Antiviral Drugs: Oseltamivir and Zanamivir

Antiviral Drugs

• Oseltamivir and Zanamivir:
  • No interference with vaccines
  • Active against Influenza A and B viruses
  • Administered prior to exposure or within 48 hours after onset of symptoms
  • 5-day course
  • MOA: Selectively inhibit neuraminidase, preventing the release of new virions
  • PK: Oseltamivir is a prodrug, administered orally, and activated by hepatic esterases; Zanamivir is active, administered via inhalation; both are excreted in the urine
  • Adverse effects: Oseltamivir - nausea and vomiting (minimized with food), headache; Zanamivir - respiratory discomfort; caution in patients with airway diseases
  • Resistance: Mutations of the neuraminidase enzyme

Antiviral Drugs

• Adamantane antivirals (e.g. Amantadine and Rimantadine):
  • Active against Influenza A viruses only
  • Administered prior to exposure or within 48 hours after onset of symptoms
  • Due to high resistance, no longer recommended
  • MOA: Block M2 proton ion channel, blocking viral uncoating
  • PK: Amantadine is excreted unchanged in the urine; Rimantadine is extensively metabolized before urinary excretion
  • Use of Amantadine in Parkinson's disease

Antiviral Drugs

• Acyclovir:
  • MOA: Inhibits viral DNA synthesis
  • PK: Oral, IV, and topical administration; partially metabolized to an inactive drug; drug and metabolites excreted in the urine
  • Oral acyclovir has low bioavailability (15-20%); absorption is not affected by food; no systemic concentrations are detected by the topical route
  • Diffuses readily into most tissues and body fluids (20-50% of serum values inside CSF)
  • IV: Used for herpes simplex encephalitis, neonatal HSV infections, and serious HSV or VZV infections
  • Topical: Used for cold sores, genital herpes, and ophthalmic; no benefit in treating recurrent genital herpes

Antiviral Drugs

• NRTIs:
  • PK: Administered orally (zidovudine available also as IV); renally excreted (except abacavir, which is hepatically eliminated)
  • Adverse effects: Toxicities due to inhibition of mitochondrial DNA polymerase gamma; lactic acidosis with hepatic steatosis, lipodystrophy
  • Abacavir: Hypersensitivity (fever, fatigue, rash, GI disturbances, respiratory distress)
  • Resistance: Alterations of viral RT; cross-resistance occurs between agents of the same analog class

Antiviral Drugs

• NNRTIs:
  • Boosters: Ritonavir and cobicistat

Antiviral Drugs

• Entry Inhibitors:
  • Enfuvirtide: Fusion inhibitor; polypeptide that binds to viral gp41 required for entry into CD4 cells; administered via SC injection; causes pain, erythema, induration, and nodules
  • Maraviroc: Entry inhibitor; blocks the CCR5 coreceptor that works with viral gp41 to facilitate HIV entry; hepatotoxic

Antiviral Drugs

• Integrase Inhibitors:
  • Examples: Raltegravir, elvitegravir, dolutegravir, and bictegravir
  • Inhibits the insertion of proviral DNA into the host cell genome
  • Adverse effects: Nausea, diarrhea

Antiprotozoal Drugs

• Amebiasis:
  • Diloxanide furoate: Not used in pregnancy; adverse effects: flatulence (common), nausea, and abdominal cramps (infrequent), rashes (rare)
  • Iodoquinol: Active against luminal cysts and trophozoites; 90% retained in the intestine; excreted in feces; remainder is absorbed, glucuronidated, and excreted in the urine
  • Adverse effects: Diarrhea, anorexia, nausea, vomiting, abdominal pain, headache, rash, and pruritus
  • Paromomycin sulfate: Aminoglycoside antibiotic; active against luminal forms of Entamoeba histolytica; not significantly absorbed; small amount absorbed is excreted unchanged in urine