Rifampin

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Dosage-adjustment-in-renal-failure 6 Pharmacokinetics 7 Monitor 8 Antimicrobial-activity 9 Adverse-effects 10 Drug-interactions 11 Laboratory 12 Mechanism-of-action 13 More General Terms 14 Additional Terms 15 Internet Database 16 References

Introduction

• Tradename: Rifadin, Rimactane.

Indications

• treatment of tuberculosis in combination with other agents, especially isoniazid, pyrazinamide & ethambutol
• prophylaxis for meningiococcal meningitis (post-exposure)
• adjunctive agent for treatment of Staphylococcal infection
• prophylaxis of Haemophilus influenzae type B

Contraindications

• (& cautions)
• MUST be in conjunction with a bactericidal agent in the treatment of Staphylococcal infection due to the rapid emergence of resistance
• NOT effective for Staphyloccal urinary tract infections
• diminishes effectivenss of oral contraceptives: use backup method of contraception to prevent pregnancy
  

• pregnancy category = c
• safety in lactation = ?

Dosage

• tuberculosis: 10-20 mg/kg up to 600 mg PO/ IV QD
• 600 mg PO QD as adjunctive agent for treatment of Staphylococcus infection
• 600 mg PO BID for 4 days for meningiococcal exposure & Haemophilus influenzae exposure

• Tabs: 150 & 300 mg.
• Powder for injection: 600 mg (contains sulfite).

Dosage-adjustment-in-renal-failure

*    creatinine clearance        dosage 
*    > 50-90 mL/min              600 mg every 24 hours        
*      10-50 mL/min              300-600 mg every 24 hours 
*       < 10 mL/min*             300-600 mg every 24 hours

• * No additional dosing for hemodialysis

Pharmacokinetics

• well absorbed orally
• food delays absorption
• 1st pass hepatic metabolism is saturated with higher doses
• penetrates well into cells & most tissues
• penetration through non-inflammed meninges is poor, but good CSF concentrations are obtained through inflammed meninges
• peak serum concentrations 1.5-2 hours after oral ingestion
• serum levels of 6-7 ug/mL with usual dose
• MIC of 0.5 ug/mL for most strains of M. tuberculosis
• eliminated by deacetylation in the liver

• metabolite desacetylrifampin is less active than parent compound

• 12-15% excreted in the urine, thus minimally effective for urinary tract infections (Staphylococcus)
• elimination 1/2life is 3 hours (3-11 hours ESRD)

• shorter after the 1st few days of therapy
• increases with increasing dosage & decreases with chronic administration
  

• elimination via liver
• elimination via kidney
• 1/2life = 2.6-5.1 hours
• protein binding = 75-90 %
• elimination by hemodialysis = -
• elimination by peritoneal dialysis = -

Monitor

• liver function tests ( serum AST, serum ALT, serum bilirubin) baseline & within 180 days, all patients
• in patients with symptoms of liver dysfunction, check serum ALT & serum AST every2-4 weeks [8,10]

Antimicrobial-activity

• Gram positive

• Streptococcus, groups A, B, C, G
• Streptococcus pneumonia
• Enterococcus faecalis (+/-)
• Staphylococcus aureus ( MSSA)
• Staphylococcus epidermidis

• Gram negative

• Neisseria gonorrhoeae
• Moraxella catarrhalis
• Haemophilus influenzae
• Francisella tularensis
• Brucella species

• Atypical bacteria

• Chlamydia species
• Mycobacterium tuberculosis

Adverse-effects

• not common (1-10%)

• diarrhea
• epigastric cramps
• discoloration of urine, feces, saliva, sputum, sweat & tears (reddish orange)*
• fungal overgrowth

• uncommon (< 1%)

• drowsiness, fatigue, ataxia, confusion, fever, headache, rash, pruritis, nausea/vomiting, stomatitis, eosinophilia, blood dyscrasias, leukopenia, thrombocytopenia, hepatitis, irritation at site of IV injection, renal failure, flu-like syndrome

• other

• GI upset (most common): nausea/vomiting
• skin eruptions
• cholestatic jaundice (rare)
• acute renal failure at doses > 10 mg/kg

• interstitial nephritis

• * Rifampin is excreted in the urine, tears, sweat & other body fluids coloring them orange. Permanent discoloration of soft contact lenses may occur.

Drug-interactions

• rifampin induces cyt P450s CYP1A2, CYP2C9 & CYP3A4 decreasing levels of:

• methadone, warfarin, glucocorticoids, estrogens*, digoxin, oral hypoglycemic agents, digitoxin, quinidine, verapamil, mexiletine, theophylline, anticonvulsants, ketoconazole, cyclosporine, barbiturates, chloramphenicol

• halothane
• benzodiazepines
• beta-blockers
• isoniazid in combination increases hepatotoxicity
• pyrazinamide in combination may increase hepatotoxicity [9]
• rifampin decreases serum levels of:

• atovaquone
• saquinavir

• others

• opiates, verapamil, clofibrate, progestins, disopyramide, probenecid, dapsone

• * diminishes effectiveness of oral contraceptives
  

• drug interaction(s) of antibiotics with warfarin
• drug interaction(s) of beta-adrenergic receptor antagonists with rifampin

Laboratory

• specimen:

• serum, plasma ( heparin, EDTA)
• stable for 3 months at -20 degrees C

• methods: MB, HPLC

Mechanism-of-action

• inhibits DNA-dependent RNA polymerase of mycobacteria & other microorganisms
• bactericidal for M. tuberculosis

More General Terms

• rifamycin (rifamycin SV, Rifocin)
• heterocyclic compound, 4 or more rings
• heterocyclic compound, bridged-ring
• ester
• ether
• ketone
• phenol
• alcohol
• alkene; olefin
• amide
• amine
• prokaryote-specific molecule

Additional Terms

• cytochrome p450 1A2 (cytochrome P3-450, phenacetin deethylase, cytochrome p450-4, CYP1A2)
• cytochrome P450 2C9; cytochrome P450 BP-1; cytochrome P450 MP-4; S-mephenytoin-4-hydroxylase; limonene 6-monooxygenase; limonene 7-monooxygenase (CYP2C9, CYP2C10)
• cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

Internet Database

PubChem: 25839
PubChem: 5280982
PubChem: 5068
PubChem: 161976

References

1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
2. Sanford Guide to antimicrobial therapy 1997
3. Am Thoracic Soc, Am J Respir Crit Care Med 149:1359, 1994
4. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
5. Kaiser Permanente Northern California Regional Drug Formulary, 1998
6. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
7. Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
8. Prescriber's Letter 8(8):48, 2001
9. Journal Watch 21(19):155, 2001 MMWR Morb Mort Wkly Rep 50:733, 2001
10. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: [1] (subscription needed) [2]

rifampin; rifampicin (Rifadin, Rimactane)