What class of drug is Foscarnet and How Does It Work?

October 9, 2025 •

3 min read

Before the advent of highly active antiretroviral therapy (HAART), Cytomegalovirus (CMV) retinitis affected 25-40% of all AIDS patients. Foscarnet is a crucial antiviral medication used to treat these and other serious viral infections. So, what class of drug is Foscarnet? It is classified as a pyrophosphate analog DNA polymerase inhibitor.

Quick Summary

Foscarnet is an antiviral drug classified as a pyrophosphate analog DNA polymerase inhibitor. It treats drug-resistant herpes viruses, including CMV and HSV, by directly blocking viral DNA replication.

Key Points

Drug Class: Foscarnet is an antiviral classified as a pyrophosphate analog DNA polymerase inhibitor.
Mechanism of Action: It directly blocks the pyrophosphate binding site on viral DNA polymerase, halting viral DNA replication without needing prior activation by viral enzymes.
Primary Use: It is primarily used to treat cytomegalovirus (CMV) retinitis in AIDS patients and acyclovir-resistant Herpes Simplex Virus (HSV) infections in immunocompromised individuals.
Key Advantage: Its mechanism makes it effective against viral strains that have developed resistance to other antivirals like acyclovir and ganciclovir.
Administration: Foscarnet must be administered intravenously with adequate hydration to reduce the risk of kidney damage.
Major Toxicities: The drug has black box warnings for severe renal impairment and seizures due to electrolyte disturbances, such as hypocalcemia.
Monitoring: Patients require frequent monitoring of kidney function and serum electrolytes throughout the course of treatment.

Understanding Foscarnet: A Key Antiviral Agent

Foscarnet, sold under the brand name Foscavir, is an important intravenous antiviral medication used in specific clinical situations, particularly for immunocompromised patients. It belongs to a unique pharmacological class and functions differently from many other common antiviral drugs. Its primary role is in managing severe viral infections caused by the Herpesviridae family, including Cytomegalovirus (CMV), Herpes Simplex Virus types 1 and 2 (HSV-1, HSV-2), and Varicella-Zoster Virus (VZV). Before the development of modern antiretroviral therapies, CMV retinitis was a common opportunistic infection in up to 40% of patients with AIDS, highlighting the need for effective treatments like Foscarnet.

What is Foscarnet's Drug Class and Mechanism of Action?

Foscarnet is classified as a pyrophosphate analog DNA polymerase inhibitor. Its mechanism of action is distinct and highly selective. It functions as a structural mimic of the pyrophosphate anion. During viral replication, DNA polymerase enzymes build new viral DNA chains. This process involves cleaving a pyrophosphate molecule from deoxynucleotide triphosphates. Foscarnet directly and non-competitively inhibits the pyrophosphate binding site on the viral DNA polymerase. By blocking this site, it prevents the cleavage of pyrophosphate, effectively halting the elongation of the viral DNA chain and stopping viral replication.

A key advantage of this mechanism is that Foscarnet does not require activation by viral kinases (like thymidine kinase or UL97). Other antiviral drugs, such as acyclovir and ganciclovir, depend on these viral enzymes for their activation. Viruses can develop mutations in these kinase genes, rendering them resistant to those drugs. Because Foscarnet bypasses this step, it remains effective against many acyclovir- and ganciclovir-resistant strains of HSV and CMV, making it a critical second-line or salvage therapy.

Clinical Indications for Foscarnet

Foscarnet is reserved for serious infections in specific patient populations due to its toxicity profile and intravenous-only administration.

Primary Uses:

CMV Retinitis: It is indicated for the treatment of CMV retinitis in patients with AIDS. It can be used as a primary or second-line treatment, sometimes combined with ganciclovir for relapsed disease.
Acyclovir-Resistant Mucocutaneous HSV Infections: Used for HSV infections in immunocompromised patients unresponsive to acyclovir.
Acyclovir-Resistant VZV Infections: Effective against acyclovir-resistant VZV in immunocompromised hosts.

