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Isoniazid

Drug Nomenclature

International Nonproprietary Names (INNs) in main languages (French, Latin, Russian, and Spanish):

Synonyms: INAH; INH; Isoniatsidi; Isoniazid; Isoniazida; Isoniazidum; Isonicotinic Acid Hydrazide; Isonicotinylhydrazide; Isonicotinylhydrazine; Izoniazid; Izoniazidas; Tubazid
BAN: Isoniazid
INN: Isoniazid [pINN (en)]
INN: Isoniazida [pINN (es)]
INN: Isoniazide [pINN (fr)]
INN: Isoniazidum [pINN (la)]
INN: Изониазид [pINN (ru)]
Chemical name: Isonicotinohydrazide
Molecular formula: C6H7N3O =137.1
CAS: 54-85-3
ATC code: J04AC01
Read code: y02S1

Note. The name Isopyrin, which has been applied to isoniazid, has also been applied to ramifenazone.

Pharmacopoeias

In China, Europe, International, Japan, US, and Vietnam. European Pharmacopoeia, 6th ed., 2008 and Supplements 6.1 and 6.2 (Isoniazid). A white or almost white, crystalline powder or colourless crystals. Freely soluble in water; sparingly soluble in alcohol. A 5% solution in water has a pH of 6.0 to 8.0. The United States Pharmacopeia 31, 2008 (Isoniazid). Colourless, or white, odourless crystals, or white crystalline powder. Soluble 1 in 8 of water and 1 in 50 of alcohol; slightly soluble in chloroform; very slightly soluble in ether. pHofa 10% solution in water is between 6.0 and 7.5. Store in airtight containers at a temperature of 25°, excursions permitted between 15° and 30°. Protect from light.

Isoniazid

Incompatibility

It has been recommended that sugars such as glucose, fructose, and sucrose should not be used in isoniazid syrup preparations because the absorption of the drug was impaired by the formation of a condensation product. Sorbitol may be a suitable substitute if necessary.

Sterilisation

Solutions of isoniazid should be sterilised by autoc laving.

Adverse Effects

Isoniazid is generally well tolerated at currently recommended doses. However, patients who are slow acetylators of isoniazid and those with advanced HIV disease appear to have a higher incidence of some adverse effects. Also patients whose nutrition is poor are at risk of peripheral neuritis which is one of the commonest adverse effects of isoniazid. Other neurological adverse effects include psychotic reactions and convulsions. Pyridoxine may be given to prevent or treat these adverse effects. Optic neuritis has also been reported. Transient increases in liver enzymes occur in 10 to 20% of patients during the first few months of treatment and usually return to normal despite continued treatment. Symptomatic hepatitis occurs in about 0.1 to 0.15% of patients given isoniazid as monotherapy, but this can increase with age, regular alcohol consumption, and in those with chronic liver disease. The influence of acetylator status is uncertain. Elevated liver enzymes associated with clinical signs of hepatitis such as nausea and vomiting, or fatigue may indicate hepatic damage; in these circumstances, isoniazid should be stopped pending evaluation and should only be reintroduced cautiously once hepatic function has recovered. Fatalities have occurred due to liver necrosis. Haematological effects reported on use of isoniazid include various anaemias, agranulocytosis, thrombocy-topenia, and eosinophilia. Hyper sensitivity reactions occur infrequently and include skin eruptions (including erythema multiforme), fever, and vasculitis. Other adverse effects include nausea, vomiting, dry mouth, constipation, pellagra, purpura, hyperglycaemia, lupus-like syndrome, vertigo, hyperreflexia, urinary retention, and gynaecomastia. Symptoms of overdosage include slurred speech, metabolic acidosis, hallucinations, hyperglycaemia, respiratory distress or tachypnoea, convulsions, and coma; fatalities can occur.

