What is Aptivus?
Aptivus is a drug containing the active substance tipranavir. It is available in pink capsules (250 mg) and as an oral solution (100 mg / ml).
What is Aptivus used for?
Aptivus is an antiviral drug used for therapy in patients at least 2 years of age with human immunodeficiency virus type 1 (HIV-1), a virus that causes the acquired immunodeficiency syndrome (AIDS). Aptivus is used in combination with low dose ritonavir (another antiviral medicine) and with other antiviral medicines.
Aptivus should only be used in the absence of alternative treatments. It is used in patients who have already been treated with other antiviral medicines against HIV infection and who do not respond to several other drugs of the same class as Aptivus (protease inhibitors). Doctors should prescribe Aptivus only after considering the previous antiviral drugs taken by the patient and the probable response of the virus to the medicine.
The medicine can only be obtained with a prescription.
How is Aptivus used?
Treatment with Aptivus should be started by a doctor who has experience in the treatment of HIV-1 infection.
In patients at least 12 years of age the recommended dose of Aptivus is 2 capsules twice a day. Children between the ages of two and 12 should use the oral solution. The dose of the oral solution depends on the body surface (calculated based on the weight and height of the child). Each dose of Aptivus should be taken together with ritonavir and with food. For more information, see the package leaflet.
How does Aptivus work?
The active substance in Aptivus, tipranavir, is a protease inhibitor. It blocks an enzyme called protease that is involved in the reproduction of HIV. If the enzyme is blocked, the virus is unable to reproduce normally, which slows the spread of the infection.
Ritonavir is another protease inhibitor, which is used as an "enhancer". It slows down the speed at which tipranavir is assimilated, thus increasing its concentration in the blood. This allows a smaller amount of tipranavir to be used to achieve the same antiviral effect.
Aptivus, taken in combination with other antiviral medicines, reduces the amount of HIV in the blood and keeps it at a low level. Aptivus does not cure HIV infection or AIDS, but it may delay the damage to the immune system and the development of infections and diseases associated with AIDS.
What studies have been carried out on Aptivus?
Aptivus has been studied in two main studies involving 1 483 adults who had previously taken many other anti-HIV drugs and who did not respond to the ongoing treatment including a protease inhibitor. In both studies, the effects of Aptivus were compared with those of another protease inhibitor chosen on the basis of previous therapies followed by patients and the expected response. The main measures of effectiveness were the number of patients responding to the therapy, and the amount of time needed for the therapy to stop taking effect in the first 48 weeks of the same. "Response" meant a reduction in HIV levels in the blood (viral load) of 90% or more maintained until the end of the 48-week period.
Aptivus has also been studied in a study involving 63 children aged between two and 12 years, 52 adolescents aged between 12 and 18, almost all of whom have been subjected to HIV therapies in the past. All patients started therapy with the oral solution, while adolescents taking the full adult dose switched to capsules after four weeks. The safety and efficacy of Aptivus and the level of the drug in patients' blood were observed in the studies.
In all three studies, all patients were also given ritonavir and a combination of other anti-HIV drugs chosen based on the best chance of reducing HIV levels in the blood.
What benefit has Aptivus shown during the studies?
Aptivus capsules, taken in combination with ritonavir, were more effective than the comparator medicine in patients with few remaining alternatives for effective HIV treatment. In the two adult studies taken together, 34% of patients who took Aptivus (251 out of 746) responded to treatment, compared with 16% of patients who took the comparator protease inhibitors (113 out of 737). On average, 113 days had elapsed for the treatment to stop taking effect in adults taking Aptivus. This was compared with an average of zero days for those who took the comparator, meaning that most patients who took the comparator did not respond to treatment.
In studies on children and adolescents, 31% of the adolescents who took the capsules (9 out of 29) and 50% of the children who took the oral solution (31 out of 62) reached and maintained viral loads below 400 copies / ml after 48 weeks.
What is the risk associated with Aptivus?
In adults, the most common side effects with Aptivus in combination with ritonavir (seen in more than 1 patient in 10) are diarrhea and nausea. Similar side effects have been observed in children and adolescents, although vomiting, rash and pyrexia (fever) have been observed more commonly than in adults. For the full list of all side effects reported with Aptivus, see the Package Leaflet.
Aptivus should not be used in people who may be hypersensitive (allergic) to tipranavir or any of the other ingredients. Aptivus should not be used in patients with moderate to severe liver problems or being treated with any of the following drugs:
- rifampicin (for the treatment of tuberculosis);
- St. John's wort (vegetable preparation used in the treatment of depression);
- drugs that are metabolized in the same way as Aptivus or ritonavir and that are dangerous if they reach high concentrations in the blood. For the full list of these medicines, see the package leaflet.
As with other anti-HIV drugs, patients receiving Aptivus may be at risk of lipodystrophy (changes in the distribution of body fat), osteonecrosis (death of bone tissue) or immune reactivation syndrome (inflammatory symptoms caused by the reactivation of the immune system) . Patients with liver problems (including hepatitis B or C infection) may be at greater risk of liver damage if they are taking Aptivus.
Why has Aptivus been approved?
The Committee for Medicinal Products for Human Use (CHMP) found that the studies supported the use of Aptivus capsules in adults. Although the committee had doubts about the study design methods for children and adolescents, he found that the results of the study supported the use of capsules in adolescents and the oral solution in children aged 2 to 12 years. The CHMP therefore decided that the benefits of Aptivus capsules, when given together with ritonavir in low doses, outweigh its risks compared to the combination of antiretroviral treatment of HIV-1 infection in adults and adolescents at least 12 years old with intense preliminary treatment, suffering from viruses resistant to multiple protease inhibitors. The committee also decided that the benefits of Aptivus oral solution outweigh its risks in children undergoing intensive pre-treatment between the ages of 2 and 12 years. There was, however, insufficient information to support the use of the oral solution in patients at least 12 years of age.
The Committee recommended that Aptivus be given marketing authorization. However, the Committee concluded that the drug should only be used as a "last choice" therapy, when no other protease inhibitor is expected to be effective.
Aptivus was originally authorized in "exceptional circumstances" since, for scientific reasons, it was not possible to obtain complete information on the medicine. Since the company provided the additional information requested, the condition referring to "exceptional circumstances" was removed on 15 April 2008.
More information on Aptivus:
On 25 October 2005, the European Commission issued a marketing authorization for Aptivus, valid throughout the European Union, to Boehringer Ingelheim International GmbH.
For the full EPAR of Aptivus, click here.
Last update of this summary: 05-2009
