Antiviral drugs

Definition

Antiviral drugs act against diseases caused by viruses.

Description

Viruses represent a large group of infective agents that are composed of a core of nucleic acids, either RNA or DNA, surrounded by a layer of protein. They are not really living organisms according to general understanding, since they lack the cell membrane that is associated with living cells. Viruses can reproduce only inside a living cell, and they cause many diseases. Viruses are not normally affected by antibiotics but a small number of viruses can either be destroyed or have their growth stopped by drugs.

The drugs as of 2004 available for treatment of viral diseases in children are:

Acyclovir (Zovirax), used for treatment of diseases caused by the erpes simplex virus and herpes zoster virus. Although it is approved only for children over the age of six months, the drug has been used for newborn infants with encephalitis . This drug is most reliable when given intravenously.
Amantidine (Symmetrel), used to prevent or treat infections of the influenza virus type A. It is recommended for patients who cannot or should not receive influenza virus vaccine. As of 2004 it has not been studied in children below the age of one year.
Foscarnet (Foscavir), is not recommended for young children but may be given to adolescents. It is used to treat cytomegalovirus infections of the eye, and for herpes simplex infections that are resistant to other drugs.
Ganciclovir (Cytovene), used to treat cytomegalovirus infections of the eye. Although the manufacturer does not recommend use of ganciclovir in patients below the age of 12 years, the drug is recommended by standard pediatric references for children as young as three months.
Oseltamivir (Tamiflu), used for treatment of influenza virus infections of children over the age of 13 years. In adults, oseltamivir has also been used for prevention if influenza, but this use has not been studied in children.
Ribavirin (Rebetol, Virazol), used for treatment of hospitalized infants and young children with severe lower respiratory tract infections caused by respiratory syncytial virus (RSV), but its value is controversial.
Rimantidine (Flumadine), used to protect against the influenza virus type A.
Valacyclovir (Valtrex), used for treatment of diseases caused by the herpes simplex virus and herpes zoster virus. This drug is converted to acyclovir inside the body and is more reliable for oral use. Although the manufacturer says that safety and efficacy in children have not been established, valacyclovir is recommended for use in standard pediatric resources.
Vidarabine (Vira-A), used to treat severe herpes infections in the newborn, but its primary value is in the form of an eye ointment to treat herpes infections of the eye.
Zanamivir (relenza), used to treat influenza infections caused by viruses types A and B in adults and children over the age of seven.

In addition to the above drugs, there are drugs which treat retrovirus infections. Retroviruses are composed of RNA molecules instead of DNA, and the only treatable one is the one that causes acquired immune deficiency syndrome ( AIDS ). The drugs in this group that are appropriate for treatment of children are as follows:

abacavir (Ziagen)
amprenavir (Agenerase), for children above the age of four
didanosine (Videx)
efavirenz (Sustiva), for children over the age of three
indinavir (Crixavan), according to the manufacturer safety and efficacy of which in children has not been established, but the drug has been recommended in standard pediatric references
lamivudine (Epivir), for treatment of hepatitis B as well as for AIDS
lopinavir/Ritonavir fixed combination (Kaletra), used in children as young as six months
stavudine (Zerit)
nelfinavir (Viracept), the manufacturer of which does not recommend use of this drug for children younger than two, but it has been studied with some success in children as young as newborns
ritonavir (Norvir)
saquinavir (Fortovase, Invirase)
zalcitabine (Hivid)
zidovudine (Retrovir)

Other drugs for treatment of HIV disease are marketed, but there have been neither sufficient studies not clinical experience to recommend their use in children.

General use

The antiviral drugs are used to prevent or treat the diseases listed above. These drugs are specific for individual viruses and offer no benefit for conditions caused by other viruses.

Precautions

Each of the drugs listed has specific warnings. See specific drugs references or ask a pediatrician.

Side effects

Each of the drugs listed has its own side effects. See specific drugs references or ask a pediatrician.

Indinavir (Crixivan) has the unique adverse effects of causing changes in patterns of fat distribution. This has been called Crix belly and may be more distressing to the patient than more serious side effects caused by other drugs since these effects are clearly visible. As of 2004 it is not clear whether this effect can be reversed when the drug is discontinued. Antiretroviral drugs should not be discontinued unless there is an alternative antiretroviral regimen to adopt.

Interactions

See specific drugs references or ask a pediatrician about interactions for an antiviral drug that has been prescribed.

Patients should use these drugs exactly as directed. With regard to the AIDS drugs in particular, the drugs should not be discontinued without consultation with the prescriber. AIDS drugs are normally prescribed in combinations of two and three drugs used together, and discontinuing any single drug may lead to the virus developing resistance to the other agents.

