fostemsavir

General

Pronunciation:
fos-tem-sa-vir


Trade Name(s)

  • Rukobia

Ther. Class.

antiretrovirals

Pharm. Class.

GP120 attachment inhibitors

Indications

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).

Action

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.

Therapeutic Effect(s):

Reduction in viral load.

Pharmacokinetics

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)

ROUTEONSETPEAKDURATION
PO Rapid2 hr12 hr

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity
  • 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

Derm: rash

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.

Interactions

Drug-Drug

  •  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.

Drug-Natural Products:

 St. John's wort  may ↓ levels and lead to loss of virologic response; concurrent use contraindicated.

Route/Dosage

PO (Adults): 600 mg twice daily.

Availability

Extended-release tablets: 600 mg

Assessment

  • 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.

Implementation

  • Administer twice daily without regard to food.  DNC: Swallow tablets whole; do not crush, chew, or split. 

Patient/Family Teaching

  • 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.

Evaluation/Desired Outcomes

  • Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
  • Decrease in viral load and increase in CD4 cell counts.
fostemsavir is a sample topic from the Davis's Drug Guide.

To view other topics, please or .

Davis’s Drug Guide for Nurses App + Web from F.A. Davis and Unbound Medicine covers 5000+ trade name and generic drugs. Includes App for iPhone, iPad, and Android smartphone + tablet. Handbook covers dosage, side effects, interactions, uses. Davis Drug Guide PDF. .