Pyrazinamide

(BAN, rINN)
Pyrazinamide Chemical formula
Synonyms: Pirazinamid; Pirazinamida; Pirazinamidas; Pirazynamid; Pyratsiiniamidi; Pyrazinamid; Pyrazinamidum; Pyrazinoic Acid Amide. Pyrazine-2-carboxamide.
Cyrillic synonym: Пиразинамид.

💊 Chemical information

Chemical formula: C5H5N3O = 123.1.
CAS — 98-96-4.
ATC — J04AK01.
ATC Vet — QJ04AK01.

Pharmacopoeias.

In Chin., Eur., Int., Jpn, US, and Viet.

Ph. Eur. 6.2

(Pyrazinamide). A white or almost white, crystalline powder. Sparingly soluble in water, slightly soluble in alcohol and in dichloromethane.

USP 31

(Pyrazinamide). A white to practically white, odourless or practically odourless, crystalline powder. Soluble 1 in 67 of water, 1 in 175 of dehydrated alcohol, 1 in 135 of chloroform, 1 in 1000 of ether, and 1 in 72 of methyl alcohol; slightly soluble in alcohol.

💊 Adverse Effects and Treatment

Hepatotoxicity is the most serious adverse effect of pyrazinamide therapy and its frequency appears to be dose related. However, in currently recommended doses, when given with isoniazid and rifampicin, the incidence of hepatitis has been reported to be less than 3%. Patients may have a transient increase in liver enzyme values; more seriously hepatomegaly, splenomegaly, and jaundice may develop and on rare occasions death has occurred. Hyperuricaemia commonly occurs and may lead to attacks of gout. Other adverse effects are anorexia, nausea, vomiting, aggravation of peptic ulcer, arthralgia, malaise, fever, sideroblastic anaemia, thrombocytopenia, and dysuria. Photosensitivity, pellagra, and skin rashes have been reported on rare occasions.

Effects on the cardiovascular system.

Acute hypertension was associated with pyrazinamide in a previously normotensive woman.1
1. Goldberg J, et al. Acute hypertension as an adverse effect of pyrazinamide JAMA 1997; 277: 1356.

Effects on the liver.

The risk of hepatitis with antituberculous regimens containing pyrazinamide may be lower than suggested by early studies, in which large doses were used, often for long periods. The incidence of hepatitis in studies1 of short-course regimens containing pyrazinamide has ranged from 0.2% in Africa, to 0.6% in Hong Kong, to 2.8% in Singapore. These and later studies2-4 have shown that hepatotoxicity is not increased when pyrazinamide is added to the initial phase of short-term chemotherapy containing rifampicin and isoniazid. Nevertheless, a report5 of 4 cases of fulminant hepatic failure in patients given triple therapy with the potentially hepatotoxic drugs rifampicin, isoniazid, and pyrazinamide (1 patient also received ethambutol) highlighted the importance of strict liver function monitoring and this was reinforced by others. The Joint Tuberculosis Committee of the British Thoracic Society has produced recommendations6 for initial measurement of liver function in all patients and regular monitoring in patients with pre-existing liver disease, as well as the response to deteriorating liver function; prompt re-introduction of appropriate antituberculosis therapy is recommended once normal liver function is restored. Similar guidelines have been produced for the USA.7,8 For further information on hepatotoxicity caused by antituberculous drugs see Effects on the Liver, under Isoniazid. The incidence of severe hepatotoxicity was found to be lower in patients receiving isoniazid, rifampicin, and pyrazinamide for initial treatment of active disease, than in those receiving rifampicin and pyrazinamide for 2 months for latent tuberculosis infection. For further information on hepatotoxicity caused by rifampicin and pyrazinamide see Effects on the Liver, under Rifampicin.
1. Girling DJ. The role of pyrazinamide in primary chemotherapy for pulmonary tuberculosis. Tubercle 1984; 65: 1–4
2. Parthasarathy R, et al. Hepatic toxicity in South Indian patients during treatment of tuberculosis with short-course regimens containing isoniazid, rifampicin and pyrazinamide. Tubercle 1986; 67: 99–108
3. Combs DL, et al. USPHS tuberculosis short-course chemotherapy trial 21: effectiveness, toxicity, and acceptability: the report of final results. Ann Intern Med 1990; 112: 397–406
4. le Bourgeois M, et al. Good tolerance of pyrazinamide in children with pulmonary tuberculosis. Arch Dis Child 1989; 64: 177–8
5. Mitchell I, et al. Anti-tuberculous therapy and acute liver failure. Lancet 1995; 345: 555–6
6. Joint Tuberculosis Committee of the British Thoracic Society. Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998. Thorax 1998; 53: 536–48. [Although these guidelines were replaced by ones issued by NICE in 2006 the latter do not "explain tuberculosis or its treatment in detail" and therefore reference to the earlier guidelines has been retained] Also available at: http://www.brit-thoracic.org.uk/Portals/0/ Clinical%20Information/Tuberculosis/Guidelines/Chemotherapy.pdf (accessed 29/07/08
7. American Thoracic Society, CDC, and the Infectious Diseases Society of America. Treatment of tuberculosis. MMWR 2003; 52 (RR-11): 1–77. Also available at: http://www.cdc.gov/mmwr/ PDF/rr/rr5211.pdf (accessed 03/10/07) Correction. ibid. 2005; 53: 1203. [dose
8. Saukkonen JJ, et al. American Thoracic Society. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med 2006; 174: 935–52. Also available at: http:// www.thoracic.org/sections/publications/statements/resources/ hepatotoxicity-of-antituberculosis-therapy.pdf (accessed 05/10/07)

