 (1%). Hypokalaemia was considered to be life-threatening in 2 patients. Hyperuricaemia occurred in 54 patients (9.2%), of whom 40 also had volume depletion, and clinical gout developed in 2. T l tc dng ph Trong mt cuc kho st 553 bnh vin inpatients1 tip nhn 220 bnh nhn furosemide (40%) c 480 phn ng ph. Ri lon in gii xy ra trong 130 (23,5%) bnh nhn v s suy gim lng ngoi bo 50 (9%). phn ng bt li c ph bin hn nhng ngi c bnh gan, v gan, hn m xy ra 20 bnh nhn b x gan gan. Mt cuc kho st tng t ti 585 bnh vin inpatients2 tc ng bt li cho thy 177 trong 123 (21%). Nhng s suy gim khi lng bao gm 85 bnh nhn (14,5%), h kali mu 21 (3,6%), v hyponatraemia trong 6 (1%). H kali mu c xem l e da tnh mng trong 2 bnh nhn. Hyperuricaemia xy ra trong 54 bnh nhn (9,2%), trong 40 cng c s suy gim khi lng, v bnh gout pht trin trong 2 Effects on the ears

Ototoxicity and deafness during furosemide therapy is most frequently associated with elevated blood concentrations resulting from rapid intravenous infusion1 or delayed excretion in patients with renal impairment.2 Of 29 cases of furosemide-induced deafness reported to the FDA3 in the USA, most patients had renal disease or had received the drug intravenously. Eight patients had also received another ototoxic drug. However, deafness occurred in 11 patients after oral use, and in 4 of these hearing loss occurred in the absence of renal disease or other ototoxic drugs. Hearing loss was generally transient, lasting from one-half to 24 hours, but permanent hearing loss occurred in 3 patients, one of whom had taken furosemide orally. Deafness was not always associated with high doses; six patients had received a total of 200 mg or less of furosemide. Tc dng trn tai Ototoxicity v ic trong khi iu tr furosemide l thng xuyn nht c lin quan vi nng trong mu tng cao kt qu ca tim tnh mch nhanh chng infusion1 hoc bi tit b tr hon bnh nhn suy thn impairment.2 Trong 29 trng hp b ic furosemide gy ra bo co cho cc FDA3 M, hu ht bnh nhn b bnh thn hoc nhn c cc loi thuc tim tnh mch. Tm bnh nhn cng nhn c mt loi thuc c tai. Tuy nhin, ic xy ra 11 bnh nhn sau khi s dng ng ung, v trong 4 trong s ny mt thnh lc xy ra trong trng hp khng c bnh thn hoc thuc c tai khc. Nghe km ni chung l thong qua, ko di t mt na n 24 gi, nhng thng xuyn mt thnh lc xy ra 3 bnh nhn, mt trong nhng ngi a furosemide bng ming. ic khng phi lun lun lin quan vi liu cao, su bnh nhn nhn c tng s l 200 mg hoc t hn ca furosemide

Effects on electrolyte balance Calcium Furosemide increases renal calcium excretion. There is a danger of hypocalcaemic tetany during furosemide use in hypoparathyroid patients1 and it has also been reported2 in a patient with latent hypoparathyroidism following thyroidectomy. The decrease in serum-calcium concentrations could also induce hyperparathyroidism. In a study involving 36 patients with heart failure, furosemide was associated with elevations in both parathyroid hormone and alkaline phosphatase concentrations, possibly indicating accelerated bone remodelling such as that found in primary hyperparathyroidism.3

Tc dng trn s cn bng in Canxi Furosemide lm tng bi tit canxi thn. C mt mi nguy him ca tetany hypocalcaemic trong khi s dng furosemide trong hypoparathyroid patients1 v n cng c reported2 trong mt bnh nhn vi tuyn gip tim n hypoparathyroidism sau y. S gim nng canxi trong huyt thanh cng c th gy cng cn gip. Trong mt nghin cu lin quan n 36 bnh nhn b suy tim, furosemide c kt hp vi cao ni tit t tuyn cn gip trong c v nng phosphatase kim, c th ch ra tu sa xng tng tc nh c tm thy trong cng cn gip chnh Magnesium, potassium, and sodium For discussions of the effects of diuretics on these electrolytes see under the Adverse Effects of Hydrochlorothiazide, Magi, kali, v natri i vi cc cuc tho lun v tc ng ca thuc li tiu trn cc in nhn thy di tc hi ca hydrochlorothiazide Effects on lipid metabolism Most studies into the effects of diuretics on blood-lipid concentrations have used thiazides (see Hydrochlorothiazide, short-term use.1 Tc dng trn chuyn ha lipid Hu ht cc nghin cu v tc dng ca thuc li tiu trn nng lipid mu s dng thiazide (xem hydrochlorothiazide,). Cc nghin cu t vo nhng nh hng ca furosemide cho rng, ging nh thiazide, n bt li c th nh hng n nng lipid mu trong thi gian s dng ngn hn ). The few studies into the effects of furosemide suggest that, like thiazides, it may adversely influence blood-lipid concentrations during and .

Precautions

Precautions and contra-indications for furosemide that are dependent on its effects on fluid and electrolyte balance are similar to those of the thiazide diuretics (see Hydrochlorothiazide, ). Although furosemide is used in high doses for oliguria due to chronic or acute renal impairment it should not be given in anuria or in renal failure caused by nephrotoxic or hepatotoxic drugs nor in renal failure associated with hepatic coma. Furosemide should not be given in pre-comatose states associated with hepatic cirrhosis. It should be used with care in patients with prostatic hyperplasia or impairment of micturition since it can precipitate acute urinary retention. To reduce the risk of ototoxicity, licensed product information recommends that furosemide should not be injected intravenously at a rate exceeding 4 mg/minute although the BNF advises that a single dose of up to 80 mg may be given more rapidly. Furosemide should be used with caution during pregnancy and breast feeding since it crosses the placenta and also appears in breast milk. Furosemide may compromise placental perfusion by reducing maternal blood volume; it may also inhibit lactation. Bin php phng nga Bin php phng nga v ch dn ngc cho furosemide m ph thuc vo hiu ng ca n trn s cn bng cht lng v cht in phn cng tng t nh thuc li tiu thiazide ca (xem hydrochlorothiazide,). Mc d furosemide c s dng trong liu cao cho thiu niu do suy thn mn tnh hoc cp tnh khng nn c a ra trong anuria hoc suy thn gy ra bi thuc c thn hay hi gan hay suy thn lin quan n hn m gan. Furosemide khng nn c a ra trong trng thi hn m trc khi c kt hp vi bnh x gan. N s c s dng thn bnh nhn tng sn tuyn tin lit hoc lm suy gim ca binh i ai rt v n c th kt ta b tiu cp tnh. gim nguy c ototoxicity, thng tin sn phm c cp giy php ngh furosemide rng khng nn tim tnh mch vi tc vt qu 4 mg / pht mc d BNF cc t vn rng mt liu duy nht ln n 80 mg c th c nhanh hn. Furosemide nn c dng thn trng trong qu trnh mang thai v cho con b v n i qua nhau thai v cng xut hin trong sa m. Furosemide c th tha hip ti mu nhau thai bng cch gim th tch mu ca m, n cng c th c ch s tit sa. Hepatic impairment

In patients with chronic heart failure and moderate liver congestion, high-dose furosemide therapy could produce increases in liver enzymes suggestive of hepatitis.1 Special care should be taken with the dosage and mode of administration of furosemide in such patients to avoid severe ischaemic liver damage caused by a drop in systemic blood pressure. As with the thiazides, furosemide should be avoided in patients with severe hepatic impairment. Suy gan bnh nhn suy tim sung huyt gan mn tnh v va, liu cao c th sn xut furosemide tr gia tng men gan gi chm sc c bit hepatitis.1 nn dng vi liu lng v phng thc qun l ca furosemide cho bnh nhn nh vy trnh thit hi nghim trng gan thiu mu cc b gy ra bi s gim huyt p h thng. Nh vi cc thiazide, furosemide nn trnh bnh nhn suy gan nng

Porphyria Furosemide has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients. Porphyria Furosemide c lin quan n cc cuc tn cng cp tnh ca porphyria v c xem l khng an ton nhng bnh nhn porphyric

Interactions The interactions of furosemide that are due to its effects on fluid and electrolyte balance are similar to those of hydrochlorothiazide (see ).

Furosemide may enhance the nephrotoxicity of cephalosporin antibacterials such as cefalotin and can enhance the ototoxicity of aminoglycoside antibacterials and other ototoxic drugs. Tng tc Cc tng tc ca furosemide m l do nh hng ca n trn s cn bng cht lng v

cht in phn cng tng t nh ca hydrochlorothiazide (xem). Furosemide c th tng cng thn ca cephalosporin antibacterials nh cefalotin v c th nng cao ototoxicity ca antibacterials aminoglycoside v thuc c tai khc.

Pharmacokinetics Furosemide is fairly rapidly absorbed from the gastrointestinal tract; bioavailability has been reported to be about 60 to 70% but absorption is variable and erratic. The half-life of furosemide is up to about 2 hours although it is prolonged in neonates and in patients with renal and hepatic impairment. Furosemide is up to 99% bound to plasma albumin, and is mainly excreted in the urine, largely unchanged. There is also some excretion via the bile and non-renal elimination is considerably increased in renal impairment. Furosemide crosses the placental barrier and is distributed into breast milk. The clearance of furosemide is not increased by haemodialysis. The pharmacokinetics of furosemide have been extensively reviewed.1-6 The development of an analytical method using HPLC with fluorescence has produced greater sensitivity and more consistent results. Absorption after oral use is erratic and is subject to large inter- and intra-individual variation. It is influenced by the dosage form, underlying disease processes, and by the presence of food. Furosemide absorption in patients with heart failure has been reported to be even more erratic than in healthy subjects. The bioavailability of furosemide from oral dosage forms is also highly variable with reported values ranging from 20 to 100%. It is influenced by factors affecting absorption but the poor solubility of furosemide does not appear to have a major influence on bioavailability and in vitro dissolution data may not reflect in vivo bioavailability. Bioavailability tends to be decreased by about 10% in patients with renal disease, and slightly increased in liver disease. Values are erratic in patients with heart disease. Furosemide is highly bound to plasma proteins, almost exclusively to albumin. The proportion of free (unbound) furosemide is higher in patients with heart disease, renal impairment, and cirrhosis of the liver. Patients with liver disease also have an increased apparent volume of distribution which is proportionally greater than the observed decrease in protein binding. Patients with nephrotic syndrome have significant proteinuria and secondary hypoalbuminaemia. This results in reduced protein binding in

the blood, particularly at higher blood concentrations, and binding to proteins present in the urine, which may account for the resistance to furosemide therapy reported in these patients. A glucuronide metabolite of furosemide is produced in varying amounts. The site of metabolism is unknown at present. There is debate over another potential metabolite, 4chloro-5-sulfamoyl anthranilic acid (CSA). It has been argued3 that it is an artefact produced during the extraction procedures although there is some evidence to refute this.4 A half-life for furosemide in healthy subjects has generally been reported in the range of 30 to 120 minutes. In patients with end-stage renal disease the average half-life is 9.7 hours. The half-life may be slightly longer in patients with hepatic dysfunction and a range of 50 to 327 minutes has been reported in patients with heart failure. In severe multi-organ failure the half-life may range from 20 to 24 hours. Furosemide clearance is influenced by age, underlying disease state, and drug interactions. Clearance reduces with increasing age, probably due to declining renal function. Renal impairment in renal or cardiac disease reduces renal clearance, although this may be compensated for by increases in non-renal clearance. Hepatic impairment has little impact on clearance. Renal and non-renal clearance may be reduced by probenecid and indometacin. The effectiveness of furosemide as a diuretic depends upon it reaching its site of action, the renal tubules, unchanged. About one-half to two-thirds of an intravenous dose or onequarter to one-third of an oral dose are excreted unchanged, the difference being largely due to the poor bioavailability from the oral route. The effect of furosemide is more closely related to its urinary excretion than to the plasma concentration. Urinary excretion may be reduced in renal impairment due to reduced renal blood flow and reduced tubular secretion. Dc ng hc Furosemide l kh hp thu nhanh qua ng tiu ha, sinh kh dng c bo co l khong 60 n 70% nhng s hp th l bin v tht thng. Cuc sng na ca furosemide l vo khong 2 gi mc d n c ko di tr s sinh v bnh nhn suy thn v gan. Furosemide l ln n 99% lin kt vi albumin huyt tng, v ch yu

c bi tit trong nc tiu, phn ln khng thay i. Ngoi ra cn c mt s bi tit thng qua vic loi b mt v thn khng tng ng k trong suy thn. Furosemide vt qua hng ro nhau thai v c phn phi vo sa m. Vic gii phng mt bng ca furosemide khng tng chy thn nhn to. Dc ng hc ca furosemide c rng ri reviewed.1-6 S pht trin ca mt phng php phn tch s dng HPLC vi hunh quang to ra nhy cao hn v nhiu hn na nhng kt qu nht qun. Hp th sau khi s dng ung tht thng v c th bin i lin v c nhn trong ni b ln. N chu nh hng ca cc hnh thc liu lng, c bn qu trnh mc bnh, v bi s hin din ca thc phm. Furosemide hp th bnh nhn suy tim c bo co l nhiu hn bt thng so vi cc i tng khe mnh. Cc sinh kh dng ca furosemide t dng thuc ung cng rt khc nhau vi cc gi tr c bo co t 20 n 100%. N chu nh hng bi cc yu t nh hng n s hp th, nhng ha tan ngi ngho ca furosemide khng xut hin c mt nh hng ln n sinh kh dng v cc d liu gii th in vitro c th khng phn nh trong kh dng sinh hc c th. Kh dng sinh hc c xu hng gim khong 10% bnh nhn b bnh thn, v hi tng ln trong bnh gan. Gi tr l tht thng nhng bnh nhn b bnh tim. Furosemide l rt gn kt vi protein huyt tng, hu nh ch vi albumin. T l furosemide (rng buc) min ph l cao hn nhng bnh nhn b bnh tim, suy thn v x gan. Bnh nhn c bnh gan cng c mt khi lng tng ln r rng ca phn phi m l t l ln hn gim c quan st trong protein rng buc. Bnh nhn c hi chng thn h c protein niu ng k v hypoalbuminaemia th cp. iu ny dn n gim protein lin kt trong mu, c bit nng trong mu cao hn, v gn kt vi protein c trong nc tiu, c th ti khon cho cc khng furosemide tr liu bo co nhng bnh nhn ny. Mt cht chuyn ha glucuronide ca furosemide c sn xut hm lng khc nhau. Trang web ca s trao i cht l khng r hin nay. C cuc tranh lun v mt cht chuyn ha tim nng, acid anthranilic 4-chloro-5-sulfamoyl (CSA). N c argued3 rng n l mt vt phm c sn xut trong cc th tc khai thc mc d c mt s bng chng bc b this.4 Mt na cuc i cho furosemide trong khe mnh thng c bo co trong khong t 30 n 120 pht. bnh nhn bnh thn giai on cui na cuc i trung bnh l 9,7 gi. Cuc sng na-c th l hi di bnh nhn ri lon chc nng gan v

mt lot cc 50-327 pht c bo co bnh nhn suy tim. Trong suy a tng nng vi cuc sng na-c th khong 20-24 gi. Furosemide gii phng mt bng chu nh hng ca tui tc, c bnh tiu bang, v tng tc thuc. Gii phng mt bng lm gim cng vi tui tc ngy cng tng, c th l do suy gim chc nng thn. Suy thn bnh thn hoc tim lm gim thanh thi qua thn, mc d iu ny c th c bi thng bng cch gia tng gii phng mt bng khng thn. Suy gan c t tc ng ti gii phng mt bng. Thn v gii phng mt bng khng thn c th b gim bi probenecid v indometacin. Hiu qu ca thuc li tiu furosemide l mt ph thuc vo n vo trang web ca mnh v hnh ng, cc ng thn, khng thay i. Gii thiu v mt na n hai phn ba ca mt liu tim tnh mch hoc mt phn t ti mt phn ba ca mt liu ung c bi tit khng thay i, s khc bit l phn ln l do kh dng sinh hc ngho t ng ung. Hiu qu ca furosemide l cht ch hn lin quan n bi tit nc tiu ca mnh hn l s tp trung huyt tng. bi tit nc tiu c th b gim trong suy thn do gim lu lng mu thn v ng tit gim. Uses and Administration Furosemide is a potent diuretic with a rapid action. Like the other loop or high-ceiling diuretics it is used in the treatment of oedema associated with heart failure ( ), including pulmonary oedema, and with renal and hepatic disorders (but see Precautions, ) and may be effective in patients unresponsive to thiazide diuretics. It is also used in high doses in the management of oliguria due to renal failure or insufficiency. Furosemide is also used in the treatment of hypertension ( antihypertensives. Furosemide inhibits the reabsorption of electrolytes primarily in the thick ascending limb of the loop of Henle and also in the distal renal tubules. It may also have a direct effect in the proximal tubules. Excretion of sodium, potassium, calcium, and chloride ions is increased and water excretion enhanced. It has no clinically significant effect on carbonic anhydrase. See Action, , for further reference to its mechanism of action. ), either alone or with other

