Fosamprenavir - Uses, Dose, Side effects, MOA, Brands

Fosamprenavir (Telzir, Lexiva) is a protease inhibitor that is used in combination with other antiretroviral drugs for the treatment of HIV-1 infection.

Fosamprenavir Uses:

Treatment of HIV-1 infection:
- It is used in the treatment of HIV-1 infection in combination with other antiretroviral agents

Fosamprenavir Dose in adults

Fosamprenavir Dose in the treatment of HIV-1 infection:

Antiretroviral therapy-naive patients: Oral:
- Unboosted regimen: 1,400 mg two times in a day(without ritonavir);
- Note: This regimen has inferior potency compared to other protease inhibitor-dependent regimens and the potential for cross-resistance to darunavir.
ritonavir-boosted regimens:
- Once in a day regimen: Fosamprenavir 1,400 mg one time in a day plus ritonavir 100 to 200 mg one time in a day.
- Two times in a day regimen: Fosamprenavir 700 two times in a day plus ritonavir 100 mg two times in a day.
Protease inhibitor (PI)-experienced patients:
- Fosamprenavir 700 mg twice in a day plus ritonavir 100 mg twice times in a day. Note: One time in a day administration is not required in protease inhibitor experienced patients.

Fosamprenavir Dose in Children

Fosamprenavir Dose in the treatment of HIV-1 infection: Use in combination with other antiretroviral agents:

Note:

The maximum dose should not exceed the adult dose.
One time in a day dosing of fosamprenavir is not required in pediatric patients; data from a pediatric once in a day dosing study of fosamprenavir plus ritonavir were insufficient to support one time in a day dosing in any pediatric patient population.
Protease inhibitor-naive patients:

Note: Fosamprenavir should not be used for starting therapy in pediatric patients.

Ritonavir unboosted regimen:
- Infants and Children <2 years:
  - It is not approved for use in children younger than 2 years of age and the appropriate dose is unknown
- Children ≥2 years and Adolescents:
  - AIDS info guidelines:
    - Restricted to use because of low systemic exposure.
  - Manufacturer's labeling:
    - Oral: 30 mg per kg per dose two times a day;
    - The maximum dose is 1,400 mg per dose
Ritonavir boosted regimen:
- Infants, Children, and Adolescents:
  - AIDSinfo guidelines:
    - Do not use in young children or in a newborn less than 6 months due to low systemic exposure.
  - Manufacturer's labeling:
    - Use only in infants born at 38 or more than 38 weeks GA and who are at least 28 days PNA: Oral:
    - <11 kg:
      - Fosamprenavir 45 mg per kg per dose plus ritonavir 7 mg per kg per dose twice in a day
    - 11 to <15 kg:
      - Fosamprenavir 30 mg per kg per dose plus ritonavir 3 mg per kg per dose two times a day.
    - 15 to <20 kg:
      - Fosamprenavir 23 mg per kg per dose plus ritonavir 3 mg per kg per dose two times in a day.
    - ≥20 kg:
      - Fosamprenavir 18 mg per kg per dose (maximum dose: 700 mg per dose) two times in a day plus ritonavir 3 mg per kg per dose (maximum dose: 100 mg per dose) two times in a day.

Note: When combined with ritonavir, fosamprenavir tablets may be administered to children who weigh ≥39 kg.

Protease inhibitor-experienced:
- Ritonavir boosted regimen:
  - Infants <6 months:
    - Not approved for use; appropriate dose is unknown
  - Infants ≥6 months, Children, and Adolescents:
    - <11 kg:
      - Fosamprenavir 45 mg per kg per dose plus ritonavir 7 per kg per dose twice in a day.
    - 11 to <15 kg:
      - Fosamprenavir 30 per kg per dose plus ritonavir 3 per kg per dose twice in a day.
    - 15 to <20 kg:
      - Fosamprenavir 23 per kg per dose plus ritonavir 3 per kg per dose twice in a day
    - ≥20 kg:
      - Fosamprenavir 18 per kg per dose (maximum dose: 700 mg/dose) twice daily plus ritonavir 3 per kg per dose two times in a day (maximum dose: 100 mg/dose) twice daily

Note: When combined with ritonavir, fosamprenavir tablets may be administered to children who weigh of 39 kg or more than 39 kg

Dosing adjustments for concomitant therapy:
- There are no pediatric-specific recommendations;
- Based on the experience in adult patients, may need to consider dosing adjustment with concomitant efavirenz or maraviroc.

