Rifabutin Protease inhibitors

In patients taking rifabutin, protease inhibitors can significantly increase the area under the concentration-time curve. High concentrations of rifabutin can provoke uveitis. If the combination of rifabutin and a protease inhibitor is essential, dose adjustments are recommended. 

RIFABUTIN PROTEASE INHIBITORS t efficacy and t adverse effects of rifabutin Inhibition of CYP3A4-mediated metabolism. Nelfinavir also competitively inhibits 2C19 1 rifabutin dose by at least 50% when given with amprenavir, indinavir or nelfinavir, and by 75% with atazanavir, ritonavir (with or without lopinavir) or tipranavir... 

Rifampin Daily for 4 months For persons who are contacts of patients with isoniazid-resistant rifampin susceptible TB. In HIV-infected patients, protease inhibitors or NNRTIs generally should not be administered concurrently with rifampin rifabutin can be used as an alternative for patients treated with indinavir, nelfinavir, amprenivir, ritonavir, orefavirenz, and possibly with nevirapine or soft-gel saquinavir5 B (II) B (III)... 

Drugs that affect voriconazole include the following barbiturates (long acting), cimetidine, nonnucleoside reverse transcriptase inhibitors (NNRIs), phenytoin, protease inhibitors, proton pump inhibitors, rifampin, rifabutin. 

Drugs affected by voriconazole include the following benzodiazepines, calcium channel blockers, cisapride, coumarin anticoagulants, cyclosporine, ergot alkaloids, HMG-CoA reductase inhibitors, NNRTIs, phenytoin, protease inhibitors, pimozide, proton pump inhibitors, quinidine, prednisolone, rifabutin, sirolimus, sulfonylureas, tacrolimus, vinca alkaloids. 

HIV - The initial phase of a 6-month tuberculosis regimen consists of isoniazid, rifabutin, pyrazinamide, and ethambutol for patients receiving therapy with protease inhibitors or nonnucleoside reverse transcriptase inhibitors. These drugs are administered a) daily for at least the first 2 weeks, followed by twice weekly dosing for 6 weeks or b) daily for 8 weeks to complete the 2-month induction phase. The second phase of treatment consists of rifabutin and isoniazid administered twice weekly or daily for 4 months. 

Drugs that might be affected by lopinavir/ritonavir include ergot derivatives, oral contraceptives, antiarrhythmics, HMG-CoA reductase inhibitors, HIV protease inhibitors, atovaquone, calcium channel blockers, ketoconazole, itraconazole, pimozide, cisapride, clarithromycin, disulfiram, metronidazole, immunosuppressants, midazolam, triazolam, narcotic analgesics, rifabutin and rifabutin metabolite, sildenafil, warfarin, bupropion, clozapine, desipramine, piroxicam, quinidine, theophylline, and zolpidem. 

A triple therapy regimen with combinations of clarithromycin or azithromycin plus ethambutol plus rifabutin is the current standard of care. However rifabutin may be omitted in HIV-infected patients on protease inhibitors because of significant interactions (Table 19). 

Other major untoward reactions are the result of rifampin s ability to induce hepatic cytochrome P-450 enzymes, leading to an increased metabolism of many drugs this action has especially complicated the treatment of tuberculosis in HIV-infected patients whose regimen includes protease inhibitors and nonnucleoside reverse transcriptase. Since rifabutin has relatively little of these effects, it is commonly substituted for rifampin in the treatment of tuberculosis in HIV-infected patients. 

Updated Guidelines for the Use of Rifabutin or Rifampin for the Treatment and Prevention of Thberculosis Among HIV-infected Patients Taking Protease Inhibitors or Non-nucleoside Reverse Transcriptase Inhibitors. Centers For Disease Control and Prevention MMWR 2000 49 185. 

It is similar to rifampicin and shows significant activity against M. tuberculosis, M. avium complex and M. fortuitum. Rifabutin is both substrate and cytochrome 450 enzyme inducer. Because it is less potent inducer, rifabutin is used (in place of rifampicin) for the treatment of tuberculosis in HIV-infected patients, who are on concurrent antiretroviral therapy with a protease inhibitor. It is used alone or in combination with pyrazi-namide. 