Administration and dosage. Furosemide's effects are evident within 30 minutes to 1 hour after an oral dose, peak at 1 to 2 hours, and last for about 4 to 6 hours; after

intravenous injection its effects are evident in about 5 minutes and last for about 2 hours. It is given orally, usually in the morning. Alternatively it may be given intramuscularly or intravenously as the sodium salt; doses are expressed in terms of furosemide base. 10.7 mg of furosemide sodium is equivalent to about 10 mg of furosemide base. Licensed product information recommends that whether by direct intravenous injection or by infusion the rate of intravenous dosage should not exceed 4 mg/minute although the BNF advises that a single dose of up to 80 mg may be given more rapidly. Unlike the thiazide diuretics where, owing to their flat dose-response curve, very little is gained by increasing the dose, furosemide has a steep dose-response curve, which gives it a wide therapeutic range. In the treatment of oedema, the usual initial oral dose is 40 mg once daily, adjusted as necessary according to response. Mild cases may respond to 20 mg daily or 40 mg on alternate days. Some patients may need doses of 80 mg or more daily given as one or two doses daily, or intermittently. Severe cases may require gradual titration of the furosemide dosage up to 600 mg daily. In an emergency or when oral therapy cannot be given, 20 to 50 mg of furosemide may be given by slow intravenous injection; intramuscular injection may be given in exceptional cases but is not suitable for acute conditions. If necessary further doses may be given, increasing by 20-mg increments and not given more often than every 2 hours. If doses above 50 mg are required they should be given by slow intravenous infusion. For pulmonary oedema, if an initial slow intravenous injection of 40 mg does not produce a satisfactory response within one hour, a further 80 mg may be given slowly intravenously. For children, the usual oral dose is 1 to 3 mg/kg daily up to a maximum of 40 mg daily; doses by injection are 0.5 to 1.5 mg/kg daily up to a maximum of 20 mg daily. In the treatment of hypertension, furosemide is given in oral doses of 40 to 80 mg daily, either alone, or with other antihypertensives. High-dose therapy. In the management of oliguria in acute or chronic renal failure where the glomerular filtration rate is less than 20 mL/minute but greater than 5 mL/minute, furosemide 250 mg diluted to 250 mL in a suitable diluent is infused over one hour. If urine output is insufficient within the next hour, this dose may be followed

by 500 mg added to an appropriate infusion fluid, the total volume of which must be governed by the patient's state of hydration, and infused over about 2 hours. If a satisfactory urine output has still not been achieved within one hour of the end of the second infusion then a third dose of 1 g may be infused over about 4 hours. The rate of infusion should never exceed 4 mg/minute. In oliguric patients with significant fluid overload, the injection may be given without dilution directly into the vein, using a constant rate infusion pump with a micrometer screw-gauge adjustment; the rate should still never exceed 4 mg/minute. Patients who do not respond to a dose of 1 g probably require dialysis. If the response to either dosage method is satisfactory, the effective dose (of up to 1 g) may then be repeated every 24 hours. Dosage adjustments should subsequently be made according to the patient's response. Alternatively, oral treatment may be maintained; 500 mg should be given orally for each 250 mg required by injection. When used in chronic renal impairment, an initial oral dose of 250 mg may be given, increased, if necessary in steps of 250 mg every 4 to 6 hours to a maximum of 1.5 g in 24 hours; in exceptional cases up to 2 g in 24 hours may be given. Dosage adjustments should subsequently be made according to the patient's response. During treatment with these high-dose forms of furosemide therapy, careful laboratory control is essential. Fluid balance and electrolytes should be carefully controlled and, in particular, in patients with shock, measures should be taken to correct the blood pressure and circulating blood volume, before commencing this type of treatment. High-dose furosemide therapy is contra-indicated in renal failure caused by nephrotoxic or hepatotoxic drugs, and in renal failure associated with hepatic coma. S dng v Qun tr Furosemide l mt thuc li tiu mnh vi mt hnh ng nhanh chng. Cng ging nh cc vng khc hay thuc li tiu trn cao n c s dng trong iu tr ph n kt hp vi suy tim (), bao gm c ph phi, v cc ri lon thn v gan (nhng xem Thn trng,) v c th c hiu qu nhng bnh nhn khng p ng vi thuc li tiu thiazide . N cng c s dng liu cao trong vic qun l ca thiu niu do suy thn hoc suy. Furosemide cng c s dng trong iu tr tng huyt p (), hoc mt mnh hoc vi thuc h huyt p khc. Furosemide c ch ti hp thu cc cht in ch yu trong cc chi tng dn dy ca cc

vng lp ca Henle v cng ng thn xa. N cng c th c tc ng trc tip trong ng gn. Bi tit natri, kali, canxi, v cc ion clorua c tng ln v nc thi c tng cng. N khng nh hng ng k trn lm sng carbonic anhydrase. Xem hnh ng,, tham kho thm c ch hot ng ca n. Qun tr v liu lng. Furosemide l hiu ng c hin nhin trong vng 30 pht n 1 gi sau mt liu ung, cao im t 1 n 2 ting, v ko di khong 4 n 6 gi, sau khi tim tnh mch tc dng ca n l hin nhin trong khong 5 pht v ko di khong 2 gi. N c a ra bng ming, thng l vo bui sng. Ngoi ra n c th c tim bp hay tim tnh mch l mui natri; liu c th hin v c s furosemide. 10,7 mg natri furosemide l tng ng vi khong 10 mg ca cc c s furosemide. Cp giy php thng tin sn phm khuyn co rng d bng cch tim tnh mch trc tip hoc bng cch truyn t l liu tim tnh mch khng c vt qu 4 mg / pht mc d BNF cc t vn rng mt liu duy nht ln n 80 mg c th c nhanh hn. Khng ging nh cc thuc li tiu thiazide u, do ng cong liu lng-phn ng bng phng ca h, rt t l t c bng cch tng liu, furosemide c mt ng cong liu-p ng dc, mang n cho n mt rng phm vi iu tr. Trong khi iu tr ph, thng thng liu ung ban u l 40 mg mt ln mi ngy, iu chnh khi cn thit theo phn ng. Trng hp nh c th p ng n 20 mg / ngy hoc 40 mg vo ngy thay th. Mt s bnh nhn c th cn liu 80 mg hoc nhiu hn hng ngy cho l mt hay hai liu hng ngy, hoc lin tc. Trng hp nng c th yu cu chun dn dn ca furosemide liu n 600 mg / ngy. Trong trng hp khn cp hoc khi iu tr rng ming c th khng c cho, 20-50 mg furosemide c th c bng cch tim tnh mch chm, tim bp c th c a ra trong trng hp c bit nhng khng ph hp vi iu kin cp tnh. Nu liu lng cn thit hn na c th c, tng 20-mg gia tng v khng c thng xuyn hn mi 2 gi. Nu liu trn 50 mg c yu cu h phi c a ra bi truyn tnh mch chm. i vi ph phi, nu mt ban u chm tim tnh mch 40 mg khng to ra mt p ng tha ng trong vng mt gi, mt mg 80 cn c th c cho tim tnh mch chm. i vi tr em, liu ung thng thng l 1-3 mg / kg mi ngy ln n ti a l 40 mg / ngy, liu tim l 0,5-1,5 mg / kg mi ngy ln n ti a l 20 mg / ngy. Trong khi iu tr tng huyt p, furosemide c cho liu ung 4-80 mg mi ngy, hoc mt mnh, hoc vi cc thuc h huyt p khc. Liu cao iu tr. Trong vic qun l ca thiu niu trong suy thn cp tnh hoc mn

tnh, ni t l lc cu thn di 20 ml / pht, nhng ln hn 5 mL / pht, furosemide 250 mg pha long n 250 ml trong mt pha long thch hp l truyn hn mt gi. Nu khng lng nc tiu trong vng mt gi tip theo, liu ny c th c tip theo l 500 mg thm vo mt dung dch tim truyn thch hp, tng khi lng phi c iu chnh bi nh nc ca bnh nhn ca hydrat ha, v truyn qua khong 2 gi. Nu mt lng nc tiu t yu cu vn cha c t c trong vng mt gi ca s kt thc ca truyn th hai sau mt liu th ba ca 1 g c th c truyn qua khong 4 gi. T l tim truyn khng bao gi c vt qu 4 mg / pht. bnh nhn oliguric vi tnh trng qu ti cht lng ng k, tim c th c cho m khng cn pha long trc tip vo tnh mch, s dng mt my bm tc truyn thng xuyn vi mt iu chnh vt-o micromet, t l nn vn khng bao gi vt qu 4 mg / pht. Bnh nhn khng p ng vi mt liu lng 1 g c th yu cu lc mu. Nu cu tr li cho mt trong hai phng php liu lng l tha ng, liu hiu qu (ln n 1 g), sau c th c lp i lp li mi 24 gi. Liu dng iu chnh sau phi c thc hin theo p ng ca bnh nhn. Ngoi ra, iu tr rng ming c th c duy tr; 500 mg nn cho ung 250 mg cho mi yu cu ca tim. Khi c s dng trong suy thn mn tnh, mt u ung 250 mg c th c a ra, tng ln, nu cn thit trong cc bc ca 250 mg mi 4-6 gi n ti a l 1,5 g trong 24 gi, trong trng hp c bit ln n 2 g trong 24 gi c th c. Liu dng iu chnh sau phi c thc hin theo p ng ca bnh nhn. Trong thi gian iu tr vi cc hnh thc liu cao iu tr furosemide, kim sot trong phng th nghim cn thn l cn thit. Cn bng cht lng v cht in gii phi c kim sot cn thn v c bit, nhng bnh nhn b sc, cn c bin php sa cha huyt p v lng mu lu thng, trc khi bt u loi iu tr. Furosemide liu cao tr liu l chng ch nh trong suy thn gy ra bi thuc c thn hay hi gan, v trong suy thn lin quan n hn m gan. Action The mechanism of action of furosemide is not fully understood.1 It appears to act primarily by inhibiting active reabsorption of chloride ions in the ascending limb of the loop of Henle. Urinary excretion of sodium, chloride, potassium, hydrogen, calcium, magnesium, ammonium, bicarbonate, and possibly phosphate is increased; the chloride excretion exceeds that of sodium and there is an enhanced exchange of sodium for

potassium leading to greater excretion of potassium. The resulting low osmolality of the medulla inhibits the reabsorption of water by the kidney. There is a possibility that furosemide may also act at a more proximal site. In addition to its diuretic actions, furosemide has been shown to increase peripheral venous capacitance and reduce forearm blood flow. It also reduces renal vascular resistance with a resultant increase in renal blood flow the degree of which is proportional to the initial resistance. Furosemide has been shown to increase plasma-renin activity, plasma-noradrenaline concentrations, and plasma-arginine-vasopressin concentrations. Alterations in the reninangiotensin-aldosterone system may play a part in the development of acute tolerance. Furosemide increases renal-prostaglandin concentrations but it is not known whether this is due to increased synthesis or inhibition of degradation or both. Prostaglandins appear to mediate the diuretic/natriuretic action. The primary effects appear to be alterations in renal haemodynamics with subsequent increases in electrolyte and fluid excretion. The diuretic response to furosemide is related to the concentration in the urine, not to that in the plasma. Furosemide is delivered to the renal tubules by a non-specific organic acid pump in the proximal tubules.1 In some cases sodium intake may be sufficient to overcome the diuretic effect, and limiting sodium intake could restore responsiveness.2 Hnh ng C ch tc ng ca furosemide l khng hon ton understood.1 N xut hin hnh ng ch yu bng cch c ch ti hp thu hot ng ca cc ion clorua trong chi tng dn ca cc vng lp ca Henle. tiu phosphate bi tit natri, clorua, kali, hydro, canxi, magi, amoni, bicarbonate, v c th c tng ln; s bi tit clorua natri ln hn v c mt cuc trao i nng cao ca sodium cho kali dn n s bi tit nhiu hn kali. Cc osmolality thp kt qu ca ty c ch s ti hp thu nc ca thn. C mt kh nng rng furosemide cng c th hnh ng ti mt a im u gn hn. Ngoi hnh ng li tiu ca n, furosemide c hin th tng dung tnh mch ngoi bin v gim lu lng mu cng tay. N cng lm gim sc khng mch mu thn vi kt qu tng lu lng mu thn mc trong t l vi cc khng ban u.

Furosemide c c hin th tng hot ng renin trong huyt tng, huyt tng, nng noradrenaline, v plasma-arginine vasopressin-nng . S thay i trong h thng renin-angiotensin-aldosterone c th ng mt phn trong s pht trin ca lng khoan dung cp tnh. Furosemide lm tng nng prostaglandin thn, nhng khng bit liu iu ny l do tng hp tng hoc c ch s xung cp hoc c hai. Prostaglandin xut hin ha gii cc hnh ng li tiu / natriuretic. Cc tc dng chnh xut hin c thay i trong haemodynamics thn vi tng tip theo trong s bi tit cht in phn v cht lng. Cc phn ng thuc li tiu furosemide l lin quan n nng trong nc tiu, khng c trong huyt tng. Furosemide l giao cho cc ng thn bng mt my bm acid hu c khng c th trong u gn tubules.1 Trong mt s trng hp natri lng c th l vt qua tc dng li tiu, v hn ch lng natri c th phc hi p ng. Administration Continuous intravenous infusion of loop diuretics may be more effective than intermittent intravenous bolus injection and may provide a more consistent urine flow with fewer alterations in urine balance.1,2 Bumetanide was more effective by continuous infusion than as bolus doses in 8 patients with severe chronic renal impairment.3 In 20 patients with chronic heart failure requiring high-dose furosemide therapy, furosemide given by continuous infusion was more effective than the same dose by bolus injection.4 The lower plasma concentrations associated with continuous infusion may also reduce the risk of toxicity. Hnh chnh Truyn tnh mch lin tc ca cc thuc li tiu vng lp c th hiu qu hn so vi tim truyn tnh mch lin tc vin thc n v c th cung cp mt lu lng nc tiu nhiu hn ph hp vi s thay i trong nc tiu t hn balance.1, 2 bumetanid c hiu qu hn bng cch truyn dch lin tc hn l liu vin thc n trong 8 bnh nhn mn tnh nghim trng thn impairment.3 Trong 20 bnh nhn b suy tim mn tnh cn iu tr furosemide liu cao, furosemide cho bi truyn lin tc c hiu qu hn so vi liu lng tng t ca vin thc n injection.4 Nng huyt tng thp lin kt vi truyn lin tc cng c th lm gim nguy c ng c .

Ascites

Dietary sodium restriction and diuretics are mainstays of the management of cirrhotic ascites ( ). Spironolactone is usually the diuretic of first choice, but furosemide may be added to therapy as necessary. C trng Ch n ung hn ch mui v thuc li tiu l tr ct chnh ca x gan c trng qun l (). Spironolactone thng l thuc li tiu ca s la chn u tin, nhng furosemide c th c thm vo iu tr khi cn thit Obstructive airways disease In patients with asthma, furosemide given by oral inhalation has been found to protect against bronchoconstriction induced by exercise1 and external stimuli,2,3 although it did not improve bronchial hyperresponsiveness in a 4-week study4 and provided no additional benefit when added to salbutamol for the treatment of acute asthma in a small study in children.5 A number of mechanisms have been suggested for the protective effect of furosemide, including inhibition of electrolyte transport across epithelium, inhibition of inflammatory mediators, or an effect on mast cell function.6 The potential for clinical applications remains unclear6 and furosemide is not a part of the accepted schedules for the treatment of asthma ( ).

A small study7 in patients with chronic obstructive pulmonary disease found that inhalation of furosemide relieved bronchoconstriction and dyspnoea induced by exercise. Inhaled furosemide has also been used to relieve dyspnoea in patients with terminal cancer.8 Tc nghn ng h hp bnh nhng bnh nhn b bnh hen suyn, furosemide do ht phi ung c tm thy bo v chng co tht ph qun gy ra bi exercise1 v kch thch bn ngoi, 2,3 mc d n khng ci thin hyperresponsiveness ph qun trong mt tun-4 study4 v cung cp khng c li ch b sung khi thm vo salbutamol cho iu tr hen suyn cp tnh trong mt nghin cu nh trong children.5 Mt s c ch c xut cho hiu qu bo v ca furosemide, bao gm c s c ch vn chuyn in trn biu m, c ch cc cht trung gian gy vim, hoc c hiu lc mt ngy function.6 t bo mast Cc tim nng cho

cc ng dng lm sng vn cn unclear6 v furosemide khng phi l mt phn ca k hoch c chp nhn iu tr bnh hen suyn (). Mt study7 nh bnh nhn b bnh nghn phi mn tnh thy thuyn gim co tht ph qun ht phi furosemide v kh th gy ra bi tp th dc. furosemide ht cng c s dng lm gim kh th bnh nhn ung th b u cui 2.kalium

Ch : 1 mmol tng ng 75 mg kali clorid. Ch nh Kali clorid thng c la chn iu tr gim kali mu, v ion clorid cng cn iu chnh gim clo mu thng xy ra cng vi gim kali mu. Kali clorid c ch nh iu tr gim kali mu nng ngi bnh dng thuc li tiu thi kali. Kali clorid cn c dng phng gim kali mu nhng ngi c bit c nguy c gim kali mu (v d: ngi bnh dng digitalis b lon nhp tim nng, v gim kali mu lm tng c tnh ca glycosid tim). Kali clorid cng c th ch nh cho ngi b x gan c chc nng thn bnh thng, mt s trng thi a chy, k c do s dng thuc nhun trng di ngy, nn ko di, hi chng Bartter, bnh thn gy mt kali, v nhng ngi bnh (k c tr em) iu tr corticosteroid ko di. Liu lng v cch dng Ung mui kali phi ung vo ba n hoc sau ba n vi nhiu nc. Thuc nc phi pha long trc khi dng.

Tim tnh mch: Phi pha long nng kali clorid vi mt th tch ln (1000 ml) ca dch thch hp truyn tnh mch, nng kali tt nht l 40 mmol trong mt lt, v khng vt qu 80 mmol trong mt lt. trnh tng kali mu trong khi truyn tnh mch, tc truyn khng c nhanh, tc 10 mmol trong mt gi thng l an ton, khi lng nc tiu thi ra tha ng (trong iu tr cp cu, tc truyn l 20 mmol/gi). Thng thng, tc truyn khng bao gi c php vt qu 1 mmol trong mt pht cho ngi ln v 0,02 mmol cho mt kg th trng trong mt pht i vi tr em. Nu tc truyn vt qu 0,5 mmol/kg/gi, thy thuc phi ngi bn cnh v theo di in tm lin tc. Trong sut thi gian dng tc cao, ngi bnh cn c theo di thng xuyn v lm sng v in tm . Nu c ri lon chc nng thn, c bit l suy thn cp nh c du hiu thiu niu v/ hoc tng creatinin huyt thanh, xy ra trong khi truyn kali clorid, cn ngng truyn ngay. C th truyn li nu cn, nn dng rt thn trng v theo di cht ch. iu tr gim kali mu Ngi ln: Ung phng trong liu php li niu: 40 mmol/ngy kali clorid c th phng c gim kali huyt phn ln s ngi bnh dng thuc li niu di ngy. i vi ngi tng huyt p khng bin chng, khng ph, iu tr ngoi tr, thng khng cn b sung kali; tuy nhin, nu kali huyt thanh di 3 mmol/lt, nn dng 50 - 60 mmol kali/ngy. i vi ngi bnh ph (th d suy tim, x gan c trng) cho 40 - 80 mmol/ngy (thiu nh) hoc 100 - 120 mmol/ngy (thiu nng) km theo di cn thn kali huyt thanh. Tim truyn nh git tnh mch ngoi bin (kali huyt thanh nh hn 2,5 mmol/lt) tc truyn 10 - 20 mmol/gi; dnh tc nhanh hn 20 mmol/gi cho nhng trng hp cp cu; c th lp li cch 2 - 3 gi

nu cn, nhng nng kali trong dch truyn khng c vt qu nng ti a 40 mmol/lt. Tng tc thuc Phi hp nguy him : mc 4: Thuc l tiu gi kali( spinorolacton): phi hp c nguy c dn n tng kali mu Khi dng kali clorid kt hp vi thuc li tiu thiazid (lm mt nhiu kali), c nguy c tng kali mu nu ngng thuc li tiu.