Pregnancy Risk Category: C

Fosamprenavir is a drug that has a low transfer rate across the human placenta.
The data from the antiretroviral pregnancy registry do not provide sufficient information to assess human teratogenic risks.
Although maternal antiretroviral treatment (ART) may increase preterm birth rates, information is not available due to variability in maternal factors (disease severity and gestational age at the initiation of therapy).
Some studies have shown an increased risk of stillbirth and low birth weight in infants under gestational age. However, not all studies have confirmed this.
Maternal ART is a benefit that should be given. However, it shouldn't be delayed due to the potential for adverse neonatal outcomes.
All infants who have been exposed to antiretroviral medication should be followed up for a long time.
Children with significant organ system abnormalities (especially the heart or CNS) that are not of known etiology should be examined for possible mitochondrial dysfunction.
Protease inhibitors have been linked to hyperglycemia, diabetes mellitus onset, and diabetic ketoacidosis. It is unclear if this risk increases during pregnancy.
Health and Human Services (HHS), Perinatal HIV Guidelines, do not recommend fosamprenavir use in pregnancy.
Females who are pregnant with fosamprenavir must be switched to a recommended regimen.
If use is continued in pregnant females who are virologically suppressed on a stable fosamprenavir-containing regimen, fosamprenavir should only be given with standard ritonavir-boosted twice-daily dosing and close monitoring of viral load (lower exposure has been observed during pregnancy).
It is not recommended to take unboosted fosamprenavir or once daily doses with ritonavir.
All pregnant women with HIV must receive ART to reduce their viral load and prevent perinatal transmission.
Monitoring during pregnancy is more common than monitoring in adults who are not pregnant.
All females with HIV should continue ART postpartum and be able to be modified after delivery.
Health care providers are encouraged to enter pregnant females exposed to antiretroviral medications immediately in pregnancy as possible in the Antiretroviral Pregnancy Registry (http://www.APRegistry.com).

Fosamprenavir use during breastfeeding:

Fosamprenavir may be present in breast milk, but it is unknown.
Postnatal HIV transmission is not completely eliminated by infant or maternal antiretroviral treatment.
Additionally, multiclass-resistant virus was also detected in breastfed infants despite maternal therapy.
In the US, where the price of the formula is affordable, safe and accessible and there is low risk of infant death due to diarrhea or respiratory infections, pregnant women with HIV should stop breastfeeding in order to reduce the possibility of HIV transmission.

Dose in Kidney Disease:

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, dosage adjustment unlikely due to minimal (eg, 1 percent) renal elimination of unchanged amprenavir.

Dose in Liver disease:

Mild impairment (Child-Pugh class A):
- Reduce dosage of fosamprenavir to 700 mg twice daily without concurrent ritonavir (therapy-naive) or
- fosamprenavir 700 mg twice daily plus ritonavir 100 mg once daily (therapy-naive or PI experienced).
Moderate impairment (Child-Pugh class B):
- Reduce dosage of fosamprenavir to 700 mg twice daily without concurrent ritonavir (therapy-naive) or
- fosamprenavir 450 mg twice daily plus ritonavir 100 mg once daily (therapy-naive or PI experienced).
Severe impairment (Child-Pugh class C):
- Reduce dosage of fosamprenavir to 350 mg twice daily without concurrent ritonavir (therapy-naive) or
- fosamprenavir 300 mg twice daily plus ritonavir 100 mg once daily (therapy-naive or PI experienced).

Common Side Effects of Fosamprenavir:

Dermatologic:
- Skin Rash
Endocrine & Metabolic:
- Hypertriglyceridemia
Gastrointestinal:
- Diarrhea

Less Common Side Effects Of Fosamprenavir:

Central Nervous System:
- Fatigue
- Headache
Dermatologic:
- Pruritus
Endocrine & Metabolic:
- Hyperglycemia
Gastrointestinal:
- Increased Serum Lipase
- Nausea
- Vomiting
- Abdominal Pain
Hematologic & Oncologic:
- Neutropenia
Hepatic:
- Increased Serum Transaminases

Contraindications to Fosamprenavir:

Clinically significant hypersensitivity, such as Stevens-Johnson syndrome to fosamprenavir or amprenavir or any component of formulation
Coadministration of drugs that are highly dependent upon CYP3A4 to clear and for which high plasma concentrations are associated w/ serious and potentially life-threatening events (eg rifampin and alfuzosin; methylergonovine, dihydroergotamine and ergonovine);
Use of lurasidone, flecainide, or propafenone with concomitant ritonavir therapy.

