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 Zambia HIV National Guidelines
 


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 Guide Editors
 Editor In Chief
    Joel E. Gallant, MD, MPH

Pharmacology Editor
    Paul Pham, PharmD, BCPS

Zambia Guideline Team
   Peter Mwaba MMed PhD FRCP
   Alywn Mwinga MMed
   Isaac Zulu MMed MPH
   Velepie Mtonga MMed
   Albert Mwango MBChB
   Jabbin Mulwanda MMed FCS
 

 

 

Drugs>Antimicrobial Agents>
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Rifampin

Paul A. Pham, Pharm D. and John G. Bartlett, M.D.
11-02-2010

Zambia Specific Information

  • 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.
  • 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 q8 weeks, norethisterone enantate to 200 mg q 6 weeks, 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.

INDICATIONS

FDA

  • Treatment of active TB
  • Treatment of asymptomatic carriers of Neisseria meningitidis to eliminate meningococci from the nasopharynx.
NON-FDA APPROVED USES

  • Treatment of latent TB
  • Treatment of orthopedic implant-related staphylococcal infections (in combination)
  • Treatment of prosthetic valve endocarditis (in combination with vancomycin plus aminoglycoside)

FORMS

brand 
name
 
generic 
Mfg 
brand 
forms
 
cost* 
Rifadin Rifampin (RIF)Eonoral
capsule
150 mg; 300 mg
$2.57; $3.64
Rifamate RIF 300 mg/isoniazid (INH) 150 mgAventisoral
capsule
RIF 300 mg + INH 150 mg
$4.19
Rifater RIF 120 mg/INH 50 mg/pyrazinamide (PZA) 300 mgAventisoral
capsule
RIF 120 mg + INH 50 mg + PZA 300 mg
$3.10

*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.

USUAL ADULT DOSING

  • TB treatment (in combination with other anti-TB drugs): 10 mg/kg/d (max 600 mg PO or IV once daily). DOT: 600 mg 2-3x/wk. HIV+ pts with CD4 <100 should received DOT 3x/wk (not 2x/wk, since they are more prone to rifamycin resistance).
  • Rifamate: 2 caps (RIF/INH 600/300 mg) once daily, 1 hr before or 2 hrs after meals.
  • Rifader: <44 kg - 4 tabs once daily; 45-54 kg - 5 tabs once daily; >55 kg - 6 tabs once daily, administered 1 hr before or 2 hrs after meals.
  • Treatment of latent TB: 10 mg/kg (max 600 mg) once daily for 4 mos (alternative to INH in pts intolerant of INH or exposed to INH-resistant TB).
  • Meningococcal prophylaxis: 600 mg twice-daily x 2 d. Due to reports of fluoroquinolone resistance, rifampin recommended in selected counties in North Dakota and Minnesota (MMWR 2008; 57:173)
  • Contraindicated with all PIs except with LPV/r + RTV (see below)
  • With LPV/r: consider LPV/r 400/100 mg (2 tabs) + RTV 300 mg twice daily (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 once daily + RIF 600 mg once daily (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 twice daily + RIF 600 mg once daily (AIDS 2003;17:637). No data;CDC recommends considering NVP 300 mg twice daily with RIF co-administration.
  • With ETR: avoid co-administration.
  • With MVC: MVC 600 mg twice daily
  • With RAL: avoid or use with close monitoring of virologic efficacy.

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

Usual dose

DOSING FOR GLOMERULAR FILTRATION OF 10-50

Usual dose

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

Usual dose. Some recommend a 50% decrease in dose.

DOSING IN HEMODIALYSIS

300-600mg once daily

DOSING IN PERITONEAL DIALYSIS

300-600mg once daily

DOSING IN HEMOFILTRATION

No data

ADVERSE DRUG REACTIONS

COMMON

  • Orange discoloration of urine, tears, sweat.
OCCASIONAL

  • 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):Sx include fever and chills, headache, dizziness, bone pain, abdominal pain, and generalized pruritus.
RARE

  • Hypersensitivity (0.07-0.3%)
  • Thrombocytopenia, hemolytic anemia, and leukopenia
  • Headache and dizziness
  • Drug fever

DRUG INTERACTIONS

Substrate and potent inducer of CYP3A4. Also and inducer of CYP 2B6, 2C8, 2C9, 2C19, 2D6, and glucuronosyl transferase.

