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Definition

Antiviral drugs are medicines that cure or control virus infections.

Purpose

Antivirals are used to treat infections caused by viruses. Unlike antibacterial drugs, which may cover a wide range of pathogens, antiviral agents tend to be narrow in spectrum, and have limited efficacy.

Description

Exclusive of the antiretroviral agents used in HIV (AIDS) therapy, there are currently only 11 antiviral drugs available, covering four types of virus. Acyclovir (Zovirax), famciclovir (Famvir), and valacyclovir (Valtrex) are effective against herpesvirus, including herpes zoster and herpes genitalis. They may also be of value in either conditions caused by herpes, such as chickenpox and shingles. These drugs are not curative, but may reduce the pain of a herpes outbreak and shorten the period of viral shedding.

Amantadine (Symmetrel), oseltamivir (Tamiflu), rimantidine (Flumadine), and zanamivir (Relenza) are useful in treatment of influenza virus. Amantadine, rimantadine, and oseltamivir may be administered throughout the flu season as preventatives for patients who cannot take influenza virus vaccine.

Cidofovir (Vistide), foscarnet (Foscavir), and ganciclovir (Cytovene) have been beneficial in treatment of cytomegalovirus in immunosupressed patients, primarily HIV-positive patients and transplant recipients. Ribavirin (Virazole) is used to treat respiratory syncytial virus. In combination with interferons, ribavirin has shown some efficacy against hepatitis C, and there have been anecdotal reports of utility against other types of viral infections.

As a class, the antivirals are not curative, and must be used either prophylactically or early in the development of an infection. Their mechanism of action is typically to inactivate the enzymes needed for viral replication. This will reduce the rate of viral growth, but will not inactive the virus already present. Antiviral therapy must normally be initiated within 48 hours of the onset of an infection to provide any benefit. Drugs used for influenza may be used throughout the influenza season in high risk patients, or within 48 hours of exposure to a known carrier. Antiherpetic agents should be used at the first signs of an outbreak. Anti-cytomegaloviral drugs must routinely be used as part of a program of secondary prophylaxis (maintenance therapy following an initial response) in order to prevent reinfection in immunocompromised patients.

Recommended dosage

Dosage varies with the drug, patient age and condition, route of administration, and other factors. See specific references.

Precautions

Ganciclovir is available in intravenous injection, oral capsules, and intraoccular inserts. The capsules should be reserved for prophylactic use in organ transplant patients, or for HIV infected patients who cannot be treated with the intravenous drug. The toxicity profile of this drug when administered systemically includes granulocytopenia, anemia and thrombocytopenia. The drug is in pregnancy category C, but has caused significant fetal abnormalities in animal studies including cleft palate and organ defects. Breast feeding is not recommended.

Cidofovir causes renal toxicity in 53% of patients. Patients should be well hydrated, and renal function should be checked regularly. Other common adverse effects are nausea and vomiting in 65% or patients, asthenia in 46% and headache and diarrhea, both reported in 27% of cases. The drug is category C in pregnancy, due to fetal abnormalities in animal studies. Breast feeding is not recommended.

Foscarnet is used in treatment of immunocompromised patients with cytomegalovirus infections and in acyclovir-resistant herpes simples virus. The primary hazard is renal toxicity. Alterations in electrolyte levels may cause seizures. Foscarnet is category C during pregnancy. The drug has caused skeletal abnormailities in developing fetuses. It is not known whether foscarnet is excreted in breast milk, however the drug does appear in breast milk in animal studies.

Valaciclovir is metabolized to acyclovir, so that the hazards of the two drugs are very similar. They are generally well tolerated, but nausea and headache are common adverse effects. They are both pregnancy category B. Although there have been no reports of fetal abnormalities attributable to either drug, the small number of reported cases makes it impossible to draw conclusions regarding safety in pregnancy. Acyclovir is found in breast milk, but no adverse effects have been reported in the newborn. Famciclovir is similar in actions and adverse effects.

Ribavirin is used by aerosol for treatment of hospitalized infants and young children with severe lower respiratory tract infections due to respiratory syncytial virus (RSV). When administered orally, the drug has been used in adultys to treat other viral diseases including acute and chronic hepatitis, herpes genitalis, measles, and Lassa fever, however there is relatively little information about these uses. In rare cases, initiation of ribavirin therapy has led to deterioration of respiratory function in infants. Careful monitoring is essential for safe use.

The anti-influenza drugs are generally well tolerated. Amantadine, which is also used for treatment of Parkinsonism, may show more frequent CNS effects, including sedation and dizziness. Rapid discontinuation of amantidine may cause an increase in Parkinsonian symptoms in patients using the drug for that purpose. All are schedule C for pregnancy. In animal studies, they have caused fetal malformations in doses several times higher than the normal human dose. Use caution in breast feeding.

Interactions

Consult specific references for information on drug interactions.

Use particular caution in HIV-positive patients, since these patients are commonly on multi-drug regimens with a high frequency of interactions. Ganciclovir should not be used with other drugs which cause hematologic toxicity, and cidofovir should not be used with other drugs that may cause kidney damage.

Key Terms

Asthenia

Muscle weakness.

 

Cytomegalovirus (CMV)

A type of virus that attacks and enlarges certain cells in the body. The virus also causes a disease in infants.

 

Herpes simplex

A virus that causes sores on the lips (cold sores) or on the genitals (genital herpes).

 

HIV

Acronym for human immunodeficiency virus, the virus that causes AIDS.

 

Parkinsonism

A group of conditions that all have these typical symptoms in common: tremor, rigidity, slow movement, and poor balance and coordination.

 

Pregnancy category

A system of classifying drugs according to their established risks for use during pregnancy. Category A: Controlled human studies have demonstrated no fetal risk. Category B: Animal studies indicate no fetal risk, but no human studies, or adverse effects in animals, but not in well-controlled human studies. Category C: No adequate human or animal studies, or adverse fetal effects in animal studies, but no available human data. Category D: Evidence of fetal risk, but benefits outweigh risks. Category X: Evidence of fetal risk. Risks outweigh any benefits.

 

Prophylactic

Guarding from or preventing the spread or occurrence of disease or infection.

 

Retrovirus

A group of viruses that contain RNA and the enzyme reverse transcriptase. Many viruses in this family cause tumors. The virus that causes AIDS is a retrovirus.

 

Shingles

An disease caused by an infection with the Herpes zoster virus, the same virus that causes chickenpox. Symptoms of shingles include pain and blisters along one nerve, usually on the face, chest, stomach, or back.

 

Virus

A tiny, disease-causing structure that can reproduce only in living cells and causes a variety of infectious diseases.

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