Administration and Pharmacokinetics

Foscarnet has low oral bioavailability and must be given intravenously over 1-2 hours. Slow infusion is necessary to avoid severe hypocalcemia. Adequate hydration with saline or dextrose is crucial to reduce the risk of kidney damage. Dosage is based on weight and kidney function, requiring monitoring. It's excreted in urine, with about 20% depositing in bone, contributing to a long half-life.

Comparison of Antivirals for CMV

Foscarnet is often considered alongside other antivirals like Ganciclovir and Cidofovir for treating CMV. Each has a distinct profile.


Feature	Foscarnet	Ganciclovir	Cidofovir
Drug Class	Pyrophosphate Analog	Guanosine Analog	Cytosine Nucleotide Analog
Mechanism	Directly inhibits DNA polymerase at the pyrophosphate binding site.	Requires viral kinase (UL97) for initial phosphorylation to inhibit DNA polymerase.	Does not require viral kinase but needs cellular kinases for phosphorylation to inhibit DNA polymerase.
Activity vs. Resistant Strains	Active against many ganciclovir-resistant strains because it does not require kinase activation.	Ineffective against strains with UL97 kinase mutations.	Active against many ganciclovir-resistant strains.
Primary Toxicity	Nephrotoxicity, electrolyte imbalances (hypocalcemia, hypomagnesemia).	Bone marrow suppression (neutropenia, thrombocytopenia).	Severe nephrotoxicity (requires co-administration with probenecid and hydration).
Administration	Intravenous only.	Intravenous, oral (as valganciclovir).	Intravenous only.

Black Box Warnings and Major Adverse Effects

Foscarnet has black box warnings due to significant risks.

Renal Impairment: This is the primary toxicity, requiring frequent kidney function monitoring and dose adjustment. Hydration is essential to minimize risk.
Seizures: Can occur due to electrolyte imbalances caused by Foscarnet chelating metal ions, leading to hypocalcemia, hypomagnesemia, hypokalemia, and phosphate disturbances. Monitoring for symptoms is necessary.

Other common side effects include fever, nausea, diarrhea, headache, and anemia. Genital irritation can also occur from urine concentration.

Conclusion

Foscarnet, a pyrophosphate analog, is a powerful antiviral primarily for CMV and acyclovir/ganciclovir-resistant HSV. Its unique mechanism directly inhibits viral DNA polymerase. Due to IV administration and risks like kidney damage and electrolyte imbalances, its use requires careful monitoring, typically in a hospital.

Visit the NCBI StatPearls article on Foscarnet for more in-depth clinical information.

Frequently Asked Questions

Foscarnet is in the antiviral drug class known as pyrophosphate analogs, which act as non-competitive DNA polymerase inhibitors.

Foscarnet works by directly inhibiting the viral DNA polymerase enzyme. It mimics pyrophosphate and blocks its binding site, which prevents the virus from replicating its DNA.

Acyclovir requires activation by a viral enzyme (thymidine kinase). Viruses can become resistant by mutating this enzyme. Foscarnet does not need this activation step and acts directly on the DNA polymerase, so it remains effective against many of these resistant strains.

The most serious side effects, noted in its black box warnings, are severe kidney damage (nephrotoxicity) and seizures. The seizures are often related to the drug causing electrolyte imbalances, especially low calcium in the blood (hypocalcemia).

No, Foscarnet is not available as a pill. It has poor oral bioavailability and must be administered as a slow intravenous (IV) infusion in a hospital or clinical setting.

CMV retinitis is a serious viral infection of the eye's retina caused by Cytomegalovirus. It primarily affects immunocompromised individuals, such as those with AIDS, and can lead to blindness if left untreated.

Foscarnet directly inhibits viral DNA polymerase, while Ganciclovir must first be activated by a viral kinase enzyme (UL97). This difference makes Foscarnet effective against many Ganciclovir-resistant viruses. Their main toxicities also differ: Foscarnet is primarily associated with kidney damage and electrolyte issues, whereas Ganciclovir is known for causing bone marrow suppression.