Canadian labeling: Additional contraindications not in US labeling

Coadministration with antihistamines, diazepam, flurazepam, lidocaine GI motility agents, amiodarone (systemic), and quetiapine.

Warnings and precautions

Increased body fat
- It could lead to an increase in body weight.
Hemolytic anemia
- Amprenavir has been associated with acute hemolytic anemia.
Hepatic effects
- Transaminase elevations, Hepatitis and/or Exacerbation of pre-existing hepatic dysfunction may occur.
- Patients with underlying liver disease such as cirrhosis or hepatitis B, C should be cautious.
Hypersensitivity reactions
- A variety of hypersensitivity reactions have been linked to protease inhibitors, including anaphylaxis (rare), angioedema (rare), bronchospasm and erythema multife (rare).
- If severe rash occurs or you have other symptoms, it is best to stop taking the medication.
Immune reconstitution syndrome:
- The immune reconstitution syndrome can occur in patients with HIV.
- This could lead to an inflammatory response to an indolent, residual opportunistic HIV infection, activation of autoimmune disorders (eg polymysitis, Guillain Barre syndrome,Graves disease) or a recurrence of the condition after treatment.
- Additional evaluation and treatment may also be required.
Elevations of the lipids
- There have been reports of an increase in total cholesterol and triglycerides.
- Screening should take place prior to treatment and every so often throughout the course of treatment.
Nephrolithiasis
- Postmarketing surveillance has been used to report cases.
- If symptoms persist, it is worth considering temporary or permanent discontinuation therapy.
Allergy to sulfonamide
- Patients with sulfonamide allergy should be cautious.
- Clinical trials showed that rash incidence did not differ between patients who had sulfonamide allergies and those without.
Diabetes:
- Patients who have received protease inhibitors have reported changes in glucose tolerance, hyperglycemia and exacerbation or diabetes.
Hemophilia A and B:
- Patients with hemophilia A and B should be cautious.
- Reports have indicated an increase in bleeding after receiving protease inhibitor therapy.
Hepatic impairment
- Take care.
- Adjustment of dosage is required.

