Protease inhibitors.

Amprenavir

Capsules: soft capsules, oblong, opaque, off-white to cream coloured, printed with 'GX CC1' (50mg) or 'GX CC2' (150mg). Oral solution: clear, pale yellow to yellow solution with grape, bubblegum and peppermint flavouring.

Capsules, amprenavir 50mg , 150mg . Oral solution, amprenavir 15mg/ mL.

Treatment of protease inhibitor experienced HIV-1 infected adults and children above the age of four years, in combination with other antiretroviral agents. The choice of amprenavir should be based on individual viral resistance testing and treatment history of patients. In protease inhibitor naive patients, Agenerase is less effective than indinavir. In heavily pretreated protease inhibitor experienced  protease inhibitor experienced patients, the use of Agenerase has not been sufficiently studied.

Therapy should be initiated by a physician experienced in the management of HIV infection. Agenerase can be taken with or without food. Capsules: Adults and adolescents aged 12 years and over (>50kg body weight): 1200mg twice daily in combination with other antiretroviral agents. If used in combination with ritonavir, reduced doses of amprenavir (600mg twice daily) and ritonavir (100-200mg twice daily) are recommended.

Children (four to 12 years) and patients <50kg body weight: 20mg/ kg body weight twice a day, in combination with other antiretroviral agents, without exceeding a total daily dose of 2,400mg. Oral solution: amprenavir is 14% less bioavailable from the oral solution than the capsules; therefore, the capsules and oral solution are not interchangeable on a milligram per milligram basis.

Patients should discontinue the oral solution as soon as they are able to swallow the capsules. Patients of four years and older unable to swallow the capsules: 17mg (1.1mL) per kg three times a day in combination with other antiretroviral agents, without exceeding a total daily dose of 2,800mg.

Under four years, not recommended; four years and over, see above.

Capsules and Oral Solution : Known hypersensitivity to amprenavir or to any ingredient of Agenerase capsules or oral solution. Lactation. Concurrent administration with medicinal products with narrow therapeutic windows that are substrates of cytochrome P450 3A4. Concurrent administration with terfenadine, diazepam, midazolam, flurazepam, ergotamine, dihydroergotamine, astemizole, rifampicin or products containing St John's Wort ( Hypericum perforatum ).

Oral Solution only: Because of the potential risk of toxicity from the large amount of the excipient propylene glycol, the oral solution is contraindicated in infants and children below the age of four years, pregnant women, patients with hepatic or renal failure and patients treated with disulfiram or metronidazole.

Capsules and Oral Solution : Amprenavir should be used in combination with at least two other antiretrovirals. Hepatic impairment. Caution is advised when co-adminstered with any medicinal products that are inducers, inhibitors or substrates of CYP3A4. Efficacy of hormonal contraceptives may be reduced - additional reliable barrier methods of contraception are recommended for women of childbearing potential. Agenerase capsules contain vitamin E (109 i.u. per 150mg capsule and 46 i.u. per mL of oral solution), therefore additional supplementation is not recommended. Skin rash may occur; discontinue treatment if rash is accompanied by systemic or allergic symptoms or mucosal involvement.

Diabetes. Measurement of serum lipid and blood glucose should be considered. Pregnancy. Haemophilia. Oral Solution only: Renal impairment or a decreased ability to metabolise propylene glycol (eg, those of Asian origin) should be monitored for adverse reactions potentially related to the high propylene glycol content, such as seizures, stupor, tachycardia, hyperosmolarity, lactic acidosis, renal toxicity, haemolysis. Concomitant administration with disulfiram or other medicinal products that reduce alcohol metabolism (eg, metronidazole) or ritonavir oral solution) or additional propylene glycol should be avoided.

Capsules and Oral Solution : Ritonavir, nevirapine, delavirdine, rifampicin (see contraindications), rifabutin, benzodiazepines (see contraindications), calcium- channel blockers (diltiazem, nicardipine, nifedipine, nimodipine), sildenafil, statins, methadone and opiate derivatives, hormonal contraceptives, St John's Wort (see contraindications), clozapine, carbamazepine, cimetidine, dapsone, itraconazole, loratidine. Antacids, didanosine: should be administered at least one hour apart from Agenerase.

Oral Solution only: disulfiram or other medicinal products that reduce alcohol metabolism (eg, metronidazole), preparations containing alcohol or propylene glycol.

Gastrointestinal symptoms (nausea, vomiting, gaseaous symptoms, diarrhoea, abdominal discomfort and pain, dyspeptic symptoms, loose stools), rash, oral/perioral paraesthesia. Also, headache, sleep disorders, tremors, mood disorders, depressive disorders, fatigue, anorexia. Rarely, Stevens-Johnson syndrome.

GlaxoSmithKline(GSK)

(POM)

04 June 2009