Parental concerns

Liquid dosage forms must always be measured with a calibrated teaspoon or dropper, never with a household teaspoon. Household teaspoons vary in the volume they deliver and may result in inadvertent overdose or under dose.

Anti-influenza drugs should be used only for patients who cannot receive vaccinations. Annual vaccination remains the preferred method of preventing influenza.

Antiretroviral drugs are routinely given in combinations of three to four drugs at a time. In some cases, fixed combinations of medications are the most practical way to administer these drugs, since they require the lowest number of doses each day.

Some antiviral drugs, particularly the antiretroviral agents, have potentially severe adverse effects. They should be prescribed only by qualified professionals experienced in their use. These drugs must be routinely monitored. Regular laboratory testing is essential for safe and effective use. Adverse effects and side effects must be reported to the prescriber as soon as they are observed.

Antiherpetic drugs may have only a limited value in reducing the severity or duration of herpes attacks. They are more important for their effect in reducing the period of viral shedding, the period of time in which a person infected with herpes virus can infect other people. For this reason, continued use of the drugs is important to family members and those in close proximity to the patient. The drugs should not be discontinued, even if there is no observed benefit.

KEY TERMS

Herpes virus —A family of viruses including herpes simplex types 1 and 2, and herpes zoster (also called varicella zoster). Herpes viruses cause several infections, all characterized by blisters and ulcers, including chickenpox, shingles, genital herpes, and cold sores or fever blisters.

Influenza virus type —The nature of the proteins in the outer coat of an influenza virus. Depending on the proteins, influenza viruses may be classified as A, B, or C.

Retrovirus —A family of RNA viruses containing a reverse transcriptase enzyme that allows the viruses' genetic information to become part of the genetic information of the host cell upon replication. Human immunodeficiency virus (HIV) is a retrovirus.

Virus —A small infectious agent consisting of a core of genetic material (DNA or RNA) surrounded by a shell of protein. A virus needs a living cell to reproduce.

Resources

BOOKS

Beers, Mark H., and Robert Berkow, eds. The Merck Manual , 2nd home ed. West Point, PA: Merck & Co., 2004.

Mcevoy, Gerald, et al. AHFS Drug Information 2004. Bethesda, MD: American Society of Healthsystems Pharmacists, 2004.

PERIODICALS

Bell, G. S. "Highly active antiretroviral therapy in neonates and young infants." Neonatal Netword: The Journal of Neonatal Nursing 23, no. 2 (March-April 2004: 55–64.

Eksborg, S. "The pharmacokinetics of antiviral therapy in pediatric patients." Herpes 10, no. 3 (December 2003): 66–71.

Fraaij, Pieter L., et al. "Therapeutic drug monitoring in children with HIV/AIDS." Therapeutic Drug Monitoring 26, no. 2 (April 2004): 122–6.

Feder, Henry M., Jr., and Diane M. Hoss. "Herpes zoster in otherwise healthy children." Pediatric Infectious Diseases Journal 23, no. 5 (May 2004): 451–7.

Jaspan, H. B., and R. F. Garry. "Preventing neonatal HIV: a review." Current HIV Research 1, no. 3 (July 2003): 321–7.

Kamin, D., and C. Hadigan C. "Hyperlipidemia in children with HIV infection: an emerging problem." Expert Reviews in Cardiovascular Therapy 1, no. 1 (May 2003): 143–50.

Maggon, Krishan, and Sailen Barik. "New drugs and treatment for respiratory syncytial virus." Reviews in Medical Virology 14, no. 3 (May-June 2004): 149–68.

Rakhmanina, Natella Y., et al. "Therapeutic drug monitoring of antiretroviral therapy." AIDS Patient Care and STDS 18, no. 1 (January 2004): 7–14.

Whitley, Richard. "Neonatal herpes simplex virus infection." Current Opinion in Infectious Diseases 17, no. 3 (June 2004): 243–6.

ORGANIZATIONS

Elisabeth Glaser Pediatric AIDS Foundation. 1140 Connecticut Avenue NW, Suite 200, Washington, DC 20036. Web site: http://www.charitywire.com/charity60/.

WEB SITES

National Institute of Allergy and Infectious Diseases. Available online at http://www.niaid.nih.gov/default.htm (accessed October 17, 2004).

National Institute of Child Health & Human Development. Available online at http://www.nichd.nih.gov/ (accessed October 17, 2004).

National Pediatric AIDS Network. Available online at http://www.npan.org/ (accessed October 17, 2004).

The Pediatric AIDS Clinical Trials Group. Available online at http://pactg.s-3.com/ (accessed October 17, 2004)

"Pediatric Antiretroviral Drug Information." Available online at http://aidsinfo.nih.gov/guidelines/pediatric%5CSUP_PED_012004.html (accessed October 17, 2004).

Samuel Uretsky, PharmD