Fosamprenavir: Drug Interaction

Risk Factor C (Monitor therapy)
Abacavir	Protease Inhibitors may decrease the serum concentration of Abacavir.
Abemaciclib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Abemaciclib.
Amiodarone	Fosamprenavir may increase the serum concentration of Amiodarone.
AmLODIPine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of AmLODIPine.
Antidiabetic Agents	Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Apixaban	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Apixaban.
ARIPiprazole	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations.
Benzhydrocodone	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased.
Blonanserin	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin.
Brexpiprazole	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer.
Cannabidiol	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabidiol.
Cannabis	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased.
Clorazepate	Fosamprenavir may increase the serum concentration of Clorazepate.
Codeine	CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Codeine.
Cyclophosphamide	Protease Inhibitors may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, the incidences of neutropenia, infection, and mucositis may be increased.
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
CYP3A4 Substrates (High risk with Inhibitors)	CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Exceptions: Alitretinoin (Systemic); Praziquantel; Trabectedin; Vinorelbine.
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Dexamethasone (Systemic)	May decrease the serum concentration of Fosamprenavir. Fosamprenavir may increase the serum concentration of Dexamethasone (Systemic).
DiazePAM	Fosamprenavir may increase the serum concentration of DiazePAM.
Dofetilide	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dofetilide.
Dronabinol	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol.
Enfuvirtide	Protease Inhibitors may increase the serum concentration of Enfuvirtide. Enfuvirtide may increase the serum concentration of Protease Inhibitors.
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Estrogen Derivatives	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Estrogen Derivatives.
Flurazepam	Fosamprenavir may increase the serum concentration of Flurazepam.
Fosphenytoin	May increase the serum concentration of Fosamprenavir. Fosamprenavir may decrease the serum concentration of Fosphenytoin.
Halofantrine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Halofantrine. Management: Extreme caution, with possibly increased monitoring of ECGs, should be used if halofantrine is combined with moderate CYP3A4 inhibitors. Drugs listed as exceptions to this monograph are discussed in separate drug interaction monographs.
Histamine H2 Receptor Antagonists	May decrease the serum concentration of Fosamprenavir. Cimetidine may also inhibit the metabolism of the active metabolite amprenavir, making its effects on fosamprenavir/amprenavir concentrations difficult to predict.
HYDROcodone	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of HYDROcodone.
Ifosfamide	CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide.
Imatinib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Imatinib.
Levomethadone	Fosamprenavir may decrease the serum concentration of Levomethadone.
Manidipine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Manidipine.
Methadone	May decrease serum concentrations of the active metabolite(s) of Fosamprenavir. Specifically, amprenavir concentrations may be reduced. This effect has been demonstrated with Amprenavir alone but not with Fosamprenavir / Ritonavir. The potential impact on Fosamprenavir alone has not been investigated. Fosamprenavir may decrease the serum concentration of Methadone.
Mirodenafil	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil.
Naldemedine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naldemedine.
Nalfurafine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nalfurafine.
NiMODipine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NiMODipine.
Orlistat	May decrease the serum concentration of Antiretroviral Agents.
OxyCODONE	CYP3A4 Inhibitors (Moderate) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased.
PARoxetine	Fosamprenavir may decrease the serum concentration of PARoxetine. The active metabolite amprenavir is likely responsible for this effect.
P-glycoprotein/ABCB1 Inhibitors	May increase the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of pglycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.).
Phenytoin	Fosamprenavir may decrease the serum concentration of Phenytoin. The active amprenavir metabolite is likely responsible for this effect. Phenytoin may increase the serum concentration of Fosamprenavir. Specifically, phenytoin may increase the concentration of the active metabolite amprenavir.
Pimecrolimus	CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus.
Posaconazole	May increase serum concentrations of the active metabolite(s) of Fosamprenavir. Fosamprenavir may decrease the serum concentration of Posaconazole.
QuiNIDine	Fosamprenavir may increase the serum concentration of QuiNIDine.
Rupatadine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rupatadine.
Ruxolitinib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ruxolitinib.
Salmeterol	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol.
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
SAXagliptin	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SAXagliptin.
Silodosin	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Silodosin.
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Tacrolimus (Topical)	Protease Inhibitors may decrease the metabolism of Tacrolimus (Topical).
Tamsulosin	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin.
Telithromycin	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Telithromycin.
Tetrahydrocannabinol	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol.
Ticagrelor	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Trabectedin	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin.
Tricyclic Antidepressants	Protease Inhibitors may increase the serum concentration of Tricyclic Antidepressants.
Udenafil	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Udenafil.
Valproate Products	Protease Inhibitors may decrease the serum concentration of Valproate Products.
Vilazodone	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone.
