Drugs List

Therapeutic Indications

Uses

HIV infection-combined with other antiretrovirals

Treatment of Human Immunodeficiency Virus (HIV-1) infection in combination with low dose ritonavir and other antiretroviral agents.

In moderately antiretroviral experienced adults, fosamprenavir in combination with low dose ritonavir has not been shown to be as effective as lopinavir with ritonavir. No comparative studies have been undertaken in children or adolescents.
In heavily pre-treated patients, fosamprenavir in combination with low dose ritonavir has not been studied sufficiently.
In protease inhibitor experienced patients, the choice of fosamprenavir should be based on individual viral resistance and treatment history.

Contraindications

Children under 6 years
Acute porphyria
Breastfeeding

Precautions and Warnings

Patients over 65 years
Diabetes mellitus
Haemophilia
Hepatic impairment
Hepatitis B
Hepatitis C
Pregnancy

Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
Some formulations contain hydroxybenzoate
Monitor blood glucose before treatment, after 3 to 6 months, then annually
Monitor serum lipids before treatment, after 3 to 6 months, then annually
Autoimmune disorders can occur many months after initiation of treatment
Evaluate for physical signs of fat redistribution
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Inflammatory symptoms should be evaluated and treated appropriately
May exacerbate diabetes mellitus
May precipitate diabetes mellitus
Risk of developing opportunistic infections
Discontinue if rash with systemic, allergic or mucosal symptoms occurs
Discontinue if severe skin reaction occurs
Advise patient not to take St John's wort concurrently
Female: Barrier or non-hormonal contraception advised during treatment
Advise haemophiliac patients of possibility of increased bleeding

Fosamprenavir must be administered in combination with other antiretroviral agents.

Fosamprenavir contains a sulfonamide moiety and should be used with caution in patients with a sulfonamide allergy.

Patients with chronic hepatitis B or C who are treated with combination antiretroviral therapy have an increased risk of developing severe and potentially fatal hepatic adverse effects, and therefore should be closely monitored during treatment. The product literature relating to concurrent treatments for hepatitis B or C should be consulted. If hepatic disease worsens in these patients, interruption or discontinuation of therapy should be considered. Patients with pre-existing hepatic impairment, including chronic active hepatitis, have an increased risk of developing hepatic function abnormalities during therapy. These patients should be closely monitored and treatment interruption or discontinuation should be considered if hepatic disease worsens in these patients.

Protease inhibitors have been associated with increased bleeding including spontaneous skin haematomas and haemarthroses in patients with haemophilia types A and B. In some patients the administration of factor VIII was required. Patients with haemophilia should be warned of an increased risk of bleeding.

The redistribution of body fat (lipodystrophy) has occurred in HIV patients receiving combination antiretroviral therapy. The long term consequences and mechanisms of this effect are unknown, but a connection between visceral lipomatosis and protease inhibitors and lipoatrophy and nucleoside reverse transcriptase inhibitors has been suggested. There is believed to be an increased risk of lipodystrophy in older patients, and with a longer treatment duration and associated metabolic disturbances. Clinical examinations should include evaluation for physical signs of fat redistribution.

When combination antiretroviral therapy is initiated in HIV-infected patients with severe immune deficiency, an inflammatory reaction to asymptomatic or residual opportunist pathogens may arise. This can lead to the aggravation of symptoms or other serious clinical conditions such as cytomegalovirus retinitis, mycobacterial infections or Pneumocystis carinii pneumonia. These reactions are usually observed within the first few weeks or months after treatment initiation. Any inflammatory symptoms should be evaluated and treated appropriately.

Cases of osteonecrosis have been reported in patients with advanced HIV disease and/or long term exposure to combination antiretroviral therapy. The aetiology of this condition is thought to be due to several factors including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index. Patients should be advised to seek medical advice if they experience joint aches or pains, joint stiffness or difficulty in movement.

Pregnancy and Lactation

Pregnancy

Use fosamprenavir with caution in pregnancy.

At the time of writing there is limited published experience concerning the use of fosamprenavir in pregnant women. In animal studies at systemic plasma exposures to amprenavir lower than therapeutic exposure in patients treated with fosamprenavir, some developmental toxicity was observed. The potential developmental toxicity of fosamprenavir has not been fully determined. The risk-benefit ratio to the mother and foetus should be considered when treatment with fosamprenavir is being considered and treatment should be based upon each individual. If indicated, protease inhibitors, including fosamprenavir should not be withheld in pregnancy because the expected benefit to the HIV positive mother outweighs the unknown risk to the foetus. Pregnant women taking protease inhibitors should be monitored for hyperglycaemia.