Effects on the nervous system.

Convulsions that developed in a 2-year-old child receiving antituberculous therapy appeared to be due to pyrazinamide, given in a dose of 250 mg daily.1
1. Herlevsen P, et al. Convulsions after treatment with pyrazinamide. Tubercle 1987; 68: 145–6.

Hyperuricaemia.

Hyperuricaemia during therapy with pyrazinamide may be due to inhibition of uric acid excretion by pyrazinoic acid, the main metabolite of pyrazinamide.1 In a large multicentre study,2 the incidence of elevated serum concentrations of uric acid for patients receiving rifampicin, isoniazid, and pyrazinamide was 52.2% at 8 weeks while the incidence for patients receiving rifampicin and isoniazid was 5.4%. Arthralgia was reported in 6 of 617 patients receiving rifampicin, isoniazid, and pyrazinamide, but in none of 445 patients receiving rifampicin and isoniazid. Slight increases in plasma concentrations of uric acid occurred in 9 of 43 children after one month’s treatment with rifampicin, isoniazid, ethambutol, and pyrazinamide. Arthralgias and gout did not occur. Uric acid concentrations were normal on completion of treatment with pyrazinamide.3 Some studies4 have suggested a relationship between elevated serum uric acid levels and arthralgia, but this has not been confirmed.5
1. Ellard GA, Haslam RM. Observations on the reduction of the renal elimination of urate in man caused by the administration of pyrazinamide. Tubercle 1976; 57: 97–103
2. Combs DL, et al. USPHS tuberculosis short-course chemotherapy trial 21: effectiveness, toxicity, and acceptability: the report of final results. Ann Intern Med 1990; 112: 397–406
3. le Bourgeois M, et al. Good tolerance of pyrazinamide in children with pulmonary tuberculosis. Arch Dis Child 1989; 64: 177–8
4. Hong Kong Tuberculosis Treatment Services/British MRC. Adverse reactions to short-course regimens containing streptomycin, isoniazid, pyrazinamide and rifampicin in Hong Kong. Tubercle 1976; 57: 81–95
5. Jenner PJ, et al. Serum uric acid concentrations and arthralgia among patients treated with pyrazinamide-containing regimens in Hong Kong and Singapore. Tubercle 1981; 62: 175–9.

Pellagra.

Pellagra, probably due to pyrazinamide, developed in a 26-year-old woman receiving antituberculous therapy.1 Symptoms regressed, despite continued therapy, on giving nicotinamide.
1. Jørgensen J. Pellagra probably due to pyrazinamide: development during combined chemotherapy of tuberculosis. Int J Dermatol 1983; 22: 44–5.