Carcinogenicity

Concern about the carcinogenicity of isoniazid arose in the 1970s when an increased risk of bladder cancer in patients treated with isoniazid was reported. However, no evidence to support a carcinogenic effect of isoniazid was found in more than 25 000 patients followed up for 9 to 14 years in studies organised by the USA Public Health Service and in 3842 patients followed up for 16 to 24 years in the UK.

Isoniazid

Effects on the blood

In addition to the effects mentioned above, rare reports of adverse effects of isoniazid on the blood include bleeding associated with acquired inhibition of fibrin stabilisation or of factor XIII, and red cell aplasia. For a reference to neutropenia, see Effects on the Blood, under Ethambutol Hydrochloride.

Effects on the CNS

In addition to the peripheral neuropathy that is a well-established adverse effect of isoniazid, effects on the CNS have also been reported, including ataxia and cerebellar toxicity, psychotic reactions (generally characterised by delusions, hallucinations, and confusion), and seizures, particularly after overdosage. Encephalopathy has been reported in dialysis patients. Encephalopathy may also be a symptom of pellagra, which may be associated with isoniazid treatment.

Effects on the liver

Transient abnormalities in liver function are common during the early stages of antituberculous therapy with isoniazid and other first-line antituberculous drugs, but sometimes hepatotoxicity may be more serious and require a change of treatment. Drug-induced hepatitis usually occurs within the first few weeks of treatment and it may not be possible to identify which drug or drugs are responsible. Isoniazid and pyrazinamide are thought to have a greater potential for hepatotoxicity than rifampicin. Risk factors for hepatotoxicity include alcoholism, old age, female gender, malnutrition, HIV infection, and chronic hepatitis B andC infections. Speculation that fast acetylators of isoniazid could be at increased risk of hepatotoxicity due to production of a hepatotoxic hydrazine metabolite has not been supported; in fact, slow acetylators have generally been found to have a higher risk than fast acetylators. This could reflect a reduced rate of subsequent metabolism to non-toxic compounds. In addition, concentrations of hydrazine in the blood have not been found to correlate with acetylator status. A multicentre study considered the incidence of hepatotoxicity from a short-term regimen of daily isoniazid, rifampicin, and pyrazinamide for 8 weeks in the initial phase followed by daily isoniazid and rifampicin for 16 weeks in the continuing phase. Analysis from 617 patients showed an incidence of hepatotoxic reactions of 1.6%; the incidence of elevated aspartate ami-notransferase was 23.2%. In the same study, 445 patients on a 9-month regimen of daily isoniazid and rifampicin had a 1.2% incidence of hepatotoxicity and 27.1% incidence of elevated liver enzymes. A similar incidence of hepatitis of 1.4% among 350 patients on a 9-month regimen of rifampicin and isoniazid has also been reported. A retrospective analysis of 430 children on isoniazid and rifampicin revealed hepatotoxic reactions in 3.3%, the highest incidence being in children with severe disease. The Joint Tuberculosis Committee of the British Thoracic Society has published recommendations for initial measurement of liver function in all patients and regular monitoring in patients with known chronic liver disease. Details are given concerning the response to deteriorating liver function depending on the clinical situation, and guidelines included for prompt re-introduction of appropriate antituberculosis therapy once normal liver function is restored. Similar guidelines have been produced in the USA. The incidence of hepatotoxicity is lower in patients receiving isoniazid for prophylaxis than in those receiving treatment for active disease. During a 7-year period an incidence of 0.15% was recorded in 11 141 patients who started prophylactic therapy, whereas it was 1.25% amongst 1427 patients receiving treatment. A similar study in a slightly older patient population reported an incidence of 0.56%. No cases of hepatotoxicity were reported in 556 HIV-infected patients taking a 3-month prophylactic regimen of isoniazid and rifampicin for latent tuberculosis. A meta-analysis concluded that daily isoniazid and rifampicin for 3 months appeared to be as safe as treatment with isoniazid alone for 6 to 12 months.

