Efavirenz dosage

The manufacturer notes that neither aluminium/magnesium hydroxide antacids nor famotidine had any effect on the absorption of efavirenz. No efavirenz dosage adjustment is expected to be necessary with these drugs. Other drugs that reduce gastric acidity are not expected to affect efavirenz absorption. ... 

Weissburg, R.P. Montgomery, E.R. Jurmier, L.A. Segretario, J. Cook, S. Hovsepian, P.K. Investigation of critical factors for the resolution of SR695, a key impurity, from efavirenz in the reversed-phase assay of efavirenz dosage forms, J.Pharm.Biomed.Anal., 2002,28, 45-56. 

Concomitant medication with inducers of drug c/earance. Patients on rifampin should receive caspofungin 70 mg/day. Patients on nevirapine, efavirenz, carbamazepine, dexamethasone, or phenytoin may require an increase in dosage to caspofungin 70 mg/day. 

Lopinavir/Ritonavir Pediatric Dosage Without Efavirenz or Nevirapine... 

Adults The recommended dosage is 600 mg once daily in combination with a protease inhibitor or nucleoside analog reverse transcriptase inhibitors (NRTIs). It is recommended that efavirenz be taken on an empty stomach, preferably at bedtime. The increased efavirenz concentration following administration of efavirenz with food may lead to an increase in adverse events. 

Drug/Food interactions Food increases efavirenz concentrations and may increase the frequency of adverse events (see Administration and Dosage). 

HIV infection (in combination with other antiretrovirals) PO 800 mg (two 400-mg capsules) q8h. Dosage adjustments when given concomitantly Delavirdine, itraconazole, ketoconazok Reduce dose to 600 mg q8h. Efavirenz-. Increase dose to 1,000 mg q8h. Lopinavir/ritonavir Reduce dose to 600 mg twice a day. Nevirapine-. Increase dose to 1,000 mgqSh. Rifabutin-. Reduce rifabutin by lA and increase indinavir to 1,000 mg q8h. Ritonavir 100-200 mg twice a day and indinavir 800 mg twice a day or ritonavir 400 mg twice a day and indinavir 400 mg twice a day. 

Dosage adjustments in comhination therapy Amprenavir. Amprenavir 1,200 mg and ritonavir 200 mg once a day or amprenavir 600 mg and ritonavir 100 mg twice a day. Am-penavirandefavirenz. Amprenavir 1,200 mg twice a day and ritonavir 200 mg twice a day with standard dose of efavirenz. Indinavir. Indinavir 800 mg twice a day and ritonavir 100-200 mg twice a day or indinavir400 mg twice a day and ritonavir 400 mg twice a day. Nelfinavirorsaquinavir. Ritonavir 400 mg twice a day. Rifabutin. Decrease rifabutin dosage to 150 mg every other day. 

The most common adverse effects associated with nelfinavir are diarrhea and flatulence. Diarrhea often responds to antidiarrheal medications but can be dose-limiting. Nelfinavir is an inhibitor of the CYP3A system, and multiple drug interactions may occur (Tables 49-3 and 49-4). An increased dosage of nelfinavir is recommended when co-administered with rifabutin (with a decreased dose of rifabutin), whereas a decrease in saquinavir dose is suggested with concurrent nelfinavir. Co-administration with efavirenz should be avoided due to decreased indinavir levels. Nelfinavir has a favorable safety and pharmacokinetic profile for pregnant women compared with that of other Pis (Table 49-5) there is no evidence of human teratogenicity. 

Increased dosage of indinavir is recommended if efavirenz is co-administered (25). 

Following a report of withdrawal symptoms in three patients taking methadone maintenance therapy, serum methadone concentrations were measured before and after starting efavirenz in one patient (26). Serum methadone concentrations were as follows (R)-methadone (the active enantiomer) 168 ng/ml and 90 ng/ml before and after efavirenz. The corresponding (5)-methadone concentrations were 100 and 28 ng/ml. The dosage of methadone was increased from 100 to 180 mg/day before the patient s withdrawal symptoms resolved. 

In a pharmacokinetic study, 11 patients taking methadone 35 to 100 mg daily were given efavirenz with two nucleoside analogues. Nine of the patients developed methadone withdrawal symptoms and needed dose increases of 15 to 30 mg (mean 22%). A pharmacokinetic study of these patients found that 3 weeks after starting efavirenz their mean methadone AUCs were reduced by 57% and their maximum plasma levels by 48%. Similar results were found in another study in 5 HIV-positive patients taking methadone 4 patients experienced opioid withdrawal symptoms and a mean methadone dose increase of 52% was required. In another retrospective study, 6 out of 7 patients needed methadone dosage increases of 8% to 200% within 2 weeks to 8 months of starting an efavirenz-based... 

The manufacturer notes that there were no clinically significant pharmacokinetic interactions between efavirenz and zidovudine or iamivudine in patients with HIV. " No dosage adjustments are required on concurrent use. No pharmacokinetic interactions are anticipated with other NRTIs. ... 

Voriconazole is not recommended for use in combination with efavirenz however, if they are co-administered, the dosage of voriconazole should be increased to 400 mg 12-hourly and the dosage of efavirenz reduced to 300 mg/day, in order to provide systemic exposure similar to standard-dose monotherapy [SEDA-32, 498]. The combination of voriconazole and efavirenz in doses adjusted according to steady-state plasma concentrations has been studied in a 40-year-old man with AIDS, cryptococcosis, and mild liver cirrhosis [154 ]. Adequate concentrations of voriconazole in both plasma and cerebrospinal fluid were obtained and target plasma concentrations of efavirenz were achieved at the final dosage adjustment (oral voriconazole 200 mg bd plus oral efavirenz 300 mg/day). There was stable suppression of cryptococcosis and plasma HIV viremia at long-term follow-up (66 weeks), with no significant adverse events. 

Drug-drug interactions Maraviroc is a substrate of P glycoprotein and CYP3A4, by which it is about 65% metabolized. Maraviroc should therefore be used with caution when inhibitors of CYP3A4 are used concomitantly. Potent CYP 3A4 inhibitors, such as ketoconazole and protease inhibitors, except tipranavir + ritonavir, increase maraviroc exposure dosage reduction can compensate [246 ]. Conversely, enzyme inducers, such as rifampicin and efavirenz, reduce exposure [247 ]. In contrast, drugs... 

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