  • NVP: NVP Cmin decreased by 37-68% and AUC decreased 37-58%. RIF AUC increased by 11%. Due to higher risk of hypersensitivity reaction with NVP 300 mg twice-daily, CDC recommends standard dose NVP with rifampin co-administration. Consider rifabutin with co-administration.
Drug-to-Drug Interactions

Drug-to-Drug Interaction

DrugEffect of InteractionRecommendations/Comments
Efavirenz EFV AUC decreased 26%. No change in rifampin area under the curve. Recommended dosing: EFV 600-800 mg/day with rifampin 600 mg once daily (monitor for EFV central nervous system side effects). May decrease to EFV 600 mg/day if 800 mg dose not easily tolerated.
Nevirapine NVP Cmin decreased 37%-68%. NVP AUC decreased 37%-58%. Rifampin area under the curve increased 11% (not significant). Avoid co-administration.
Zidovudine AZT AUC decreased 47%. Intracellular concentrations not measured. Consider switching to rifabutin.
Fosamprenavir No data, but significant decrease in amprenavir serum concentrations expected. When studied with APV, AUC decreased 82%; Cmin decreased 92% Contraindicated. Use rifabutin with co-administration.
Atazanavir ATVr Cmin decreased 60%-93%. Contraindicated. Use rifabutin with co-administration.
Indinavir IDV AUC decreased 89%. Contraindicated. Use rifabutin with co-administration.
Nelfinavir NFV AUC decreased 82%. Contraindicated. Use rifabutin with co-administration.
Ritonavir RTV AUC decreased 35%. RTV standard dosage recommended by manufacturer, but coadministration with rifampin should be avoided.
Saquinavir SQV AUC decreased 70% (SQV soft gel capsules without RTV-boosting). Contraindicated due to the high incidence of hepatitis with SQV 1000 mg + RTV 100 mg twice daily.
Indinavir Unboosted IDV AUC decreased 92%. Contraindicated. Use rifabutin with co-administration.
Lopinavir/ritonavir LPV AUC decreased 75%, and Cmin decreased 99%. Coadministration not recommended. Although studies used LPV/r 400/100 mg twice-daily (2 tabs) plus RTV 300 mg twice-daily or LPV/r 3 to 4 tabs twice-daily to overcome this interaction, high incidence of nausea, vomiting, and grade 4 LFTs elevation were common. Consider rifabutin with LPV/r co-administration.
Maraviroc MVC AUC decreased by 63%. Increase MVC dose to 600 mg twice-daily with rifampin co-administration.
Etravirine ETR serum concentrations may be significantly decreased. Avoid co-administration until more data becomes available.
Doxycycline Doxycycline serum concentrations may be decreased. Clinical significance unclear.
Fluconazole Fluconazole serum concentrations decreased by 23-56%. Consider switching to rifabutin with co-administration.
Dapsone Dapsone serum concentrations may be decreased. For PCP prophylaxis, if unable to tolerate TMP/SMX, consider using aerosolized pentamidine.
Clarithromycin Clarithromycin serum concentrations may be significantly decreased. Consider azithromycin
Tipranavir/ritonavirMay significantly decrease TPV serum concentrations. Contraindicated. Use rifabutin with co-administration.
Darunavir/ritonavirDRV serum concentrations may be significantly decreased. Contraindicated. Use rifabutin with co-administration.
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
Amiodarone Amiodarone serum concentrations may be significantly decreased. Monitor EKG with co-administration. Amiodarone dose may need to be increased.
Amlodipine Amlodipine serum concentrations may be significantly decreased. Titrate to effect.
Aprepitant Aprepitant serum concentrations may be decreased. Apretitant dose may need to be increased.
Atorvastatin Atorvastatin decreased by 80%. Titrate to effect. Pravastatin or rosuvastatin less likely to interact with rifampin.
Atovaquone atovaquone AUC decreased by approximately 50% Avoid co-administration. Consider Aerosolized pentamidine for PCP prophylaxis
Bisoprolol Bisoprolol serum concentrations may be significantly decreased. Bisoprolol dose may need to be increased