Effects on the pancreas

Cases of isoniazid-induced pancreatitis have been rarely reported; pancreatitis resolved in these patients once treatment with isoniazid was stopped, and recurred on rechallenge. It is recommended if isoniazid-induced pancreatitis is proven that the drug should be permanently avoided. Chronic pancreatic insufficiency, after an acute episode, was reported in a patient given isoniazid, rifampicin, ethambutol, and pyrazinamide and was considered to be a drug hypersensitivity reaction.

Effects on the skin and hair

Isoniazid causes cutaneous drug reactions in less than 1% of patients. These reactions include urticaria, purpura, acneform syndrome, a lupus erythematosus-like syndrome (see below), and exfoliative dermatitis. Pellagra is also associated with isoniazid. Isoniazid was considered the most likely cause of alopecia in 5 patients receiving antituberculosis regimens which also included rifampicin, ethambutol, and pyrazinamide.

Lupus

Antinuclear antibodies have been reported to occur in up to 22% of patients receiving isoniazid; however, patients are usually asymptomatic and overt lupoid syndrome is rare. The incidence of antibody induction has been reported to be higher in slow acetylators than in fast acetylators, but the difference was not statistically significant and acetylator phenotype is not considered an important determinant of the risk of isoniazid-induced lupus. The syndrome appeared to be due to isoniazid itself rather than its metabolite acetylisoniazid.

Treatment of Adverse Effects

Pyridoxine hydrochloride 10 mg daily is usually recommended for prophylaxis of peripheral neuritis associated with isoniazid although up to 50 mg daily may be used. A dose of 50 mg three times daily may be given for treatment of peripheral neuritis if it develops. Nicotinamide has been given, usually with pyridoxine, to patients who develop pellagra. Isoniazid doses of 1.5 g or more are potentially toxic and doses of 10 to 15 g may be fatal without appropriate treatment. Treatment of overdosage is symptomatic and supportive and consists of activated charcoal, correction of metabolic acidosis, and control of convulsions. Large doses of pyridoxine may be needed intravenously for control of convulsions (see below) and should be given with diazepam. Isoniazid is removed by haemodialysis or peritoneal dialysis.

Overdosage

In adults an initial intravenous dose of pyridoxine hydrochloride equivalent to the estimated amount of isoniazid ingested (or, if the amount ingested is unknown, pyridoxine hydrochloride 5 g) has been recommended by the UK National Poisons Information Service for the management of convulsions; diazepam should also be given. For children the recommended dose of pyridoxine hydrochloride is 70 mg/kg (to a maximum of 5 g). If convulsions continue or recur, this dose may be repeated. Oral activated charcoal (50 g for adults and 10 to 15 g in children) may be considered if this is given within 1 hour of inges-tion of isoniazid.

Pyridoxine deficiency

Pyridoxine deficiency associated with isoniazid in doses of 5 mg/kg daily is uncommon. Patients at risk of developing pyridoxine deficiency include those with diabetes, uraemia, alcoholism, HIV infection, and malnutrition.,t Supplementation with pyridoxine should be considered for these at-risk groups as well as for pregnant women and patients with seizure disorders. For the prophylaxis of peripheral neuritis it is common practice to give pyridoxine 10 mg daily, although 6 mg daily might be sufficient. However, in one patient a dose of pyridoxine 10 mg daily failed to prevent psychosis, the symptoms of which only resolved after stopping isoniazid and increasing the pyridoxine dosage to 100 mg daily.

Precautions

Isoniazid should be used with caution in patients with convulsive disorders, a history of psychosis, or hepatic or renal impairment. Patients who are at risk of neuropathy or pyridoxine deficiency, including those who are diabetic, alcoholic, malnourished, uraemic, pregnant, or infected with HIV, should be given pyridoxine, usually in a dose of 10 mg daily, although up to 5 0 mg daily may be used. If symptoms of hepatitis develop, such as malaise, fatigue, anorexia, and nausea, isoniazid should be stopped pending evaluation. Liver function should be checked before treatment with isoniazid and special care should be taken in alcoholic patients or those with pre-existing liver disease.