💊 Precautions

Pyrazinamide should be used with caution in patients with liver disorders and is contra-indicated in established chronic or severe liver disease. In patients with liver disorders, liver function should be assessed before and regularly during treatment. The British Thoracic Society has recommended that pyrazinamide treatment should be suspended if serum aminotransferase concentrations are elevated to 5 times the normal upper limit or if 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. WHO recommends that pyrazinamide not be reintroduced if the hepatitis produced a clinical jaundice. Pyrazinamide should not be given to patients with acute gout or hyperuricaemia and should be used with caution in patients with a history of gout. Caution should also be observed in patients with renal impairment. Increased difficulty has been reported in controlling diabetes mellitus when diabetics are given pyrazinamide.

Porphyria.

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

Pregnancy.

Although detailed teratogenicity data are not available, WHO,1 the IUATLD,2 the British Thoracic Society,3 and the CDC4 do not contra-indicate pyrazinamide in pregnant patients.
1. WHO. Treatment of tuberculosis: guidelines for national programmes. Geneva: WHO, 2003 (and 2004 revision). Available at: http://whqlibdoc.who.int/hq/2003/WHO_CDS_TB_2003.313_ eng.pdf (accessed 03/10/07
2. Caminero Luna JA. A tuberculosis guide for specialist physicians. Paris: International Union Against Tuberculosis and Lung Disease (IUATLD), 2004. Available at: http://www.tbrieder.org/ publications/specialists_en.pdf (accessed 03/10/07
3. Joint Tuberculosis Committee of the British Thoracic Society. Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998. Thorax 1998; 53: 536–48. [Although these guidelines were replaced by ones issued by NICE in 2006 the latter do not "explain tuberculosis or its treatment in detail" and therefore reference to the earlier guidelines has been retained] Also available at: http://www.brit-thoracic.org.uk/ Portals/0/Clinical%20Information/Tuberculosis/Guidelines/ Chemotherapy.pdf (accessed 29/07/08
4. American Thoracic Society, CDC, and the Infectious Diseases Society of America. Treatment of tuberculosis. MMWR 2003; 52 (RR-11): 1–77. Also available at: http://www.cdc.gov/ mmwr/PDF/rr/rr5211.pdf (accessed 03/10/07) Correction. ibid. 2005; 53: 1203. [dose]

💊 Interactions

Antigout drugs.

The complex interactions occurring when pyrazinamide and probenecid are given to patients with gout have been studied.1 Urinary excretion of urate depends on the relative size and timing of doses of the two drugs. Probenecid is known to block the excretion of pyrazinamide. A pharmacokinetic study2 in 6 healthy subjects found that allopurinol, a xanthine oxidase inhibitor, increases concentrations of pyrazinoic acid (the main metabolite of pyrazinamide) thereby worsening pyrazinamide-induced hyperuricaemia. Allopurinol would therefore also appear to be unsuitable for treating pyrazinamideinduced hyperuricaemia.
1. Yü TF, et al. The effect of the interaction of pyrazinamide and probenecid on urinary uric acid excretion in man. Am J Med 1977; 63: 723–8
2. Lacroix C, et al. Interaction between allopurinol and pyrazinamide. Eur Respir J 1988; 1: 807–11.

Zidovudine.

Low or undetectable concentrations of pyrazinamide occurred in 4 patients also taking zidovudine.1 In the same study, 6 of 7 patients with HIV infection taking pyrazinamide without zidovudine had normal serum pyrazinamide concentrations.
1. Peloquin CA, et al. Low antituberculosis drug concentrations in patients with AIDS. Ann Pharmacother 1996; 30: 919–25.

💊 Antimicrobial Action

Pyrazinamide has a bactericidal effect on Mycobacterium tuberculosis but appears to have no activity against other mycobacteria or micro-organisms in vitro. It is almost completely inactive at a neutral pH, but
is effective against persisting tubercle bacilli within the acidic intracellular environment of the macrophages. The initial inflammatory response to chemotherapy increases the number of organisms in the acidic environment. As inflammation subsides and pH increases, the sterilising activity of pyrazinamide decreases. This pHdependent activity explains the clinical effectiveness of pyrazinamide as part of the initial 8-week phase in short-course treatment regimens. Resistance to pyrazinamide rapidly develops when it is used alone.

Action.

