Fostemsavir is used in adult patients with multidrug-resistant HIV-1 infection, but it must be strictly avoided in patients with severe hepatic impairment and in those receiving concomitant strong CYP3A4 inducers, as otherwise toxicity may increase or efficacy may be lost. The following explains this from two aspects.

I. Patients with Severe Hepatic Impairment

1.Basis for Contraindication

Fostemsavir is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C).

Drug exposure is significantly increased in such patients, raising the risk of hepatotoxicity and systemic adverse reactions.

2.Clinical Manifestations of Risk

Elevated transaminases, jaundice, and other signs of liver injury may occur.

Worsening hepatic function can affect drug metabolism and further aggravate accumulation.

3.Management of Mild to Moderate Hepatic Impairment

Dosage adjustment is generally not required in patients with mild to moderate hepatic impairment, but hepatic function monitoring should be strengthened.

Liver enzymes should be rechecked regularly during treatment, and whether to continue the drug should be evaluated promptly if abnormalities occur.

II. Concomitant Use with Strong CYP3A4 Inducers

1.Contraindicated Concomitant Drugs

Concomitant use with strong CYP3A4 inducers is prohibited, such as rifampin, carbamazepine, phenytoin, phenobarbital, and St. John's wort.

Such drugs significantly reduce Fostemsavir plasma concentrations, leading to loss of antiviral efficacy.

2.Consequences of Risk

Decreased plasma concentrations can lead to virologic failure.

Viral replication rebound increases the risk of resistance mutations and affects subsequent treatment options.

3.Alternatives and Monitoring

When concomitant antituberculosis, antiepileptic, or antidepressant drugs are needed, alternative drugs with weak CYP3A4 induction should be selected.

If their use is unavoidable, a specialist should be consulted to evaluate the regimen, and viral load monitoring should be strengthened.

III. Other Populations Requiring Attention

1.Pregnancy and Lactation

Use during pregnancy should weigh the benefits and risks; it is not recommended during lactation because the drug may be secreted into breast milk.

2.Pediatric Patients

Safety and effectiveness have not been fully established, and individualized dosing should follow guidelines.

3.Patients Receiving Concomitant Medications

When used with certain antiretroviral drugs, antacids, and other drugs, interactions should be assessed, and the dosing time adjusted if necessary.