Regular monitoring of liver function is recommended in patients with pre-existing liver disease, and the British Thoracic Society has recommended that isoniazid treatment be suspended if serum aminotransferase concentrations are elevated to more than 5 times the normal upper limit or the bilirubin concentration rises. They allow cautious sequential re-introduction of antimycobacterial drugs once liver function has returned to normal: first isoniazid, then rifampicin, and then pyrazinamide. Careful monitoring should be considered for black and Hispanic women, in whom there may be an increased risk of fatal hepatitis. When visual symptoms occur during isoniazid treatment periodic eye examinations have been suggested.

Breast feeding

Peak concentrations of isoniazid in breast milk were 6 micrograms/mL after a dose of 5 mg/kg and were 16.6 micrograms/mL after a 300-mg dose. However, drug concentrations in the breast milk are too low to prevent or treat tuberculosis in infants. Adverse effects on breast-fed infants have not been reported and the American Academy of Pediatrics thus considers isoniazid to be usually compatible with breast feeding, although such infants should be monitored for toxic reactions.

Porphyria

Isoniazid is considered to be unsafe in patients with porphyria although there is conflicting experimental evidence of porphyrinogenicity.

Pregnancy and the neonate

In a review of antituberculous treatment in pregnant patients it was reported that over 95% of 1480 pregnancies in which isoniazid had been given resulted in a normal term infant. Slightly more than 1% of the infants/fetuses were abnormal and many of these abnormalities were CNS related. Isoniazid is therefore recognised as being suitable for use in regimens for the treatment of tuberculosis in pregnant patients. Pyridoxine supplementation is recommended (see Treatment of Adverse Effects, above). Preventive therapy with isoniazid is generally delayed until after delivery unless other risk factors are present.

Interactions

The risk of hepatotoxicity may be increased in patients receiving isoniazid with a rifamycin or other potentially hepatotoxic drugs, including alcohol. Isoniazid can inhibit the hepatic metabolism of a number of drugs, in some cases leading to increased toxicity. These include the antiepileptics carbamazepine, ethosuximide, primidone, and phenytoin, the benzodiazepines diazepam and triazolam, chlorzoxazone, theophylline, and disulfiram. The metabolism of enflurane (see Effects on the Kidneys) may be increased in patients receiving isoniazid, resulting in potentially nephrotoxic levels of fluoride. Isoniazidhas been associated with increased concentrations and enhanced effects or toxicity of clofazimine, cycloserine, and warfarin. For interactions affecting isoniazid, see below.

Alcohol

The metabolism of isoniazid may be increased in chronic alcoholics: this may lead to reduced isoniazid effectiveness. These patients may also be at increased risk of developing isoniazid-induced peripheral neuropathies and hepatic damage (see Precautions, above).

Antacids

Oral absorption of isoniazid is reduced by aluminium-containing antacids; isoniazid should be given at least 1 hour before the antacid.

Antifungals

Serum concentrations of isoniazid were below the limits of detection in a patient also receiving rifampicin and ketoconazole For the effect of isoniazid on ketoconazole.

Antivirals

The clearance of isoniazid was approximately doubled when zalcitabine was given to 12 HIV-positive patients. In addition, care is needed since stavudine and zalcitabine may also cause peripheral neuropathy; use of isoniazid with stavudine has been reported to increase its incidence.

Corticosteroids

Giving prednisolone 20 mg to 13 slow acetylators and 13 fast acetylators receiving isoniazid 10 mg/kg reduced plasma concentrations of isoniazid by 25 and 40% respectively. Renal clearance of isoniazid was also enhanced in both acetylator phenotypes and the rate of acetylation increased in slow acetylators only. The clinical significance of this effect is not established.

Food

Palpitations, headache, conjunctival irritation, severe flushing, tachycardia, tachypnoea, and sweating have been reported in patients taking isoniazid after ingestion of cheese, red wine and some fish. Accumulation of tyramine or histamine has been proposed as the cause of these food-related reactions, and they could be mistaken for anaphylaxis.

