Darunavir and Cobicistat and Rifabutin

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.

Cobicistat may significantly increase the blood levels of rifabutin. This may increase the risk of serious side effects including low white blood cell count and an eye condition known as uveitis, which causes inflammation and swelling of the middle layer of the eye and can lead to blindness. Rifabutin may also significantly reduce the blood levels of cobicistat, which may reduce its effectiveness in treating HIV infection. 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.

GENERALLY AVOID: Coadministration with cobicistat may significantly increase the plasma concentrations of rifabutin and its metabolite, 25-O-desacetylrifabutin. The proposed mechanism is cobicistat inhibition of rifabutin metabolism via CYP450 3A4. In 12 healthy volunteers, administration of rifabutin 150 mg once every other day in combination with 150 mg once daily each of cobicistat and elvitegravir had no significant effect on the pharmacokinetics of rifabutin, but increased mean 25-O-desacetyl-rifabutin peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by approximately 4.8-, 6.3- and 4.9-fold, respectively, compared to administration of rifabutin alone at 300 mg once daily. Uveitis and neutropenia secondary to rifabutin toxicity may occur. On the other hand, cobicistat plasma concentrations may be significantly decreased due to CYP450 3A4 induction by rifabutin. In the same study mentioned above, the Cmin of cobicistat decreased by 66%.

MANAGEMENT: Concomitant use of cobicistat-containing fixed combination antiretroviral products with rifabutin is not recommended. However, if concomitant use is needed, to minimize the risk of rifabutin toxicity including leucopenia, uveitis, arthralgias, and skin discoloration, some authorities recommend that the rifabutin dosage be reduced to 150 mg every other day or three times a week in patients treated with cobicistat. A further dosage reduction of rifabutin to 150 mg twice weekly may be necessary for patients in whom the 150 mg three times per week dose is not tolerated. A complete blood count should be performed at least weekly and as clinically indicated to monitor for development of neutropenia. Due to the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, close monitoring of antiretroviral response is also recommended. Current guidelines should be consulted for the appropriate treatment of tuberculosis in HIV-infected patients.

Darunavir and Cobicistat

Generic Name: cobicistat / darunavir

Brand name: Prezcobix

Synonyms: Cobicistat and darunavir

What is Darunavir and Cobicistat?

Rifabutin

Generic Name: rifabutin

Brand name: Mycobutin

Synonyms: n.a.

What is Rifabutin?