Liver toxicity, rash and nevirapine

Liver toxicity
Nevirapine

Liver toxicity

Associated drugs: nevirapine (Viramune), ritonavir (Norvir), tipranavir (Aptivus). Most anti-HIV drugs have potential for liver toxicity.

Location of liver in abdomen Most HIV drugs can affect your liver as this is the way that they are filtered by your body. This is why your routine blood tests will include tests to check your liver function.

Ritonavir, nevirapine and tipranavir are particularly associated with liver toxicity. Several studies have shown that liver toxicity may be similar between nevirapine and efavirenz.

The following factors can increase the risk of liver complications from HIV treatment.

Gender: women are more prone to liver problems with HIV drugs.
Viral hepatitis: hepatitis A, B or C (or other liver disease).
Increased alcohol consumption.
Use of other drugs, including recreational drugs, that are toxic to the liver alongside HIV therapy.

Your doctor will normally test your liver function at the same time as testing CD4 count and viral load. If you have hepatitis or previous liver damage, use therapeutic drug monitoring (TDM) when using protease inhibitors or NNRTIs, as you may need to use a lower dose.

When taking anti-HIV drugs you should report any side effects to your doctor. Especially if you have abdominal pain, nausea and vomiting, yellowing of the skin or the whites of the eyes.

Where liver toxicity is suspected, the drugs will normally be stopped to allow the liver to rest and return to normal. When the liver tests have returned to normal HIV drugs may be restarted. This is often with a different combination of drugs or reduced doses.

Nevirapine

The risk of nevirapine-related liver toxicity is different between men and women. This risk is related to CD4 count when starting treatment.

Women starting treatment for the first time should not use nevirapine if their CD4 count is over 250 cells/mm3 and men should not use nevirapine if their CD4 count is over 400 cells/mm3.

These CD4 levels are not thought important if you already have an undetectable are switching one of your current drugs to nevirapine. They do not relate to pregnant women who are using a single dose of nevirapine as part of treatment to reduce the risk of transmitting HIV to their baby.

Close monitoring (every two weeks) in the first two months of therapy is recommended for anyone who starts a nevirapine-based combination. This is when liver problems first start to occur. Liver toxicity may also build up slowly and so routine monitoring after the first two months is also important.

Nevirapine must be taken as one tablet (200 mg) once daily for the first two weeks.

Only if you have none of the symptoms listed below and your liver function tests are within the acceptable levels can you increase your nevirapine dose to one tablet (200 mg) twice a day.

Blood samples should be taken every two weeks in the first two months to check liver function, then at the end of the third month, and then every three to four months if they are within normal limits.

During this first eight weeks you should contact your doctor straight away if you have any of the following symptoms:

Rash.
Blistering of the skin – seek immediate medical. attention.
Mouth sores.
Facial or general swelling.
Fever.
Flu-like symptoms, aching muscles or joint pains.

Your doctor will do another liver function blood test if you have one of these symptoms.

If the results are not higher than twice the normal limit, and depending on the severity of your symptoms, a decision will be made whether or not to continue with nevirapine. If a decision is made to continue, you will be very closely monitored to ensure that the symptoms do not progress or your liver function tests get worse.

If at any point your liver function tests get to five times the normal limit or mild symptoms get worse, then your nevirapine must be stopped. Your doctor will recommend whether you need to stop all your treatments or just switch the nevirapine to another drug.

If you stop nevirapine for these reasons, you must not take it again in the future.