Combination therapy does not prevent vertical transmission of HIV to the newborn.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

HIV is known to be transmitted in milk. Therefore, HIV infected mothers should avoid breastfeeding in order to prevent transmission of the disease.

Fosamprenavir is contraindicated in breastfeeding.

It is not known if amprenavir is excreted in human breast milk however, the molecular weight is low enough that excretion should be expected.

Amprenavir-related material was found in rat milk. The offspring, who were exposed pre and post-natally to fosamprenavir, showed signs of developmental toxicity.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Anaemia
Anaphylaxis
Angioedema
Anorexia
Autoimmune disorders
Autoimmune hepatitis
Blood disorders
Creatine phosphokinase increased
Diabetes mellitus
Diarrhoea
Dizziness
Elevated serum lipase
Erythematous rash
Exacerbation of diabetes
Fatigue
Flatulence
Gastro-intestinal disturbances
Graves' disease
Headache
Hepatic impairment
Hypercholesterolaemia
Hyperglycaemia
Hyperlactataemia
Hypersensitivity reactions
Hypertriglyceridaemia
Immune Reactivation/Reconstitution Syndrome
Increase in serum ALT/AST
Increased spontaneous bleeding (haemophiliacs)
Insulin resistance
Ketoacidosis
Lipodystrophy
Maculopapular rash
Metabolic disorders
Myalgia
Myositis
Nausea
Neutropenia
Osteonecrosis
Pancreatitis
Paraesthesia
Pruritus
Rash
Rhabdomyolysis
Severe cutaneous skin eruptions
Sleep disturbances
Soft or liquid stools
Stevens-Johnson syndrome
Taste disturbances
Thrombocytopenia
Vomiting

Presentation

Oral formulations of fosamprenavir as fosamprenavir calcium

Drugs List

Therapeutic Indications

Uses

HIV infection-combined with other antiretrovirals

Treatment of Human Immunodeficiency Virus (HIV-1) infection in combination with low dose ritonavir and other antiretroviral agents.

In moderately antiretroviral experienced adults, fosamprenavir in combination with low dose ritonavir has not been shown to be as effective as lopinavir with ritonavir. No comparative studies have been undertaken in children or adolescents.
In heavily pre-treated patients, fosamprenavir in combination with low dose ritonavir has not been studied sufficiently.
In protease inhibitor experienced patients, the choice of fosamprenavir should be based on individual viral resistance and treatment history.

Dosage

Fosamprenavir must be given with low dose ritonavir (as a pharmacokinetic enhancer of amprenavir) and in combination with other antiretroviral medications.

Fosamprenavir is a pro-drug of amprenavir and must not be administered concurrently with any other amprenavir-containing product.

The importance of complying with the full recommended dosing regimen should be highlighted to all patients.

Adults

Elderly

Children

Patients with Hepatic Impairment

Contraindications

Children under 6 years
Acute porphyria
Breastfeeding

Precautions and Warnings

Patients over 65 years
Diabetes mellitus
Haemophilia
Hepatic impairment
Hepatitis B
Hepatitis C
Pregnancy

Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
Some formulations contain hydroxybenzoate
Monitor blood glucose before treatment, after 3 to 6 months, then annually
Monitor serum lipids before treatment, after 3 to 6 months, then annually
Autoimmune disorders can occur many months after initiation of treatment
Evaluate for physical signs of fat redistribution
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Inflammatory symptoms should be evaluated and treated appropriately
May exacerbate diabetes mellitus
May precipitate diabetes mellitus
Risk of developing opportunistic infections
Discontinue if rash with systemic, allergic or mucosal symptoms occurs
Discontinue if severe skin reaction occurs
Advise patient not to take St John's wort concurrently
Female: Barrier or non-hormonal contraception advised during treatment
Advise haemophiliac patients of possibility of increased bleeding

Fosamprenavir must be administered in combination with other antiretroviral agents.

Fosamprenavir contains a sulfonamide moiety and should be used with caution in patients with a sulfonamide allergy.

Patients with chronic hepatitis B or C who are treated with combination antiretroviral therapy have an increased risk of developing severe and potentially fatal hepatic adverse effects, and therefore should be closely monitored during treatment. The product literature relating to concurrent treatments for hepatitis B or C should be consulted. If hepatic disease worsens in these patients, interruption or discontinuation of therapy should be considered. Patients with pre-existing hepatic impairment, including chronic active hepatitis, have an increased risk of developing hepatic function abnormalities during therapy. These patients should be closely monitored and treatment interruption or discontinuation should be considered if hepatic disease worsens in these patients.