Vindesine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine.
Voriconazole	May increase serum concentrations of the active metabolite(s) of Fosamprenavir. Specifically, amprenavir concentrations may be increased. Fosamprenavir may increase the serum concentration of Voriconazole.
Warfarin	Fosamprenavir may increase the serum concentration of Warfarin.
Zidovudine	Protease Inhibitors may decrease the serum concentration of Zidovudine.
Zuclopenthixol	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol.
Risk Factor D (Consider therapy modification)
Acalabrutinib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use.
AtorvaSTATin	Protease Inhibitors may increase the serum concentration of AtorvaSTATin. Management: See full monograph for recommended dose limits. Avoid atorvastatin with tipranavir/ritonavir.
Avanafil	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil. Management: The maximum avanafil adult dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects.
Bosentan	May decrease the serum concentration of Fosamprenavir. Fosamprenavir may increase the serum concentration of Bosentan. Management: Use bosentan 62.5 mg/day or every other day in adult patients taking fosamprenavir for at least 10 days. Temporarily stop bosentan (for at least 36 hrs) before starting fosamprenavir; wait at least 10 days before restarting bosentan.
Brigatinib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inhibitors when possible. If such a combination cannot be avoided, reduce the dose of brigatinib by approximately 40% (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg).
Budesonide (Topical)	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased.
Calcium Channel Blockers (Nondihydropyridine)	Protease Inhibitors may decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Increased serum concentrations of the calcium channel blocker may increase risk of AV nodal blockade. Management: Avoid concurrent use when possible. If used, monitor for CCB toxicity. The manufacturer of atazanavir recommends a 50% dose reduction for diltiazem be considered. Saquinavir, tipranavir, and darunavir/cobicistat use with bepridil is contraindicated.
CarBAMazepine	May increase the metabolism of Protease Inhibitors. Protease Inhibitors may decrease the metabolism of CarBAMazepine.
Cilostazol	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving moderate inhibitors of CYP3A4.
Clarithromycin	Protease Inhibitors may diminish the therapeutic effect of Clarithromycin. Specifically, certain protease inhibitors may decrease formation of the active 14-hydroxyclarithromycin metabolite, which may negatively impact clarithromycin effectiveness vs. H. influenzae and other non-MAC infections. Protease Inhibitors may increase the serum concentration of Clarithromycin. Clarithromycin dose adjustment in renally impaired patients may be needed. Clarithromycin may increase the serum concentration of Protease Inhibitors. Management: Saquinavir is contraindicated with clarithromycin. Avoid clarithromycin adult doses over 1000 mg/day with a protease inhibitor. Further dose reductions may be needed with impaired renal function. Consider alternative antimicrobial for a non-MAC infection.
Colchicine	Fosamprenavir may increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are receiving ritonavir-boosted fosamprenavir. In those with normal renal and hepatic function, reduce colchicine dose as directed.
CycloSPORINE (Systemic)	Protease Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Protease Inhibitors.
CYP3A4 Inducers (Strong)	May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
Dabrafenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
Dapoxetine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4.
Deflazacort	CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor.
Dolutegravir	Fosamprenavir may decrease the serum concentration of Dolutegravir. Specifically, Fosamprenavir/Ritonavir may decrease the serum concentration of Dolutegravir. The individual contributions of Fosamprenavir and Ritonavir to this effect are unknown. Management: Increase dolutegravir to 50 mg twice daily in adults and pediatric patients (12 yrs or older and at least 40 kg). Seek alternatives to fosamprenavir/ritonavir in INSTI-experienced patients with suspected or certain INSTI resistance.
DOXOrubicin (Conventional)	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided.
Efavirenz	May decrease serum concentrations of the active metabolite(s) of Fosamprenavir. Management: For once-daily fosamprenavir/ritonavir with efavirenz, an increased ritonavir dose to 300 mg/day is recommended in adult patients. No ritonavir dose adjustment is required if using twice-daily fosamprenavir/ritonavir.
Eletriptan	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eletriptan. Management: The use of eletriptan within 72 hours of a moderate CYP3A4 inhibitor should be avoided.
Eliglustat	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details.
Encorafenib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Encorafenib. Management: Avoid concomitant use of encorafenib and moderate CYP3A4 inhibitors whenever possible. If concomitant administration is unavoidable, decrease the encorafenib dose to one-half of the encorafenib dose used prior to initiation of the CYP3A4 inhibitor.
Enzalutamide	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring.
Eplerenone	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: When used concomitantly with moderate inhibitors of CYP3A4, eplerenone dosing recommendations vary by indication and international labeling. See full drug interaction monograph for details.
Estrogen Derivatives (Contraceptive)	Protease Inhibitors may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Use oral contraceptives containing at least 35mcg ethinyl estradiol with atazanavir/ritonavir, or no more than 30mcg in patients receiving atazanavir alone. Use of an alternative, non-hormonal contraceptive is recommended with other protease inhibitors.
Everolimus	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for most indications. See full monograph or prescribing information for specific dose adjustment and monitoring recommendations.
FentaNYL	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Monitor patients closely for several days following initiation of this combination, and adjust fentanyl dose as necessary.