Drugs That Interfere with Hormonal Contraceptives Concomitant use of HIV-protease inhibitors, griseofulvin, modafinil, penicillins, rifampin, rifabutin, phenytoin, carbamazepine, or certain herbal supplements such as St. John s wort with hormonal contraceptive agents may reduce the effectiveness of the contraception and up to one month after discontinuation of these concomitant therapies. Therefore, women requiring treatment with one or more of these drugs must use two other effective or highly effective methods of contraception or abstain from heterosexual sexual contact while taking thalidomide... 

Reduced ethinyl estradiol concentrations have been associated with concomitant use of substances that induce hepatic microsomal enzymes, such as rifampin, rifabutin, barbiturates, phenylbutazone, phenytoin sodium, griseofulvin, topiramate, some protease inhibitors, modafinil, and possibly St. John s wort ... 

Induction of increased hepatic enzyme activity Nicardipine, imatinib, protease inhibitors, phenytoin, carbamazepine, phenobarbital, rifampin, rifabutin... 

The typical dose of rifabutin is 300 mg/d unless the patient is receiving a protease inhibitor, in which case the dose should be reduced to 150 mg/d. If efavirenz (also a P450 inducer) is used, the recommended dose of rifabutin is 450 mg/d. 

Lopinavir/Ritonavir (Kaletra) [Anrirelroviral/Protease Inhibitor] Uses HIV Infxn Action Protease inhibitor Dose Adults. Tx naive 2 tab PO daily or 1 tab PO bid Tx experiencedpt 1 tab PO bid (T dose if w/ amprenavir, efavirenz, fosamprenavir, nelfinavir, nevirapine) Peds. 7-15 kg 12/3 mg/kg PO bid 15-40 kg 10/2.5 mg/kg PO bid >40 kg Adult dose w/ food Caution [C, /-] Numerous interactions Contra w/drugs dependent on CYP3A/CYP2D6 (Table VI-8) Disp Tab, soln SE Avoid disulfiram (soln has EtOH), metronidazole GI upset, asthenia, T cholesterol/triglycerides, pancreatitis protease metabolic synd Interactions T Effects Wl clarithromycin, erythromycin T effects OF amiodarone, amprenavir, azole andfungals, bepridil, cisapride, cyclosporine, CCBs, ergot alkaloids, flecainide, flurazepam, HMG-CoA reductase inhibitors, indinavir, lidocaine, meperidine, midazolam, pimozide, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, tacrolimus, terfenadine, triazolam, zolpidem 1 effects Wl barbiturates, carbamazepine, dexamethasone, didanosine, efavirenz, nevirapine, phenytoin, rifabutin, rifampin, St. John s wort 1 effects OF OCPs, warfarin EMS Use andarrhythmics and benzodiazepines... 

Delavirdine should not be used in combination with drugs that are CYP3A4 substrates such as pimozide, midazolam, triazolam, amiodarone, propafenone and ergot derivatives. Inducers of the hepatic P-450 system, rifampin, rifabutin, pheno-barbital, phenytoin or carbamazepine, should not be used in combination with delaviridine. It also increases the plasma levels of HIV protease inhibitors. 

The use of rifampicin with the protease inhibitors indinavir, nelfinavir, and amprenavir is contraindicated. However, these agents can be used with rifabutin after appropriate dosage reduction. Failure to reduce the dosage of rifabutin can result in toxic manifestations, such arthralgia and uveitis. 

Centers for Disease Control and Prevention (CDC). Updated guidelines for the use of rifabutin or rifampin for the treatment and prevention of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors. MMWR Morb Mortal Wkly Rep 2000 49(9) 185-9. 

Rifampin s potent induction of hepatic enzymes, especially cytochrome P450 (CYP) 3A4, may enhance the ehmination of many other drugs, most notably the protease inhibitors used to treat HIV (Table 110-7). HIV-positive patients may beneht from the use of rifabutin instead of rifampin (see below). ° Also, women who use oral contraceptives must use another form of contraception during therapy because increased clearance of the hormones may lead to unexpected pregnancies. Patient records should be reviewed for potential drug interactions before dispensing rifampin. Rifampin may turn urine and other secretions orange-red and may permanently stain some types of contact lenses. 

Antiinfectives HIV-1 protease inhibitors (saquinavir, indinavir, Can be used with rifabutin. Ritonavir, 400-600 mg twice daily, probably... 

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