3.Verospiron(spinorolacton) Theo dc th
Spironolacton l cht i khng mineralocorticoid, tc dng qua vic c ch cnh tranh vi aldosteron v cc mineralocorticoid khc, lm tng bi tit natri v nc. Spironolacton lm gim bi tit cc ion kali, amoni (NH4+) v H+. C tc dng li tiu v chng tng huyt p u qua c ch . Spironolacton bt u tc dng tng i chm, cn phi 2 hoc 3 ngy mi t tc dng ti a v thuc gim tc dng chm trong 2 - 3 ngy khi ngng thuc. V vy khng dng spironolacton khi cn gy bi niu nhanh. S tng bi tit magnesi v kali ca cc thuc li tiu thiazid v li tiu quai (furosemid) s b gim khi dng ng thi vi spironolacton. Spironolacton v cc cht chuyn ha chnh ca n (7 alpha - thiomethyl - spironolacton v canrenon) u c tc dng khng mineralocorticoid. Spironolacton lm gim c huyt p tm thu v tm trng, tc dng h huyt p ti a t c sau 2 tun iu tr. V spironolacton l cht i khng cnh tranh vi aldosteron, liu dng cn thit c iu chnh theo p ng iu tr. Tng aldosteron tin pht him gp. Tng aldosteron th pht xy ra trong ph th pht do x gan, hi chng thn h v suy tim sung huyt ko di v sau khi iu tr vi thuc li tiu thng thng. Tc dng li tiu c tng cng khi dng phi hp vi cc thuc li tiu thng thng, spironolacton khng gy tng acid uric huyt hoc tng glucose huyt, nh xy ra khi dng thuc li tiu thiazid liu cao. Dc ng hc

Spironolacton c hp thu qua ng tiu ha, t nng ti a trong mu sau khi ung 1 gi, nhng vn cn vi nng c th o c t nht 8 gi sau khi ung 1 liu. Sinh kh dng tng i l trn 90% so vi sinh kh dng ca dung dch spironolacton trong polyetylen glycol, dng hp thu tt nht. Spironolacton v cc cht chuyn ha ca n o thi ch yu qua nc tiu, mt phn qua mt.

Ch nh
C trng do x gan. Ph gan, ph thn, ph tim khi cc thuc cha ph khc km tc dng, c bit khi c nghi ng chng tng aldosteron. Tng huyt p, khi cch iu tr khc km tc dng hoc khng thch hp.

Tc dng khng mong mun (ADR)

Cc phn ng khng lin quan n liu dng trong ngy v thi gian iu tr. Nguy c phn ng c hi thp khi dng liu thp hn 100 mg. Thng thng nht l to v n ng do tng nng prolactin nhng thng hi phc sau iu tr. Tng kali huyt lun phi c xem xt nhng ngi gim chc nng thn. Nguy c ny thp khi dng liu di 100 mg/ngy ngi c chc nng thn bnh thng, vi iu kin khng dng thm kali v phi kim sot vic nhn kali qua n ung khng theo ch .

Liu lng v cch dng

Ngi ln: Li tiu khi ph khng tr do x gan, hi chng thn h, suy tim sung huyt, c bit nghi ng c tng aldosteron, thng phi hp vi furosemid, cc thiazid hoc cc thuc li tiu tng t: Liu ban u l ung 25 - 200 mg/ngy, chia 2 - 4 ln, dng t nht 5 ngy, liu duy tr l 75 - 400 mg/ngy, chia 2 - 4 ln. Chng tng huyt p: Liu ban u ung 50 - 100 mg/ngy, chia 2 - 4 ln, dng t nht 2 tun; liu duy tr iu chnh theo tng ngi bnh. Nhng hin nay t c dng iu tr tng huyt p. Tng aldosteron tin pht: 100 - 400 mg/ngy, chia 2 - 4 ln trc khi phu thut. Liu thp nht c hiu qu c th duy tr trong thi gian di i vi ngi bnh khng th phu thut.

Tng tc thuc

S dng ng thi spironolacton vi cc cht c ch enzym chuyn (ACE - 1) c th dn ti ''tng kali huyt" nng, e da tnh mng, c bit ngi c suy thn. Tc dng chng ng ca coumarin, hay dn cht indandion hay heparin b gim khi dng cng vi spironolacton. Cc thuc chng vim khng steroid, c bit l indomethacin lm gim tc dng chng tng huyt p ca spironolacton. S dng ng thi lithi v spironolacton c th dn n ng c lithi, do gim thanh thi. S dng ng thi cc thuc c cha kali vi spironolacton lm tng kali huyt. Na i sinh hc ca digoxin v cc glycosid tim c th tng khi dng ng thi vi spironolacton.

Adverse Effects
Spironolactone may give rise to headache and drowsiness, and gastrointestinal disturbances, including cramp and diarrhoea. Ataxia, mental confusion, and skin rashes have been reported as adverse effects. Gynaecomastia is not uncommon and in rare cases breast enlargement may persist. Other endocrine disorders include hirsutism, deepening of the voice, menstrual irregularities, and impotence. Transient increases in blood-ureanitrogen concentrations may occur and mild acidosis has been reported. Spironolactone has been shown to cause tumours in rats. Spironolactone may cause hyponatraemia and hyperkalaemia.

Hiu ng bt li
Spironolactone c th lm gia tng s au u v bun ng v ri lon tiu ha, bao gm c chut rt v tiu chy. Mt iu ha, tinh thn l ln, v pht ban da c bo co l tc dng ph. Gynaecomastia khng phi l khng ph bin v trong trng hp him v m rng c th ko di. ri lon ni tit khc bao gm rm lng, su sc ca ging ni, kinh nguyt khng u, v bt lc. Tng thong qua nng ur mu-nit c th xy ra v toan nh c bo co. Spironolactone c chng minh gy ra khi u chut. Spironolactone c th gy ra hyponatraemia v hyperkalaemia.

Incidence of adverse effects

A survey found that of 788 patients given spironolactone 164 developed adverse effects.1 These included hyperkalaemia in 8.6%, dehydration in 3.4%, hyponatraemia in 2.4%, gastrointestinal disorders in 2.3%, neurological disorders in 2%, rash, and gynaecomastia. Hyperkalaemia was associated with renal impairment and the use of potassium

supplements: only 2.8% of nonuraemic patients not receiving potassium chloride developed hyperkalaemia, while 42.1% of those with marked uraemia and treated with potassium chloride became hyperkalaemic. In a study2 of 54 patients (53 female, 1 male) taking spironolactone 200 mg daily for hirsutism or acne adverse effects were reported in 91%.2 Menstrual disturbances occurred in 72% of patients, breast tenderness in 39%, dry skin in 39%, and breast enlargement in 24%. Other adverse effects included nausea and vomiting, dizziness, headache, drowsiness, and skin rashes. Two patients developed a chloasma-like pigmentation of the face. The gynaecological effects were reduced in patients taking oral contraceptives.

T l tc dng ph
Mt cuc kho st thy rng l 788 bnh nhn c pht trin spironolactone 164 effects.1 hyperkalaemia Nhng bt li bao gm trong 8,6%, mt nc trong 3,4%, hyponatraemia 2,4%, ri lon tiu ha 2,3%, ri lon thn kinh 2%, pht ban, v gynaecomastia. Hyperkalaemia c kt hp vi suy thn v s dng kali b sung: ch c 2,8% bnh nhn khng nhn c hyperkalaemia nonuraemic kali clorua pht trin, trong khi 42,1% ca nhng ngi c chng niu c nh du v iu tr vi clorua kali tr thnh hyperkalaemic. Trong mt study2 ca 54 bnh nhn (53 n, 1 nam) ang spironolactone 200 mg mi ngy cho rm lng hoc tc dng ph mn c bo co trong 91% ri lon kinh nguyt 0,2 xy ra 72% bnh nhn, m au 39%, kh da trong 39 %, v v to 24%. tc dng ph khc bao gm bun nn v nn ma, chng mt, nhc u, bun ng, v pht ban da. Hai bnh nhn pht trin mt sc t chloasma ging nh ca khun mt. Cc tc dng ph khoa c gim nhng bnh nhn ung thuc nga thai.

Carcinogenicity
Breast cancer was reported in 5 patients taking spironolactone and hydrochlorothiazide for prolonged periods1 although it was suggested2 that the association with spironolactone therapy was unlikely to be causal. Although the rat may not be an appropriate model for determining long-term safety in man,3,4 evidence of carcinogenicity in this species prompted the UK CSM to limit the

product licences of spironolactone-containing products to exclude use in essential hypertension or idiopathic oedema.5

Gy ung th
ung th v c bo co trong 5 bnh nhn dng spironolactone v hydrochlorothiazide cho periods1 ko di mc d n c suggested2 rng s lin kt vi liu php spironolactone khng c quan h nhn qu. Mc d nhng con chut khng c th l mt m hnh thch hp xc nh an ton lu di trong con ngi, 3,4 bng chng gy ung th loi ny nhc nh cc CSM Anh gii hn giy php sn phm ca spironolactone c cha sn phm loi tr s dng trong cao huyt p cn thit hoc ph t pht .5

Effects on electrolyte balance

Calcium
A report1 suggested that spironolactone may have a calcium-sparing effect, in addition to its well known potassium-sparing properties.
1. 1. Puig JG, et al. Hydrochlorothiazide versus spironolactone: long-term metabolic modifications in patients with essential hypertension. J Clin Pharmacol 1991; 31: 455 61. PubMed

Canxi
Mt report1 cho rng spironolactone c th c hiu lc ti thiu canxi, ngoi ra cng c bit n thuc tnh ca n kali ti thiu. 1. 1. Puig JG, et al. Hydrochlorothiazide so vi spironolactone: di hn trao i cht thay i bnh nhn cao huyt p cn thit. J Clin Pharmacol nm 1991; 31: 455-61. PubMed

Potassium
There have been reports1-3 of severe hyperkalaemia in patients taking spironolactone, including patients with renal impairment and those with a high potassium intake from either dietary sources or potassium supplements. In the Boston Collaborative Drug

Surveillance Program4 hyperkalaemia was reported in 42.1% of patients with uraemia taking spironolactone and receiving potassium supplements compared with 2.8% of those without uraemia and not receiving potassium supplements. Two deaths were attributed to hyperkalaemia in patients taking spironolactone and potassium chloride. Potassium supplements should be avoided in patients receiving spironolactone, and plasmapotassium concentrations should be carefully monitored in those with renal impairment.

Kali
c reports1-3 ca hyperkalaemia nng bnh nhn dng spironolactone, bao gm c bnh nhn suy thn v nhng ngi c lng kali cao t hai ngun thc phm b sung kali. Trong Boston hp tc thuc st hyperkalaemia Program4 c bo co 42,1% bnh nhn dng chng niu c spironolactone v kali nhn c b sung so vi 2,8% ca nhng ngi khng c chng niu c v khng nhn c b sung kali. Hai ngi t vong do hyperkalaemia bnh nhn ang dng spironolactone v clorua kali. b sung kali cn trnh nhng bnh nhn spironolactone, v nng kali trong huyt tng nn c theo di cn thn nhng ngi suy thn.

Effects on endocrine function

Spironolactone has been associated with disturbances of endocrine function. The most prominent in men is gynaecomastia which appears to be related to both dose and duration of treatment. Incidences of 62%1 and 100%2 have been reported. Gynaecomastia has also been accompanied by impotence.3,4 The effects are generally reversible on stopping treatment. Reversal of male-pattern baldness has also been reported.5 In women symptoms include breast enlargement and tenderness.6 The incidence of menstrual abnormalities may be high: unspecified disturbances have been reported in 33 of 53 women,6 secondary amenorrhoea in 6 of 9,7 and secondary and primary amenorrhoea in 1 and 2 patients, respectively.8 The incidence of gynaecological disturbances has been found to be lower in women taking oral contraceptives.6 The mechanism of the effects of spironolactone on the endocrine system is unclear. Some workers9 suggested that although spironolactone affects testosterone synthesis, the more likely explanation was its anti-androgenic action, and reduction in 17-hydroxylase activity. Others10 found an alteration in the testosterone/oestrogen ratio due to an increase

in testosterone clearance and increased peripheral conversion to estradiol. In addition, spironolactone is reported to inhibit binding of dihydrotestosterone to receptors.

Tc dng trn chc nng ni tit

Spironolactone c lin quan vi ri lon chc nng ni tit. Ni bt nht nam gii l gynaecomastia xut hin c lin quan n c hai liu lng v thi gian iu tr. T l mc l 62% 1 v 100% 2 c bo co. Gynaecomastia cng c km theo impotence.3, 4 Cc hiu ng ny thng hi phc trn ngng iu tr. o chiu ca chng hi u kiu nam gii cng c reported.5 ph n cc triu chng bao gm m rng v v tenderness.6 t l ny ca k kinh nguyt bt thng c th cao: ri lon khng xc nh c bo co trong 33 ca 53 ph n, 6 trung v kinh 6 / 9,7 v v kinh trung hc v tiu hc ti 1 v 2 bnh nhn, respectively.8 T l mc ri lon ph khoa c tm thy l thp hn ph n ang ung contraceptives.6 C ch tc dng ca spironolactone trn h thng ni tit khng r rng. Mt s workers9 cho rng mc d nh hng n s tng hp testosterone spironolactone, gii thch nhiu kh nng l hnh ng ca mnh chng androgen, v gim hot ng 17-hydroxylase. Others10 tm thy mt thay i trong testosterone t l estrogen / do s gia tng gii phng testosterone v tng chuyn i ngoi vi ca estradiol. Ngoi ra, spironolactone c bo co c ch rng buc ca dihydrotestosterone th.

Effects on lipid metabolism

Unlike thiazide diuretics, spironolactone appeared not to increase serum-cholesterol concentrations in a study of 23 patients.1
1. 1. Ames RP, Peacock PB. Serum cholesterol during treatment of hypertension with diuretic drugs. Arch Intern Med 1984; 144: 71014. PubMed

Tc dng trn chuyn ha lipid

Khng ging nh thuc li tiu thiazide, spironolactone xut hin khng phi tng nng cholesterol trong huyt thanh trong mt nghin cu ca 23 patients.1 1. 1. Ames RP, Peacock PB. Cholesterol trong huyt thanh iu tr tng huyt p vi cc thuc li tiu. Arch Intern Med 1984; 144: 710-14. PubMed

Effects on the liver

Hepatotoxicity characterised by cholestatic lesions has been reported in a patient receiving spironolactone.1 Only one other published case of spironolactone-associated hepatotoxicity was known to the authors.
1. 1. Renkes P, et al. Spironolactone and hepatic toxicity. JAMA 1995; 273: 3767. PubMed

Tc dng trn gan

c trng bi tn thng gan mt c bo co mt bnh nhn nhn c spironolactone.1 Ch c mt trng hp khc c pht hnh c hi gan spironolactone-lin quan c bit n vi cc tc gi. 1. 1. Renkes P, et al. Spironolactone v c tnh gan. JAMA 1995; 273: 376-7. PubMed

Effects on the skin

Lichen-planus-like skin eruptions developed in a 62-year-old woman who was taking digoxin, propranolol, diazepam, spironolactone, and iron tablets.1 Flares of the lichenplanus-like eruption seemed to be associated with use of spironolactone and there was evidence of resolution when spironolactone was withdrawn. Cutaneous vasculitis was associated with spironolactone on 3 occasions in an 80-year-old man.2 A chloasma-like pigmentation of the face was reported in 2 patients receiving spironolactone for hirsutism or acne.3 1. 1. Downham TF. Spironolactone-induced lichen planus. JAMA 1978; 240: 1138. PubMed 2. 2. Phillips GWL, Williams AJ. Spironolactone induced vasculitis. BMJ 1984; 288: 368.
3. 3. Hughes BR, Cunliffe WJ. Tolerance of spironolactone. Br J Dermatol 1988; 118: 687 91. PubMed

Hiu ng trn da
a y phun tro da-planus nh pht trin mt ngi ph n 62 tui dng digoxin, propranolol, diazepam, spironolactone, v st tablets.1 pho sng ca cc v phun tro a y-planus nh dng nh c lin quan n s dng v spironolactone c bng chng v phn gii khi spironolactone c thu hi. vasculitis da c lin

quan vi spironolactone, ngy 3 ln trong mt mu 80-nm tui Mt man.2 chloasma ging nh ca khun mt c bo co 2 bnh nhn spironolactone cho rm lng hoc acne.3 1. 1. Downham TF. Spironolactone planus a y gy ra. JAMA 1978; 240: 1138. PubMed 2. 2. Phillips GWL, Williams AJ. Spironolactone gy ra vim mch. BMJ 1984; 288: 368. 3. 3. Hughes BR, Cunliffe WJ. Khoan dung vi nhng spironolactone. Br J Dermatol nm 1988; 118: 687-91. PubMed

Hypersensitivity
Eosinophilia and a rash developed in 2 patients with alcoholic cirrhosis while taking spironolactone.1
1. 1. Wathen CG, et al Eosinophilia associated with spironolactone. Lancet 1986; i: 91920. PubMed

Mn cm
Bch cu i toan v pht ban pht trin 2 bnh nhn b x gan do ru trong khi dng spironolactone.1 1. 1. Wathen CG, bch cu i toan v cc cng s lin kt vi spironolactone. Lancet 1986; i: 919-20. PubMed

Precautions
Spironolactone should not be used in patients with hyperkalaemia or severe renal impairment. It should be used with care in patients who are at increased risk of developing hyperkalaemia; such patients include the elderly, those with diabetes mellitus, and those with some degree of renal or hepatic impairment. It should also be given with care to patients likely to develop acidosis. Serum electrolytes and blood-urea-nitrogen should be measured periodically.

Bin php phng nga

Spironolactone khng c s dng bnh nhn hyperkalaemia hoc suy thn nng. N

s c s dng vi chm sc trong bnh nhn c nguy c pht trin hyperkalaemia; bnh nhn ny bao gm ngi gi, nhng ngi c bnh tiu ng, v nhng ngi c mt mc suy thn hoc gan. N cng cn c chm sc cho bnh nhn c kh nng pht trin toan. in phn ur huyt thanh v mu--nit cn c o lng nh k.

Breast feeding
The concentration of canrenone was measured1 in the serum and milk of a breast-feeding woman taking 25 mg of spironolactone four times daily. The milk to serum concentration ratios of canrenone at 2 and 14.5 hours after a dose of spironolactone were 0.72 and 0.51 respectively, and it was estimated that the amount of canrenone ingested by the infant would be 0.2% of the mother's daily dose of spironolactone. The serum potassium and sodium levels of the infant were in the normal range. The American Academy of Pediatrics2 considers that spironolactone is therefore usually compatible with breast feeding.

Cho con b
S tp trung ca canrenone c measured1 trong huyt thanh v sa ca mt ph n cho con b ung 25 mg ca spironolactone bn ln / ngy. Cc sa t l nng huyt thanh canrenone vo gi 2 v 14,5 sau mt liu spironolactone c 0,72 v 0,51 tng ng, v ngi ta c tnh rng s lng tr s sinh n phi canrenone s c 0,2% liu hng ngy ca m ca spironolactone. Cc cp kali v natri trong huyt thanh ca tr s sinh c mc bnh thng. Hc vin M xem xt Pediatrics2 spironolactone l do thng tng thch vi cho con b.