Opioid analgesics

For a report of an interaction between isoniazid and pethidine, attributed to isoniazid’s inhibitory actions on monoamine oxidase.

Antimicrobial Action

Isoniazid is highly active against Mycobacterium tuberculosis and may have activity against some strains of other mycobacteria including M. kansasii. Although it is rapidly bactericidal against actively dividing M. tuberculosis, it is considered to be only bac-teriostatic against semi-dormant organisms and has less sterilising activity than rifampicin or pyrazinamide. Resistance of M. tuberculosis to isoniazid develops rapidly if it is used alone in the treatment of clinical infection, and may be due in some strains to loss of the gene for catalase production. Resistance is delayed or prevented by the combination of isoniazid with other antimycobacterials which appears to be highly effective in preventing emergence of resistance to other an-tituberculous drugs. Resistance does not appear to be a problem when isoniazid is used alone in prophylaxis, probably because the bacillary load is low.

Mycobacterium avium complex

Synergistic activity of isoniazid plus streptomycin and, to a lesser degree, isoniazid plus clofazimine, against Mycobacterium avium complex (MAC) has been demonstrated in vitro and in vivo.

Pharmacokinetics

Isoniazid is readily absorbed from the gastrointestinal tract and after intramuscular injection. Peak concentrations of about 3 to 7 micrograms/mL appear in blood 1 to 2 hours after an oral fasting dose of 300 mg. The rate and extent of absorption of isoniazid is reduced by food. Isoniazid is not considered to be bound appreciably to plasma proteins and distributes into all body tissues and fluids, including the CSF. It appears in fetal blood if given during pregnancy (see below), and is distributed into breast milk (see under Precautions, above). The plasma half-life for isoniazid ranges from about 1 to 6 hours, with shorter half-lives in fast acetylators. The primary metabolic route is the acetylation of isoniazid to acetylisoniazid by N-acetyltransferase found in the liver and small intestine. Acetylisoniazid is then hydrolysed to isonicotinic acid and monoacetylhydrazine; isonicotinic acid is conjugated with glycine to isonicotinyl glycine (isonicotinuric acid) and monoacetylhydrazine is further acetylated to diacetylhydrazine. Some unmetabolised isoniazid is conjugated to hydrazones. The metabolites of isoniazid have no tuberculostatic activity and, apart from possibly monoacetylhydrazine, they are also less toxic. The rate of acetylation of isoniazid and monoacetylhydrazine is genetically determined and there is a bimodal distribution of persons who acetylate them either slowly or rapidly. Ethnic groups differ in their proportions of these genetic phenotypes. When isoniazid is given daily or 2 or 3 times weekly, clinical effectiveness is not influenced by acetylator status. In patients with normal renal function, over 75% of a dose appears in the urine in 24 hours, mainly as metabolites. Small amounts of drug are also excreted in the faeces. Isoniazid is removed by haemodialysis.

Distribution

Therapeutic concentrations of isoniazid have been detected in CSF and synovial fluid several hours after an oral dose. Diffusion into saliva is good and it has been suggested that salivary concentrations could be used in place of serum concentrations inpharmacokinetic studies.

HIV-infected patients

Malabsorption of isoniazid and other antituberculous drugs may occur in patients with HIV infection and tuberculosis, and may contribute to acquired drug resistance and reduced efficacy of tuberculosis treatment. For further information on the absorption of antituberculous drugs in HIV-infected patients see Pharmacokinetics, under Rifampicin.

Pregnancy

Isoniazid crosses the placenta and average fetal concentrations of 61.5 and 72.8% of maternal serum or plasma concentration have been reported. The half-life of isoniazid may be prolonged in neonates.

