Fosamprenavir

Registered South African indications:

• HIV infection

Contraindications

• Known hypersensitivity to fosamprenavir, amprenavir, ritonavir, or any of the excipients of these medicines
• Patients with severe hepatic impairment
• Concomitant treatment with ketoconazole
• Fosamprenavir in combination with ritonavir must not be administered concurrently with medicines with narrow therapeutic windows that are substrates of cytochrome P450 3A4 (CYP 3A4)
  - Co-administration may result in elevated plasma concentrations, leading to serious and life-threatening adverse events such as cardiac dysrhythmia (e.g., cisapride, pimozide), hypotension (e.g., alfuzosin), prolonged sedation or respiratory depression (e.g., triazolam, midazolam, quetiapine), peripheral vasospasm or ischaemia (e.g., ergot derivatives), or rhabdomyolysis (e.g., lovastatin, simvastatin)
• Fosamprenavir/ritonavir must not be administered concomitantly with the antipsychotic medicinal product lurasidone (refer to the full prescribing information for ritonavir for other potential interactions)
• Fosamprenavir/ritonavir must not be administered concomitantly with sildenafil when used for the treatment of pulmonary arterial hypertension (for use of sildenafil in patients with erectile dysfunction, specific warnings apply)
• Fosamprenavir in combination with ritonavir should not be co-administered with medicines that are highly dependent on CYP2D6 metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening results. These medicinal products include flecainide and propafenone (refer to full prescribing information for ritonavir for further details)
• Fosamprenavir in combination with ritonavir must not be administered concurrently with rifampicin due to expected large decreases in plasma concentrations of amprenavir
• Herbal preparations containing St John’s Wort (Hypericum perforatum) must not be used while taking fosamprenavir in combination with ritonavir due to the risk of decreased plasma concentrations and reduced clinical effects of amprenavir
• The pharmacokinetics, safety, and efficacy of the fosamprenavir/ritonavir combination in children below 2 years of age have not yet been established

Cautions

• Pregnancy
• Breastfeeding
• Mild to moderate hepatic impairment
• Elderly
• Sulphonamide allergy
• Doses of ritonavir greater than 100mg, 12hrly
• Chronic hepatitis B or C
• Haemophilia
• Underlying infections
• Underlying autoimmune conditions
• Higher body mass index
• Severe immunosuppression

Forms avail. in SA and covered in this monograph: fct, sus

South African registered indications and dosages

Therapy should be initiated by a medical practitioner experienced in the management of HIV infection

Human Immunodeficiency Virus (HIV) infected patients for use in combination with other antiretroviral medicines
- In combination with low-dose ritonavir

Therapy naïve patients

• Oral (fct, sus): 1400mg, once daily with 200mg ritonavir, once daily OR 700mg, twice daily with 100mg ritonavir, twice daily

PI-experienced patients

• Oral (fct, sus): 700mg, twice daily with 100mg ritonavir, twice daily

Fosamprenavir is not recommended for use as monotherapy, due to the rapid emergence of resistant virus. All regimens must be administered in combination with other antiretroviral medicines. The importance of complying with the full recommended dosing regimen should be stressed to all patients

Do not exceed the recommended dose

Administration of film-coated tablets
Fosamprenavir tablets in combination with ritonavir can be taken with or without food. In addition to tablets, fosamprenavir is also available as an oral suspension for use in adults unable to swallow tablets
Administration of suspension
Fosamprenavir oral suspension in combination with ritonavir should be taken without food and on an empty stomach. Shake the bottle vigorously for 20 seconds before the first dose is removed. Shake the bottle before subsequent doses are removed. Do not mix with other medicines

Higher than approved dose combinations of fosamprenavir with ritonavir are not recommended for use. Once daily administration of fosamprenavir with ritonavir is not recommended in protease inhibitor (PI) experienced patients

Forms avail. in SA and covered in this monograph: fct, sus

South African registered indications and dosages

Therapy should be initiated by a medical practitioner experienced in the management of HIV infection

Human Immunodeficiency Virus (HIV) infected patients for use in combination with other antiretroviral medicines
- In combination with low-dose ritonavir

Younger than 2 years

• Not established for use

Older than 2 years

• Oral (sus)

The fosamprenavir oral suspension is the recommended formulation for the most accurate dosing in children based on body weight. The adult tablet regimens of fosamprenavir 700mg twice daily plus 100mg ritonavir twice daily (for protease inhibitor naïve or experienced patients) may be used in children and adolescents if they weigh at least 39kg and can swallow the tablets whole. Ritonavir 100mg capsules may be used in children and adolescents taking the fosamprenavir oral suspension if they weigh at least 33kg and can swallow the tablets whole

The oral suspension should be taken with food by children and adolescents. Shake the bottle before use
The tablet can be taken with or without food

Consult HIV/infectious disease specialists prior to any decisions related to ARV regimen termination/switch

Pregnancy

• Caution; not recommended

Breastfeeding

• Caution, not recommended

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Mild to moderate: Caution; dose adjustment recommended
• Severe: Contraindicated

Elderly

• Caution; no information available

Nervous system Disorders

• Headache
• Dizziness
• Fatigue
• Oral paraesthesia

Gastrointestinal Disorders

• Diarrhoea
• Loose stools
• Nausea and vomiting
• Abdominal pain

Endocrine and Metabolic Disorders

• Increased blood cholesterol
• Increased blood triglycerides
• Increased alanine aminotransferase 
• Increased aspartate aminotransferase
• Increased lipase

Skin and Subcutaneous Tissue Disorders

• Stevens Johnson syndrome
• Angioedema
• Rash 

• Cytochrome P450 3A4 (CYP 3A4) substrates
• Triazolam
• Midazolam
• Ergot derivatives
• Lurasidone
• Alcohol
• Corticosteroids
• Etravirine
• Lopinavir/ritonavir
• Raltegravir
• Dolutegravir
• Maraviroc
• Telaprevir
• Boceprevir
• Simeprevir
• Daclatasvir
• Paritaprevir
• Amiodarone
• Bepridil
• Quinidine
• Flecainide
• Propafenone
• Dihydroergotamine
• Ergotamine
• Ergonovine
• Methylergonovine
• Cisapride
• Astemizole
• Terfenadine
• Pimozide
• Quetiapine
• Clarithromycin
• Erythromycin
• Rifabutin
• Rifampicin
• Ketoconazole
• Itraconazole
• Phenytoin
• Phenobarbital
• Lidocaine
• Halofantrine
• Sildenafil
• Vardenafil
• Tadalafil
• Fluticasone propionate
• Alfuzosin
• St John's wort
• Lovastatin
• Simvastatin
• Atorvastatin
• Cyclosporin
• Rapamycin
• Tacrolimus
• Central nervous system depressants
• Oral anticoagulants
• Oral contraceptives
• Selective serotonin reuptake inhibitors

None routine. Specific cases may require

• Hepatic function
• Blood glucose 
• Serum lipids

The in vitro antiviral activity observed with fosamprenavir is due to the presence of trace amounts of amprenavir. Amprenavir is a competitive inhibitor of the HIV-1 protease. Amprenavir binds to the active site of HIV-1 protease and thereby prevents the processing of viral gag and gag-pol polyprotein precursors, resulting in the formation of immature non-infectious viral particles.

Tablet 700mg 

• Telzir (GSK) originator

Suspension (per ml) 50mg

• Telzir (GSK) originator