GP120 attachment inhibitors
Human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced patients with multidrug-resistant HIV-1 infection who have failed their current antiretroviral regimen due to resistance, intolerance, or safety considerations (in combination with other antiretroviral agents).
Fostemsavir is a prodrug that is hydrolyzed to the active form, temsavir. Temsavir binds directly to the gp120 subunit within the HIV-1 envelope glycoprotein gp160 and selectively prevents attachment of the virus to the CD4 receptors on cells.
Reduction in viral load.
Absorption: 27% of temsavir absorbed following oral administration; absorption ↑ with high-fat meal.
Distribution: Moderately distributed to extravascular tissues.
Metabolism and Excretion: Fostemsavir is a prodrug that is hydrolyzed to the active form, temsavir. Temsavir undergoes metabolism to inactive metabolites through the liver via hydrolysis and oxidation (via the CYP3A4 isoenzyme). Primarily excreted in urine (51%, <2% as unchanged drug), with 33% excreted in feces (1% as unchanged drug).
Half-life: 11 hr.
TIME/ACTION PROFILE (plasma concentrations)
|PO||Rapid||2 hr||12 hr|
- Concurrent use of carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, and St. John's wort.
- Lactation: Breastfeeding not recommended for HIV-infected patients.
Use Cautiously in:
- History of QTc prolongation or cardiovascular disease
- Hepatitis B and/or C coinfection (↑ risk of liver enzyme elevation)
- OB: Safety not established in pregnancy;
- Pedi: Safety and effectiveness not established in children;
- Geri: May be at ↑ risk of QT interval prolongation.
Adverse Reactions/Side Effects
CV: QT interval prolongation
Endo: Graves' disease, hyperglycemia
GI: nausea, abdominal pain, autoimmune hepatitis, diarrhea, dyspepsia, hyperbilirubinemia, ↑ lipase, ↑ liver enzymes, vomiting
GU: ↑ serum creatinine
Hemat: anemia, neutropenia
Metabolic: hypercholesterolemia, hyperuricemia
MS: ↑ creatine kinase, polymyositis
Neuro: Guillain-Barré syndrome, headache, insomnia, sedation
Misc: fatigue, immune reconstitution syndrome
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Strong CYP3A4 inducers, including carbamazepine, enzalutamide, mitotane, phenytoin, and rifampin may ↓ levels and lead to loss of virologic response; concurrent use contraindicated.
- QT interval prolonging medications may ↑ risk of QT interval prolongation.
- May ↑ levels and risk of toxicity of grazoprevir or voxilaprevir ; use alternative regimen for hepatitis C, if possible.
- May ↑ levels and risk of toxicity of oral contraceptives containing ethinyl estradiol ; do not exceed ethinyl estradiol dose of 30 mcg/day.
- May ↑ levels and risk of toxicity of atorvastatin, fluvastatin, pitavastatin, rosuvastatin, or simvastatin ; use lowest possible statin dose.
St. John's wort may ↓ levels and lead to loss of virologic response; concurrent use contraindicated.
PO (Adults): 600 mg twice daily.
Extended-release tablets: 600 mg
- Assess for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
Lab Test Considerations:
Monitor viral load and CD4 cell count regularly during therapy.
- Monitor liver function tests before and periodically during therapy, especially in patients with hepatitis B and/or C co-infection. May cause ↑ AST and ALT.
- Administer twice daily without regard to food. DNC: Swallow tablets whole; do not crush, chew, or split.
- Emphasize the importance of taking fostemsavir as directed, at the same time each day. Do not take more than prescribed amount and do not stop taking without consulting health care professional. Take missed doses as soon as remembered; do not double doses. Missed doses may result in development of resistance. Advise patient to read Patient Information prior to starting therapy and with each Rx refill in case of changes.
- Inform patient that Rukobia tablets may have a slight vinegar-like odor.
- Instruct patient that fostemsavir should not be shared with others.
- Inform patient that fostemsavir does not cure AIDS or prevent associated or opportunistic infections. Fostemsavir may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and to avoid sharing needles or donating blood to prevent spreading the AIDS virus to others.
- Immune reconstitution syndrome may trigger opportunistic infections or autoimmune disorders. Notify health care professional if symptoms (signs and symptoms of an infection or inflammation) occur.
- May cause changes in ECG (QT prolongation). Advise patient to notify health care professional if dizziness, lightheadedness, abnormal heart rhythm, or loss of consciousness occur.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's Wort.
- Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breast feeding. Encourage women who become pregnant during fostemsavir therapy to join the Antiviral Pregnancy Registry that monitors pregnancy outcomes in women exposed to antiretrovirals during pregnancy. Enroll patient by calling 1-800-258-4263.
- Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.
- Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
- Decrease in viral load and increase in CD4 cell counts.