Although the antimicrobial activity of pyrazinamide has been recognised since the 1950s, the mode of action is still unclear. One proposal is that pyrazinoic acid is the active moiety. Pyrazinamidase produced by the tubercle bacilli is known to convert pyrazinamide to pyrazinoic acid. A further proposal1 is that the pyrazinoic acid formed within the macrophage would be trapped, thereby lowering intracellular pH to levels toxic to tubercle bacilli.
1. Salfinger M, et al. Pyrazinamide and pyrazinoic acid activity against tubercle bacilli in cultured human macrophages and in the BACTEC system. J Infect Dis 1990; 162: 201–7.

Activity with other antimicrobials.

Pyrazinamide exhibited synergistic activity against Mycobacterium tuberculosis with clarithromycin.1
1. Mor N, Esfandiari A. Synergistic activities of clarithromycin and pyrazinamide against Mycobacterium tuberculosis in human macrophages. Antimicrob Agents Chemother 1997; 41: 2035–6.

💊 Pharmacokinetics

Pyrazinamide is readily absorbed from the gastrointestinal tract. Peak serum concentrations occur about 2 hours after an oral dose and have been reported to be about 33 micrograms/mL after 1.5 g, and 59 micrograms/mL after 3 g. Pyrazinamide is widely distributed in body fluids and tissues and diffuses into the CSF. The half-life has been reported to be about 9 to 10 hours. It is metabolised primarily in the liver by hydrolysis to the major active metabolite pyrazinoic acid, which is subsequently hydroxylated to the major excretory product 5-hydroxypyrazinoic acid. It is excreted via the kidneys mainly by glomerular filtration. About 70% of a dose appears in the urine within 24 hours mainly as metabolites and about 4% as unchanged drug. Pyrazinamide is removed by dialysis. Pyrazinamide is distributed into breast milk.
In the major metabolic pathway, pyrazinamide was deaminated to pyrazinoic acid which was hydroxylated to hydroxypyrazinoic acid; in the minor pathway, pyrazinamide was hydroxylated to hydroxypyrazinamide which was then deaminated to hydroxypyrazinoic acid. The limiting step was deamination; oxidation by xanthine oxidase occurred very quickly.
1. Lacroix C, et al. Pharmacokinetics of pyrazinamide and its metabolites in healthy subjects. Eur J Clin Pharmacol 1989; 36: 395–400.

Bioavailability.

The oral bioavailability of rifampicin and isoniazid, but not of pyrazinamide, was decreased by food in a study.1However, another report2 showed slightly reduced peak serum concentrations when pyrazinamide was given with a high-fat meal, and the authors suggested that pyrazinamide should preferably be given on an empty stomach.
1. Zent C, Smith P. Study of the effect of concomitant food on the bioavailability of rifampicin, isoniazid and pyrazinamide. Tubercle Lung Dis 1995; 76: 109–13
2. Peloquin CA, et al. Pharmacokinetics of pyrazinamide under fasting conditions, with food, and with antacids. Pharmacotherapy 1998; 18: 1205–11.

Breast feeding.

The peak concentration of pyrazinamide in breast milk of a 29-year-old woman was 1.5 micrograms/mL 3 hours after a 1-g dose.1 The peak plasma concentration was 42 micrograms/mL after 2 hours.
1. Holdiness MR. Antituberculosis drugs and breast-feeding. Arch Intern Med 1984; 144: 1888.

Distribution.

Pyrazinamide was given to 28 patients with suspected tuberculous meningitis in doses of 34 to 41 mg/kg. The mean concentration of pyrazinamide in the CSF after 2 hours was 38.6 micrograms/mL and represented about 75% of that in serum; concentrations at 5 and 8 hours were 44.5 and 31.0 micrograms/mL respectively and were about 10% higher than those in serum.1 The use of corticosteroids appeared to have no influence on penetration of pyrazinamide into the CSF of patients with tuberculous meningitis.2
1. Ellard GA, et al. Penetration of pyrazinamide into the cerebrospinal fluid in tuberculous meningitis. BMJ 1987; 294: 284–5
2. Woo J, et al. Cerebrospinal fluid and serum levels of pyrazinamide and rifampicin in patients with tuberculous meningitis. Curr Ther Res 1987; 42: 235–42.

Hepatic impairment.

