Monitoring the safety of antiretroviral drugs
- Medicines and Healthcare products Regulatory Agency
- 1 May 2008
- Therapeutic area:
- Infectious disease
Healthcare professionals should monitor the use and safety of antiretroviral drugs for the treatment of HIV as they are advanced.
Article date: May 2008
The first antiretroviral drug, zidovudine, became available more than 20 years ago, and since then there have been substantial advances in the treatment options available to patients with HIV and in their prognosis. The advent of new drug classes and in combination therapy has not only led to important benefits for patients, but also to the need for ongoing monitoring and management of the risks associated with treatment.
The clinical need for new or improved treatments for HIV is usually perceived as urgent and most new treatments are made available for use as quickly as possible. Therefore, knowledge of a drug’s safety is incomplete when it first becomes available and it is monitored closely after marketing.
Recent examples of new treatments or new formulations or combinations, of treatments, for HIV include:
- Maraviroc (celsentri ▼): the first CCR5 inhibitor
- Raltegravir (isentress ▼): the first integrase inhibitor
- Duranavir (prezista ▼): a new protease inhibitor for highly pretreated patients
- Atripla: a new combination tablet of efavirenz, tenofovir, and emtricitabine
To help improve knowledge about the safety of a new medicine, a company that holds a marketing authorisation for it now produces a risk-management plan. A summary of the plan can be found in the European Public Assessment Report of the medicine.
Of course, safety issues are not only associated with newer drugs. As a consequence of the short-term nature (ie, actual treatment periods) of clinical trials, the long-term safety profile of all antiretrovirals is continually changing.
Recent examples of safety issues associated with older antiretrovirals
- abacavir and didanosine: increased risk of myocardial infarction (findings from the D:A:D study: see article in Drug Safety Update, May 2008) and position statement from D:A:D steering committee)
- norvir (ritonavir): new drug interactions (eg, with buprenorphine)
- crixivan (indinavir): renal failure
- sustiva (efavirenz): gynaecomastia
- viread (tenofovir): risk of hepatitis B reactivation after withdrawal
- telzir (fosamprenavir): angioedema
- all antiretrovirals: osteonecrosis (see British National Formulary 54th edn, September 2007, section 5.3.1 HIV infection, p 325)
- effect of proton pump inhibitors on protease inhibitor blood levels (for Reyataz and Kaletra)
- kaletra (lopinavir with ritonavir): overdosing of neonates
Report suspected adverse drug reactions
The Yellow Card Scheme is an important way of detecting emerging safety issues for medicines. We use reports of suspected adverse effects of drugs (or interactions with other drugs, herbal products, or food supplements) from healthcare professionals and patients or carers to determine whether information for a medicine accurately reflects its safety profile.
For all Yellow Cards we receive, it is important to note that patient and reporter confidentiality is maintained. Specific guidance on the reporting of suspected adverse reactions to antiretrovirals can be found on our website. In addition to the basic information included on a
Yellow Card report, it is very helpful for our assessment of these reports to know the:
- CD4 count
- lowest ever CD4 count
- CD4 count at start of treatment
- HIV viral load
- relevant test results (including baseline values)
- drug-resistance profile
- previous illness
- previous side effects
For more information on monitoring the safety of antiretroviral drugs.
Article citation: Drug Safety Update May 2008; Vol 1, Issue 10: 7
Published: 1 May 2008
Therapeutic area: Infectious disease