Antiviral agents

Drug_Mechanism of action_Main indications_Important adverse effects/toxicity| Aciclovir_Guanosine nucleoside analogue; initially phosphorylated by viral thymidine kinase and then by host-cell kinases. The active triphosphate inhibits viral DNA polymerase and causes DNA-chain termination_HSV and VZV infections_Crystalline nephropathy, particularly with intravenous treatment; neurotoxicity, especially in renal impairment| Valaciclovir_Oral prodrug of aciclovir with substantially greater bioavailability_HSV and VZV infections_Headache, nausea; crystalline nephropathy and neurotoxicity, particularly in renal impairment| Famciclovir_Oral prodrug of penciclovir; phosphorylated by viral thymidine kinase and inhibits viral DNA polymerase_HSV and VZV infections_Headache, nausea; dose reduction required in renal impairment| Ganciclovir_Guanosine nucleoside analogue; initially phosphorylated by the CMV UL97 kinase and then by host-cell kinases. The active triphosphate inhibits viral DNA polymerase and DNA-chain elongation_Treatment of severe CMV infection, particularly in immunocompromised patients_Myelosuppression, particularly neutropenia; thrombocytopenia, anaemia, teratogenicity| Valganciclovir_Oral prodrug of ganciclovir with improved bioavailability_Treatment and prevention of CMV disease, including following solid-organ transplantation_Myelotoxicity, particularly neutropenia; teratogenicity| Letermovir_Inhibits the CMV terminase complex, preventing cleavage and packaging of viral DNA_Prophylaxis of CMV infection and disease following allogeneic haematopoietic stem-cell transplantation; selected solid-organ transplant recipients_Nausea, diarrhoea, peripheral oedema; important drug interactions, including with immunosuppressants| Maribavir_Inhibits CMV UL97 protein kinase, disrupting viral DNA replication, encapsidation and nuclear egress_Refractory or resistant CMV infection following haematopoietic stem-cell or solid-organ transplantation_Dysgeusia, nausea, vomiting; interactions with tacrolimus and other immunosuppressants; should not be combined with ganciclovir or valganciclovir| Foscarnet_Pyrophosphate analogue that directly inhibits viral DNA polymerase without requiring intracellular phosphorylation_Ganciclovir-resistant CMV; aciclovir-resistant HSV_Nephrotoxicity, hypocalcaemia, hypomagnesaemia, other electrolyte disturbances and seizures| Cidofovir_Acyclic nucleotide phosphonate analogue; phosphorylated by host-cell kinases and therefore does not require activation by viral enzymes. The active metabolite inhibits viral DNA polymerase_CMV retinitis; selected resistant HSV, adenovirus and other DNA-virus infections under specialist care_Nephrotoxicity; intravenous hydration and probenecid are given to reduce renal tubular toxicity| Oseltamivir_Oral prodrug whose active metabolite inhibits influenza neuraminidase, preventing the release of newly formed virions_Treatment and post-exposure prophylaxis of influenza A and B, particularly in patients at increased risk of complications_Nausea, vomiting, headache; rare neuropsychiatric reactions| Zanamivir_Inhaled neuraminidase inhibitor_Treatment and post-exposure prophylaxis of influenza A and B_Bronchospasm; avoid or use cautiously in asthma and COPD| Baloxavir marboxil_Prodrug converted to baloxavir, which inhibits the influenza cap-dependent endonuclease and prevents viral mRNA transcription_Single-dose treatment or post-exposure prophylaxis of uncomplicated influenza A and B, where locally recommended_Headache, diarrhoea; absorption reduced by polyvalent cations, antacids and calcium-rich products; resistance may emerge| Amantadine_Blocks the influenza A M2 proton channel, preventing viral uncoating; also enhances dopaminergic activity and has NMDA-receptor antagonist activity_Parkinson's disease; no longer recommended for influenza because of widespread resistance_Confusion, hallucinations, ataxia, livedo reticularis and ankle oedema| Ribavirin_Guanosine nucleoside analogue with several actions, including inhibition of inosine monophosphate dehydrogenase, interference with viral RNA synthesis and mRNA capping, and promotion of viral mutagenesis_Selected hepatitis C regimens; selected severe RSV infections, particularly in immunocompromised patients_Haemolytic anaemia; highly teratogenic; cough and bronchospasm with inhaled administration| Nirmatrelvir/ritonavir_Nirmatrelvir inhibits the SARS-CoV-2 main protease, preventing cleavage of viral polyproteins; ritonavir inhibits CYP3A and increases nirmatrelvir concentrations_Early COVID-19 in patients at increased risk of progression to severe disease_Dysgeusia, diarrhoea; numerous potentially serious CYP3A-mediated drug interactions; dose adjustment in renal impairment| Remdesivir_Adenosine nucleotide prodrug whose active metabolite inhibits viral RNA-dependent RNA polymerase and causes delayed RNA-chain termination_COVID-19 in selected hospitalised patients and high-risk patients treated early in the illness_Raised transaminases, nausea, infusion reactions and bradycardia| Tenofovir disoproxil_Adenosine nucleotide analogue that inhibits viral reverse transcriptase and causes DNA-chain termination_Chronic hepatitis B; HIV treatment and pre-exposure prophylaxis_Renal tubular toxicity, reduced bone-mineral density; monitor renal function| Tenofovir alafenamide_Prodrug of tenofovir that produces higher intracellular and lower plasma tenofovir concentrations_Chronic hepatitis B and HIV treatment_Less renal and bone toxicity than tenofovir disoproxil; weight gain and increased lipid concentrations may occur| Entecavir_Guanosine nucleoside analogue that inhibits HBV polymerase, including reverse transcription and viral DNA synthesis_Chronic hepatitis B_Headache, nausea; hepatitis may flare following discontinuation; rare lactic acidosis| Sofosbuvir/velpatasvir_Sofosbuvir inhibits the HCV NS5B RNA polymerase; velpatasvir inhibits the HCV NS5A replication complex_Pangenotypic treatment of chronic hepatitis C, usually as a finite oral course_Headache and fatigue; clinically important interactions; proton-pump inhibitors reduce velpatasvir absorption; severe bradycardia may occur with amiodarone| Glecaprevir/pibrentasvir_Glecaprevir inhibits the HCV NS3/4A protease; pibrentasvir inhibits the HCV NS5A replication complex_Pangenotypic treatment of chronic hepatitis C_Headache, fatigue and nausea; important drug interactions; protease-inhibitor component is unsuitable in decompensated cirrhosis| Interferon-#alpha#_Binds type I interferon receptors and activates JAK-STAT signalling, inducing antiviral proteins that inhibit viral replication and protein synthesis_Selected cases of chronic hepatitis B and certain malignancies; use in hepatitis C has largely been replaced by direct-acting antivirals_Flu-like symptoms, depression, anorexia, myelosuppression, autoimmune disease and thyroid dysfunction| RSV prevention

• nirsevimab and palivizumab are monoclonal antibodies that provide passive immunisation; they are not directly acting antiviral drugs

Hepatitis C

• direct-acting antiviral combinations have largely replaced interferon-#alpha# and ribavirin
• the principal targets are NS3/4A protease, NS5A replication complex and NS5B RNA polymerase

HIV

• antiretroviral drugs are usually classified separately into nucleoside/nucleotide reverse-transcriptase inhibitors, non-nucleoside reverse-transcriptase inhibitors, protease inhibitors, integrase inhibitors, entry inhibitors and capsid inhibitors