AccessPak for HIV PEP Expanded with Kaletra and Ketoconazole (Systemic)

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Ritonavir may significantly increase the blood levels of ketoconazole. This can increase the risk of potentially serious and life-threatening cardiovascular side effects and liver problems. You may need a dose adjustment or more frequent monitoring to safely use both medications. Talk to your doctor if you have any questions or concerns. Your doctor may already be aware of the interaction, but has determined that this is the best course of treatment for you and has taken appropriate precautions and is monitoring you closely for any potential complications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

ADJUST DOSE: Coadministration with ritonavir may significantly increase the plasma concentrations of itraconazole and ketoconazole. The mechanism is ritonavir inhibition of CYP450 3A4 metabolism. In 12 study subjects, administration of ketoconazole (200 mg orally daily for 7 days) with ritonavir (500 mg orally twice a day for 10 days) increased mean ketoconazole peak plasma concentration (Cmax) by 55% and systemic exposure (AUC) by nearly 250% compared to ketoconazole administered alone. Ritonavir also increased the mean half-life of ketoconazole from 2.7 to 13.2 hours. Conversely, ritonavir Cmax and AUC increased by just 10% and 18%, respectively, in the presence of ketoconazole. A published study involving 12 HIV-infected subjects supported the modest effect of ketoconazole on plasma ritonavir levels. However, cerebrospinal fluid (CSF) ritonavir levels were increased by 178%, which is thought to be due primarily to ketoconazole inhibition of CSF-to-plasma active transport systems (e.g., P-glycoprotein) and secondarily to decreased systemic clearance of ritonavir. Theoretically, the increase in CSF ritonavir concentrations may lead to improved antiretroviral response in the central nervous system. Limited data suggest that ritonavir may similarly affect the plasma levels of itraconazole. A pharmacokinetic study was conducted in an HIV+ patient being treated with itraconazole and lopinavir-ritonavir. The patient had received itraconazole 200 mg twice a day for 10 days prior to starting antiretroviral therapy containing lopinavir-ritonavir (400 mg-100 mg twice a day). Because an interaction was anticipated, the patient's itraconazole dosage was reduced to 200 mg once a day with the start of lopinavir-ritonavir. Despite the dosage adjustment, total exposure (AUC of both itraconazole and active hydroxy metabolite) was similar before and one day after initiation of lopinavir-ritonavir. Five weeks later, itraconazole levels had exceeded 2000 ng/mL, and its terminal half-life increased from 16 hours to more than 160 hours. There were no signs of itraconazole-related toxicity, and the patient was doing well several months later. Itraconazole had negligible effects on the pharmacokinetics of lopinavir and ritonavir.

MANAGEMENT: During coadministration with ritonavir, the dosage of ketoconazole should generally not exceed 200 mg/day so as to avoid excessive plasma drug levels, which may be associated with impairment of testosterone and cortisol production and possibly an increased risk of hepatotoxicity. Some experts also recommend limiting the dosage of itraconazole to 200 mg/day when prescribed with ritonavir.

AccessPak for HIV PEP Expanded with Kaletra

Generic Name: emtricitabine / lopinavir / ritonavir / tenofovir

Brand name: AccessPak for HIV PEP Expanded with Kaletra

Synonyms: n.a.

What is AccessPak for HIV PEP Expanded with Kaletra?

Ketoconazole (Systemic)

Generic Name: ketoconazole

Brand name: Nizoral

Synonyms: Ketoconazole

What is Ketoconazole (Systemic)?