Chemical formula: C₂₅H₃₅N₃O₆S Molecular mass: 505.627 g/mol PubChem compound: 65016
Amprenavir interacts in the following cases:
There are no adequate data from the use of amprenavir in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown.
This medicinal product should be used during pregnancy only after careful weighing of the potential benefits compared to the potential risk to the foetus.
Amprenavir-related material was found in rat milk, but it is not known whether amprenavir is excreted in human milk. A reproduction study in pregnant rats dosed from the time of uterine implantation through lactation showed reduced body weight gains in the offspring during the nursing period. The systemic exposure to the dams associated with this finding was similar to exposure in humans, following administration of the recommended dose. The subsequent development of the offspring, including fertility and reproductive performance, was not affected by the maternal administration of amprenavir.
It is therefore recommended that mothers being treated with amprenavir do not breast-feed their infants. Additionally, it is recommended that HIV infected women do not breast-feed their infants in order to avoid transmission of HIV.
No studies on the effects on ability to drive and use machines have been performed.
The safety of amprenavir 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 amprenavir are gastro-intestinal symptoms, rash and oral/peri-oral paraesthesia. Most undesirable effects associated with amprenavir 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 amprenavir, 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 amprenavir 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.
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.
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. In study PROAB3006, seven cases (3%) were reported in 245 NRTI-experienced subjects treated with amprenavir and in 27 (11%) of 241 subjects treated with indinavir, in combination with various NRTIs for a median duration of 56 weeks (p<0.001).
Combination antiretroviral therapy has been associated with metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactataemia.
Common: Mood disorders, depressive disorders
Very Common: Headache
Common: Oral/perioral paraesthesia, tremors, sleep disorders
Very Common: Diarrhoea, nausea, flatulence, vomiting
Common: Abdominal pain, abdominal discomfort, dyspeptic symptoms, loose stools
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.
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. Severe or life-threatening skin reactions have also occurred in patients treated with amprenavir.
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). The frequency of this is unknown.
Very Common: Fatigue
In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise.
In PI experienced patients receiving amprenavir 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 ¾ laboratory abnormalities were similar to those observed with amprenavir alone, with the exception of elevated triglyceride levels, and elevated CPK levels which were very common in patients receiving amprenavir and low dose ritonavir.
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