      Document 0138
 DOCN  DRG0138
 UNIQUE IDENTIFIER        DRG-0109
 NAME OF SUBSTANCE        Rifampin [USAN 1996]
 REGISTRY NUMBER          13292-46-1
 STANDARD CHEMICAL NAME   3-(((4-Methyl-1-piperazinyl)imino)-methyl)rif-
                          amycin [Merck Index 1989]
 SYNONYMS                 Rifadin [USAN 1996]
 SYNONYMS                 Rimactane [USAN 1996]
 SYNONYMS                 Rifampicin [Merck Index 1989]
 SYNONYMS                 Rifamate [PDR 1995]
 SYNONYMS                 Rifaldazine [Merck Index 1989]
 SYNONYMS                 Rifamicin AMP [Merck Index 1989]
 SYNONYMS                 R/AMP [Merck Index 1989]
 SYNONYMS                 Abrifam [Merck Index 1989]
 SYNONYMS                 Dipicin [Merck Index 1989]
 SYNONYMS                 Eremfat [Merck Index 1989]
 SYNONYMS                 Rifa [Merck Index 1989]
 SYNONYMS                 Rifadin I.V. [PDR 1995]
 SYNONYMS                 Rifadine [Merck Index 1989]
 SYNONYMS                 Rifaldin [Merck Index 1989]
 SYNONYMS                 Rifaprodin [Merck Index 1989]
 SYNONYMS                 Rifobac [Merck Index 1989]
 SYNONYMS                 Riforal [Merck Index 1989]
 SYNONYMS                 Rifoldin [Merck Index 1989]
 SYNONYMS                 Rifoldine [Merck Index 1989]
 SYNONYMS                 Rifadin [PDR 1995]
 SYNONYMS                 Rifater [PDR 1995]
 PROTOCOL ID NUMBERS      NIAID ACTG 135
 PROTOCOL ID NUMBERS      NIAID ACTG 177
 PROTOCOL ID NUMBERS      NIAID ACTG 222
 PROTOCOL ID NUMBERS      NIAID ACTG 238
 PROTOCOL ID NUMBERS      NIAID CPCRA 004
 PROTOCOL ID NUMBERS      NIAID ACTG 309
 SECONDARY SOURCE ID      Ba 41166/E [USAN 1996]
 SECONDARY SOURCE ID      L-5103 Lepetit [USAN 1996]
 SECONDARY SOURCE ID      Netherlands Patent: 6,509,961 [Merck Index
                          1989]
 SECONDARY SOURCE ID      NSC-113926 [USAN 1996]
 SECONDARY SOURCE ID      US Patent: 3,342,810 [Merck Index 1989]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Inhibits DNA-dependent RNA
                          polymerase activity in susceptible cells.
                          Specifically, it interacts with bacterial RNA
                          polymerase but does not inhibit the mammalian
                          enzyme. Readily absorbed from the GI tract.
                          Peak blood levels in normal adults vary
                          widely from individual to individual. The
                          peak level averages 7 micrograms/ml but may
                          vary from 4 to 32 micrograms/ml. Absorption
                          of rifampin is reduced when the drug is
                          ingested with food. In normal subjects, the
                          biological half-life of rifampin in serum
                          averages about 3 hours after a 600 mg oral
                          dose, with increases up to 5.1 hours reported
                          after a 900 mg dose. With repeated
                          administration, the half-life decreases and
                          reaches average values of approximately 2-3
                          hours. It does not differ in patients with
                          renal failure at doses not exceeding 600 mg.
                          After absorption, rifampin is rapidly
                          eliminated in the bile, and an enterohepatic
                          circulation ensues. During this process,
                          rifampin undergoes progressive deactylation
                          so that nearly all the drug in the bile is in
                          this form in about six hours. Up to 30% of
                          the dose is excreted in the urine, with about
                          half of this being unchanged drug. Rifampin
                          is 80% protein bound. After intravenous
                          administration of a 300 or 600 mg dose of
                          rifampin infused over 30 minutes to healthy
                          male volunteers (n=11), mean peak plasma
                          concentrations were 9.0 and 17.5
                          micrograms/ml, respectively. [PDR 1995]
 DISEASES STUDIED/TREATED Mycobacterium avium infection (MAI, MAC).