A study1 of the pharmacokinetics of pyrazinamide was carried out in 10 patients with cirrhosis of the liver. After a dose of 19.3 mg/kg, the elimination phase was about 15 hours for pyrazinamide and 24 hours for the major metabolite pyrazinoic acid.
1. Lacroix C, et al. Pharmacokinetics of pyrazinamide and its metabolites in patients with hepatic cirrhotic insufficiency. Arzneimittelforschung 1990; 40: 76–9.

HIV-infected patients.

Malabsorption of pyrazinamide 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.

💊 Uses and Administration

Pyrazinamide is used as part of multidrug regimens for the treatment of tuberculosis, primarily in the initial 8-week phase of short-course treatment. Pyrazinamide is usually given daily or 2 or 3 times weekly. In the UK, usual recommended oral doses for adults under 50 kg are 1.5 g daily, or 2 g three times weekly, or 3 g twice weekly. The usual dose for those 50 kg or greater is 2 g daily, or 2.5 g three times weekly, or 3.5 g twice weekly. The recommended doses in the USA are 20 to 25 mg/kg daily (maximum 2 g) or 1.5 to 3 g three times weekly or 2 to 4 g twice weekly. WHO recommends 25 mg/kg daily or 35 mg/kg three times weekly. For details of doses in infants, children, and adolescents, see below. Pyrazinamide has also been used in the chemoprophylaxis of tuberculosis (see below). Fixed-dose combination products have been developed in order to improve patient compliance and avoid monotherapy; thereby decreasing the risk of acquired drug resistance. Combination products containing pyrazinamide with isoniazid, isoniazid and rifampicin, or isoniazid, rifampicin, and ethambutol are available in some countries.

Administration in children.

For the treatment of tuberculosis in infants, children, and adolescents the American Academy of Pediatrics suggests a dose of pyrazinamide of 20 to 40 mg/kg daily or 50 mg/kg (to a maximum of 2 g) twice weekly by mouth, for the initial treatment phase. For children 1 month and older the BNFC suggests a dose of 35 mg/kg (to a maximum of 1.5 g in those under 50 kg and 2 g in those over 50 kg) once daily or 50 mg/kg (to a maximum of 2 g in those under 50 kg and 2.5 g in those over 50 kg) three times a week. WHO recommends 25 mg/kg once daily or 35 mg/kg three times a week.

Administration in hepatic impairment.

See Precautions, above.

Administration in renal impairment.

Pyrazinamide is mainly metabolised in the liver, but its metabolites are excreted in the urine, therefore the CDC1 suggests that the dose may need to be reduced in patients with renal impairment. The Joint Tuberculosis Committee of the British Thoracic Society2 and WHO3consider that standard dosage may be used in such patients. Dialysis affects the clearance of pyrazinamide and CDC recommends reducing the dose to 25 to 35 mg/kg three times a week after dialysis. In a study4 of 6 patients on haemodialysis, the average amount of pyrazinamide and its metabolites removed during a dialysis session was 926 mg after an oral dose of 1700 mg. It was recommended that the usual pyrazinamide dose be given to patients on dialysis as the risk of accumulation was negligible, and that the dose on dialysis days be given after the procedure.
1. American Thoracic Society, CDC, and the Infectious Diseases Society of America. Treatment of tuberculosis. MMWR 2003; 52 (RR-11): 1–77. Also available at: http://www.cdc.gov/mmwr/ PDF/rr/rr5211.pdf (accessed 03/10/07) Correction. ibid. 2005; 53: 1203. [dose
2. Joint Tuberculosis Committee of the British Thoracic Society. Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998. Thorax 1998; 53: 536–48. [Although these guidelines were replaced by ones issued by NICE in 2006 the latter do not "explain tuberculosis or its treatment in detail" and therefore reference to the earlier guidelines has been retained] Also available at: http://www.brit-thoracic.org.uk/ Portals/0/Clinical%20Information/Tuberculosis/Guidelines/ Chemotherapy.pdf (accessed 29/07/08
3. WHO. Treatment of tuberculosis: guidelines for national programmes. 3rd ed. Geneva: WHO, 2003 (and 2004 revision). Available at: http://whqlibdoc.who.int/hq/2003/ WHO_CDS_TB_2003.313_eng.pdf (accessed 03/10/07
4. Lacroix C, et al. Haemodialysis of pyrazinamide in uraemic patients. Eur J Clin Pharmacol 1989; 37: 309–11.

