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Rifampin
Paul A. Pham, Pharm D. and John G. Bartlett, M.D.
03-31-2008
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Available formulation in Zambia: Rifampicin capsule or tablet: 150 mg; 300 mg. Rifampicin + isoniazid tablet: 60 mg + 30 mg; 150 mg + 75 mg; 300 mg + 150 mg. 60 mg + 60 mg (For intermittent use 3 times weekly). 150 mg + 150 mg (For intermittent use 3 times weekly). Rifampicin + isoniazid + pyrazinamide tablet: 60 mg + 30 mg + 150 mg; 150 mg + 75 mg + 400 mg. 150 mg + 150 mg + 500 mg (For intermittent use 3 times weekly). Rifampicin + isoniazid + pyrazinamide + ethambutol tablet: 150 mg + 75 mg + 400 mg + 275 mg.
- All new TB cases (smear positive, smear negative, extra-pulmonary TB, and smear negative relapse): INH, RIF, PZA, and EMB x 2 months, then INH plus EMB x 6 months.
- TB smear positive re-treatment cases (e.g treatment failure, treatment after default, smear positive relapse): INH, RIF, PZA, EMB, and SM x 2 months, then INH, RIF, PZA, and EMB x 6 months.
- Brucellosis: rifampicin 7.5 mg/kg q12h x 6 wks PLUS doxycycline 100 mg PO q12h x 6 wks
- Rifampicin significantly decreases LPV/r serum concentrations. Avoid co-administration.
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EFV-based regimen is preferred over NVP or LPV/r-based regimen with rifampicin co-administration.
- In HIV-TB co-infected pregnant women treated with rifampicin, EFV-based regimen is recommended in the Zambia-HIV National Guidelines in the 2nd and 3rd trimester.
- Rifampicin may decrease artemether and lumefantrine serum concentrations. Monitor closely for anti-malarial activity with co-administration. Artemether with lumefantrine may need to be increased.
- Rifampicin decreases injectable and oral contraceptives serum concentrations significantly. Use barrier form of contraception; if not possible, consider increasing injectable and oral contraceptives. Increase medroxyprogesterone to 150 mg q8weeks, norethisterone enantate to 200 mg q6weeks, ethinylestradiol to 50 mcg/d, and reduce the tablet-free interval to 4 days (from 7 days).
Zambia Information Author: Paul A. Pham Pharm.D.
- Treatment of active TB
- Treatment of asymptomatic carriers of Neisseria meningitidis to eliminate meningococci from the nasopharynx.
brand
name
| generic
| Mfg
| brand
forms
| cost*
|
|
Rifadin
| Rifampin (RIF) | Eon | oral
capsule
150mg; 300mg | $1.58; $2.24 |
|
Rifamate
| RIF 300 mg/isoniazid (INH) 150 mg | Aventis | oral
capsule
300mg RIF/150mg INH | $2.58 |
|
Rifater
| RIF 120 mg/INH 50 mg/pyrazinamide (PZA) 300 mg | Aventis | oral
capsule
120mg RIF/50mg INH/300mg PZA | $1.92 |
*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP).
AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's
information, and the McKesson database.
^Dosage is indicated in mg unless otherwise noted.
.
- TB treatment (in combination with other anti-TB drugs): 10 mg/kg/d (max 600mg po or IV qd). DOT: 600 mg 2-3x/wk. HIV-infected pts with CD4 <100 should received DOT 3x/wk (and not 2x/wk since they are more prone to rifamycin resistance).
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Rifamate: 2 caps (600 mg RIF/300 mg INH) qd, 1 hr before or 2 hrs after meals.
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Rifader: </=44 kg - 4 tabs qd; 45-54 kg - 5 tabs qd; >/=55 kg - 6 tabs qd, administered 1 hr before or 2 hrs after meals.
- Treatment of latent TB: 10 mg/kg (max 600mg) qd for 4 mos (alternative to INH in pts intolerant of INH or exposed to INH-resistant TB).
- Meningococcal prophylaxis: 600 mg q12h x 2 d.