Bosentan Bosentan AUC decreased 60% May need to increase bosentan dose.
Buprenorphine Buprenorphine serum concentrations may be decreased. Titrate buprenorphine to effect.
Caspofungin caspofungin trough concentrations decreased 30%. Use caspofungin 70 mg with rifampin co-administration.
Chlorpropamide Chlorpropamide serum concentrations decreased by up to 50%. Monitor blood glucose control with co-administration. Consider a shorter acting hypoglycemic agent.
Cyclosporine Cyclosporine serum concentrations may be significantly decreased. Monitor cyclosporine serum concentrations closely with co-administration. Cyclosporine dose may need to be increased.
Dasatinib Dasatinib AUC decreased 82% Higher dasatinib dose is recommended at steady-state (2 weeks).
Dexamethasone Dexamethasone serum concentrations may be significantly decreased. Dexamethasone dose may need to be increased.
Diazepam Diazepam serum concentrations may be significantly decreased. Titrate to effect
Digoxin Digoxin serum concentrations may be decreased by 30% to 60%. Monitor digoxin serum concentrations with co-administration.
Diltiazem Diltiazem serum concentrations may be significantly decreased. Titrate to effect.
Disopyramide Disopyramide half-life decreased by 40% Monitor EKG with co-administration. Disopyramide dose may need to be increased.
Erlotinib Erlotinib AUC decreased by approximately 67% to 80% Higher dose of Erlotinib may be needed
Everolimus Everolimus AUC decreased by 58% Monitor everolimus serum concentrations closely with co-administration. Dose may need to be increased.
Glimepiride Glimepiride serum concentrations may be significantly decreased. Monitor glucose control with co-administration.
Glyburide Glyburide serum concentrations may be significantly decreased. Monitor glucose control with co-administration.
Itraconazole Itraconazole serum concentrations may be significantly decreased. Avoid co-administration. Consider rifabutin with monitoring of itraconazole serum concentrations and monitor for uveitis.
Ketoconazole Ketoconazole serum concentrations decreased by 50%. Avoid co-administration. Consider rifabutin.
Lamotrigine Lamotrigine AUC decreased by approximately 40% Titrate to effect
Levothyroxine Levothyroxine serum concentrations may be significantly decreased. Monitor TSH. May need higher levothyroxine dose with co-administration.
Linezolid Case reports of significant decrease in linezolid serum concentrations with co-administration. Avoid or use with caution
Linezolid Linezolid AUC decreased 32% with co-administration. Clinical significance unknown. Consider linezolid 600 mg q8h for severe infections.
Lovastatin Lovastatin serum concentrations may be significantly decreased. Titrate to effect. Pravastatin or rosuvastatin less likely to interact with rifampin.
Mefloquine Mefloquine AUC decreased 68%. Consider an alternative anti-malarial drug.
Methadone and other opiate agonists Opiate serum concentrations may be significantly decreased. Methadone AUC decreased 30-65%. Monitor for signs and symptoms of withdrawal and titrate opiate to effect.
Metoprolol Metoprolol serum concentrations decreased by 33%. Titrate to effect
Mexiletine Mexiletine half-life decreased by 5-9 hours. Monitor EKG with co-administration. Mexiletine dose may need to be increased.
Midazolam Midazolam serum concentrations may be significantly decreased. Titrate to effect
Montelukast Montelukast AUC decreased by 40%. Dose of montelukast may need to be increased.
Morphine Morphine AUC decreased by 45%. Titrate to effect.
Moxifloxacin Moxifloxacin serum concentrations decreased by approximately 30%. Monitor for therapeutic efficacy. Consider levofloxacin
Mycophenolate Mofetil Mycophenolate AUC decreased 67%. Mycophenolate dose may need to be increased.
Nifedipine Nifedipine serum concentrations may be decreased up to 70%. Titrate to effect.