                          Must always be used in conjunction with at
                          least one other antituberculosis drug [AmFAR
                          Tx Dir 1995;7(4)] [USP DI 1995] [NIAID ACTG
                          135]
 DISEASES STUDIED/TREATED Frequently used regimens are rifampin and
                          isoniazid; rifampin, isoniazid, and
                          pyrazinamide; rifampin, isoniazid, and
                          ethambutol; and rifampin and ethambutol
                          [AmFAR Tx Dir 1995;7(4)] [USP DI 1995] [NIAID
                          ACTG 135]
 CLASSIFICATION CODE      Antibacterial [USAN 1996]
 OTHER MAJOR USES         A standard treatment for tuberculosis; it is
                          being investigated for tuberculosis
                          prophylaxis. Also indicated for asymptomatic
                          carriers of Neisseria meningitidis [PDR 1995]
 SUBSTANCE INTERACTIONS   Has liver enzyme-inducing properties and may
                          reduce the activity of a number of drugs,
                          including anticoagulants, corticosteroids,
                          cyclosporine, cardiac glycosides, quinidine,
                          oral contraceptives, oral hypoglycemic agents
                          (sulfonylureas), dapsone, narcotics, and
                          analgesics. May diminish the effects of
                          concurrently administered methadone,
                          barbiturates, diazepam, verapamil,
                          beta-adrenergic blockers, clofibrate,
                          progestins, disopyramide, mexiletine,
                          theophylline, chloramphenicol, and
                          anticonvulsants. Probenecid and halothane
                          administered concurrently with rifampin
                          increase hepatotoxicity of both drugs while
                          ketoconazole is reported to diminish serum
                          levels of both. [PDR 1995]
 ADVERSE EFFECTS          Adverse effects include heartburn, epigastric
                          distress, anorexia, nausea, vomiting,
                          jaundice, flatulence, cramps, diarrhea,
                          thrombocytopenia, cerebral hemorrhage,
                          transient leukopenia, hemolytic anemia,
                          decreased hemoglobin, headache, fever,
                          drowsiness, fatigue, ataxia, dizziness,
                          inability to concentrate, mental confusion,
                          behavioral changes, muscle weakness,
                          numbness, pain in the extremities, visual
                          disturbances, menstrual disturbances,
                          elevations in BUN and serum uric acid,
                          hemolysis, hemoglobinuria, hematuria,
                          interstitial nephritis, renal insufficiency,
                          acute renal failure, flushing, itching, rash,
                          edema of face and extremities, pruritis,
                          urticaria, pemphigoid reaction, eosinophilia,
                          sore mouth, sore tongue, conjunctivitis,
                          flu-like symptoms, shortness of breath,
                          wheezing, decrease of blood pressure, and
                          shock. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients with history of
                          hypersensitivity to any of the rifamycins or
                          impaired liver function. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Semisynthetic antibiotic
                          derivative of rifamycin B. Rifampin is
                          obtained by reacting 3-formylrifamycin SV
                          with 1-amino-4-methylpiperazine in
                          tetrahydrofuran [PDR 1995] [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C43H58N4O12 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 822.96 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C62.75%, H7.10%,
                          N6.81%, O23.33% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Freely soluble in CH3CL, DMSO;
                          soluble in ethyl acetate, methanol,
                          tetrahydrofuran; slightly soluble in water,
                          acetone, carbon tetrachloride [Merck Index
                          1989]
 CHEMICAL/PHYSICAL DATA   STABILITY: The reconstituted powder for
                          injection is stable at room temperature for
                          24 hours [PDR 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: When added to the recommended
                          dextrose 5% for injection infusion the
                          solution is stable for 4 hours [PDR 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Extemporaneously prepared oral
                          suspensions are stable for 4 weeks at room
                          temperature or when refrigerated at 2-8 C
                          [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: Rifampin is a zwitterion
                          with pKa 1.7 related to the 4-hydroxy and pKa
                          7.9 related to the 3-piperazine nitrogen
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Red brown crystalline
                          powder [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Capsules (300 mg) or lyophilized
                          powder (600 mg) in glass vials. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: IV injection; oral
                          ingestion. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Avoid excessive heat (above 40 C
                          (104 F)). Protect from light. [PDR 1995]
 MANUFACTURERS            Merrell Dow
 REFERENCES               Harries AD, Mbewe LN, Maher D, Salaniponi,
                          Nyangulu DS. Regimen containing short-term
                          rifampicin for pulmonary tuberculosis in
                          HIV-infection [letter; comment]. Lancet. 1995
                          Jan 28;345(8944):264-5.
