CLASSES

Other Topical Agents Used In Viral Infections

DEA CLASS

OTC

DESCRIPTION

Topical non-prescription drug for herpes labialis; also called behenyl alcohol; MOA differs from other antivirals (e.g., acyclovir); not virucidal; some activity against HSV but not considered a true antiviral.

COMMON BRAND NAMES

Abreva

HOW SUPPLIED

Abreva/Docosanol Topical Cream: 10%

DOSAGE & INDICATIONS

For the treatment of herpes labialis due to either herpes simplex virus 1 or herpes simplex virus 2.

Topical dosage

Adults, Adolescents, and Children >= 12 years

Apply five times a day to lesions beginning at the onset of symptoms. This dosage regimen is based on data from a randomized, double-blind, placebo-controlled, cross-over trial of docosanol for the treatment of recurrent herpes labialis. Patients used the cream at the first sign or symptom of a herpes recurrence and subsequently applied the cream five times a day until the lesions healed, up to a maximum of 10 days. Efficacy was measured from the healing time, which was the time between the initiation of treatment and complete re-epithelialization. This study found that patients who applied docosanol as early treatment (i.e., started at the prodromal or erythema stage) showed significantly shorter healing times compared with placebo and 'late' treatment (i.e., defined as treatment started at the papule stage or later). The overall mean reduction of healing time for patients using docosanol was 4.6 days (95% CI 2.6 to 6.6 days).

For the treatment of Kaposi's sarcoma†.

Topical dosage

Adults

Preliminary information suggests that 10% docosanol cream may be useful in Kaposi's sarcoma (KS). Of the KS lesions evaluated, treatment with docosanol resulted in a significant decrease in lesion size and lightening of the lesion pigmentation after four weeks. The data concerning the use of docosanol for this indication is limited to press releases from the manufacturer. A specific drug regimen was not stated. (press release May 9, 1997)

†Indicates off-label use

MAXIMUM DOSAGE

Adults

5 applications/day topically.

Elderly

5 applications/day topically.

Adolescents

5 applications/day topically.

Children

>= 12 years: 5 applications/day topically.

< 12 years: Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

ADMINISTRATION

Topical Administration

Docosanol is applied topically to lesions on the lips and face. Avoid application on or near the eyes.

STORAGE

Abreva:

- Do not freeze

- Store between 68 to 77 degrees F

CONTRAINDICATIONS / PRECAUTIONS

Ophthalmic administration

Docosanol should only be used on the lips and face. Docosanol is not for ophthalmic administration; care should be taken to avoid application on or near the eyes since the drug may cause irritation.

Pregnancy

Pregnancy category information is not available for docosanol and there are no adequate, well-controlled studies in pregnant women. Therefore, pregnant women should only use docosanol under the direction of their health care provider and only if clearly needed.

Immunosuppression

The efficacy of docosanol has not been established in patients with immunosuppression.

Breast-feeding

Data are unavailable regarding use of docosanol during breast-feeding and it's excretion into human milk after topical administration is unknown. Therefore, women who are nursing should cautiously consider using the drug. Acyclovir may be a potential alternative to consider. However, patient factors, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

Children

Safety and effectiveness of docosanol have not been established in children.

ADVERSE REACTIONS

Mild

skin irritation / Early / 3.0-3.0

headache / Early / Incidence not known

DRUG INTERACTIONS

There are no drug interactions associated with Docosanol products.

PREGNANCY AND LACTATION

Pregnancy

Pregnancy category information is not available for docosanol and there are no adequate, well-controlled studies in pregnant women. Therefore, pregnant women should only use docosanol under the direction of their health care provider and only if clearly needed.

Data are unavailable regarding use of docosanol during breast-feeding and it's excretion into human milk after topical administration is unknown. Therefore, women who are nursing should cautiously consider using the drug. Acyclovir may be a potential alternative to consider. However, patient factors, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

MECHANISM OF ACTION

Docosanol is not directly virucidal. It appears to interfere with one or more of the common pathways for viral entry into the target cell and subsequent migration to the cell nucleus. Docosanol exerts its action by inhibiting the fusion between the plasma membrane and the herpes simplex virus (HSV) envelope. It does not interfere with binding of HSV to HSV-specific receptors on target cells. It exhibits preferential activity against lipid-enveloped viruses which use fusion mechanisms for entering susceptible target cells compared to non-enveloped viruses. True antivirals inhibit viral DNA replication, which may result in mutations of HSV rendering them resistant. Since docosanol does not affect the synthesis and replication of the virus, but modulates the host cell to prevent entry of the virion, development of resistance to docosanol is unlikely.

•Microbiology: Docosanol is active against herpes viruses types 1 and 2, cytomegalovirus, influenzae virus, human herpesvirus-6, respiratory syncytial virus (RSV), all of which are enveloped viruses. Some in vivo data show docosanol's activity against CMV and RSV. However, clinical studies have yet to be conducted demonstrating its usefulness for these other viruses (i.e., RSV, CMV, HIV-1, etc.). Preliminary in vitro data suggest that docosanol also inhibits replication of HIV-1 and other retroviruses such as HTLV-1 and -2. It is not active against poliovirus, which does not contain a lipid envelope.

PHARMACOKINETICS

Docosanol is applied topically to the lips or the face. Specific pharmacokinetic information for docosanol is not yet available.

Topical Route

Animal studies report that the topical application of radiolabeled 10% docosanol to the skin of mice showed limited system absorption. Less than 0.0003% of the amount of docosanol applied appeared in the plasma.