Tuberculosis chemoprophylaxis.

In the USA, the American Thoracic Society and the CDC recommended a dose of pyrazinamide 15 to 20 mg/kg daily (maximum 2 g daily) with rifampicin 600 mg daily as an alternative to isoniazid monotherapy for the treatment of latent tuberculosis infection.1 (In those unable to take rifampicin, it was substituted with rifabutin 300 mg daily.) However, owing to reports of serious and fatal liver damage (see Effects on the Liver, under Adverse Effects, above) the CDC and the American Thoracic Society now recommend that the combination of pyrazinamide with rifampicin should not be offered to persons with latent tuberculosis.2.
1. American Thoracic Society and CDC. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000; 161 (suppl): S221–S247
2. CDC. Update: adverse event data and revised American Thoracic Society/CDC recommendations against the use of rifampin and pyrazinamide for treatment of latent tuberculosis infection—United States, 2003. MMWR 2003; 52: 735–9. Also available at: http:// www.cdc.gov/mmwr/PDF/wk/mm5231.pdf (accessed 05/10/07)

💊 Preparations

BP 2008: Pyrazinamide Tablets; USP 31: Pyrazinamide Tablets; Rifampin, Isoniazid, and Pyrazinamide Tablets; Rifampin, Isoniazid, Pyrazinamide, and Ethambutol Hydrochloride Tablets.

Proprietary Preparations

Austral.: Zinamide; Austria: Pyrafat; Belg.: Tebrazid; Braz.: Pirazinon; Canad.: Tebrazid; Cz.: Tisamid†; Fin.: Tisamid; Fr.: Pirilene; Ger.: Pyrafat; PZA; Hong Kong: Pyrafat; India: Actizid†; P-Zide; Pyzina; PZA-Ciba; Rifacom E-Z; Indon.: Corsazinamid; Neotibi; Pezeta-Ciba; Prazina; Sanazet; Siramid; TB ZET; Irl.: Zinamide†; Ital.: Piraldina; Malaysia: PZA; Mex.: Nizamyl; NZ: Zinamide; Philipp.: Pyramin; Pyrasol; PZA-Ciba; Zapedia; Zcure; Zinaplex; Port.: Piraside†; Pramide; S.Afr.: Pyrazide†; Singapore: PZA; Thai.: Myrin-P; Pyramide; Pyratab†; PZA; Turk.: Pirazinid. Multi-ingredient: Austria: Rifater; Canad.: Rifater; Denm.: Rimstar; Fin.: Rimstar; Fr.: Rifater; Ger.: Rifater; tebesium Trio; Gr.: Rifater; Hong Kong: Rifater; India: Akt-4; Coxina-4; Cx-5; Gocox-3; R-Cinex Z; RHZ; RHZ-Plus; Rifacomb Plus†; Rimactazid + Z; Tricox; Wokex-4; Xeed-4; Indon.: Rimcure; Rimstar; Irl.: Rifater; Ital.: Rifater; Malaysia: Rimcure; Mex.: Arpisen; Finateramida; Rifater; Philipp.: 4D; CombiKids; CombiPack; Econokit; Econokit-MDR; Econopack; Fixcom 4; Kidz Kit 3; Myrin-P; Quadtab; Refam Pedia Kit; Rifater; Rimcure; Rimstar; SVM-Polypac-A; Triofix; Viper; Port.: Rifater; Rus.: Isocomb (Изокомб); Lomecomb (Ломекомб); Phthizopiram (Фтизопирам); Protiocomb (Протиокомб); Repin B (Репин В ); Rifacomb Plus (Рифакомб Плюс); Rimecure 3-FDC (Римкур 3-ФДС); Rimstar 4-FDC (Римстар 4-ФДС); S.Afr.: Myrin Plus†; Rifafour; Rifater; Rimcure; Rimstar; Spain: Rifater; Rimcure; Rimstar; Swed.: Rimcure; Rimstar; Switz.: Rifater; Thai.: Rifafour; Rifampyzid; Rifater; Rimcure 3-FDC; Rimstar; UK: Rifater; USA: Rifater; Venez.: Rimcure.
Published May 08, 2019.