Protease inhibitors have been associated with increased bleeding including spontaneous skin haematomas and haemarthroses in patients with haemophilia types A and B. In some patients the administration of factor VIII was required. Patients with haemophilia should be warned of an increased risk of bleeding.

The redistribution of body fat (lipodystrophy) has occurred in HIV patients receiving combination antiretroviral therapy. The long term consequences and mechanisms of this effect are unknown, but a connection between visceral lipomatosis and protease inhibitors and lipoatrophy and nucleoside reverse transcriptase inhibitors has been suggested. There is believed to be an increased risk of lipodystrophy in older patients, and with a longer treatment duration and associated metabolic disturbances. Clinical examinations should include evaluation for physical signs of fat redistribution.

When combination antiretroviral therapy is initiated in HIV-infected patients with severe immune deficiency, an inflammatory reaction to asymptomatic or residual opportunist pathogens may arise. This can lead to the aggravation of symptoms or other serious clinical conditions such as cytomegalovirus retinitis, mycobacterial infections or Pneumocystis carinii pneumonia. These reactions are usually observed within the first few weeks or months after treatment initiation. Any inflammatory symptoms should be evaluated and treated appropriately.

Cases of osteonecrosis have been reported in patients with advanced HIV disease and/or long term exposure to combination antiretroviral therapy. The aetiology of this condition is thought to be due to several factors including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index. Patients should be advised to seek medical advice if they experience joint aches or pains, joint stiffness or difficulty in movement.

Pregnancy and Lactation

Pregnancy

Use fosamprenavir with caution in pregnancy.

At the time of writing there is limited published experience concerning the use of fosamprenavir in pregnant women. In animal studies at systemic plasma exposures to amprenavir lower than therapeutic exposure in patients treated with fosamprenavir, some developmental toxicity was observed. The potential developmental toxicity of fosamprenavir has not been fully determined. The risk-benefit ratio to the mother and foetus should be considered when treatment with fosamprenavir is being considered and treatment should be based upon each individual. If indicated, protease inhibitors, including fosamprenavir should not be withheld in pregnancy because the expected benefit to the HIV positive mother outweighs the unknown risk to the foetus. Pregnant women taking protease inhibitors should be monitored for hyperglycaemia.

Combination therapy does not prevent vertical transmission of HIV to the newborn.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

HIV is known to be transmitted in milk. Therefore, HIV infected mothers should avoid breastfeeding in order to prevent transmission of the disease.

Fosamprenavir is contraindicated in breastfeeding.

It is not known if amprenavir is excreted in human breast milk however, the molecular weight is low enough that excretion should be expected.

Amprenavir-related material was found in rat milk. The offspring, who were exposed pre and post-natally to fosamprenavir, showed signs of developmental toxicity.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Anaemia
Anaphylaxis
Angioedema
Anorexia
Autoimmune disorders
Autoimmune hepatitis
Blood disorders
Creatine phosphokinase increased
Diabetes mellitus
Diarrhoea
Dizziness
Elevated serum lipase
Erythematous rash
Exacerbation of diabetes
Fatigue
Flatulence
Gastro-intestinal disturbances
Graves' disease
Headache
Hepatic impairment
Hypercholesterolaemia
Hyperglycaemia
Hyperlactataemia
Hypersensitivity reactions
Hypertriglyceridaemia
Immune Reactivation/Reconstitution Syndrome
Increase in serum ALT/AST
Increased spontaneous bleeding (haemophiliacs)
Insulin resistance
Ketoacidosis
Lipodystrophy
Maculopapular rash
Metabolic disorders
Myalgia
Myositis
Nausea
Neutropenia
Osteonecrosis
Pancreatitis
Paraesthesia
Pruritus
Rash
Rhabdomyolysis
Severe cutaneous skin eruptions
Sleep disturbances
Soft or liquid stools
Stevens-Johnson syndrome
Taste disturbances
Thrombocytopenia
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: October 2014

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press Accessed on 8 October, 2014.

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications Accessed on 8 October, 2014.

Summary of Product Characteristics: Telzir 700mg film-coated tablets. ViiV Healthcare UK Ltd. Revised October 2018.
Summary of Product Characteristics: Telzir oral suspension. ViiV Healthcare UK Ltd. Revised October 2018.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Fosamprenavir. Last revised: 1 August, 2014
Last accessed: 8 October, 2014.