Garlic	May decrease the serum concentration of Protease Inhibitors. Management: Concurrent use of garlic supplements with protease inhibitors is not recommended. If this combination is used, monitor closely for altered serum concentrations/effects of protease inhibitors, and particularly for signs/symptoms of therapeutic failure.
GuanFACINE	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination.
Ibrutinib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib. Management: When treating B-cell malignancies, decrease ibrutinib to 280 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions.
Itraconazole	May increase serum concentrations of the active metabolite(s) of Fosamprenavir. Specifically, amprenavir concentrations may be increased. Fosamprenavir may increase the serum concentration of Itraconazole. Management: Limit the adult maximum itraconazole dose to 200 mg/day with fosamprenavir/ritonavir. In patients receiving fosamprenavir without ritonavir, patients receiving greater than 400 mg/day itraconazole may also require dose reduction.
Ivacaftor	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult full monograph content for specific age- and weight-based recommendations. No dose adjustment is needed when using ivacaftor/lumacaftor with a moderate CYP3A4 inhibitor.
Ivosidenib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivosidenib. Management: Avoid use of moderate CYP3A4 inhibitors with ivosidenib whenever possible. If combined, monitor for increased ivosidenib toxicities. Drugs listed as exceptions are discussed in further detail in separate drug interaction monographs.
Ketoconazole (Systemic)	May increase serum concentrations of the active metabolite(s) of Fosamprenavir. Specifically, amprenavir concentrations may be increased. Fosamprenavir may increase the serum concentration of Ketoconazole (Systemic). Management: Limit the adult maximum ketoconazole dose to 200 mg/day with fosamprenavir/ritonavir. In patients receiving fosamprenavir without ritonavir, patients receiving greater than 400 mg/day ketoconazole may also require dose reduction.
Lorlatinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.
Lurasidone	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: Lurasidone US labeling recommends reducing lurasidone dose by half with a moderate CYP3A4 inhibitor. Some non-US labeling recommends initiating lurasidone at 20 mg/day and limiting dose to 40 mg/day; avoid concurrent use of grapefruit products.
Meperidine	Protease Inhibitors may enhance the adverse/toxic effect of Meperidine. Protease Inhibitors may decrease the serum concentration of Meperidine. Concentrations of the toxic Normeperidine metabolite may be increased.
MiFEPRIStone	Fosamprenavir may increase the serum concentration of MiFEPRIStone. Management: Limit mifepristone adult dose, when used for treatment of hyperglycemia in Cushing's syndrome, to a maximum of 600 mg/day when combined with fosamprenavir. Monitor for increased mifepristone toxicity regardless of dose or indication.
Mitotane	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane.
Nefazodone	Protease Inhibitors may increase the serum concentration of Nefazodone. Management: Consider alternatives to, or reduced doses of, nefazodone in patients treated with HIV protease inhibitors. Monitor patients receiving these combinations closely for toxic effects of nefazodone.
Nevirapine	May decrease serum concentrations of the active metabolite(s) of Fosamprenavir. Management: Coadministration of nevirapine and fosamprenavir is not recommended without concurrent ritonavir. However, when nevirapine and fosamprenavir/ritonavir (twice daily) are used in combination, no dose adjustment is required.
Olaparib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors in patients being treated with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 150 mg twice daily.
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir	May increase serum concentrations of the active metabolite(s) of Fosamprenavir. Fosamprenavir may increase the serum concentration of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir. Management: Use of ritonavir-boosted fosamprenavir with ombitasvir/paritaprevir/ritonavir/dasabuvir is not recommended. Consider a reduced dose of fosamprenavir 1400 mg once daily (unboosted) when used with ombitasvir/paritaprevir/ritonavir/dasabuvir.
Pitolisant	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant.
Progestins (Contraceptive)	May decrease serum concentrations of the active metabolite(s) of Fosamprenavir. Fosamprenavir may decrease the serum concentration of Progestins (Contraceptive). Management: Consider using an alternative or additional means of contraception. Injected depot medroxyprogesterone acetate may be used without a need for additional contraception.
Protease Inhibitors	May increase the serum concentration of other Protease Inhibitors. Management: Atazanavir--indinavir combination contraindicated. Tipranavir/ritonavir or atazanavir/ritonavir not recommended with other protease inhibitors (PI). Darunavir/cobicistat not recommended with PI that require boosting.Other combos may require dose changes.
Raltegravir	Fosamprenavir may decrease the serum concentration of Raltegravir. Raltegravir may decrease the serum concentration of Fosamprenavir.
Ranolazine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine adult dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin, etc.).
Rifabutin	Fosamprenavir may increase serum concentrations of the active metabolite(s) of Rifabutin. Rifabutin may increase the serum concentration of Fosamprenavir. Fosamprenavir may increase the serum concentration of Rifabutin. Management: Reduce rifabutin doses. See full monograph for specific recommendations.
Riociguat	Protease Inhibitors may increase the serum concentration of Riociguat. Management: Consider starting with a reduced riociguat dose of 0.5 mg three times a day (for adults). Patients receiving such a combination should also be monitored extra closely for signs or symptoms of hypotension.
Rosuvastatin	Protease Inhibitors may increase the serum concentration of Rosuvastatin. Management: Start at the lowest rosuvastatin dose and monitor for toxicity. See full drug interaction monograph for details.
Sildenafil	Protease Inhibitors may increase the serum concentration of Sildenafil. Management: Erectile dysfunction: sildenafil max = 25 mg/48 hrs with ritonavir, atazanavir, or darunavir; starting dose = 25 mg with other protease inhibitors (adult doses). Contraindicated if sildenafil being used for pulmonary arterial hypertension.
