Active Substance: efavirenz
Common Name: efavirenz
ATC Code: J05AG03
Marketing Authorisation Holder: Bristol-Myers Squibb Pharma EEIG
Active Substance: efavirenz
Authorisation Date: 1999-05-28
Therapeutic Area: HIV Infections
Pharmacotherapeutic Group: Antivirals for systemic use
Sustiva is indicated in antiviral combination treatment of human-immunodeficiency-virus-1 (HIV-1)-infected adults, adolescents and children 3 years of age and older.
Sustiva has not been adequately studied in patients with advanced HIV disease, namely in patients with CD4 counts < 50 cells/mm3, or after failure of protease-inhibitor (PI)-containing regimens. Although cross-resistance of efavirenz with PIs has not been documented, there are at present insufficient data on the efficacy of subsequent use of PI-based combination therapy after failure of regimens containing Sustiva.
What is Sustiva?
Sustiva is a medicine that contains the active substance efavirenz. It is available as capsules (yellow and white: 50 mg; white: 100 mg; yellow: 200 mg), as yellow, capsule-shaped tablets (600 mg) and as an oral solution (30 mg/ml).
What is Sustiva used for?
Sustiva is an antiviral medicine. It is used together with other antiviral medicines to treat adults and children aged three years or older infected with human immunodeficiency virus type 1 (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS).
The medicine can only be obtained with a prescription.
How is Sustiva used?
Treatment with Sustiva should be started by a doctor who has experience in the management of HIV infection. Sustiva must be given in combination with other antiviral medicines. It is recommended that Sustiva be taken on an empty stomach and without food, preferably at bedtime.
The recommended dose of Sustiva for adults is 600 mg once a day. In patients aged three to 17 years, the dose depends on body weight. For patients who are unable to swallow the capsules or tablets, Sustiva can be given using the oral solution. If the patient cannot tolerate the oral solution, mixing the contents of the capsules with a small amount of food (around two teaspoons) can be considered. The dose of Sustiva needs to be reduced in patients taking voriconazole (used to treat fungal infections). Patients taking rifampicin (an antibiotic) may need to take a higher dose of Sustiva.
For full details, see the summary of product characteristics (also part of the EPAR).
How does Sustiva work?
The active substance in Sustiva, efavirenz, is a non-nucleoside reverse transcriptase inhibitor (NNRTI). It blocks the activity of reverse transcriptase, an enzyme produced by HIV that allows it to infect cells in the body and make more viruses. By blocking this enzyme, Sustiva, taken in combination with other antiviral medicines, reduces the amount of HIV in the blood and keeps it at a low level. Sustiva 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.
How has Sustiva been studied?
Sustiva has been studied in three main studies involving over 1,100 adults:
- in the first study, Sustiva in combination with lamivudine and zidovudine or with indinavir (other antiviral medicines) was compared with the combination of indinavir, lamivudine and zidovudine;
- the second study compared Sustiva in combination with nelfinavir and two other antiviral medicines with the same combination without Sustiva;
- the third study compared adding Sustiva or placebo (a dummy treatment) to a combination of antiviral medicines that included indinavir and two other antiviral medicines, in patients who had already been receiving treatment for HIV infection.
Sustiva has also been studied in 57 children aged between three and 16 years, in combination with nelfinavir and other antiviral medicines.
What benefit has Sustiva shown during the studies?
All of the studies showed that combinations including Sustiva were at least as effective as the comparator medicines:
- the first study showed that 67% of the adults treated with Sustiva in combination with zidovudine and lamivudine had viral loads below 400 copies/ml after 48 weeks, compared with 54% of the patients treated with Sustiva and indinavir, and 45% of the patients treated with indinavir, lamivudine and zidovudine;
- in the second study, Sustiva in combination with nelfinavir was superior to the combination without Sustiva: 70% and 30% of the patients, respectively, had viral loads below 500 copies/ml after 48 weeks;
- the third study showed that more patients receiving Sustiva had viral loads below 400 copies/ml than those taking placebo after 24 weeks.
Similar results were seen in the study in children.
What is the risk associated with Sustiva?
The most common side effect with Sustiva (seen in more than 1 patient in 10) is rash. Sustiva is also associated with nervous-system symptoms, such as dizziness, insomnia (difficulty sleeping), somnolence (sleepiness), impaired concentration and abnormal dreaming, and with psychiatric disorders, including severe depression, suicidal thoughts, suicide attempts and aggressive behaviour, especially in patients with a history of mental illness. Taking Sustiva with food may lead to an increase in the frequency of side effects. For a more complete list of side effects reported with Sustiva, see the package leaflet.
Sustiva should not be used in patients who may be hypersensitive (allergic) to efavirenz or any of the other ingredients. It must not be used in patients with severe liver disease or who are taking any of the following medicines:
- astemizole, terfenadine (commonly used to treat allergy symptoms - these medicines may be available without prescription);
- dihydroergotamine, ergotamine, ergonovine, methylergonovine (used to treat migraine headache);
- midazolam, triazolam (used to relieve anxiety or difficulty sleeping);
- pimozide (used to treat mental illnesses);
- cisapride (used to relieve certain stomach problems);
- bepridil (used to treat angina);
- St John’s wort (a herbal preparation used to treat depression).
Caution is also needed when Sustiva is taken at the same time as other medicines. See the package leaflet for further details.
As with other anti-HIV medicines, patients taking Sustiva may be at risk of lipodystrophy (changes in the distribution of body fat), osteonecrosis (death of bone tissue) or immune reactivation syndrome (symptoms of infection caused by the recovering immune system). Patients who have problems with their liver (including hepatitis-B or -C infection) may be at an elevated risk of liver damage when taking Sustiva.
Why has Sustiva been approved?
The Committee for Medicinal Products for Human Use (CHMP) decided that Sustiva’s benefits are greater than its risks in antiviral combination treatment of HIV-infected adults, adolescents and children three years of age and older. The Committee noted that Sustiva has not been studied adequately in patients with advanced disease (CD4 cell counts below 50 cells/mm3) or after treatment with protease inhibitors (another type of antiviral medicine) that was not working. The Committee also noted that there is little information on the benefits of treatment including a protease inhibitor in patients who have been treated with Sustiva in the past but which stopped working, although there is no evidence to suggest that protease inhibitors may not work in these patients. The Committee recommended that Sustiva be given marketing authorisation.
Other information about Sustiva:
The European Commission granted a marketing authorisation valid throughout the European Union for Sustiva on 28 May 1999. The marketing-authorisation holder is Bristol-Myers Squibb Pharma EEIG. The marketing authorisation was renewed on 28 May 2004 and on 28 May 2009.
Source: European Medicines Agency
Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.