Interference with laboratory estimations

Spironolactone and canrenoate can interfere with some assays for plasma-digoxin concentrations.1-3 However, spironolactone may also produce actual changes in digoxin concentrations (see ) and results of assays should be interpreted with caution.

Can thip vi cc c tnh trong phng th nghim

Spironolactone v canrenoate c th can thip vi mt s xt nghim cho digoxin-plasma concentrations.1-3 Tuy nhin, spironolactone cng c th sn xut thc t thay i nng digoxin (xem) v kt qu xt nghim cn c din gii mt cch thn trng.

Porphyria
Spironolactone has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients.

Porphyria
Spironolactone c lin kt vi cc cuc tn cng cp tnh ca porphyria v c xem l khng an ton nhng bnh nhn porphyric.

Interactions
There is an increased risk of hyperkalaemia if spironolactone is given with potassium supplements or with other potassium-sparing diuretics. Hyperkalaemia may occur as well in patients also given ACE inhibitors, angiotensin II receptor antagonists, NSAIDs, ciclosporin, or trilostane. In patients given spironolactone with NSAIDs or ciclosporin the risk of nephrotoxicity may also be increased. Diuretics may reduce the excretion of lithium and increase the risk of lithium toxicity. Hyponatraemia may occur in patients taking a potassium-sparing diuretic with a thiazide; this risk may be increased in patients given chlorpropamide. Spironolactone may reduce the ulcer-healing properties of carbenoxolone. As with other diuretics, spironolactone may enhance the effects of other antihypertensive drugs and may reduce vascular responses to noradrenaline.

Tng tc
C mt nguy c gia tng ca hyperkalaemia nu spironolactone c a ra vi cc cht b sung kali hoc vi thuc li tiu khc kali ti thiu. Hyperkalaemia c th xy ra bnh nhn cng c cc cht c ch ACE, thuc i khng th th angiotensin II, NSAIDs, ciclosporin, hoc trilostane. bnh nhn c spironolactone vi NSAID hoc ciclosporin nguy c thn cng c th c tng ln. Thuc li tiu c th lm gim s bi tit ca lithium v tng nguy c ng c lithium. Hyponatraemia c th xy ra bnh nhn dng potassium-sparing li tiu thiazide mt vi, nguy c ny c th tng ln nhng bnh nhn c chlorpropamide. Spironolactone c th lm gim cc tnh cht lot-cha bnh ca carbenoxolone. Nh vi thuc li tiu khc, spironolactone c th lm tng tc dng ca thuc h huyt p khc v c th lm gim phn ng mch mu noradrenaline.

ACE inhibitors and angiotensin II receptor antagonists

Severe hyperkalaemia has been reported in patients given spironolactone with ACE inhibitors or angiotensin II receptor antagonists and fatalities have occurred. In a study1 of 44 patients taking such combinations for heart failure who were admitted to hospital with life-threatening hyperkalaemia, 37 required haemodialysis and 2 developed fatal complications. In another group2 of 25 patients given spironolactone with ACE inhibitors who were admitted with severe hyperkalaemia, 2 died and 4 others developed severe cardiac arrhythmias. Advanced age, renal impairment or diabetes mellitus were risk factors for hyperkalaemia in both studies. It was suggested that combinations of spironolactone with ACE inhibitors or angiotensin II receptor antagonists should be used with caution in such patients and that they should not be given doses of spironolactone above 25 mg daily.

Cht c ch ACE v thuc i khng th th angiotensin II

hyperkalaemia nng c bo co bnh nhn c spironolactone vi cht c ch ACE hoc i khng th th angiotensin II v t vong xy ra. Trong mt study1 ca 44 bnh nhn dng kt hp nh vy i vi suy tim nhng ngi nhp vin vi hyperkalaemia e da tnh mng, 37 chy thn nhn to cn thit v 2 bin chng pht trin gy t vong. Trong mt group2 ca 25 bnh nhn c spironolactone vi cht c ch ACE nhng ngi tha nhn vi hyperkalaemia nng, 2 cht v 4 ngi khc pht trin ri lon nhp tim nghim trng. Nng cao tui, suy thn hoc bnh i tho ng c yu t nguy c hyperkalaemia trong c hai nghin cu. N c cho rng s kt hp ca spironolactone vi cht c ch ACE hoc i khng angiotensin II receptor cn c dng thn trng nhng bnh nhn ny v rng h khng nn cho liu spironolactone trn 25 mg / ngy.

Cardiac glycosides
For discussions of the effects of spironolactone on digoxin and digitoxin, see . Glycosides tim i vi cc cuc tho lun v tc ng ca spironolactone trn digoxin v digitoxin, xem v, tng ng. Xem thm can thip vi cc phng th nghim c tnh, theo phng, and

, respectively. See also Interference with Laboratory Estimations, under Precautions,

Mitotane

For a report of the inhibition of the action of mitotane by spironolactone, see

Mitotane
i vi mt bo co v s c ch hot ng ca mitotane bi spironolactone, xem

Warfarin
For reference to the interaction between warfarin and spironolactone, see .

Warfarin
tham kho cho s tng tc gia warfarin v spironolactone, xem

Pharmacokinetics
Spironolactone is well absorbed from the gastrointestinal tract, with a bioavailability of about 90%. It is about 90% bound to plasma proteins. Spironolactone is metabolised extensively to a number of metabolites including canrenone and 7-thiomethylspirolactone, both of which are pharmacologically active. The major metabolite may be 7-thiomethylspirolactone, although it is uncertain to what extent the actions of spironolactone are dependent on the parent compound or its metabolites. Spironolactone is excreted mainly in the urine and also in the faeces, in the form of metabolites. Spironolactone or its metabolites may cross the placental barrier, and canrenone is distributed into breast milk.

Dc ng hc
Spironolactone c hp thu tt qua ng tiu ha, vi mt kh dng sinh hc ca khong 90%. l khong 90% gn vi protein huyt tng. Spironolactone c chuyn ha rng ri vi mt s cht chuyn ha bao gm canrenone v thiomethylspirolactone-7, c hai u c hot tnh dc. Cc cht chuyn ha chnh c th c 7-thiomethylspirolactone, mc d n l khng chc chn n mc no cc hnh ng ca spironolactone ph thuc vo cc hp cht hoc cht chuyn ha ca n. Spironolactone c bi tit ch yu l trong nc tiu v cng c trong phn, dng cht chuyn ha. Spironolactone hoc cht chuyn ha ca n c th qua c hng ro nhau thai, v canrenone c phn phi vo sa m

Uses and Administration

Spironolactone, a steroid with a structure resembling that of the natural adrenocortical hormone aldosterone, acts on the distal portion of the renal tubule as a competitive antagonist of aldosterone. It acts as a potassium-sparing diuretic, increasing sodium and water excretion and reducing potassium excretion. Spironolactone is reported to have a relatively slow onset of action, requiring 2 or 3 days for maximum effect, and a similarly slow diminishment of action over 2 or 3 days on stopping. Spironolactone is used in the management of heart failure, both to treat refractory oedema and in lower doses as an adjunct to standard therapy (see ). It is also used for ), or refractory oedema associated with cirrhosis of the liver (with or without ascites,

the nephrotic syndrome, and in ascites associated with malignancy. It is frequently given with the thiazides, furosemide, or similar diuretics, where it adds to their natriuretic but diminishes their kaliuretic effects, hence conserving potassium in those at risk from hypokalaemia. Diuretic-induced hypokalaemia and its management, including the role of potassium-sparing diuretics, is discussed under Effects on the Electrolyte Balance in the Adverse Effects of Hydrochlorothiazide, . It has been used in the treatment of essential hypertension (in lower doses than for oedema), but in the UK is no longer recommended for use in either essential hypertension or idiopathic oedema; doubts have been expressed over its safety during long-term administration. Spironolactone is also used in the diagnosis and treatment of primary hyperaldosteronism ( ).

Other conditions in which spironolactone has been tried on the basis of its antiandrogenic properties include hirsutism, particularly in the polycystic ovary syndrome. In the treatment of oedema, spironolactone is usually given in an initial oral dose of 100 mg daily, subsequently adjusted as necessary; some patients may require doses of up to 400 mg daily. In hepatic cirrhosis with ascites and oedema, patients with a urinary

sodium/potassium ratio greater than 1 may be given an initial dose of spironolactone 100 mg daily while patients with a ratio of less than 1 may be given initial doses of 200 to 400 mg daily. Spironolactone is given in doses of 400 mg daily in the presumptive diagnosis of primary hyperaldosteronism; in doses of 100 to 400 mg daily for the pre-operative management of hyperaldosteronism; and in the lowest effective dosage for long-term maintenance therapy in the absence of surgery. Suggested doses of spironolactone for children range from 1 to 3 mg/kg daily, in divided doses. Potassium supplements should not be given with spironolactone.

S dng v Qun tr
Spironolactone, mt steroid c cu trc tng t nh l ca hormone aldosterone adrenocortical t nhin, hnh vi phn xa ca ng thn nh l mt cht i khng cnh tranh ca aldosterone. N hot ng nh mt cht li tiu ti thiu kali, natri v tng bi tit nc v bi tit kali gim. Spironolactone c bo co l c mt s khi u tng i chm ca hnh ng, yu cu 2 hoc 3 ngy cho hiu qu ti a, v diminishment mt hnh ng tng t chm hn 2 hoc 3 ngy dng li. Spironolactone c s dng trong qun l ca suy tim, c hai iu tr ph chu la v vi liu lng thp hn nh mt thuc h tr iu tr tiu chun (xem). N cng c s dng cho ph chu la kt hp vi bnh x gan (c hoc khng c c trng,), hi chng thn h hoc, v trong c trng kt hp vi bnh c tnh. N thng c a ra vi cc thiazide, furosemide, hoc thuc li tiu tng t, ni m n thm vo natriuretic ca h, nhng lm gim hiu ng kaliuretic ca h, do bo tn kali trong nhng ngi c nguy c b h kali mu. Li tiu h kali mu gy ra v qun l ca n, bao gm vai tr ca thuc li tiu ti thiu kali, c tho lun theo Tc dng trn s cn bng in gii trong cc tc hi ca hydrochlorothiazide. N c s dng trong iu tr tng huyt p cn thit (vi liu lng thp hn cho ph), nhng Anh khng cn khuyn co s dng trong hoc cao huyt p cn thit hoc ph t pht; nghi ng c by t v an ton ca n trong qun l lu di.

Spironolactone cng c s dng trong chn on v iu tr cc hyperaldosteronism chnh (). Cc iu kin khc m trong spironolactone c th nghim trn c s tnh cht ca n chng androgen bao gm rm lng, c bit trong hi chng bung trng a nang. Trong khi iu tr ph, spironolactone thng c a ra trong mt liu ung ban u l 100 mg / ngy, sau iu chnh khi cn thit, mt s bnh nhn c th cn liu ln n 400 mg / ngy. Trong x gan c trng gan v ph n, bnh nhn c natri niu / t l kali ln hn 1 c th c cho mt liu ban u l 100 mg mi ngy trong khi bnh nhn spironolactone vi mt t l nh hn 1 c th c cho dng liu ban u l 200-400 mg / ngy . Spironolactone c a ra trong liu 400 mg / ngy trong chn on khon ca hyperaldosteronism tiu hc; liu 100 n 400 mg / ngy cho vic qun l trc tc ca hyperaldosteronism; v liu lng thp nht c hiu qu cho iu tr duy tr lu di trong s vng mt ca phu thut. ngh liu spironolactone cho tr em phm vi 1-3 mg / kg / ngy, chia liu. b sung kali khng nn c vi spironolactone

Acne
Spironolactone has been used for its anti-androgenic properties in some cases of acne ( ) where standard therapy is unsuccessful. Beneficial responses to oral therapy have been reported in patients with acne from both open1 and placebo-controlled2,3 studies. Topical application has been tried4,5 but response has been variable. It is possible that the vehicle may affect the response. In women, spironolactone may be useful when treatment with an oestrogen is contra-indicated.

Mn trng c
Spironolactone c s dng cho cc thuc tnh ca n chng androgen trong mt s trng hp mn trng c (), ni iu tr tiu chun l khng thnh cng. phn ng c li iu tr rng ming c bo co bnh nhn mn trng c t c hai open1 v gi dc-controlled2, 3 nghin cu. ti ng dng c tried4, 5, nhng phn ng c thay i. C th l chic xe c th nh hng n phn ng. ph n, spironolactone c th hu ch khi iu tr bng estrogen mt l chng ch nh.

Heart failure
Drug therapy of heart failure ( ) is based on the use of diuretics, ACE inhibitors,

cardiac glycosides, beta blockers, and vasodilators. Spironolactone has been used as a diuretic for refractory oedema, but it also has an additional role as an aldosterone antagonist.1,2 Although the precise neurohormonal mechanisms leading to the development of heart failure are still not clear, there is evidence that raised levels of aldosterone may contribute to the pathophysiology.3,4 ACE inhibitor therapy suppresses aldosterone production but this effect is not complete and the use of spironolactone with ACE inhibitors has therefore been studied. In the Randomized Aldactone Evaluation Study (RALES)5 in patients with severe heart failure, addition of spironolactone in a dose of 25 to 50 mg daily to therapy with ACE inhibitors and loop diuretics reduced the risk of death or hospitalisation,5 and the use of spironolactone should therefore be considered in such patients.6-8 A small study9 has also shown benefit in patients with less severe heart failure. However, use of spironolactone with ACE inhibitors may lead to hyperkalaemia and careful monitoring of potassium concentrations is required10,11 (see Interactions, A retrospective analysis12 of heart failure patients found that over 10% had to stop spironolactone because of hyperkalaemia, and a further 10% stopped because of worsening renal function. Risk factors were advanced age and higher baseline plasmapotassium concentrations. ).

S ngt i
Thuc iu tr suy tim () c da trn vic s dng thuc li tiu, cht c ch ACE, glycoside tim, thuc chn beta, v cc thuc gin mch. Spironolactone c s dng nh mt thuc li tiu cho ph chu la, nhng n cng c mt vai tr b sung nh mt aldosterone antagonist.1, 2 Mc d cc c ch neurohormonal chnh xc dn n s pht trin ca suy tim vn cn cha r rng, c bng chng rng mc tng aldosterone c th ng gp vo s pathophysiology.3, 4 cht c ch ACE liu php ngn chn sn xut aldosterone nhng hiu qu ny khng hon ton v vic s dng spironolactone vi cht c ch ACE c nn c nghin cu. Trong ngu nhin nh gi Aldactone hc (RALES) 5 bnh nhn suy tim nng, b sung spironolactone trong mt liu t 25 n 50 mg mi ngy iu tr vi thuc c ch ACE v thuc li tiu vng lp gim nguy c t vong hay nhp vin, 5 v s dng spironolactone do cn phi c xem xt

trong patients.6-8 Mt nh study9 cng th hin li ch bnh nhn suy tim nng hn. Tuy nhin, vic s dng spironolactone vi cht c ch ACE c th dn n hyperkalaemia v theo di cn thn nng kali l required10, 11 (xem Tng tc,). Mt truy analysis12 ca bnh nhn suy tim thy rng hn 10% phi dng li v hyperkalaemia spironolactone, v thm 10% dng li v chc nng thn xu i. Yu t nguy c c nng cao tui v cao hn ng c s nng kali trong huyt tng.

High-altitude disorders
Acetazolamide is generally the drug of choice for prophylaxis of high-altitude disorders ( ). Anecdotal reports1-4 and a small-scale double-blind study5 suggested that spironolactone could be useful in preventing acute mountain sickness, although a deterioration in pulmonary function despite spironolactone prophylaxis has been noted in a patient.6

Ri lon cao cao

Acetazolamide thng l thuc c la chn d phng cc ri lon cao cao (). Giai thoi reports1-4 v m i quy m nh study5 cho rng spironolactone c th hu ch trong vic ngn nga bnh tt ni cp tnh, mc d s suy gim chc nng phi mc d d phng spironolactone c ghi nhn trong mt patient.6

Hirsutism
Hirsutism ( ) is frequently treated with anti-androgens, usually cyproterone or

spironolactone. Spironolactone in doses of 50 to 200 mg daily has produced both subjective and objective improvement in hirsutism in patients with idiopathic hirsutism or polycystic ovary syndrome,1-4 and its use has been reviewed.5 It is preferably used with oral contraceptives,6,7 to improve efficacy and menstrual irregularity and to avoid the risk of feminisation to a male fetus. Most studies have involved premenopausal women and it has been suggested4,8 that spironolactone would be useful in women in whom cyproterone is contra-indicated or not tolerated. A randomised study (not placebo-controlled) found spironolactone 100 mg daily and cyproterone 100 mg daily to be equally effective,9 while a systematic review10 of the use of spironolactone in hirsutism concluded that it was

significantly more effective than both cyproterone and finasteride for up to 12 months after treatment.

Rm lng
Rm lng () l thng xuyn iu tr bng khng androgen, thng cyproterone hoc spironolactone. Spironolactone liu t 50 n 200 mg / ngy sn xut c hai ci tin ch quan v khch quan trong rm lng nhng bnh nhn t pht hoc hi chng rm lng bung trng a nang ,1-4 v s dng ca n c reviewed.5 N l tt hn c s dng vi thuc ung nga thai, 6,7 ci thin hiu qu v kinh nguyt bt thng v trnh cc nguy c feminisation cho mt bo thai nam. Hu ht cc nghin cu c lin quan n ph n tin mn kinh v n c suggested4, 8 rng spironolactone c th hu ch ph n trong c cyproterone l chng ch nh hoc khng dung np. Mt nghin cu ngu nhin (khng phi kim sot gi dc) c tm thy spironolactone 100 mg mi ngy v cyproterone 100 mg mi ngy c hiu qu nh nhau, 9, trong khi mt h thng review10 ca vic s dng spironolactone trong rm lng kt lun rng n c ng k hiu qu hn c cyproterone v finasteride ln n 12 thng sau khi iu tr

Hyperaldosteronism
Hyperaldosteronism (aldosteronism) is a disorder characterised by mineralocorticoid excess due to high circulating levels of aldosterone.1-4 Mineralocorticoid excess due to other mineralocorticoids is rare. Primary hyperaldosteronism is usually caused by an aldosterone-producing adenoma (Conn's syndrome) or primary adrenal hyperplasia. Other causes include aldosterone-producing adrenal carcinoma, and glucocorticoidsuppressible hyperaldosteronism. Secondary hyperaldosteronism is more common and results from conditions in which there is activation of the renin-angiotensin-aldosterone system, including diuretic therapy, and oedematous conditions such as heart failure, hepatic cirrhosis, and nephrotic syndrome. Bartter's syndrome ( ) also results in hyperaldosteronism.

