Warning issued over bleeding within the skull in patients taking tipranavir

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Tipranavir (Aptivus) may be associated with an increased risk of bleeding within the skull when boosted with low-dose ritonavir (Norvir), according to a warning issued by tipranavir’s manufacturer Boehringer Ingelheim on Friday.

The company issued a ‘Dear Healthcare Provider’ letter in the United States, explaining that 14 cases of intracranial haemorrhage have been identified in 6840 patients receiving ritonavir-boosted tipranavir as part of an anti-HIV combination in clinical trials. Eight of the patients have died.

The manufacturer claims that most of the patients had other risk factors for intracranial haemorrhage. These include lesions in the brain, head injury, recent brain surgery, blood clotting disorders, high blood pressure and alcohol abuse, as well as use of medications that can increase bleeding. However, it did not reveal how many of the patients did not have a known risk factor for bleeding.


boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.


A person who has previously taken treatment for a condition. Treatment-experienced people may have taken several different regimens before and may have a strain of HIV that is resistant to multiple drug classes.


The general term for the body’s response to injury, including injury by an infection. The acute phase (with fever, swollen glands, sore throat, headaches, etc.) is a sign that the immune system has been triggered by a signal announcing the infection. But chronic (or persisting) inflammation, even at low grade, is problematic, as it is associated in the long term to many conditions such as heart disease or cancer. The best treatment of HIV-inflammation is antiretroviral therapy.


Small scrapes, sores or tears in tissue. Lesions in the vagina or rectum can be cellular entry points for HIV.

high blood pressure

When blood pressure (the force of blood pushing against the arteries) is consistently too high. Raises the risk of heart disease, stroke, kidney failure, cognitive impairment, sight problems and erectile dysfunction.

It took a median of 525 days from the start of treatment with ritonavir-boosted tipranavir for the haemorrhage to occur.

The company has advised that patients who may be at risk of bleeding due to surgery, injury, other conditions or other medications should use ritonavir-boosted tipranavir with caution.

Intracranial haemorrhage is a serious emergency medical condition, which causes dangerous increases in the pressure within the skull. Bleeding can occur within the brain, or between the skull and the membranes that surround the brain tissue.

Patients given tipranavir in clinical trials did not show any blood clotting abnormalities. However, some test-tube studies and animal experiments did find some reductions in the ability of blood clots to form. Boehringer Ingelheim is carrying out more investigations into the link between tipranavir and bleeding.

Tipranavir was licensed for use in treatment-experienced HIV patients in 2005. Its standard dose is 500mg with 200mg ritonavir, twice a day. Its main side-effect is an increased risk of liver inflammation.