Sirolimus	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sirolimus. Management: Monitor for increased serum concentrations of sirolimus if combined with a moderate CYP3A4 inhibitor. Lower initial sirolimus doses or sirolimus dose reductions will likely be required.
Sonidegib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions).
Suvorexant	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy.
Tacrolimus (Systemic)	Protease Inhibitors may decrease the metabolism of Tacrolimus (Systemic).
Temsirolimus	Protease Inhibitors may enhance the adverse/toxic effect of Temsirolimus. Levels of sirolimus, the active metabolite, may be increased, likely due to inhibition of CYP-mediated metabolism.
Tezacaftor	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tezacaftor. Management: When combined with moderate CYP3A4 inhibitors, tezacaftor/ivacaftor (100 mg/150 mg) should be given in the morning, every other day. Ivacaftor (150 mg) alone should be given in the morning, every other day on alternate days from tezacaftor/ivacaftor.
Tolvaptan	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Management: Jynarque dose requires adjustment when used with a moderate CYP3A4 inhibitor. See labeling or full interaction monograph for specific recommendations. Use of Samsca with moderate CYP3A4 ihibitors should generally be avoided.
TraZODone	Fosamprenavir may increase the serum concentration of TraZODone. Management: Consider using a lower dose of trazodone when used in combination with fosamprenavir.
Venetoclax	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations.
Zopiclone	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone. Management: The starting adult dose of zopiclone should not exceed 3.75 mg if combined with a moderate CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined.
Risk Factor X (Avoid combination)
Alfuzosin	Protease Inhibitors may increase the serum concentration of Alfuzosin.
Aprepitant	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Aprepitant.
Asunaprevir	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Asunaprevir.
Bosutinib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib.
Budesonide (Systemic)	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic).
Cisapride	Protease Inhibitors may increase the serum concentration of Cisapride. This may result in QTc prolongation and malignant cardiac arrhythmias. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Cobicistat	May increase the serum concentration of Fosamprenavir. However, the magnitude of this change is unclear, and dosing recommendations for this combination are not available.
Cobimetinib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cobimetinib. Management: Avoid the concomitant use of cobimetinib and moderate CYP3A4 inhibitors. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose to 20 mg daily.
Delavirdine	Fosamprenavir may decrease the serum concentration of Delavirdine. The active metabolite amprenavir is likely responsible for this effect. Delavirdine may increase the serum concentration of Fosamprenavir. Specifically, delavirdine may increase concentrations of the active metabolite amprenavir.
Domperidone	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Domperidone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Ergot Derivatives	Protease Inhibitors may increase the serum concentration of Ergot Derivatives. Exceptions: Cabergoline; Nicergoline; Pergolide.
Etravirine	May increase serum concentrations of the active metabolite(s) of Fosamprenavir. Specifically, amprenavir concentrations may increase.
Flecainide	Fosamprenavir may increase the serum concentration of Flecainide. Management: Concurrent use of ritonavir-boosted fosamprenavir with flecainide is contraindicated. The use of non-ritonavir-boosted fosamprenavir with flecainide is not specifically contraindicated but should only be undertaken with caution.
Flibanserin	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin.
Fosaprepitant	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosaprepitant.
Ivabradine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine.
Lomitapide	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide.
Lopinavir	Fosamprenavir may decrease the serum concentration of Lopinavir. Specifically, amprenavir (the active metabolite of fosamprenavir) may decrease the serum concentration of lopinavir. Lopinavir may decrease the serum concentration of Fosamprenavir. Specifically, lopinavir/ritonavir may decrease the serum concentration of amprenavir (the active metabolite of fosamprenavir)
Lovastatin	Protease Inhibitors may increase the serum concentration of Lovastatin.
Midazolam	Protease Inhibitors may increase the serum concentration of Midazolam. Management: Oral midazolam contraindicated with all protease inhibitors. IV midazolam contraindicated with fosamprenavir and nelfinavir; other protease inhibitors recommend caution, close monitoring, and consideration of lower IV midazolam doses with concurrent use.
Naloxegol	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol.
Neratinib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Neratinib.
Pimozide	Protease Inhibitors may increase the serum concentration of Pimozide.
Pimozide	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimozide.
Propafenone	Fosamprenavir may increase the serum concentration of Propafenone. Management: Concurrent use of ritonavir-boosted fosamprenavir with propafenone is contraindicated. The use of non-ritonavir-boosted fosamprenavir with propafenone is not specifically contraindicated but should only be undertaken with caution.
RifAMPin	May decrease the serum concentration of Fosamprenavir. Specifically, concentrations of amprenavir (active metabolite) may be decreased.
Simeprevir	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
Simeprevir	Protease Inhibitors may increase the serum concentration of Simeprevir. Simeprevir may increase the serum concentration of Protease Inhibitors.
Simvastatin	Protease Inhibitors may increase the serum concentration of Simvastatin.
St John's Wort	May increase the metabolism of Protease Inhibitors.
Tipranavir	May decrease the serum concentration of Protease Inhibitors.
Ulipristal	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combination should be monitored for ulipristal toxicity.