Most patients with primary hyperaldosteronism are asymptomatic, although they may present with signs or symptoms of mineralocorticoid excess ( ). Diagnosis often

follows the incidental discovery of hypokalaemia. Symptomatic hypokalaemia ( may develop in some patients, particularly those taking diuretics. Diagnosis is confirmed by the presence of raised plasma and urinary aldosterone concentrations. However, the concentrations may be affected by serum-potassium

concentration, posture, and time of day, and interpretation may be difficult. The plasma aldosterone:renin ratio may also be measured. In primary hyperaldosteronism the aldosterone concentration is raised but renin is suppressed, although this does not necessarily prove the diagnosis; in secondary hyperaldosteronism both are raised. Radiological and nuclear imaging are useful for further differentiating between adenoma and hyperplasia. Hyperaldosteronism due to an aldosterone-producing adenoma is usually treated surgically. The aldosterone antagonist spironolactone may be given pre-operatively to lower the blood pressure and normalise the serum potassium. In patients who are not suitable for surgery, long-term medical management involves spironolactone, initially in high doses but reduced to the lowest dose for maintenance. If spironolactone is not tolerated, amiloride may be used as an alternative, but high doses are required. There has also been a report5 of the successful use of eplerenone, another aldosterone antagonist; gynaecomastia had developed with spironolactone but resolved when treatment was changed to eplerenone. Trilostane, an adrenal suppressant, has been used to inhibit aldosterone synthesis. In primary adrenal hyperplasia surgery is not usually effective and medical management with spironolactone or amiloride is required. Additional antihypertensive therapy may also be needed. Glucocorticoid-suppressible hyperaldosteronism, also known as familial hyperaldosteronism type I (FH-I), is a rare autosomal dominant form and may be treated with dexamethasone. However, this may not control the blood pressure and spironolactone or amiloride may be required in addition. In secondary hyperaldosteronism the underlying condition should be treated, but spironolactone may be of benefit as part of the therapy. For further information on the substances mentioned above, see:

Hyperaldosteronism
Hyperaldosteronism (aldosteronism) l mt ri lon c trng bi s d tha mineralocorticoid do mc cao lu thng ca aldosterone.1-4 d tha mineralocorticoid do mineralocorticoids khc l rt him. hyperaldosteronism tiu thng c gy ra bi mt u tuyn aldosterone-sn xut (ca hi chng Conn) hoc tng sn thng thn tiu hc. Cc nguyn nhn khc bao gm sn xut aldosterone ung th tuyn thng thn, v hyperaldosteronism glucocorticoid-suppressible. Trung hyperaldosteronism l ph bin hn v kt qu t iu kin, trong c kch hot ca h thng renin-angiotensin-aldosterone, bao gm liu php li tiu, v iu kin oedematous nh suy tim, x gan, v hi chng thn h. Bartter ca hi chng () cng c kt qu trong hyperaldosteronism. Hu ht bnh nhn khng triu chng hyperaldosteronism chnh, mc d h c th trnh by vi cc du hiu hoc triu chng ca tha mineralocorticoid (). Chn on thng sau s pht hin ngu nhin ca h kali mu. Triu chng h kali mu () c th pht trin mt s bnh nhn, c bit l nhng ngi ung thuc li tiu. Chn on c xc nhn bi s hin din ca huyt tng tng v nng aldosterone tit niu. Tuy nhin, nng c th b nh hng bi nng kali trong huyt thanh, t th, v thi gian trong ngy, v gii thch c th kh khn. Cc plasma aldosterone: t l renin cng c th c o lng. Trong hyperaldosteronism chnh nng aldosterone c tng ln nhng renin b c ch, mc d iu ny khng nht thit phi chng minh c chn on, trong hyperaldosteronism th hai c nng ln. Phng x v hnh nh ht nhn c ch cho thm phn bit gia u tuyn v tng sn. Hyperaldosteronism do mt u tuyn aldosterone sn xut thng c iu tr bng phu thut. Cc cht i khng aldosterone spironolactone c th c a ra trc operatively h huyt p v bnh thng ha cc kali huyt thanh. nhng bnh nhn khng ph hp vi phu thut, qun l y t di hn lin quan n vic spironolactone, ban u liu cao, nhng gim n liu thp nht bo tr. Nu spironolactone khng dung np, Amiloride c th c s dng nh l mt thay th, nhng liu lng cao c yu cu. Cng c mt report5 ca vic s dng thnh cng ca eplerenone, cht i khng aldosterone khc; gynaecomastia pht trin vi spironolactone, nhng gii quyt khi iu tr c thay i eplerenone. Trilostane, mt c ch thng thn, c s dng c ch tng hp aldosterone. Trong tiu hc tng sn thng thn phu thut thng khng c hiu qu v qun l y t

vi spironolactone hoc Amiloride l bt buc. B sung iu tr h huyt p cng c th l cn thit. Glucocorticoid-suppressible hyperaldosteronism, cn c gi l loi hyperaldosteronism gia nh ti (FH-I), l mt hnh thc ni tri NST thng him v c th c iu tr bng dexamethason. Tuy nhin, iu ny c th khng kim sot huyt p v spironolactone hoc Amiloride c th yu cu thm. Trong hyperaldosteronism trung cc iu kin c bn cn c iu tr, nhng spironolactone c th c cc li ch nh l mt phn ca liu php ny. bit thm thng tin v cc cht nu trn, hy xem: 4. CIPROBAY (CIPROFLOXACINE)
Ciprofloxacin l thuc khng sinh bn tng hp, c ph khng khun rng, thuc nhm quinolon, cn c gi l cc cht c ch DNA girase. Do c ch enzym DNA girase, nn thuc ngn s sao chp ca chromosom khin cho vi khun khng sinh sn c nhanh chng. Ciprofloxacin c tc dng tt vi cc vi khun khng li khng sinh thuc cc nhm khc (aminoglycosid, cephalosporin, tetracyclin, penicilin...) v c coi l mt trong nhng thuc c tc dng mnh nht trong nhm fluoroquinolon. Ciprofloxacin hp thu nhanh v d dng ng tiu ha. Khi c thc n v cc thuc chng toan, hp thu thuc b chm li nhng khng b nh hng mt cch ng k. Sau khi ung, nng ti a ca ciprofloxacin trong mu xut hin sau 1 - 2 gi vi kh dng sinh hc tuyt i l 70 - 80%. Vi liu 250 mg (cho ngi bnh nng 70 kg), nng ti a trung bnh trong huyt thanh l vo khong 1,2 mg/lt. Nng ti a trung bnh trong huyt thanh ng vi cc liu 500 mg, 750 mg, 1000 mg l 2,4 mg/lt, 4,3 mg/lt v 5,4 mg/lt. Nng ti a trong huyt tng sau khi truyn tnh mch trong 30 pht vi liu 200 mg l 3 - 4 mg/lt. Na i trong huyt tng l khong 3,5 n 4,5 gi ngi bnh c chc nng thn bnh thng, thi gian ny di hn ngi bnh b suy thn v ngi cao tui (xem thm phn liu lng). Dc ng hc ca thuc khng thay i ng k ngi bnh mc bnh nhy nht. Th tch phn b ca ciprofloxacin rt ln (2 - 3 lt/kg th trng) v do , lc mu hay thm tch mng bng ch rt i c mt lng nh thuc. Thuc c phn b rng khp v c nng cao nhng ni b nhim khun (cc dch c th, cc m), ni chung thuc d ngm vo m. Nng trong m thng cao hn nng trong huyt thanh, c bit l cc nhu m, c, mt v tuyn tin lit. Nng trong dch bch huyt v dch ngoi bo cng gn bng nng trong huyt thanh. Nng thuc trong nc bt, nc mi, m, dch bng,

da, sn v xng tuy c thp hn, nhng vn mc thch hp. Nu mng no bnh thng, th nng thuc trong dch no ty ch bng 10% nng trong huyt tng; nhng khi mng no b vim, th thuc ngm qua nhiu hn. Ciprofloxacin i qua nhau thai v bi tit qua sa m. Trong mt cng c nng thuc cao. Khong 40 - 50% liu ung o thi di dng khng i qua nc tiu nh lc cu thn v bi tit ng thn. Khong 75% liu tim tnh mch o thi di dng khng i qua nc tiu v 15% theo phn. Hai gi u tin sau khi ung liu 250 mg, nng ciprofloxacin trong nc tiu c th t ti trn 200 mg/lt v sau 8 - 12 gi l 30 mg/lt. Cc ng o thi khc l chuyn ha gan, bi xut qua mt, v thi qua nim mc vo trong lng rut (y l c ch o thi b tr ngi bnh b suy thn nng). Thuc c o thi ht trong vng 24 gi. Ph khng khun: Ciprofloxacin c ph khng khun rt rng, bao gm phn ln cc mm bnh quan trng. Phn ln cc vi khun Gram m, k c Pseudomonas v Enterobacter u nhy cm vi thuc. Cc vi khun gy bnh ng rut nh Salmonella, Shigella, Yersina v Vibrio cholerae thng nhy cm cao. Tuy nhin, vi vic s dng ngy cng nhiu v lm dng thuc, c bo co v tng t l khng thuc ca Salmonella. Cc vi khun gy bnh ng h hp nh Haemophilus v Legionella thng nhy cm, Mycoplasma v Chlamydia ch nhy cm va phi vi thuc. Neisseria thng rt nhy cm vi thuc. Ni chung, cc vi khun Gram dng (cc chng Enterococcus, Staphylococcus, Streptococcus, Listeria monocytogenes...) km nhy cm hn. Ciprofloxacin khng c tc dng trn phn ln cc vi khun k kh. Do c ch tc dng c bit ca thuc nn ciprofloxacin khng c tc dng cho vi cc thuc khng sinh khc nh aminoglycosid, cephalosporin, tetracyclin, penicilin... Theo bo co ca Chng trnh gim st quc gia ca Vit Nam v tnh khng thuc ca vi khun gy bnh thng gp (1997) v thng tin s 4 nm 1999, th ciprofloxacin vn c tc dng cao i vi Salmonella typhi (100%), Shigella flexneri (100%). Cc vi khun ang tng khng ciprofloxacin gm c Staphylococcus aureus khng ciprofloxacin vi t l 20,6%, Escherichia coli khng ciprofloxacin vi t l 27,8% v S. pneumoniae khng ciprofloxacin vi t l 30%. Tnh hnh khng khng sinh cc tnh pha nam c cao hn cc tnh pha bc. Vic s

dng ciprofloxacin cn phi thn trng, c ch nh ng, v khng ciprofloxacin cng ging nh khng cc thuc khng sinh khc l mt vn ngy cng thng gp (xem phn Liu lng).

Ch nh
Ciprofloxacin ch c ch nh cho cc nhim khun nng m cc thuc khng sinh thng thng khng tc dng trnh pht trin cc vi khun khng cipofloxacin: Vim ng tit niu trn v di; vim tuyn tin lit; vim xng - ty; vim rut vi khun nng; nhim khun nng mc trong bnh vin (nhim khun huyt, ngi b suy gim min dch). D phng bnh no m cu v nhim khun ngi suy gim min dch.

Chng ch nh
Ngi c tin s qu mn vi ciprofloxacin v cc thuc lin quan nh acid nalidixic v cc quinolon khc. Khng c dng ciprofloxacin cho ngi mang thai v thi k cho con b, tr khi buc phi dng.

Thn trng
Cn thn trng khi dng ciprofloxacin i vi ngi c tin s ng kinh hay ri lon h thn kinh trung ng, ngi b suy chc nng gan hay chc nng thn, ngi thiu glucose 6 phosphate dehydrogenase, ngi b bnh nhc c. Dng ciprofloxacin di ngy c th lm cc vi khun khng nhy cm vi thuc pht trin qu mc. Nht thit phi theo di ngi bnh v lm khng sinh thng xuyn c bin php iu tr thch hp theo khng sinh . Ciprofloxacin c th lm cho cc xt nghim vi khun Mycobacterium tuberculosis b m tnh. Ciprofloxacin c th gy hoa mt chng mt, u c quay cung, nh hng n vic iu khin xe c hay vn hnh my mc. Hn ch dng ciprofloxacin cho tr nh v tr ang ln (trn thc nghim, thuc c gy thoi ha sn cc khp chu trng lc).

Thi k mang thai

Ch nn dng ciprofloxacin cho ngi mang thai trong nhng trng hp nhim khun nng m khng c khng sinh khc thay th, buc phi dng ti fluoroquinolon.

Thi k cho con b

Khng dng ciprofloxacin cho ngi cho con b, v ciprofloxacin tch li trong sa v c th t n nng c th gy tc hi cho tr. Nu m buc phi dng ciprofloxacin th phi ngng cho con b.

Tc dng khng mong mun (ADR)

Ni chung, ciprofloxacin dung np tt. Tc dng ph ca thuc ch yu l ln d dy - rut, thn kinh trung ng v da. Thng gp, ADR > 1/100 Tiu ha: Bun nn, nn, a chy, au bng. Chuyn ha: Tng tm thi nng cc transaminase. t gp, 1/1000 < ADR < 1/100 Ton thn: Nhc u, st do thuc. Mu: Tng bch cu a eosin, gim bch cu lympho, gim bch cu a nhn, thiu mu, gim tiu cu. Tim - mch: Nhp tim nhanh. Thn kinh trung ng: Kch ng. Tiu ha: Ri lon tiu ha. Da: Ni ban, nga, vim tnh mch nng. Chuyn ha: Tng tm thi creatinin, bilirubin v phosphatase kim trong mu. C xng: au cc khp, sng khp. Him gp, ADR < 1/1000

Ton thn: Phn ng phn v hoc dng phn v. Mu: Thiu mu tan mu, tng bch cu, tng tiu cu, thay i nng prothrombin. Thn kinh trung ng: Cn co git, l ln, ri lon tm thn, hoang tng, mt ng, trm cm, lon cm ngoi vi, ri lon th gic k c o gic, ri lon thnh gic, tai, ri lon v gic v khu gic, tng p lc ni s. Tiu ha: Vim i trng mng gi. Da: Hi chng da - nim mc, vim mch, hi chng Lyell, ban da thnh nt, ban a dng tit dch. Gan: c bo co v mt vi trng hp b hoi t t bo gan, vim gan, vng da mt. C: au c, vim gn (gn gt) v m bao quanh. C mt vi trng hp b t gn, c bit l ngi cao tui khi dng phi hp vi corticosteroid. Tit niu - sinh dc: C tinh th niu khi nc tiu kim tnh, i ra mu, suy thn cp, vim thn k. Khc: Nhy cm vi nh sng khi phi nng, ph thanh qun hoc ph phi, kh th, co tht ph qun.

Hng dn cch x tr ADR

trnh c tinh th niu, duy tr lng nc ung vo, trnh lm nc tiu qu kim. Nu b a chy nng v ko di trong v sau khi iu tr, ngi bnh c th b ri lon nng rut (vim i trng mng gi). Cn ngng ciprofloxacin v thay bng mt khng sinh khc thch hp (v d vancomycin). Nu c bt k du hiu no v tc dng ph cn ngng dng ciprofloxacin v ngi bnh cn phi c iu tr ti mt c s y t mc d cc tc dng ph ny thng nh hoc va v s mau ht khi ngng dng ciprofloxacin.

Liu lng v cch dng

Liu ung (ciprofloxacin hydroclorid):

Mun thuc hp thu nhanh, nn ung thuc 2 gi sau ba n. Ngi bnh cn c dn ung nhiu nc v khng ung thuc chng toan d dy trong vng 2 gi sau khi ung thuc. Thi gian iu tr ciprofloxacin ty thuc vo loi nhim khun v mc nng nh ca bnh v cn c xc nh ty theo p ng lm sng v vi sinh vt ca ngi bnh. Vi a s nhim khun, vic iu tr cn tip tc t nht 48 gi sau khi ngi bnh khng cn triu chng. Thi gian iu tr thng l 1 - 2 tun, nhng vi cc nhim khun nng hoc c bin chng, c th phi iu tr di ngy hn. iu tr ciprofloxacin c th cn phi tip tc trong 4 - 6 tun hoc lu hn trong cc nhim khun xng v khp. a chy nhim khun thng iu tr trong 3 - 7 ngy hoc c th ngn hn.

Liu truyn tnh mch (ciprofloxacin lactat) Thi gian truyn tnh mch trong 60 pht. Cn phi gim liu ngi b suy gim chc nng thn hay chc nng gan. Trong trng hp ngi b suy chc nng thn, nu dng liu thp th khng cn gim liu; nu dng liu

cao th phi iu chnh liu da vo thanh thi creatinin, hoc nng creatinin trong huyt thanh.

Tr em v tr v thnh nin: Ung 7,5 - 15 mg/kg/ngy, chia 2 - 3 ln. Truyn tnh mch 5 - 10 mg/kg/ngy, truyn trong thi gian t 30 - 60 pht.

Tng tc thuc
Dng ng thi cc thuc chng vim khng steroid (ibuprofen, indomethacin...) s lm tng tc dng ph ca ciprofloxacin. Dng ng thi thuc chng toan c nhm v magnesi s lm gim nng trong huyt thanh v gim kh dng sinh hc ca ciprofloxacin. Khng nn ung ng thi ciprofloxacin vi cc thuc chng toan, cn ung thuc xa nhau (nn ung thuc chng toan 2 - 4 gi trc khi ung ciprofloxacin) tuy cch ny cng khng gii quyt trit c vn . hp thu ciprofloxacin c th b gim i mt na nu dng ng thi mt s thuc gy c t bo (cyclophosphamid, vincristin, doxorubicin, cytosin arabinosid, mitozantron). Nu dng ng thi didanosin, th nng ciprofloxacin b gim i ng k. Nn ung ciprofloxacin trc khi dng didanosin 2 gi hoc sau khi dng didanosin 6 gi. Cc ch phm c st (fumarat, gluconat, sulfat) lm gim ng k s hp thu ciprofloxacin rut. Cc ch phm c km nh hng t hn. Trnh dng ng thi ciprofloxacin vi cc ch phm c st hoc km hay ung cc th thuc ny cng xa nhau cng tt. Ung ng thi sucralfat s lm gim hp thu ciprofloxacin mt cch ng k. Nn cho ung khng sinh 2 - 6 gi trc khi ung sucralfat.

Ung ciprofloxacin ng thi vi theophylin c th lm tng nng theophylin trong huyt thanh, gy ra cc tc dng ph ca theophylin. Cn kim tra nng theophylin trong mu, v c th gim liu theophylin nu buc phi dng 2 loi thuc. Ciprofloxacin v ciclosporin dng ng thi c th gy tng nht thi creatinin huyt thanh. Nn kim tra creatinin huyt mi tun 2 ln. Probenecid lm gim mc lc cu thn v gim bi tit ng thn, do lm gim o thi thuc qua nc tiu. Warfarin phi hp vi ciprofloxacin c th gy h prothrombin. Cn kim tra thng xuyn prothrombin huyt v iu chnh liu thuc chng ng mu.

n nh v bo qun
Bo qun vin nn v nang ciprofloxacin hydroclorid trong l kn nhit di 30 0C, trnh nh sng cc tm mnh. Dung dch ciprofloxacin hydroclorid trong nc c pH t 1,5 n 7,5, gi nhit phng c th bn vng trong t nht 14 ngy. Bo qun dung dch tim ciprofloxacin lactat m c nhit 5 - 25 0C v dung dch tim truyn tnh mch ciprofloxacin nhit 5 - 300C. Ch phm thuc tim phi bo qun trnh nh sng v trnh ng bng. Bo qun thuc tra mt ciprofloxacin hydroclorid nhit 2 - 30 0C, trong l kn trnh nh sng.

