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Agenerase is a brand name for Amprenavir. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Agenerase, in combination with other antiretroviral agents, is indicated for the treatment of protease inhibitor (PI) experienced HIV-1 infected adults and children above the age of 4 years. Agenerase capsules should normally be administered with low dose ritonavir as a pharmacokinetic enhancer of amprenavir (see…
Verbatim from this product's EMA label. Tap a section to expand.
Therapy should be initiated by a physician experienced in the management of HIV infection. The importance of complying with the full recommended dosing regimen should be stressed to all patients. Agenerase is administered orally and can be taken with or without food.
Agenerase is also available as an oral solution for use in children or adults unable to swallow capsules. 2). Adults and adolescents of 12 years of age and older (greater than 50 kg body weight): the recommended dose of Agenerase capsules is 600 mg twice daily with ritonavir, 100 mg twice daily, in combination with other antiretroviral agents.
If Agenerase capsules are used without the boosting effect of ritonavir higher doses of Agenerase (1200 mg twice daily) should be used. 1). The pharmacokinetics, efficacy and safety of Agenerase in combination with low doses of ritonavir or other protease inhibitors have not yet been evaluated in children.
Therefore, such combinations should be avoided in children. 2). 2). 2). Hepatic impairment: the principal route of metabolism of amprenavir is via the liver. Agenerase capsules should be used with caution in patients with hepatic impairment.
Clinical efficacy and safety have not been determined in this patient group. For subjects with hepatic impairment, pharmacokinetic data are available for the use of Agenerase capsules without the boosting effect of ritonavir. Based on pharmacokinetic data, the dose of Agenerase capsules should be reduced to 450 mg twice a day for adult patients with moderate hepatic impairment and to 300 mg twice a day for adult patients with severe hepatic impairment.
2). The use of amprenavir in combination with ritonavir has not been studied in patients with hepatic impairment. No dose recommendations can be made regarding this combination. 3).
Medicinal product no longer authorised12 The safety of Agenerase has been studied in adults and children at least 4 years of age, in controlled clinical trials, in combination with various other antiretroviral agents. Adverse events considered associated with the use of Agenerase are gastro-intestinal symptoms, rash and oral/peri-oral paraesthesia.
Most undesirable effects associated with Agenerase therapy were mild to moderate in severity, early in onset, and rarely treatment limiting. For many of these events, it is unclear whether they are related to Agenerase, to concomitant treatment used in the management of HIV disease or to the disease process.
In children, the nature of the safety profile is similar to that seen in adults. Adverse reactions are listed below by MedDRA body system organ class and by frequency.
The frequency categories used are:
Very common ≥ 1 in 10 Common ≥ 1 in 100 and < 1 in 10 Uncommon ≥ 1 in 1,000 and < 1 in 100 Rare ≥1 in 10,000 and < 1 in 1,000 Frequency categories for the events below have been based on clinical trials and postmarketing data. Most of the adverse events below come from two clinical trials (PROAB3001, PROAB3006) involving PI naïve subjects receiving Agenerase 1200mg twice daily.
Events (grade 2-4) reported by study investigators as attributable to study medication and occurring in >1% of patients, are included as well as grade 3-4 treatment emergent laboratory abnormalities. Note that the background rates in comparator groups were not taken into account.
Metabolism and nutrition disorders Common:
Elevated triglycerides, elevated amylase, abnormal fat redistribution, anorexia Uncommon: Hyperglycaemia, hypercholesterolaemia Elevated triglycerides, elevated amylase and hyperglycaemia (grade 3-4) were reported primarily in patients with abnormal values at baseline.
Patients should be advised that Agenerase, or any other current antiretroviral therapy does not cure HIV and that they may still develop opportunistic infections and other complications of HIV infection. Current antiretroviral therapies, including Agenerase, have not been proven to prevent the risk of transmission of HIV to others through sexual contact or blood contamination.
Appropriate precautions should continue to be taken. On the basis of current pharmacodynamic data, amprenavir should be used in combination with at least two other antiretrovirals. 1). 2).
Liver Disease:
The safety and efficacy of amprenavir has not been established in patients with significant underlying liver disorders. 3). Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk of severe and potentially fatal hepatic adverse events.
In case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant product information for these medicinal products. Patients with pre-existing liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice.
If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered. 5). The HMG-CoA reductase inhibitors lovastatin and simvastatin are highly dependent on CYP3A4 for metabolism, thus concomitant use of Agenerase with simvastatin or lovastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis.