Monitoring parameters:

Prior to initiation and periodically during therapy,
Monitor viral load, CD4 count,
Glucose;
Triglycerides and cholesterol;
Liver function tests in patients with underlying hepatitis B or C.

How to administer Fosamprenavir?

Oral suspension:

Administer without food.
Readminister dose of suspension if emesis occurs within half an hour after dosing.
Shake suspension vigorously prior to use.

Tablet:

Administer with food if taken with ritonavir.
May be considered without regard to food if not taken with ritonavir.

Mechanism of action of Fosamprenavir:

Cellular phosphatases in vivo convert fosamprenavir quickly and almost entirely to amprenavir.
Amprenavir binds at the HIV-1 protease activity site and inhibits cleavage viral GagPol polyprotein precursors into functional proteins necessary for HIV infection.
This causes the formation of non-infectious, immature viral particles.

Absorption:

63 percent

Protein-binding:

About 90 percent (to alpha -acid glycoprotein);
Decreased in hepatic impairment

Metabolism:

Fosamprenavir is rapidly and almost completely converted to amprenavir by cellular phosphatases in gut epithelium;
amprenavir is hepatically metabolized via CYP isoenzymes (primarily CYP3A4);
glucuronide conjugation of oxidized metabolites also occurs

Bioavailability:

Not established;
food does not have a significant effect on absorption of tablets.
Administration of oral suspension with food reduced maximal drug concentration (C ) by 46 percent and area under the curve (AUC) by 28 percent .

Half-life elimination:

About 7.7 hours (amprenavir)

Time to peak plasma concentration:

1.5 to 4 hours (median: 2.5 hours)

Excretion:

Minimal excretion of unchanged drug in urine (1 percent ) and feces;
75 percent of the dose excreted as metabolites via the biliary tract into feces and 14 percent excreted as metabolites in urine

International Brand Names of Fosamprenavir:

Lexiva
Telzir

Fosamprenavir Brand Names in Pakistan:

There is no brand available in Pakistan.

Fosamprenavir - Uses, Dose, Side effects, MOA, Brands

Fosamprenavir Uses:

Treatment of HIV-1 infection:

Fosamprenavir Dose in adults

Fosamprenavir Dose in the treatment of HIV-1 infection:

Antiretroviral therapy-naive patients: Oral:

ritonavir-boosted regimens:

Protease inhibitor (PI)-experienced patients:

Fosamprenavir Dose in Children

Fosamprenavir Dose in the treatment of HIV-1 infection: Use in combination with other antiretroviral agents:

Protease inhibitor-naive patients:

Protease inhibitor-experienced:

Dosing adjustments for concomitant therapy:

Pregnancy Risk Category: C

Fosamprenavir use during breastfeeding:

Dose in Kidney Disease:

Dose in Liver disease:

Mild impairment (Child-Pugh class A):

Moderate impairment (Child-Pugh class B):

Severe impairment (Child-Pugh class C):

Common Side Effects of Fosamprenavir:

Dermatologic:

Endocrine & Metabolic:

Gastrointestinal:

Less Common Side Effects Of Fosamprenavir:

Central Nervous System:

Dermatologic:

Endocrine & Metabolic:

Gastrointestinal:

Hematologic & Oncologic:

Hepatic:

Contraindications to Fosamprenavir:

Warnings and precautions

Increased body fat

Hemolytic anemia

Hepatic effects

Hypersensitivity reactions

Immune reconstitution syndrome:

Elevations of the lipids

Nephrolithiasis

Allergy to sulfonamide

Diabetes:

Hemophilia A and B:

Hepatic impairment

Monitoring parameters:

How to administer Fosamprenavir?

Mechanism of action of Fosamprenavir:

International Brand Names of Fosamprenavir:

Fosamprenavir Brand Names in Pakistan:

Recent Posts

Related Posts