- Contraindicated with all PIs except with LPV/r+RTV
- With LPV/r: consider LPV/r 400 mg/100 mg (3 caps) + RTV 300 mg bid (monitor LFTs, GI intolerance, and lipids) or consider switching to rifabutin + LPV/r.
- With RTV+ SQV: Not recommended due to high incidence of hepatitis.
- With EFV: EFV 800 mg qd + RIF 600 mg qd (monitor CNS side-effects). Consider TDM.
- With NVP: co-administration not recommended by manufacturer. Consider rifabutin with NVP co-administration. Case series of favorable outcome with NVP 200 mg bid + RIF 600 mg qd (Oliva et al. AIDS 2003, 17: 637). No data; CDC recommends considering NVP 300 mg bid with RIF co-administration.
- Contraindicate with DLV
Usual dose
Usual dose
Usual dose. Some recommend a 50% decrease in dose.
300-600mg qd
300-600mg qd
No data
- Orange discoloration of urine, tears, sweat.
- Hepatitis (2.7% w/other TB Rx) with cholestatic changes in first month; jaundice
- GI intolerance
- Flu-like syndrome (0.4-0.7% when taking RIF 2x/wks):symptoms include fever and chills, headache, dizziness, bone pain, abdominal pain, and generalized pruritus.
- Hypersensitivity (0.07-0.3%)
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Thrombocytopenia and hemolytic anemia
- Headache and dizziness
Substrate and potent inducer of CYP3A4. Also and inducer of CYP 2B6, 2C8, 2C9, 2C19, and 2D6.
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EFV: EFV AUC decreased by 26%. No change in RIF AUC. Recommended dosing: EFV 800 mg qd + RIF 600 mg qd.
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NVP: NVP Cmin decreased by 37-68% and AUC decreased 37-58%. RIF AUC increased by 11%. Consider rifabutin with co-administration.
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LPV/r: LPV/r 400mg/100mg + RTV 300mg bid: adequate LPV serum levels. High GI intolerance
- Co-administration with SQV + RTV is no longer recommended due to high incidence of hepatitis.
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LPV/r, TPV/r, DRV/r, ATV, FPV, APV, SQV, NFV, and IDV: PIs serum levels decreased by approx. 80% with RIF co-administration. Do not co-administer. Consider switching to rifabutin with dose adjustment of rifabutin and PIs (see rifabutin)
- Drugs that are CYP3A4, 2B6, 2C8, 2C9, 2C19, and 2D6 substrates may be significantly decreased: warfarin (may need higher dose); levothyroxine (may need higher dose); oral contraceptives and estrogens (use an alternative form of contraception); doxycycline (consider alternative abx); theophylline (may need higher dose); diazepam, triazolam, midazolam (may need higher dose); beta-blockers (bisoprolol, metoprolol, and propranolol dose may need to be titrated up); azole antifungal (consider switching to rifabutin with fluconazole, ketoconazole, itraconazole co-administration); corticosteroids (may need higher dose); quinidine, quinine, cyclosporine (monitor levels closely; may need to increase dose); dapsone (if unable to tolerate TMP/SMX, consider using aerosolized pentamidine), digoxin (may need higher dose), oral hypoglycemic agents (glyburide, chlorpropamide, tolbutamide dose may need to be increased); disopyramide, mexiletine, and verapamil (titrate to effect)
- Aluminum containing antacids-controversial but may decrease oral absorption of RIF; some studies found no effect. Consider separate oral administration by 4 hrs.
- Aminosalicylic acid granules:absorption of RIF may be impaired by the bentonite excipient. Separate administration by 8-12 hrs intervals
- Methadone and other opiate agonists: may significantly decrease serum concentration of opiates. Monitor for signs and symptoms of withdrawal and titrate opiate to effect.
Oral and parenteral rifamycin used for treatment of active and latent TB, treatment and prophylaxis of MOTT, meningococcal prophylaxis, and occasional adjunctive therapy for infections involving S. aureus. Significant reduction of CYP3A4 substrates serum level (i.e PIs and NNRTIs) and therefore RIF should substituted with rifabutin in pts receiving most HAART regimens. Although data are limited, rifampin's biofilm penetration may make this agent an ideal candidate (in combination with other antibiotics) for treating infections associated with prosthetic devices.
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