Caution must also be exercised if Agenerase is used concurrently with atorvastatin, which is metabolized to a lesser extent by CYP3A4. In this situation, a reduced dose of atorvastatin should be considered. 5). For some medicinal products that can cause serious or life-threatening undesirable effects, such as carbamazepine, phenobarbital, phenytoin, tricyclic antidepressants and warfarin (monitor International Normalised Ratio), concentration monitoring is available; this should minimise the risk of potential safety problems with concomitant use.
Hypersensitivity to the active substance or to any of the excipients. Agenerase must not be administered concurrently with medicinal products with narrow therapeutic windows that are substrates of cytochrome P450 3A4 (CYP3A4). g. g. g.
ergot derivatives). Agenerase in combination with ritonavir is contraindicated in patients with severe hepatic impairment. Combination of rifampicin with Agenerase with concomitant low-dose ritonavir is contraindicated. 5). g. 5). 5). Medicinal product no longer authorised4
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Elevations in cholesterol were of grade 3-4 intensity. Combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV patients including the loss of peripheral and facial subcutaneous fat, increased intra-abdominal and visceral fat, breast hypertrophy and dorsocervical fat accumulation (buffalo hump).
Symptoms of abnormal fat redistribution were infrequent in PROAB3001 with amprenavir. Only one case (a buffalo hump) was reported in 113 (< 1 %) antiretroviral naive subjects treated with amprenavir in combination with lamivudine/zidovudine for a median duration of 36 weeks.
001). 4).
Psychiatric disorders Common:
Mood disorders, depressive disorders Nervous system disorders Medicinal product no longer authorised13 Very Common: Headache Common: Oral/perioral paraesthesia, tremors, sleep disorders Gastrointestinal disorders Very Common: Diarrhoea, nausea, flatulence, vomiting Common: Abdominal pain, abdominal discomfort, dyspeptic symptoms, loose stools Hepatobiliary disorders Common: Elevated transaminases Uncommon: Hyperbilirubinaemia Elevated transaminases and hyperbilirubinaemia (grade 3-4) were reported primarily in patients with abnormal values at baseline.
Almost all subjects with abnormal liver function tests were co-infected with Hepatitis B or C virus.
Skin and subcutaneous tissue disorders Very Common:
Rash Uncommon: Angioedema Rare: Stevens Johnson syndrome Rashes were usually mild to moderate, erythematous or maculopapular cutaneous eruptions, with or without pruritus, occurring during the second week of therapy and resolving spontaneously within two weeks, without discontinuation of treatment with amprenavir.
A higher incidence of rash was reported in patients treated with amprenavir in combination with efavirenz. 4). Musculoskeletal and connective tissue disorders Increased CPK, myalgia, myositis, and rarely rhabdomyolysis have been reported with protease inhibitors, particularly in combination with nucleoside analogues.
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART). 4). 4). In PI experienced patients receiving Agenerase capsules 600 mg twice daily and low dose ritonavir, 100 mg twice daily, the nature and frequency of adverse events (grade 2-4) and Grade 3/4 laboratory abnormalities were similar to those observed with Agenerase alone, with the exception of elevated triglyceride levels, and elevated CPK levels which were very common in patients receiving Agenerase and low dose ritonavir.
5). Anticonvulsants (carbamazepine, phenobarbital, phenytoin) should be used with caution. 5). 5). g. 5). 5). A reduction of rifabutin dosage of at least 50 % is recommended when administered with Agenerase. 5). Because of the potential for metabolic interactions with amprenavir, the efficacy of hormonal contraceptives may be modified, but there is insufficient information to predict the nature of the interactions.
5). Co-administration of amprenavir with methadone leads to a decrease of methadone concentrations. Therefore, when methadone is co-administered with amprenavir, patients should be monitored for opiate abstinence syndrome, in particular if low-dose ritonavir is also given.
No recommendations can currently be made regarding adjustment of amprenavir dose when amprenavir is co-administered with methadone. Agenerase capsules contain vitamin E (36 IU/50 mg capsule), therefore additional vitamin E supplementation is not recommended.
Agenerase capsules also contain sorbitol (E420). Patients with rare hereditary problems of fructose intolerance should not take this medicine. Due to the potential risk of toxicity from the high propylene glycol content of Agenerase oral solution, this formulation is contraindicated in children below the age of four years and should be used with caution in certain other patient populations.
The Summary of Product Characteristics of Agenerase oral solution should be consulted for full prescribing information. Rash / cutaneous reactions Most patients with mild or moderate rash can continue Agenerase. g. cetirizine dihydrochloride) may reduce pruritus and hasten the resolution of rash.
8). Hyperglycaemia New onset of diabetes mellitus, hyperglycaemia or exacerbations of existing diabetes mellitus have been reported in patients receiving antiretroviral therapy, including protease inhibitors. In […]