Nilotinib Nilotinib AUC decreased by 80% Avoid co-administration.
Oral contraceptives Ethinyl estradiol Cmin decreased by 79%. Norethindrone Cmin decreased by 89%. Use an alternative or additional barrier form of contraception. Despite these PK interactions, all subjects remained anovulatory as indicated by undetectable progesterone levels.
Phenytoin Phenytoin serum concentrations may be decreased. Monitor phenytoin serum concentrations closely with co-administration.
Pioglitazone Pioglitazone AUC decreased 54%. Monitor glucose control with co-administration. Pioglitazone dose may need to be increased.
Posaconazole Posaconazole serum concentrations may be significantly decreased. Contraindicated. Rifabutin may be considered if benefit outweighs the risks. Use with close monitoring of posaconazole serum concentrations and monitor for sign and symptoms of uveitis.
Praziquantel Praziquantel serum concentrations may be significantly decreased. Avoid co-administration.
Prednisone Prednisone serum concentrations decreased by up to 60% Prednisone dose may need to be increased.
Propafenone Propafenone serum concentrations may be significantly decreased. Monitor EKG with co-administration. Propafenone dose may need to be increased.
Propranolol Propranolol serum concentrations may be significantly decreased. Titrate to effect
Quinidine Quinidine serum concentrations may be significantly decreased. Monitor quinidine serum concentrations. May need to increase quinidine dose.
Quinine Quinine serum concentrations may be significantly decreased. Quinine dose may need to increased.
Raltegravir RAL AUC and Cmin decreased by 40% and 61%, respectively. Increasing RAL to 800 mg twice daily resulted in adequate AUC but Cmin was decreased by 53%. Increase RAL dose to 800 mg twice-daily with close monitoring of virologic efficacy. Consider using rifabutin with co-administration.
Ranolazine Ranolazine AUC decreased 95% Contraindicated
Repaglinide Repaglinide AUC decreased 57% Titrate to effect
Rosiglitazone Rosiglitazone AUC decreased by 54% Monitor glucose control with co-administration.
Simvastatin Simvastatin serum concentrations decreased by 56% to 94%. Titrate to effect. Pravastatin or rosuvastatin less likely to interact with rifampin.
Sirolimus Sirolimus serum concentrations decreased 82%. Monitor sirolimus serum concentrations closely with co-administration. Sirolimus dose may need to be increased.
Tacrolimus Tacrolimus serum concentrations may be significantly decreased. Monitor tacrolimus serum concentrations closely with co-administration. Tacrolimus dose may need to be increased.
Tamoxifen Tamoxifen AUC decreased 86% Higher dose may be needed.
Telithromycin Telithromycin AUC decreased 79% Avoid co-administration.
Temsirolimus Temsirolimus AUC decreased up to 56% Monitor temsirolimus serum concentration with dose titration.
Theophylline Theophylline serum concentrations decreased 18%. Monitor theophylline serum concentrations. Theophylline dose may need to be increased.
Tocainide Tocainide AUC decreased 28% Tocainide dose may need to be increased.
Tolbutamide Tolbutamide serum concentrations may be significantly decreased. Monitor blood glucose control with co-administration.
Triazolam Triazolam serum concentrations may be significantly decreased. Titrate to effect.
Verapamil Verapamil serum concentrations may be significantly decreased. Titrate to effect.
Voriconazole Voriconazole serum concentrations decreased. Both rifampin and rifabutin are contraindicated with voriconazole.
Warfarin Warfarin serum concentrations may be significantly decreased. Monitor INR closely. May need higher warfarin dose.

SPECTRUM

Detailed Spectrum of Activity

PHARMACOLOGY

Pharmacology

COMMENTS

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 ART 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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