Tng k
Dung dch tim truyn ciprofloxacin c pH t 3,9 n 4,5 v tng k vi cc thuc tim khng n nh v mt l ha khong pH ny. thy c tng k gia ciprofloxacin v heparin natri, gia ciprofloxacin hoc pefloxacin vi penicilin, fluocloxacilin, amoxycilin, dng kt hp amoxycilin v clavulanat kali, aminophylin, v clindamycin. V vy, khng c trn thuc tim ciprofloxacin vi cc thuc tim khc c pH cao.

Adverse Effects
Ciprofloxacin is generally well tolerated. The range of adverse effects associated with ciprofloxacin and the other fluoroquinolones is broadly similar to that of earlier

quinolones such as nalidixic acid ( tract, CNS, or skin.

). They most often involve the gastrointestinal

Gastrointestinal disturbances include nausea, vomiting, diarrhoea, abdominal pain, and dyspepsia and are the most frequent adverse effects. Pseudomembranous colitis, pancreatitis, and dysphagia have been reported rarely. Headache, dizziness, confusion, insomnia, and restlessness are among the commonest effects on the CNS. Others include tremor, drowsiness, nightmares, visual and other sensory disturbances, hallucinations, psychotic reactions, depression, convulsions, and intracranial hypertension. Paraesthesia and peripheral neuropathy have also been reported. In addition to rash and pruritus, hypersensitivity-type reactions affecting the skin have included, rarely, vasculitis, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Photosensitivity has occurred, although it may be more frequent with some other fluoroquinolones such as lomefloxacin and sparfloxacin. Anaphylaxis has been associated with ciprofloxacin and some other quinolones. As with other quinolones, reversible arthralgia or myalgia has sometimes occurred and joint erosions have been documented in immature animals. Tendon damage has also been reported. Other adverse effects reported with ciprofloxacin include crystalluria, transient increases in serum creatinine or blood urea nitrogen and, rarely, acute renal failure secondary to interstitial nephritis. Elevated liver enzyme values, jaundice, and hepatitis have occurred, as have haematological disturbances including eosinophilia, leucopenia, thrombocytopenia and, very rarely, pancytopenia, haemolytic anaemia or agranulocytosis. Cardiovascular adverse effects include tachycardia, hypotension, oedema, syncope, hot flushes, and sweating. Some fluoroquinolones may rarely cause prolongation of the QT interval and ventricular arrhythmias, including torsade de pointes (see ).

As with other antibacterials, superinfection with organisms not very susceptible to ciprofloxacin is possible. Such organisms include Candida, Clostridium difficile, and Streptococcus pneumoniae. There is some evidence that fluoroquinolone use may be associated with an increased risk of colonisation by MRSA.

Pain and irritation may occur at the site of infusion accompanied rarely by phlebitis or thrombophlebitis. Adverse effects reported after ocular use of ciprofloxacin include local burning or discomfort, keratopathy, corneal staining, corneal precipitates or infiltrates, and photophobia. Local discomfort, pain, or pruritus have occurred after use of ear drops containing ciprofloxacin. General reviews of the adverse effects of fluoroquinolones1-7 and ciprofloxacin specifically.8,9

Hiu ng bt li
Ciprofloxacin l ni chung c dung np tt. Phm vi ca cc tc dng ph lin kt vi ciprofloxacin v cc fluoroquinolones khc l rng ri tng t nh ca quinolone trc chng hn nh acid nalidixic (). H thng xuyn nht lin quan n ng tiu ha, thn kinh trung ng, hoc da. ri lon tiu ha bao gm bun nn, nn ma, tiu chy, au bng, v kh tiu v thng xuyn nht l cc tc dng ph. Vim i trng mng gi, vim ty, v chng kh nut c bo co him khi. Nhc u, chng mt, l ln, mt ng, v bt an l mt trong cc hiu ng ph bin trn thn kinh trung ng. Nhng ngi khc bao gm run, bun ng, c mng, ri lon th gic v cm gic khc, o gic, phn ng tm thn, trm cm, co git, v cao huyt p lc ni s. Paraesthesia v thn kinh ngoi bin cng c bo co. Ngoi vic pht ban v nga, phn ng qu mn loi nh hng n ln da bao gm, him khi hoi t, vim mch, ban multiforme, hi chng Stevens-Johnson, v c biu b. Nhy xy ra, mc d n c th c thng xuyn hn vi mt s fluoroquinolones khc nh lomefloxacin v sparfloxacin. Sc phn v c lin kt vi ciprofloxacin v mt s quinolone khc. Cng nh cc quinolone khc, au khp hoc au c th hi phc i khi xy ra v xi l doanh c ghi nhn ng vt cha trng thnh. gn thit hi cng c bo co. tc dng ph khc c bo co vi ciprofloxacin bao gm tinh th, tng creatinine huyt thanh thong qua hoc nit ure mu v him, suy thn cp th pht vim thn k. Nng

cao gi tr men gan, vng da v vim gan xy ra, khi c ri lon huyt hc bao gm bch cu i toan, gim bch cu, gim tiu cu v, rt him khi, pancytopenia, thiu mu tn huyt hoc mt bch cu ht. Tim mch tc dng ph bao gm nhp tim nhanh, h huyt p, ph n, ngt, bc ho v m hi. Mt s fluoroquinolones him khi c th gy ko di khong QT v lon nhp tm tht, bao gm torsade de pointes (xem). Nh vi antibacterials khc, bi vi cc sinh vt khng phi l rt nhy cm vi ciprofloxacin l c th. sinh vt ny bao gm Candida, Clostridium difficile, v Streptococcus pneumoniae. C mt s bng chng cho thy s dng fluoroquinolone c th lin quan vi tng nguy c ca thc dn ha bi MRSA. au v kch thch c th xy ra ti trang web ca truyn i km vi t khi do vim tnh mch hoc huyt khi. Cc tc dng ph c bo co sau khi s dng mt ca ciprofloxacin bao gm chy a phng hoc kh chu, keratopathy, nhum, kt ta gic mc gic mc hoc xm nhp, v s nh sng. a phng kh chu, au, hoc nga xy ra sau khi s dng thuc nh tai c cha ciprofloxacin. Tng nh gi nhng tc ng bt li ca fluoroquinolones1-7 v ciprofloxacin c th

Effects on the blood

Haematological disturbances including thrombocytopenia,1 eosinophilia,2 leucopenia, and, very rarely, pancytopenia,3 haemolytic anaemia,4 or agranulocytosis have been reported with ciprofloxacin and some other fluoroquinolones. There has also been a case report5 of haemolytic-uraemic syndrome associated with ciprofloxacin therapy; the patient recovered with routine supportive treatment (haemodialysis and plasma exchange) after the drug was stopped. In addition, transient reductions in factor VIII and von Willebrand's factor leading to bleeding in 2 patients receiving ciprofloxacin has been reported.6 Neutropenia that developed in an elderly patient a few days after starting treatment with intravenous moxifloxacin resolved on stopping the drug.7

Tc dng trn mu
ri lon huyt hc nh gim tiu cu, 1 bch cu i toan, gim bch cu 2, v, rt him khi, pancytopenia, 3 thiu mu tn huyt, 4 hoc mt bch cu ht c bo co vi ciprofloxacin v mt s fluoroquinolones khc. Cng c mt trng hp ca hi chng

tn huyt report5-uraemic kt hp vi liu php ciprofloxacin; cc bnh nhn phc hi vi iu tr h tr thng thng (chy thn nhn to v trao i huyt tng) sau khi thuc c dng li. Ngoi ra, gim thong qua yu t VIII v yu t von Willebrand hng u n chy mu trong 2 bnh nhn c reported.6 ciprofloxacin gim bch cu pht trin mt bnh nhn cao tui vi ngy sau khi bt u iu tr vi moxifloxacin tnh mch gii quyt v ngng drug.

Effects on the cardiovascular system

Prolongation of the QT interval,1,2 sometimes progressing to torsade de pointes,3-8 has been associated with ciprofloxacin and other fluoroquinolones although a review9 considered that ciprofloxacin was least likely to produce this effect. Licensed product information recommends that gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin, ofloxacin, and sparfloxacin should be avoided in patients with predisposing factors or who are also receiving other drugs that are known to cause this effect and that norfloxacin should be used with caution in such situations.

Tc dng trn h tim mch

Ko di khong QT, 1,2 i khi tin trin n torsade de pointes ,3-8 c lin kt vi fluoroquinolones ciprofloxacin v khc mc d mt review9 cho rng ciprofloxacin l t c kh nng sn xut ny c hiu lc. Cp giy php thng tin sn phm khuyn co rng gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, ofloxacin moxifloxacin,, v sparfloxacin nn trnh nhng bnh nhn predisposing yu t hoc nhng ngi cng nhn c cc loi thuc khc c bit l gy ra hiu ng ny v norfloxacin nn c dng thn trng nh tnh hung.

Effects on the kidneys

A review1 of case reports of renal toxicity (including interstitial nephritis, acute renal failure, acute tubular necrosis, and crystalluria) associated with ciprofloxacin and other fluoroquinolones indicated that such toxicity, although potentially serious, was rare. It was also noted that nearly all patients developing acute renal failure were over 50 years of age. Another review,2 confirming that the problem remained rare, noted that risk factors for quinolone-induced nephrotoxicity seemed to include the particular quinolone chosen, with ciprofloxacin the most often involved, as well as the use of high doses,

patient age, inadequate hydration, and use of other nephrotoxic drugs or the presence of other processes likely to contribute to renal damage such as diabetes.

Tc dng trn thn

Mt review1 bo co trng hp nhim c thn (bao gm c vim thn k, suy thn cp, hoi t ng thn cp tnh, v tinh th) lin kt vi ciprofloxacin v cc fluoroquinolones khc ch ra rng c tnh nh vy, mc d nghim trng, l him. N cng lu rng gn nh tt c bnh nhn suy thn cp tnh pht trin c hn 50 nm tui. Mt nh gi khc, 2 xc nhn rng vn vn cn him, lu rng yu t nguy c gy ra thn quinolone dng nh bao gm cc quinolone c th c la chn, vi ciprofloxacin thng xuyn nht lin quan, cng nh s dng liu cao, tui bnh nhn, hydrat ha khng , v s dng thuc c thn khc hay s hin din ca cc qu trnh khc c kh nng ng gp gy thit hi thn nh bnh tiu ng.

Effects on the liver

Fluoroquinolones, including ciprofloxacin, may cause elevated liver enzyme values. In most patients this effect is transient and reversible without stopping the drug. More serious cases of hepatotoxicity, including fatalities, have been reported both with ciprofloxacin1-5 and with other fluoroquinolones4,6-14 but they are rare. In many cases the patients were elderly and had co-morbid conditions.

Tc dng trn gan

Fluoroquinolones, trong c ciprofloxacin, c th gy ra cc gi tr men gan cao. Trong hu ht cc bnh nhn hiu ng ny l thong qua v hi phc m khng cn dng thuc. trng hp nghim trng hn ca nhim c gan, bao gm t vong, c bo co c vi ciprofloxacin1-5 v vi cc fluoroquinolones4 ,6-14 nhng h rt him. Trong nhiu trng hp bnh nhn cao tui v c iu kin hp bnh hon.

Effects on the musculoskeletal system

Reversible arthralgia has sometimes occurred with the fluoroquinolones;1 joint erosions have been documented in immature animals. In a report,2 treatment with pefloxacin may have contributed to the destructive arthropathy that occurred in a 17-year-old youth. For a

discussion of the use of fluoroquinolones in children and adolescents, see Administration in Children, under Precautions, .

There have been reports3-7 of tendinitis and tendon rupture associated with fluoroquinolones. By July 1995, the UK CSM5 had received 21 reports of tendon damage, often of the Achilles tendon, associated with these antibacterials11 with ciprofloxacin and 10 with ofloxacin. In a later case-control study8 of a cohort of 46 776 users of fluoroquinolones between July 1992 to June 1998, 704 had Achilles tendinitis and 38 had Achilles tendon rupture; the adjusted relative risk of Achilles tendon disorders with current use was 1.9. The risk of tendon damage is increased by use with corticosteroids and is more common with increasing age:5 the case-control study8 found that the relative risk for current users rose to 3.2 among those aged 60 and over, and to 6.2 in those in this age group also using corticosteroids. Another case-control study9 using data from 1988 to 1998 held on a different UK general practice database reported similar findings and concluded that ofloxacin was associated with a higher risk of tendon damage than other fluoroquinolones. A review10 of the literature between 1966 and 2001 revealed 98 case reports of fluoroquinolone-associated tendon damage. Of these, 36 were associated with pefloxacin therapy and 25 with ciprofloxacin; ofloxacin was associated with 6 cases. Renal disease or impairment was also considered as a risk factor. Onset may be rapid: rupture has occurred within 48 hours of starting therapy.11 The CSM5 warned that at the first sign of pain or inflammation the fluoroquinolone should be withdrawn and the affected limb rested until the tendon symptoms had resolved. Similar warnings have been issued in other countries, but some cases have continued to be reported.12 In the USA the FDA has required a warning to be added to prescribing information for the fluoroquinolones stating that there is an increased risk in patients over 60, in kidney, heart, and lung transplant recipients, and with use of concomitant corticosteroid therapy.13 There have been reports14,15 of rhabdomyolysis in patients given fluoroquinolones, including one fatality associated with levofloxacin therapy.14 1. 1. Alfaham M, et al. Arthropathy in a patient with cystic fibrosis taking ciprofloxacin.
BMJ 1987; 295: 699. PubMed

2. 2. Chevalier X, et al. A case of destructive polyarthropathy in a 17-year-old youth

following pefloxacin treatment. Drug Safety 1992; 7: 31014. PubMed

3. 3. Huston KA. Achilles tendinitis and tendon rupture due to fluoroquinolone antibiotics.
N Engl J Med 1994; 331: 748. PubMed

4. 4. Szarfman A, et al. More on fluoroquinolone antibiotics and tendon rupture. N Engl J

Med 1995; 332: 193. PubMed

5. 5. Committee on Safety of Medicines/Medicines Control Agency. Tendon damage

associated with quinolone antibiotics. Current Problems 1995; 21: 8. Also available at: online (accessed 12/07/06)

6. 6. Carrasco JM, et al. Tendinitis associated with ciprofloxacin. Ann Pharmacother 1997;
31: 120. PubMed 7. 7. Mathis AS, et al. Levofloxacin-associated Achilles tendon rupture. Ann Pharmacother 2003; 37: 101417. PubMed 8. 8. van der Linden PD, et al. Fluoroquinolones and risk of Achilles tendon disorders: casecontrol study. BMJ 2002; 324: 13067. PubMed

9. 9. van der Linden PD, et al. Increased risk of Achilles tendon rupture with quinolone
antibacterial use, especially in elderly patients taking oral corticosteroids. Arch Intern Med 2003; 163: 18017. PubMed

10. 10. Khaliq Y, Zhanel GG. Fluoroquinolone-associated tendinopathy: a critical review of

the literature. Clin Infect Dis 2003; 36: 140410. PubMed

11. 11. Committee on Safety of Medicines/Medicines Control Agency. Reminder:

fluoroquinolone antibiotics and tendon disorders. Current Problems 2002; 28: 34. Also available at: online (accessed 12/07/06)

12. 12. Adverse Drug Reactions Advisory Committee (ADRAC). Fluoroquinolone

antibiotics: remember tendon disorders. Aust Adverse Drug React Bull 2006; 25: 3. Also available at: online (accessed 12/07/06)

13. 13. FDA. Fluoroquinolone Antimicrobial Drugs [ciprofloxacin (marketed as Cipro and
generic ciprofloxacin), ciprofloxacin extended release (marketed as Cipro XR and Proquin XR), gemifloxacin (marketed as Factive), levofloxacin (marketed as Levaquin), moxifloxacin (marketed as Avelox), norfloxacin (marketed as Noroxin), and ofloxacin (marketed as Floxin and generic ofloxacin)] (issued 8th July, 2008). Available at: online (accessed 12/08/08)

14. 14. Petitjeans F, et al. A case of rhabdomyolysis with fatal outcome after a treatment with
levofloxacin. Eur J Clin Pharmacol 2003; 59: 77980. PubMed 15. 15. Hsiao S-H, et al. Acute rhabdomyolysis associated with ofloxacin/levofloxacin therapy. Ann Pharmacother 2005; 39: 1469. PubMed