Uses and Administration

Isoniazid is a hydrazide derivative that is the mainstay of the primary treatment of pulmonary and extrapulmonary tuberculosis. It is used with other antituberculous drugs usually in regimens including rifampicin, ethambutol, and pyrazinamide. Isoniazid is also used in high-risk subjects for the prophylaxis of tuberculosis. Isoniazid is given in the initial and continuation phases of short-course tuberculosis regimens. The usual adult dose is 5 mg/kg, to a maximum of 300 mg, daily by mouth on an empty stomach. For intermittent therapy, WHO recommends 10 mg/kg three times a week or 15 mg/kg twice a week, while the recommended dose in the UK is 15 mg/kg three times a week and in the USA 15 mg/kg once weekly or two or three times a week is recommended. Caution is required in patients with hepatic impairment and doses may need to be reduced in those with severe renal impairment. Similar doses to those used orally may be given by intramuscular injection when isoniazid cannot be taken by mouth; it may also be given by intravenous injection. Isoniazid has also been given intrathecally and intrapleurally. In the treatment of latent tuberculosis, daily doses of 300 mg for 6 months are recommended by WHO and in the UK, while in the USA the preferred treatment regimen is oral isoniazid 5 mg/kg daily or 15 mg/kg twice weekly for 9 months. As an alternative to such regimens, isoniazid may be given with rifampicin for 3 months. For details of doses in infants, children, and adolescents, see below. Isoniazid aminosalicylate (pasiniazid) and isoniazid sodium glucuronate have also been used in the treatment of tuberculosis. Fixed-dose combination products containing 2, 3, or 4 drugs have been developed in order to improve patient compliance and avoid monotherapy, thereby decreasing the risk of acquired drug resistance. Products containing isoniazid in various combinations with rifampicin, ethambutol, and pyrazinamide are available in some countries.

Administration in children

For the treatment of tuberculosis in infants, children, and adolescents the American Academy of Pediatrics (AAP) suggests an oral dose of isoniazid 10 to 15 mg/kg daily or 20 to 30 mg/kg twice weekly by mouth, for both the initial and continuation phases. For children 1 month and older the BNFC suggests oral doses of 5 to 10 mg/kg once daily or 15 mg/kg three times a week; WHO recommends 5 mg/kg once daily, or 10 mg/kg three times a week, or 15 mg/kg twice a week. For the treatment of latent tuberculosis the AAP and the American Thoracic society suggest oral doses of 10 to 20 mg/kg daily or 20 to 40 mg/kg twice weekly for 9 months. For children 1 month and older the BNFC suggests a dose of 5 mg/kg once daily for 6 months when used alone or for 3 months when given with rifampicin; WHO recommends 5 mg/kg once daily for 6 months. For daily dosing regimens the maximum oral dose of isoniazid is 300 mg and for intermittent regimens the maximum dose is 900 mg per dose.

Preparations

British Pharmacopoeia 2008: Isoniazid Injection; Isoniazid Tablets; The United States Pharmacopeia 31, 2008: Isoniazid Injection; Isoniazid Syrup; Isoniazid Tablets; Rifampin and Isoniazid Capsules; Rifampin, Isoniazid, and Pyrazinamide Tablets; Rifampin, Isoniazid, Pyrazinamide, and Ethambutol Hydrochloride Tablets.

Single-ingredient Preparations

Argentina: Isoniac; Belgium: Nicotibine; Rimifon; Canada: Isotamine; Czech Republic: Nidrazid; Finland: Tubilysin; France: Rimifon; Germany: Dipasic; Gluronazid; Isozid comp N; Isozid; Tb-Phlogin cum B6; tebesium-s; tebesium; Greece: Dianicotyl; Isozid; Nicozid; Hong Kong: Trisofort; Hungary: Isonicid; India: Isokin; Isonex; Rifacom E-Z; Israel: Inazid; Italy: Cin; Nicazide; Nicizina; Nicozid; Japan: Hydra; Hydrazide; Mexico: Dipasic; Erbazid; Hidrasix; Pas Hain; Valifol; Portugal: Hidrazida; Spain: Anidrasona; Cemidon B6; Cemidon; Dipasic; Hidrastol; Pyreazid; Rimifon; Sweden: Tibinide; Switzerland: Rimifon; Thailand: Myrin-P; Myrin; United Kingdom: Inapsade; Rimifon; United States: Laniazid; Nydrazid

