INVIRASE 500 mg film-coated tablets

Invirase is a medicine containing the active substance saquinavir. It is available as brown and green capsules (200 mg) and orange, oval tablets (500 mg).

Invirase is used to treat adults infected with human immunodeficiency virus type 1 (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS). Invirase is always used in combination with ritonavir (another antiviral medicine) and other antiviral medicines.

The medicine can only be obtained with a prescription.

Treatment with Invirase should be started by a doctor who has experience in the treatment of HIV infection.

The recommended dose of Invirase for patients over 16 years of age is 1,000 mg twice a day with 100 mg ritonavir, with or after food.

The active substance in Invirase, saquinavir, is a protease inhibitor. It blocks an enzyme called protease, which is involved in the reproduction of HIV. When the enzyme is blocked, the virus does not reproduce normally, slowing down the spread of infection. Ritonavir is another protease inhibitor that is used as a ?booster?. It slows down the rate at which saquinavir is broken down, increasing the levels of saquinavir in the blood. This allows a lower dose of saquinavir to be used for the same antiviral effect. Invirase, taken in combination with other antiviral medicines, reduces the amount of HIV in the blood and keeps it at a low level. Invirase 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.

Invirase was assessed in six main studies involving a total of 1,576 patients. The first four studies assessed the medicine?s effects without ritonavir. The combination of Invirase with ritonavir was assessed in 656 patients in two studies that compared Invirase with indinavir and with lopinavir (other antiviral medicines), both in combination with ritonavir and other antiviral medicines. These studies measured the number of patients in whom treatment had stopped working after 48 weeks, as determined by a rise in the level of HIV in the blood (viral load).

Invirase, taken in combination with other antiviral medicines, resulted in falls in viral loads and improvements in the immune system. In the studies of Invirase in combination with ritonavir, Invirase led to similar rates of treatment failure to indinavir, but higher rates than lopinavir. This was mainly caused by more patients stopping Invirase treatment rather than by any differences in the effectiveness of the medicines.

The most common side effects when taking Invirase in combination with ritonavir (seen in more than 1 patient in 10) are diarrhoea, nausea (feeling sick), increased levels of liver enzymes, cholesterol and triglycerides (a type of fat) in the blood, and decreased levels of platelets in the blood (components that help blood to clot). For the full list of all side effects reported with Invirase, see the Package Leaflet.

Invirase should not be used in people who may be hypersensitive (allergic) to saquinavir or any of the other ingredients. It must not be used in patients who have severe problems with their liver, QT prolongation (an alteration of the electrical activity of the heart), altered levels of electrolytes in the blood (especially low potassium levels), bradycardia (slow heart rate) or heart failure (when the heart does not work as well as it should). It must not be used in patients who have had arrhythmia (unstable heartbeat) in the past. It must also not be used in patients who are taking any of the following medicines, which could cause harmful side effects if taken with Invirase:

• medicines that could cause QT prolongation or PR prolongation (another type of heart activity alteration);
• midazolam taken by mouth, triazolam (used to relieve anxiety or difficulty sleeping);
• simvastatin, lovastatin (used to lower cholesterol);
• ergot alkaloids, such as ergotamine, dihydroergotamine, ergonovine and methylergonovine (used to treat migraine headache);

• rifampicin (used to treat tuberculosis).

Caution is needed when Invirase is taken at the same time as some other medicines. See the package leaflet for full details.

The CHMP decided that Invirase?s benefits are greater than its risks and recommended that it be given marketing authorisation.