Tc dng trn h thng c xng

au khp nghch i khi xy ra vi cc fluoroquinolones, 1 xi l doanh c ghi nhn ng vt cha trng thnh. Trong mt bo co, 2 ln iu tr vi pefloxacin c th gp phn vo bnh khp ph hoi xy ra trong mt thanh nin 17 tui. i vi mt cuc tho lun v vic s dng cc fluoroquinolones tr em v thanh thiu nin, xem chnh tr em, theo phng,. c reports3-7 ca vim gn v dy chng v lin kt vi fluoroquinolones. Bi thng 7 nm 1995, cc CSM5 Anh nhn c 21 bo co v thit hi gn, thng xuyn ca cc gn Achilles, lin kt vi cc antibacterials-11 vi ciprofloxacin v 10 vi ofloxacin. Trong mt kim sot sau , trng hp study8 ca on h ca 46 776 ngi s dng ca fluoroquinolones gia thng by 1992 n thng Su nm 1998, 704 Achilles vim gn v 38 t gn Achilles, nhng iu chnh tng i nguy c ri lon gn Achilles vi s dng hin ti l 1,9. Cc nguy c tn thng dy chng l tng s dng vi corticosteroid v ph bin hn vi s gia tng tui: 5 s kim sot trng hp-study8 thy rng nguy c tng i cho ngi s dng hin nay tng n 3,2 trong s nhng ngi tui t 60 tr ln, v n 6,2 trong nhng nm ny nhm tui cng s dng corticosteroids. Mt trng study9 kim sot bng cch s dng d liu 1988-1998 t chc vo mt c s d liu khc nhau Anh thc hnh bo co tng hp kt qu tng t v kt lun ofloxacin c lin kt vi mt nguy c thit hi gn hn fluoroquinolones khc. Mt review10 ca vn hc gia nm 1966 v 2001 cho thy 98 trng hp bo co thit hi gn fluoroquinolone-lin quan. Trong s ny, 36 c kt hp vi liu php pefloxacin v 25 vi ciprofloxacin, ofloxacin c lin kt vi 6 trng hp. Bnh thn hoc suy gim cng c xem nh l mt yu t nguy c. Khi pht c th nhanh chng: v xy ra trong vng 48 gi k t khi therapy.11 Cc CSM5 cnh bo rng cc du hiu u tin ca cn au hoc vim cc fluoroquinolone nn c thu hi v chn tay b nh hng ngh ngi cho n khi cc triu chng gn c gii quyt. cnh bo tng t c pht hnh nc khc, nhng mt s trng hp c tip tc c reported.12 Ti Hoa K FDA yu cu mt cnh bo c thm vo thng tin quy nh i vi cc fluoroquinolones ni rng c mt nguy c gia tng nhng bnh nhn trn 60 tui, thn, tim, v phi ghp, v vi vic s dng ng thi corticosteroid therapy.13 c reports14, 15 ca rhabdomyolysis nhng bnh nhn c fluoroquinolones,

trong c mt ca t vong lin quan vi levofloxacin therapy.14 1. 1. Alfaham M, et al. Bnh khp bnh nhn x nang dng ciprofloxacin. BMJ 1987; 295: 699. PubMed 2. 2. Chevalier X, et al. Mt trng hp ph hoi polyarthropathy trong mt thanh nin 17 tui sau iu tr pefloxacin. Thuc an ton nm 1992; 7: 310-14. PubMed 3. 3. Huston KA. Vim gn Achilles v t gn do khng sinh fluoroquinolon. N Engl J Med 1994; 331: 748. PubMed 4. 4. Szarfman A, et al. Xem thm v thuc khng sinh fluoroquinolone v t gn. N Engl J Med 1995; 332: 193. PubMed 5. 5. y ban v an ton ca thuc / Thuc C quan kim sot. Gn thit hi lin quan n thuc khng sinh quinolone. Vn hin ti nm 1995; 21: 8. Cng c sn ti: trc tuyn (truy cp 12/07/06) 6. 6. Carrasco JM, et al. Vim gn lin kt vi ciprofloxacin. Ann Pharmacother nm 1997; 31: 120. PubMed 7. 7. Mathis AS, et al. Levofloxacin-gn Achilles lin quan v. Ann Pharmacother nm 2003; 37: 1014-1017. PubMed 8. 8. van der Linden PD, et al. Fluoroquinolones v nguy c ri lon gn Achilles: kim sot trng hp nghin cu. BMJ 2002; 324: 1306-7. PubMed 9. 9. van der Linden PD, et al. Tng nguy c t gn Achilles vi vic s dng khng khun quinolone, c bit l nhng bnh nhn cao tui dng corticosteroids ng ung. Arch Intern Med 2003; 163: 1801-7. PubMed 10. 10. Khaliq Y, Zhanel GG. Fluoroquinolone-lin tendinopathy: xem xt li quan trng ca nn vn hc. Clin ly nhim Mi Hai nm 2003; 36: 1404-1410. PubMed 11. 11. y ban v an ton ca thuc / Thuc C quan kim sot. Nhc nh: fluoroquinolone khng sinh v cc ri lon gn. Vn hin ti nm 2002; 28: 3-4. Cng c sn ti: trc tuyn (truy cp 12/07/06) 12. 12. Phn ng thuc c hi Ban t vn (ADRAC). Fluoroquinolone khng sinh: nh ri lon gn. Phn ng bt li thuc Aust Bull 2006; 25: 3. Cng c sn ti: trc tuyn (truy cp 12/07/06) 13. 13. FDA. Thuc khng sinh fluoroquinolon [ciprofloxacin (Cipro v tip th nh ciprofloxacin chung chung), ciprofloxacin m rng pht hnh (th trng nh Cipro XR v Proquin XR), gemifloxacin (th trng nh l Factive), levofloxacin (th trng nh Levaquin), moxifloxacin (th trng nh Avelox), norfloxacin ( th trng

nh l Noroxin), v ofloxacin (th trng nh l Floxin v ofloxacin chung)] (pht hnh 08 thng 7 nm 2008). C sn ti: trc tuyn (truy cp 12/08/08) 14. 14. Petitjeans F, et al. Mt trng hp rhabdomyolysis vi kt qu gy t vong sau khi iu tr vi levofloxacin. Eur J Clin Pharmacol nm 2003; 59: 779-80. PubMed 15. 15. Hsiao S-H, et al. Rhabdomyolysis cp lin kt vi ofloxacin iu tr levofloxacin /. Ann Pharmacother nm 2005; 39: 146-9. PubMed

Effects on the nervous system

By 1991 the UK CSM1 had received 26 reports of convulsions associated with ciprofloxacin, 1 with norfloxacin, and 1 with ofloxacin. It was noted that convulsions could occur both in patients with epilepsy and in those with no history of convulsions. Generalised seizures have been reported in patients given gatifloxacin2 and levofloxacin.3,4 Seizures have also been associated with the use of ear drops containing ciprofloxacin.5 All 5 case reports2-5 involved patients aged 65 years and over; of these, 1 had a history (although unclear) of seizures,2 3 had chronic renal impairment,3-5 and 1 had neither.3 Other reports of CNS toxicity associated with ciprofloxacin have included eosinophilic meningitis,6 delirium,7 and acute psychoses.8,9 Peripheral neuropathy,10 dysaesthesia,11 catatonia,12 hemiparesis,13 and tinnitus14 have also been reported. Acute psychosis occurred15 in a patient using ciprofloxacin eye drops. A review16 of published and spontaneous reports found an association between adverse manic reactions and the use of certain antibacterials including ciprofloxacin and ofloxacin. There have also been reports of sleep disturbances17 and of a Tourette-like syndrome18 associated with ofloxacin. Ataxia19 and hallucinations20 have been reported with the use of gatifloxacin.

Tc dng trn h thn kinh

By 1991, Vng quc Anh CSM1 nhn c 26 bo co v co git lin kt vi ciprofloxacin, 1 vi norfloxacin, v 1 vi ofloxacin. N c ghi nhn l co git c th xy ra c nhng bnh nhn b bnh ng kinh v trong nhng ngi khng c tin s co git. H ng kinh c bo co nhng bnh nhn c gatifloxacin2 v

levofloxacin.3, 4 ng kinh cng c kt hp vi vic s dng thuc nh tai c cha ciprofloxacin.5 Tt c cc trng hp 5 reports2-5 bnh nhn tham gia t 65 tui tr ln, trong s ny, 1 c lch s (mc d khng r rng) ca cc cn ng kinh, 2 3 suy thn mn tnh ,3-5 v 1 neither.3 Cc bo co khc ca thn kinh trung ng c tnh kt hp vi ciprofloxacin bao gm vim mng no eosinophilic, m sng 6, 7 v psychoses.8, cp 9 bnh thn kinh ngoi vi, 10 dysaesthesia, 11 catatonia, 12 hemiparesis, 13 v tinnitus14 cng c bo co. Lon tm thn cp tnh occurred15 mt bnh nhn s dng thuc nh mt ciprofloxacin. Mt bo co c cng b review16 v t tm thy mt mi lin h gia phn ng hng bt li v s dng cc antibacterials nht nh bao gm ciprofloxacin v ofloxacin. Hin cng c bo co ca gic ng disturbances17 v ca mt Tourette-nh syndrome18 kt hp vi ofloxacin. Ataxia19 v hallucinations20 c bo co vi vic s dng gatifloxacin.

Hypersensitivity
Hypersensitivity and skin reactions have been associated with ciprofloxacin and other fluoroquinolones. Reports have included anaphylaxis (which has sometimes been fatal, and may occur after the first dose),1-7 serum sickness,8 Stevens-Johnson syndrome,9 toxic epidermal necrolysis (sometimes fatal),10-17 laryngeal oedema,18 and vasculitis.19-21 Fatal vasculitis has been reported with ofloxacin.22

Mn cm
V phn ng qu mn da c lin kt vi ciprofloxacin v cc fluoroquinolones khc. Bo co bao gm phn v (trong c i khi c gy t vong, v c th xy ra sau liu u tin) ,1-7 bnh huyt thanh, 8 hi chng Stevens-Johnson, 9 c hoi t biu b (i khi gy t vong) ,10-17 thanh qun ph n, 18 v vasculitis 0,19-21 vim mch gy t vong c bo co vi ofloxacin.

Superinfection

Superinfection with Streptococcus pneumoniae has been reported in patients receiving ciprofloxacin.1-3 For references to superinfection with Clostridium difficile and associated pseudomembranous colitis, see under Effects on the Gastrointestinal Tract, Fungal otitis externa is also associated with the use of ear drops containing fluoroquinolones.4 .

Bi
Bi vi Streptococcus pneumoniae c bo co bnh nhn ciprofloxacin.1-3 i vi cc ti liu tham kho bi vi Clostridium difficile v lin quan n vim i trng mng gi, xem di nh hng trn trng ng tiu ha,. Nm externa vim tai gia cng c kt hp vi vic s dng thuc nh tai c cha fluoroquinolones

Precautions
Ciprofloxacin should be used with caution in patients with epilepsy or a history of CNS disorders. Care is also necessary in those with renal impairment, G6PD deficiency, or myasthenia gravis. An adequate fluid intake should be maintained during treatment with ciprofloxacin and excessive alkalinity of the urine avoided because of the risk of crystalluria. Since ciprofloxacin and related fluoroquinolones have, like nalidixic acid, been shown to cause degenerative changes in weight-bearing joints of young animals, it has been suggested that these drugs should not generally be used in patients aged under 18 years (see also ), pregnant women, or breast-feeding mothers (but see also ) unless the benefits outweigh the risks. Tendon damage may occur rarely with fluoroquinolones (see Effects on the Musculoskeletal System, contra-indicated in these patients. Exposure to strong sunlight or sunlamps should be avoided during treatment with ciprofloxacin. The ability to drive or operate machinery may be impaired, especially when alcohol is also taken. ) and treatment should be stopped if patients experience tendon pain, inflammation, or rupture; subsequent use of fluoroquinolones is

Some fluoroquinolones have the potential to prolong the QT interval (see Effects on the Cardiovascular System, ) and should be avoided or used with caution in patients with QT prolongation or relevant risk factors such as uncorrected electrolyte disturbances, bradycardia, or pre-existing cardiac disease. Certain drugs may also increase the risk (see Interactions, ).

Ciprofloxacin and other fluoroquinolones should be avoided in MRSA infections because of the high level of resistance.

Bin php phng nga

Ciprofloxacin nn c dng thn trng nhng bnh nhn b bnh ng kinh hoc c tin s ri lon thn kinh trung ng. Chm sc cng cn thit nhng ngi suy thn, thiu G6PD, hoc nhc c nng. Mt lng cht lng y nn c duy tr trong khi iu tr vi ciprofloxacin v kim qu mc ca cc nc tiu trnh v nguy c ca tinh th. K t khi ciprofloxacin v fluoroquinolones lin quan c, nh acid nalidixic, c hin th gy ra nhng thay i thoi ha cc khp chu trng lng ca ng vt nh, n c gi rng cc loi thuc ny khng nn thng c s dng bnh nhn di 18 tui (xem thm), mang thai ph n, hoc cho con b (nhng xem thm), tr khi nhng li ch ln hn nhng ri ro. Gn thit hi c th xy ra him khi vi fluoroquinolones (xem Tc dng trn h thng c xng,) v iu tr nn c dng li nu bnh nhn c kinh nghim gn au, vim, hoc v, sau s dng cc fluoroquinolones l chng ch nh nhng bnh nhn ny. Tip xc vi nh sng mt tri mnh hay sunlamps nn trnh trong qu trnh iu tr bng ciprofloxacin. Kh nng li xe hay vn hnh my mc c th b tn, c bit l khi ung ru cng c thc hin. Mt s fluoroquinolones c tim nng ko di khong QT (xem Tc dng trn h thng tim mch,) v nn trnh hoc s dng thn trng bnh nhn ko di QT hoc cc yu t nguy c lin quan nh ri lon in gii uncorrected, nhp tim chm, hoc tn ti trc bnh tim . Mt s loi thuc cng c th lm tng nguy c (xem Tng tc,). Ciprofloxacin v fluoroquinolones khc nn trnh trong MRSA nhim v mc cao sc khng.

Administration in children

Since ciprofloxacin and other fluoroquinolones can cause degenerative changes in weight-bearing joints of young animals they should only be used in children and adolescents where their use may be justified if the benefits outweigh the risks.1-3 For example, ciprofloxacin is licensed in some countries for use in the prophylaxis and treatment of inhalational anthrax and also in the treatment of certain infections in those under 18 years of age (see under Uses and Administration, ).

A comparative cohort study2 involving about 500 children and adolescents found that the incidence of musculoskeletal adverse effects was higher (10 cases out of 264 patients) in those taking fluoroquinolones (ciprofloxacin, ofloxacin, or pefloxacin) than in those taking other antibacterials (1 out of 237). In the former group of patients, these adverse effects, mainly arthralgias, were reversible and were most frequent with pefloxacin therapy.

Qun l tr em
K t khi ciprofloxacin v cc fluoroquinolones khc c th gy ra nhng thay i thoi ha cc khp xng chu trng lng ca ng vt tr tui h ch nn c s dng tr em v thanh thiu nin, ni s dng ca h l hp l nu cc li ch ln hn risks.1-3 V d, ciprofloxacin c cp php trong mt s nc s dng trong d phng v iu tr cc bnh than ng h hp v cng trong iu tr cc bnh nhim trng nht nh trong nhng ngi di 18 tui (xem theo s dng v qun l,). Mt on h so snh study2 c khong 500 tr em v thanh thiu nin cho thy t l tc dng ph c xng cao hn (10 trng hp trong s 264 bnh nhn) trong nhng fluoroquinolones dng (ciprofloxacin, ofloxacin, hoc pefloxacin) hn so vi nhng ngi ung antibacterials khc (1 trong 237). Trong nhm trc y ca bnh nhn, nhng tc ng bt li, ch yu l arthralgias, hi phc v c hu ht thng xuyn vi cc liu php pefloxacin

Breast feeding
Ciprofloxacin was found to be undetectable in the serum of a breast-fed infant whose mother took ciprofloxacin 500 mg daily for 10 days.1 In another study2 involving 30 women who underwent termination of pregnancy, 10 each were given ciprofloxacin, ofloxacin, or pefloxacin respectively, and all 3 drugs were found to be highly concentrated in breast milk with ratios exceeding 75% of the simultaneous serum concentrations 2 hours after a dose. It was concluded that, because fluoroquinolones had

been shown to cause arthropathy in young animals, their potential benefits should be weighed against the risk to the infant before they were considered for use in breastfeeding women. The American Academy of Pediatrics3 considers that the use of ciprofloxacin is usually compatible with breast feeding.

Cho con b
Ciprofloxacin c tm thy l khng pht hin c trong huyt thanh ca mt tr s sinh b sa m m m ciprofloxacin 500 mg mi ngy trong 10 days.1 Trong study2 khc lin quan n 30 ph n tri qua chm dt thai k, 10 mi ciprofloxacin c cho, ofloxacin, hoc pefloxacin tng ng , v c 3 loi thuc c tm thy s c tp trung cao trong sa m vi t l trn 75% ca nng huyt thanh ng thi 2 gi sau khi liu. l kt lun rng, bi v fluoroquinolones c chng minh l gy ra bnh khp ng vt nh, li ch tim nng ca h nn c cn nhc ri ro i vi tr trc khi chng c xem xt s dng ph n cho con b. Hc vin M Pediatrics3 cho rng vic s dng ciprofloxacin thng tng thch vi cho con b.

Interference with diagnostic tests

Ciprofloxacin did not interfere with determination of urinary-glucose concentrations carried out with Clinitest, Diastix, or Tes-Tape,1 but pseudoglycosuria, a false-positive reaction for glucose in urine, has been reported with BM-Test-7 in elderly patients given ciprofloxacin for urinary-tract infections.2 1. 1. Tartaglione TA, Flint NB. Effect of imipenem-cilastatin and ciprofloxacin on tests for
glycosuria. Am J Hosp Pharm 1985; 42: 6025. PubMed 2. 2. Drysdale L, et al. Pseudoglycosuria and ciprofloxacin. Lancet 1988; ii: 961. PubMed

Can thip vi cc xt nghim chn on

Ciprofloxacin khng gy tr ngi xc nh nng ng tit niu-thc hin vi Clinitest, Diastix, hoc Tes-bng, 1 nhng pseudoglycosuria, mt phn ng dng tnh gi i vi glucose trong nc tiu, c bo co vi BM-Test-7 bnh nhn cao tui nht ciprofloxacin cho ng-niu infections.2 1. 1. Tartaglione TA, Flint NB. nh hng ca cilastatin-imipenem v ciprofloxacin trn cc xt nghim cho niu. Am J Hosp Pharm 1985; 42: 602-5. PubMed 2. 2. Drysdale L, et al. Pseudoglycosuria v ciprofloxacin. Lancet 1988; ii: 961. PubMed

Interactions
Fluoroquinolones, including ciprofloxacin, are known to inhibit the cytochrome P450 isoenzyme CYP1A2 and may increase plasma concentrations of drugs, such as theophylline and tizanidine, that are metabolised by this isoenzyme. Use of ciprofloxacin with tizanidine is contra-indicated, although theophylline may be used providing its dose is reduced and concentrations monitored. Ciprofloxacin is reported to enhance the effect of oral anticoagulants such as warfarin and the oral antidiabetic glibenclamide. Severe hypoglycaemia, sometimes fatal, has occurred in patients also taking glibenclamide. Renal tubular secretion of methotrexate may be inhibited by ciprofloxacin, potentially increasing its toxicity. The excretion of ciprofloxacin or related drugs is reduced and plasma concentrations may be increased by probenecid. Cations such as aluminium, calcium, magnesium, or iron reduce the absorption of oral ciprofloxacin or related drugs when given together. Changes in the pharmacokinetics of fluoroquinolones have been reported when given with histamine H2 antagonists, possibly due to changes in gastric pH, but do not seem to be of much clinical significance. Transient increases in serum creatinine have occurred when ciprofloxacin is given with ciclosporin; monitoring of serum creatinine concentrations is recommended. Altered serum concentrations of phenytoin have been reported in patients also receiving ciprofloxacin. Further details concerning some of these interactions, and others, are given below. Some fluoroquinolones have the potential to prolong the QT interval (see Effects on the Cardiovascular System, ) and should be avoided in patients also receiving class Ia antiarrhythmic drugs (such as quinidine and procainamide) or class III antiarrhythmics (such as amiodarone and sotalol). In addition, caution should be exercised when they are used with other drugs known to have this effect (such as the antihistamines astemizole and terfenadine, cisapride, erythromycin, pentamidine, phenothiazines, or tricyclic antidepressants).

