Phase III clinical trials tend to enroll carefully selected patients who have few or mild-to-moderate pre-existing health conditions. In practice, once a drug is licensed, a wide variety of patients, some of whom may have multiple health conditions, may receive a new drug. One such pre-existing condition is HIV co-infection. As HIV-positive people will most likely be taking potent combination anti-HIV therapy (commonly called ART or HAART), it is essential to study potential interactions between drugs used for HIV and drugs used for HCV.
World-renowned pharmacologist David Burger, Ph.D., has assembled and reviewed recently presented data on many potential interactions that could occur between different drugs. Here is a summary of his findings.
In experiments used to assess interactions between drugs, here are the main findings:
Dr. Burger suggests that neither darunavir-ritonavir nor fosamprenavir-ritonavir be used with telaprevir.
Note that the above only lists the effects on specific HIV medicines. The impact of these and other drugs on telaprevir will be discussed later.
Overall, concentrations of the integrase inhibitor raltegravir (Isentress) in the blood rose by 31% when used with telaprevir. Dr. Burger says that a dose adjustment of raltegravir may not be necessary in telaprevir users.
Etravirine is a non-nuke sold under the brand name Intelence. Telaprevir decreased etravirine levels in the blood by 6%, a small change.
Rilpivirine is another non-nuke sold under the brand name Edurant and found in Complera. Telaprevir raised rilpivirine levels in the blood by nearly 80%. This could result in dangerous side effects so the combination should not be used.
Efavirenz significantly reduces the concentration of telaprevir in the blood. Professor Burger suggested that efavirenz may be used but the dose of telaprevir should be increased to 1,125 mg every eight hours
In experiments on people, the following changes occurred:
Dr. Burger notes that atazanavir-ritonavir is probably the only combination from this group that is safe to use with telaprevir.
Raltegravir raised telaprevir levels by 7% -- a difference that is not significant.
Etravirine reduced telaprevir levels by 18%. When the dose of telaprevir was doubled to 1,500 mg every eight hours, unexpectedly telaprevir levels fell by 20%. This is an example of how unexpected and complex drug-drug interactions can be and why they need to be studied.
Rilpivirine caused telaprevir levels to fall by 8%.
Dr. Burger recommended that the following courses of action be taken by doctors who are contemplating prescribing telaprevir to people who are co-infected with HIV and HCV:
He recommended that the following drugs not be taken by telaprevir users:
These recommendations are very broad. Each person will likely be taking several other drugs to treat complications of HCV (or HIV infection), therefore much more information about drug interactions is needed. Until the results of large clinical trials conducted by the ACTG and ANRS are completed and consensus has emerged about which drugs to use, we urge physicians who are contemplating prescribing these or other therapies to seek guidance from regulatory authorities, consult the necessary product monographs or speak with other experts, particularly pharmacologists and other specialists who are experienced in treating co-infected patients.
Burger DM. Interactions between antiretrovirals and direct acting antivirals. In: Program and abstracts of the 8th International Workshop on HIV and Hepatitis Co-infection, 30 May - 1 June 2012, Madrid, Spain.
No comments have been made.