Fostemsavir is an HIV-1 gp120-directed attachment inhibitor indicated for the treatment of heavily treatment-experienced adult patients with multiply drug-resistant HIV-1 infection.

What Are the Side Effects of Fostemsavir?

Common Side Effects

Gastrointestinal reactions: Nausea (10%) is the most common adverse reaction; others include diarrhea (4%), abdominal pain (3%), dyspepsia (3%), and vomiting (2%).

Neurological reactions: Headache (4%), somnolence (2%).

Skin reactions: Rash (3%), pruritus.

Systemic reactions: Fatigue (3%).

Sleep disorders: Incidence of approximately 3%, including insomnia, insufficient sleep, and abnormal dreams.

Abnormal laboratory findings: Elevated ALT (5%), elevated AST (4%), elevated direct bilirubin (7%), elevated cholesterol (5%), elevated creatinine (19%), elevated triglycerides (5%), etc.

Serious Side Effects of Fostemsavir That Require Vigilance

Immune Reconstitution Syndrome

Immune reconstitution syndrome may occur when fostemsavir is used in combination with other antiretroviral drugs for treatment.

During the initial phase of treatment, immune system response may lead to inflammatory reactions against latent or residual opportunistic infections (e.g., Mycobacterium avium complex infection, cytomegalovirus, Pneumocystis jirovecii pneumonia, or tuberculosis).

Autoimmune diseases (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) may also occur, and these may develop months after the start of treatment.

QT Interval Prolongation

At 4 times the recommended dose (2400 mg twice daily), fostemsavir can significantly prolong the QTc interval on electrocardiogram (mean increase of 11.2 milliseconds).

Special caution is required for patients with the following conditions: A history of QT interval prolongation.

Patients taking drugs known to induce torsades de pointes (a type of ventricular tachycardia).

Patients with underlying heart diseases relevant to QT interval prolongation.

Elderly patients may be more sensitive to drug-induced QT interval prolongation.

Elevated Liver Enzymes in Patients with HBV/HCV Coinfection

The proportion of patients with elevated liver transaminases (14%) is significantly higher in those coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV) than in patients with HIV monoinfection (3% with elevated ALT, 2% with elevated AST). Some cases of transaminase elevation are associated with HBV reactivation after discontinuation of anti-hepatitis treatment.

Recommendation: Monitor liver function in patients with HBV/HCV coinfection.

Special attention should be paid to initiating or maintaining effective HBV treatment when starting fostemsavir therapy.

Precautions for Fostemsavir Administration

Important Drug Interactions

HCV direct-acting antiviral agents: May increase the plasma concentrations of glecaprevir or voxilaprevir; it is recommended to switch to alternative HCV treatment regimens whenever possible.

Oral contraceptives: The daily dose of ethinyl estradiol should not exceed 30 mcg.

Statins: Should be initiated at the lowest starting dose, and statin-related adverse reactions should be monitored.

Drugs that prolong QT interval: Caution is required when used concomitantly with drugs known to induce torsades de pointes.

Other Precautions

Dosage: 600 mg tablets, twice daily, swallowed whole; do not chew, crush, or split the tablets.

Effect of food: A high-fat meal can increase AUC by 81%, and a standard meal can increase AUC by 10%; it is recommended to maintain a consistent way of taking the medication (i.e., consistently with or without food).

Management of overdose: There is no specific antidote. Supportive treatment should be administered, including monitoring of vital signs and electrocardiogram (QT interval).