 REFERENCES               Okwera A, Whalen C, Byekwaso F, Vjecha M,
                          Johnson J, Huebner R, Mugerwa R, Ellner J.
                          Randomised trial of thiacetazone and
                          rifampicin-containing regimens for pulmonary
                          tuberculosis in HIV-infected Ugandans.
                          Lancet. 1994 Nov 12;344(8933):1323-8.
 REFERENCES               Kemper CA, Havlir D, Haghighat D, Dube M,
                          Bartok AE, Sison JP, Yao Y, Yangco B, Leedom
                          JM, Tilles JG, et al. The individual
                          microbiologic effect of three
                          antimycobacterial agents, clofazimine,
                          ethambutol, and rifampin, on Mycobacterium
                          avium complex bacteremia in patients with
                          AIDS. J Infect Dis. 1994 Jul;170(1):157-64.
 REFERENCES               Treatment of tuberculosis and tuberculosis
                          infection in adults and children. American
                          Thoracic Society. Monaldi Arch Chest Dis.
                          1994 Sep;49(4):327-45.
 REFERENCES               Grange JM, Winstanley PA, Davies PD.
                          Clinically significant drug interactions with
                          antituberculosis agents. Drug Saf. 1994
                          Oct;11(4):242-51.
 REFERENCES               Drayton J, Dickinson G, Rinaldi MG.
                          Coadministration of rifampin and itraconazole
                          leads to undetectable levels of serum
                          itraconazole [letter]. Clin Infect Dis. 1994
                          Feb;18(2):266.
 REFERENCES               Jacobson MA, Yajko D, Northfelt D, Charlebois
                          E, Gary D, Brosgart C, Sanders CA, Hadley WK.
                          Randomized, placebo-controlled trial of
                          rifampin, ethambutol, and ciprofloxacin for
                          AIDS patients with disseminated Mycobacterium
                          avium complex infection. J Infect Dis. 1993
                          Jul;168(1):112-9.
 REFERENCES               Burger DM, Meenhorst PL, Koks CH, Beijnen JH.
                          Pharmacokinetic interaction between rifampin
                          (RIF) and zidovudine (ZDV). Int Conf AIDS.
                          1993 Jun 6-11;9(1):504 (abstract no.
                          PO-B31-2211).
 REFERENCES               Coberly J, Halsey N, Johnson M, Desormeaux J,
                          Geiter L, Boulos R. Acceptability of twice
                          weekly short course rifampin & pyrazinamide
                          for TB preventive therapy in HIV infected
                          adults. Int Conf AIDS. 1993 Jun 6-11;9(1):328
                          (abstract no. PO-B07-1158).
 REFERENCES               Kemper CA, Meng TC, Nussbaum J, Chiu J,
                          Feigal DF, Bartok AE, Leedom JM, Tilles JG,
                          Deresinski SC, McCutchan JA. Treatment of
                          Mycobacterium avium complex bacteremia in
                          AIDS with a four-drug oral regimen. Rifampin,
                          ethambutol, clofazimine, and ciprofloxacin.
                          Ann Intern Med. 1992 Mar 15;116(6):466-72.
 ENTRY MONTH              9104
 LAST REVISION DATE       960131
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