Multi-ingredient Preparations

Argentina: Bacifim; Rifinah; Risoniac; Austria: Isoprodian; Myambutol-INH; Rifater; Rifoldin INH; Rimactan + INH; Brazil: Fluodrazin F; Isoniaton; Canada: Rifater; France: Myambutol-INH; Rifater; Rifinah; Germany: EMB-INH; Etibi-INH; Iso-Eremfat; Isoprodian; Myambutol-INH; Rifa/INH; Rifater; Rifinah; tebesium Duo; tebesium Trio; Greece: Oboliz; Rifater; Rifinah; Rimactazid; Hong Kong: Ricinis; Rifater; Rifinah; Hungary: Rifazid; India: Akt-3; Akt-4; Arzide; Bicox-E; Combunex; Coxina-3; Coxina-4; Coxinex; Cx-3; Cx-4; Cx-5; Gocox Compound; Gocox-3; Gocox-4; Inabutol Forte; Inapas; Ipcacin Kid; Ipcazide; Isokin-300; Isokin-T Forte; Isorifam; Myconex; R-Cinex Z; R-Cinex; RHZ-Plus; Rifa E; Rifa; Rifacomb Plus; Rifacomb; Rimactazid + Z; Rimpazid; Siticox-INH; Tibirim INH; Tricox; Wokex-2; Wokex-3; Wokex-4; Xeed-2; Xeed-3E; Xeed-4; Ireland: Rifater; Rifinah; Rimactazid; Italy: Emozide B6; Etanicozid B6; Etibi-INH; Miazide B6; Miazide; Rifanicozid; Rifater; Rifinah; Malaysia: Rimactazid; Mexico: Arpisen; Finater; Finateramida; Isonid; Myambutol-INH; Rifater; Rifinah; Monaco: Dexambutol-INH; Netherlands: Rifinah; New Zealand: Rifinah; Portugal: Rifater; Rifinah; Tuberen; Russia: Phthizoetham (Фтизоэтам); Phthizopiram (Фтизопирам); Rifacomb (Рифакомб); Rifacomb Plus (Рифакомб Плюс); South Africa: Isoprodian; Mynah; Myrin Plus; Myrin; Pyrifin; Rifafour; Rifater; Rifinah; Rimactazid; Rimcure; Tuberol; Singapore: Rifater; Rifinah; Rimactazid; Spain: Amiopia; Duplicalcio 150; Duplicalcio B12; Duplicalcio Hidraz; Duplicalcio; Isoetam; Poli Biocatines; Rifater; Rifazida; Rifinah; Rimactazid; Rimcure; Rimstar; Tisobrif; Victogon; Sweden: Rimactazid; Rimcure; Rimstar; Switzerland: Myambutol-INH; Rifater; Rifinah; Rifoldine-INH; Rimactazide + Z; Rimactazide; Thailand: Ricinis; Rifafour; Rifamiso; Rifampyzid; Rifater; Rifinah; Rimactazid; Rimcure 3-FDC; Rimstar; United Kingdom: Mynah; Rifater; Rifinah; Rimactazid; United States: IsonaRif; Rifamate; Rifater; Rimactane/INH Dual Pack