For physical or chemical incompatibilities with ciprofloxacin, see

Tng tc
Fluoroquinolones, trong c ciprofloxacin, c bit l c ch CYP1A2 cytochrome P450 isoenzyme v c th lm tng nng trong huyt tng ca thuc nh theophylline v tizanidine, c chuyn ha bi isoenzyme ny. S dng ciprofloxacin vi tizanidine l chng ch nh, mc d theophylline c th c s dng cung cp liu lng ca n l gim v nng theo di. Ciprofloxacin c bo co l tng cng hiu lc ca thuc chng ng ng ung nh warfarin v glibenclamide ung antidiabetic. Hypoglycaemia nghim trng, i khi gy t vong, xy ra bnh nhn cng ang glibenclamide. ng thn tit methotrexate c th b c ch bi ciprofloxacin, c tim nng tng c tnh ca n. Cc bi tit ciprofloxacin hoc cc loi thuc lin quan c gim v nng huyt tng c th tng ln bi probenecid. Cation nh nhm, canxi, magi, hoc st lm gim s hp thu ciprofloxacin ung hoc thuc c lin quan khi c cng nhau. Thay i trong dc ng hc ca fluoroquinolones c bo co khi c vi thuc i khng histamin H2, c th do thay i pH d dy, nhng dng nh khng c ngha lm sng nhiu. tng thong qua trong creatinine huyt thanh xy ra khi ciprofloxacin c a ra vi ciclosporin; theo di nng creatinine huyt thanh c khuyn khch. b bin i nng ca phenytoin c bo co bnh nhn cng nhn c ciprofloxacin. Thng tin chi tit lin quan n mt s cc tng tc, v nhng ngi khc, c a ra di y. Mt s fluoroquinolones c tim nng ko di khong QT (xem Tc dng trn h thng tim mch,) v nn trnh nhng bnh nhn cng nhn c cc loi thuc chng lon nhp loi Ia (nh quinidine v procainamide) hoc III lp chng lon nhp (nh amiodaron v sotalol). Ngoi ra, nn cn thn trng khi chng c s dng vi cc thuc khc bit l c hiu ng ny (nh cc thuc khng histamine astemizole v terfenadin, cisaprid, erythromycin, pentamidine, phenothiazin, thuc chng trm cm ba vng hoc). i vi vt l, ha hc khng tng thch vi ciprofloxacin, xem

Analgesics

Use of fenbufen with fluoroquinolones may increase the incidence of fluoroquinolone CNS adverse effects. Reviews1,2 have noted cases of convulsions associated with the use of fenbufen and enoxacin reported to the Japanese regulatory authorities. The UK CSM3 has recognised that convulsions may occur due to an interaction between the fluoroquinolones and NSAIDs; by 1991, 3 such interactions had been reported to them. Adverse neurological effects have also been reported in a patient receiving naproxen and chloroquine when ciprofloxacin was given, which abated when the antirheumatic drugs were stopped.4 Ciprofloxacin also interacts with opioid analgesics; peak serum concentrations of ciprofloxacin given by mouth pre-operatively were significantly reduced when intramuscular papaveretum was injected.5 In the UK, licensed product information for ciprofloxacin tablets recommends that opioid premedication should not be used if ciprofloxacin is given for surgical infection prophylaxis.

Thuc gim au
S dng fenbufen vi fluoroquinolones c th lm tng t l tc dng ph thn kinh trung ng fluoroquinolone. Reviews1, 2 ghi nhn trng hp co git c lin quan vi vic s dng fenbufen v enoxacin bo co vi c quan qun l Nht Bn. Cc CSM3 Anh cng nhn rng co git c th xy ra do s tng tc gia cc fluoroquinolones v NSAID; nm 1991, 3 tng tc nh c bo co cho h. Cc tc dng ph thn kinh cng c bo co trong mt naproxen bnh nhn tip nhn v chloroquine khi ciprofloxacin c a ra, m yu i, khi cc loi thuc chng thp khp c stopped.4 Ciprofloxacin cng tng tc vi thuc gim au opioid, nng nh trong huyt thanh ca ciprofloxacin c a ra bi ming trc operatively gim ng k khi tim bp papaveretum c injected.5 Ti Anh, thng tin sn phm c cp giy php cho vin ciprofloxacin khuyn co rng premedication opioid khng nn c s dng nu c cho ciprofloxacin cho d phng nhim trng trong phu thut

Antibacterials
The simultaneous use of parenteral ciprofloxacin and azlocillin has resulted in higher and more prolonged serum concentrations of ciprofloxacin.1 Steady-state plasma

concentrations of moxifloxacin are significantly reduced when given with rifampicin and isoniazid for the treatment of tuberculosis.2

Antibacterials
Vic s dng ng thi ciprofloxacin nui v azlocillin dn n nng huyt thanh cao hn v ko di nng huyt tng n nh ciprofloxacin.1 nh nc ca moxifloxacin c gim ng k khi c vi rifampicin v isoniazid iu tr bnh lao

Pharmacokinetics
Ciprofloxacin is rapidly and well absorbed from the gastrointestinal tract. Oral bioavailability is about 70 to 80% and a peak serum concentration of about 2.4 micrograms/mL occurs 1 to 2 hours after a 500-mg oral dose. Absorption of ciprofloxacin tablets may be delayed by the presence of food, but is not substantially affected overall. Plasma protein binding ranges from 20 to 40%. Ciprofloxacin is widely distributed in the body and tissue penetration is generally good. It appears in the CSF, but concentrations are only about 10% of those in serum when the meninges are not inflamed. Ciprofloxacin crosses the placenta and is also distributed into breast milk. High concentrations are achieved in bile. The elimination half-life is about 3 to 5 hours and there is evidence of modest accumulation. Half-life may be prolonged in renal impairment (a value of 8 hours has been reported in end-stage renal disease) and to some extent in the elderly. However, no dose adjustment is usually necessary in patients with renal impairment unless it is severe; similarly, usual doses can be given to the elderly except in those with severe renal impairment. There is limited information on the effect of hepatic impairment; the half-life of ciprofloxacin has been reported to be slightly prolonged in patients with severe cirrhosis of the liver. With one or two exceptions, most studies have shown that the pharmacokinetics of ciprofloxacin are not markedly affected by cystic fibrosis. Ciprofloxacin is eliminated principally by urinary excretion, but non-renal clearance may account for about one-third of elimination and includes hepatic metabolism, biliary

excretion, and possibly transluminal secretion across the intestinal mucosa. At least 4 active metabolites have been identified. Oxociprofloxacin appears to be the major urinary metabolite and sulfociprofloxacin the primary faecal metabolite. Urinary excretion is by active tubular secretion as well as glomerular filtration and is reduced by probenecid; it is virtually complete within 24 hours. About 40 to 50% of an oral dose is excreted unchanged in the urine and about 15% as metabolites. Up to 70% of a parenteral dose may be excreted unchanged within 24 hours and 10% as metabolites. Faecal excretion over 5 days has accounted for 20 to 35% of an oral dose and 15% of an intravenous dose. 1. Only small amounts of ciprofloxacin are removed by haemodialysis or peritoneal

Dc ng hc
Ciprofloxacin l nhanh chng v hp thu tt qua ng tiu ha. Kh dng sinh hc ng ung l khong 70 n 80% v nng nh trong huyt thanh ca khong 2,4 mg / ml xy ra 1 n 2 gi sau khi mt liu ung 500 mg. Hp th ca thuc ciprofloxacin c th b tr hon bi s hin din ca thc n, nhng khng ng k nh hng n tng th. Protein huyt tng khong rng buc 20-40%. Ciprofloxacin l phn phi rng ri trong c th v m thm nhp nhn chung l tt. N xut hin trong dch no ty, nhng nng ch khong 10% nhng ngi trong huyt thanh khi khng b vim mng no. Ciprofloxacin qua nhau thai v cng c phn phi vo sa m. nng cao t c trong mt. Vic bn hy l khong 3 n 5 gi v c bng chng v tch ly khim tn. Mt na cuc i c th ko di trong suy thn (mt gi tr ca 8 gi c bo co trong giai on cui bnh thn) v n mt mc no ngi cao tui. Tuy nhin, khng iu chnh liu thng l cn thit bnh nhn suy thn, tr khi n l nghim trng, tng t nh vy, liu thng thng c th c trao cho ngi cao tui, ngoi tr nhng ngi suy thn nng. Khng c gii hn thng tin v nh hng ca suy gan, mt na cuc sng ca ciprofloxacin c bo co l hi ko di bnh nhn x gan nng ca gan. Vi mt hoc hai trng hp ngoi l, hu ht cc nghin cu ch ra rng dc ng hc ca ciprofloxacin l khng ng k nh hng bi chng x nang. Ciprofloxacin l loi ch yu do bi tit nc tiu, nhng khng thn gii phng mt bng c th chim khong mt phn ba loi b v bao gm trao i cht ca gan, bi tit mt, v c th tit transluminal qua nim mc rut. t nht 4 cht chuyn ha hot ng

 c xc nh. Oxociprofloxacin hnh nh l cht chuyn ha chnh tit niu v cc cht chuyn ha chnh sulfociprofloxacin phn. Bi tit nc tiu l do hot ng tit hnh ng cng nh lc cu thn v c gim probenecid, l hu nh hon ton trong vng 24 gi. Khong 40 n 50% ca mt liu ung c bi tit khng thay i trong nc tiu v khong 15% l cht chuyn ha. Ln n 70% liu tim c th c bi tit khng thay i trong vng 24 gi v 10% l cht chuyn ha. Phn bi tit trong 5 ngy chim khong 20 n 35% ca mt liu ung v 15% liu tim tnh mch. 1. Ch mt lng nh ca ciprofloxacin c loi b bi lc mu hoc phc mc

Uses and Administration

Ciprofloxacin is a fluorinated 4-quinolone or fluoroquinolone antibacterial with a wider spectrum of activity than nalidixic acid (see Antimicrobial Action, ) and more favourable pharmacokinetics allowing its use in systemic infections. It has been used in the treatment of infections including anthrax, biliary-tract infections, infected bites and stings, bone and joint infections, cat scratch disease, chancroid, exacerbations of cystic fibrosis, ear, nose, and throat infections (including otitis externa, otitis media, and sinusitis), HACEK endocarditis, gastro-enteritis (including travellers' diarrhoea and campylobacter enteritis, cholera, salmonella enteritis, shigellosis, and yersinia enteritis), gonorrhoea, granuloma inguinale, infections in immunocompromised patients (neutropenia), legionnaires' disease, pelvic inflammatory disease, peritonitis, plague, lower respiratory-tract infections (including pseudomonal infections in cystic fibrosis, but excluding infections due to Streptococcus pneumoniae such as pneumococcal pneumonia), rickettsial infections (including Q fever, spotted fevers, and typhus), septicaemia, skin infections (including soft-tissue infections), typhoid and paratyphoid fever, and urinary-tract infections including chronic bacterial prostatitis. Ciprofloxacin is used for meningococcal meningitis prophylaxis. It is also used for surgical infection prophylaxis and in the treatment of nontuberculous mycobacterial infections and tuberculosis. Ciprofloxacin is used topically in the treatment of eye and ear infections. For details of all these infections and their treatment, see under Choice of Antibacterial, .

Administration and dosage. Ciprofloxacin is given orally as the hydrochloride or base, by intravenous infusion as the lactate, and in eye drops, eye ointment, or ear drops as the hydrochloride. Doses and strengths are expressed in terms of the base. Ciprofloxacin hydrochloride 291.1 mg is equivalent to about 250 mg of ciprofloxacin. Ciprofloxacin lactate 127 mg is equivalent to about 100 mg of ciprofloxacin. The usual adult oral dose of ciprofloxacin ranges from 250 to 750 mg twice daily depending on the severity and nature of the infection. Modified-release preparations for once-daily dosage are available in some countries. The usual adult intravenous dose is 200 to 400 mg twice daily, given over 30 to 60 minutes as a solution containing the equivalent of 1 to 2 mg/mL. Women with acute uncomplicated cystitis may be given an oral dose of 100 to 250 mg twice daily for 3 days or 100 mg twice daily by intravenous infusion. A 28-day course of treatment with an oral dose of 500 mg twice daily or an intravenous dose of 400 mg twice daily should be given for chronic bacterial prostatitis. Bone and joint infections should be treated with an oral dose of 500 to 750 mg twice daily or an intravenous dose of 400 mg two or three times daily for 4 to 6 weeks. Intravenous infusions of 400 mg three times daily have also been recommended in severe or complicated lower respiratory tract or skin infections, nosocomial pneumonia, and with piperacillin for empirical treatment of febrile neutropenic patients. For treatment and postexposure prophylaxis of inhalation anthrax, a 60-day course of treatment with initial intravenous doses of 400 mg twice daily followed by oral doses of 500 mg twice daily is recommended; although unlicensed, the same regimen is recommended by UK and US public health agencies for the treatment of gastrointestinal anthrax. In the treatment of cutaneous anthrax (also unlicensed), a 7- to 10-day course of treatment with an oral dose of 500 to 750 mg twice daily is similarly recommended; treatment may need to be extended to 60 days if infection is due to aerosol exposure. Doses should be reduced in patients with severe renal impairment (see ).

Single oral doses of 250 or 500 mg or single intravenous doses of 100 mg are used for the treatment of gonorrhoea, depending upon patterns of resistance. A single oral dose of 750 mg is used for surgical infection prophylaxis, given 60 to 90 minutes before the

procedure. Although unlicensed in the UK, the BNF suggests a single oral dose of 500 mg for meningococcal meningitis prophylaxis. For details of doses in children, including infants and adolescents, see .

For corneal ulcers and superficial ocular infections caused by susceptible strains of bacteria ciprofloxacin is given as the hydrochloride in eye drops and eye ointment containing the equivalent of 0.3% of ciprofloxacin. Ciprofloxacin is also used topically as the hydrochloride in ear drops containing the equivalent of 0.2 or 0.3% of ciprofloxacin, usually with a corticosteroid such as dexamethasone or hydrocortisone, for the treatment of otitis externa and chronic suppurative otitis media caused by susceptible strains of bacteria.

S dng v Qun tr
Ciprofloxacin l mt flo 4-quinolon hoc fluoroquinolone khng khun vi mt ph rng hn ca hot ng hn so vi acid nalidixic (xem khng sinh hnh ng,) v nhiu hn na dc ng hc thun li cho php s dng trong nhim trng h thng. N c s dng trong iu tr cc bnh nhim trng nh bnh than, ng mt, nhim khun ng, cn b nhim bnh v chch, nhim trng xng v khp, bnh u mo, ha cam mm, t cp ca bnh x nang, tai, mi, hng bnh nhim trng (bao gm vim tai gia externa, vim tai gia, vim xoang v), HACEK vim ni tm mc, vim d dy-rut (bao gm c du khch "rut tiu chy v campylobacter, t, rut salmonella, shigellosis, v rut Yersinia), bnh lu, u ht inguinale, nhim khun bnh nhn suy gim min dch (bch cu), thng 'bnh , bnh vim vng chu, vim phc mc, bnh dch hch, gim nhim trng ng h hp (bao gm c nhim trng pseudomonas trong chng x nang, nhng loi tr bnh nhim trng do Streptococcus pneumoniae nh vim phi ph cu khun), nhim trng rickettsial (bao gm Q st, pht hin st, v st pht ban), nhim trng huyt , nhim trng da (bao gm c nhim trng m mm), thng hn v ph thng hn, st v nhim khun ng tit niu, bao gm c vi khun vim tuyn tin lit mn tnh. Ciprofloxacin c s dng d phng vim mng no do no m cu. N cng c dng iu tr d phng nhim trng trong phu thut trong iu tr cc bnh nhim trng mycobacteria nontuberculous v bnh lao. Ciprofloxacin c s dng ti ch trong iu tr nhim trng mt v tai.

 bit chi tit ca tt c cc bnh nhim trng v iu tr ca h, xem theo la chn ca khng khun,. Qun tr v liu lng. Ciprofloxacin l dng ng ung nh l hydrochloride hoc c s, bi truyn tnh mch nh lactate, v trong thuc nh mt, thuc m mt, hoc thuc nh tai nh hydrochloride ny. Liu dng v th mnh c th hin trong iu khon ca c s. Ciprofloxacin hydrochloride 291,1 mg tng ng vi khong 250 mg ciprofloxacin. Ciprofloxacin 127 mg lactate tng ng vi khong 100 mg ciprofloxacin. Nhng ngi ln thng thng ung khong ciprofloxacin 250-750 mg hai ln mi ngy ty theo mc v tnh cht ca nhim trng. Sa i, pht hnh cc ch phm v liu lng ngy mt ln c sn mt s nc. Nhng ngi ln liu tim tnh mch thng thng l 200-400 mg hai ln mi ngy, vi trn 30 n 60 pht nh l mt dung dch cha tng ng vi t 1 n 2 mg / ml. Ph n vi vim bng quang khng bin chng cp tnh c th c cho mt liu ung 100 n 250 mg hai ln mi ngy trong 3 ngy hay 100 mg hai ln mi ngy bng cch truyn tnh mch. Mt kha hc 28-ngy iu tr bng mt liu ung 500 mg hai ln mi ngy hoc mt liu tim tnh mch ca 400 mg hai ln mi ngy nn c cp cho cc vi khun vim tuyn tin lit mn tnh. Xng v nhim trng khp cn c iu tr vi mt liu ung 500-750 mg hai ln mi ngy hoc mt liu 400 mg tim tnh mch ca hai hoc ba ln / ngy trong 4 n 6 tun. dch truyn tnh mch ca 400 mg ba ln mi ngy cng c ngh trong ng h hp nghim trng hoc phc tp thp hn hoc nhim trng da, vim phi bnh vin, v vi piperacillin iu tr theo kinh nghim ca bnh nhn st neutropenic. i vi iu tr v d phng sau phi nhim bnh than qua ng h hp, mt kha hc 60 ngy iu tr vi liu tim tnh mch ban u l 400 mg mi ngy hai ln sau liu ung 500 mg hai ln mi ngy c khuyn co, mc d khng c giy php, cc ch cng l ngh ca Anh v M cng cng c quan y t iu tr bnh than tiu ha. Trong iu tr bnh than da (cng khng c giy php), c 7 - hc 10 ngy iu tr bng mt liu ung 500-750 mg hai ln mi ngy l tng t nh ngh; iu tr c th cn phi c m rng n 60 ngy nu b nhim trng l do bnh phun tip xc. Liu nn c gim bnh nhn suy thn nng (xem). liu n ung 250 hoc 500 mg tim tnh mch hoc liu duy nht 100 mg c s dng iu tr bnh lu, ty theo loi khng. Mt n ung 750 mg c s dng iu tr

d phng nhim trng trong phu thut, cho 60 n 90 pht trc khi phu thut. Mc d khng c giy php Anh, BNF cho thy mt liu duy nht 500 mg ung phng bnh vim mng no do no m cu. bit chi tit v liu tr em, bao gm c tr s sinh v thanh thiu nin, nhn thy. i vi vim lot gic mc v nhim trng mt do cc chng b ngoi d b vi khun ciprofloxacin a ra nh l hydrochloride trong thuc nh mt v thuc m c cha mt tng ng vi 0,3% ca ciprofloxacin. Ciprofloxacin cng c s dng ti ch nh hydrochloride trong tai git cha tng ng l 0,2 hoc 0,3% ca ciprofloxacin, thng l vi mt corticosteroid nh dexamethasone hoc hydrocortisone, iu tr vim tai gia externa v vim tai gia mn tnh m do cc chng nhy cm ca vi khun.