Single-ingredient Preparations

The symbol denotes a preparation which is discontinued or no longer actively marketed. Argentina: Isoniac; Belgium: Nicotibine; Rimifon; Canada: Isotamine; Czech Republic: Nidrazid; Finland: Tubilysin; France: Rimifon; Germany: Dipasic; Gluronazid; Isozid comp N; Isozid; Tb-Phlogin cum B6; tebesium-s; tebesium; Greece: Dianicotyl; Isozid; Nicozid; Hong Kong: Trisofort; Hungary: Isonicid; India: Isokin; Isonex; Rifacom E-Z; Israel: Inazid; Italy: Cin; Nicazide; Nicizina; Nicozid; Japan: Hydra; Hydrazide; Mexico: Dipasic; Erbazid; Hidrasix; Pas Hain; Valifol; Portugal: Hidrazida; Spain: Anidrasona; Cemidon B6; Cemidon; Dipasic; Hidrastol; Pyreazid; Rimifon; Sweden: Tibinide; Switzerland: Rimifon; Thailand: Myrin-P; Myrin; United Kingdom: Inapsade; Rimifon; United States: Laniazid; Nydrazid;

Multi-ingredient Preparations

The symbol denotes a preparation which is discontinued or no longer actively marketed. Argentina: Bacifim; Rifinah; Risoniac; Austria: Isoprodian; Myambutol-INH; Rifater; Rifoldin INH; Rimactan + INH; Brazil: Fluodrazin F; Isoniaton; Canada: Rifater; France: Myambutol-INH; Rifater; Rifinah; Germany: EMB-INH; Etibi-INH; Iso-Eremfat; Isoprodian; Myambutol-INH; Rifa/INH; Rifater; Rifinah; tebesium Duo; tebesium Trio; Greece: Oboliz; Rifater; Rifinah; Rimactazid; Hong Kong: Ricinis; Rifater; Rifinah; Hungary: Rifazid; India: Akt-3; Akt-4; Arzide; Bicox-E; Combunex; Coxina-3; Coxina-4; Coxinex; Cx-3; Cx-4; Cx-5; Gocox Compound; Gocox-3; Gocox-4; Inabutol Forte; Inapas; Ipcacin Kid; Ipcazide; Isokin-300; Isokin-T Forte; Isorifam; Myconex; R-Cinex Z; R-Cinex; RHZ-Plus; Rifa E; Rifa; Rifacomb Plus; Rifacomb; Rimactazid + Z; Rimpazid; Siticox-INH; Tibirim INH; Tricox; Wokex-2; Wokex-3; Wokex-4; Xeed-2; Xeed-3E; Xeed-4; Ireland: Rifater; Rifinah; Rimactazid; Italy: Emozide B6; Etanicozid B6; Etibi-INH; Miazide B6; Miazide; Rifanicozid; Rifater; Rifinah; Malaysia: Rimactazid; Mexico: Arpisen; Finater; Finateramida; Isonid; Myambutol-INH; Rifater; Rifinah; Monaco: Dexambutol-INH; Netherlands: Rifinah; New Zealand: Rifinah; Portugal: Rifater; Rifinah; Tuberen; Russia: Phthizoetham (Фтизоэтам); Phthizopiram (Фтизопирам); Rifacomb (Рифакомб); Rifacomb Plus (Рифакомб Плюс); South Africa: Isoprodian; Mynah; Myrin Plus; Myrin; Pyrifin; Rifafour; Rifater; Rifinah; Rimactazid; Rimcure; Tuberol; Singapore: Rifater; Rifinah; Rimactazid; Spain: Amiopia; Duplicalcio 150; Duplicalcio B12; Duplicalcio Hidraz; Duplicalcio; Isoetam; Poli Biocatines; Rifater; Rifazida; Rifinah; Rimactazid; Rimcure; Rimstar; Tisobrif; Victogon; Sweden: Rimactazid; Rimcure; Rimstar; Switzerland: Myambutol-INH; Rifater; Rifinah; Rifoldine-INH; Rimactazide + Z; Rimactazide; Thailand: Ricinis; Rifafour; Rifamiso; Rifampyzid; Rifater; Rifinah; Rimactazid; Rimcure 3-FDC; Rimstar; United Kingdom: Mynah; Rifater; Rifinah; Rimactazid; United States: IsonaRif; Rifamate; Rifater; Rimactane/INH Dual Pack

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