SUMMARY PRODUCT INFORMATION 3 INDICATIONS AND CLINICAL USE 3 CONTRAINDICATIONS 4 WARNINGS AND PRECAUTIONS 4 ADVERSE REACTIONS 4 DRUG INTERACTIONS ....................................................................................4 DOSAGE AND ADMINISTRATION 5 OVERDOSAGE 5 ACTION AND CLINICAL PHARMACOLOGY 5 STORAGE AND STABILITY 5 DOSAGE FORMS, COMPOSITION AND PACKAGING 5
PHARMACEUTICAL INFORMATION 6 CLINICAL TRIALS 6 DETAILED PHARMACOLOGY 7 MICROBIOLOGY 7 TOXICOLOGY 8 REFERENCES 9
ABREVA(r)
10% Docosanol Cream
PART I: HEALTH PROFESSIONAL INFORMATION
| Route of Administration | Dosage Form / Strength | Clinically Relevant Nonmedicinal Ingredients |
| Topical | Docosanol Cream, 10% | sucrose stearate (and) sucrose distearate, light mineral oil, propylene glycol, benzyl alcohol, and purified water. |
ABREVA(r) (docosanol cream 10%) is indicated for the treatment of acute episodes of recurrent oral-facial herpes simplex (fever blisters or cold sores) in adults.
Patient SubsetsGeriatric Use
:
In 39 patients 65 years of age, the adverse events profile was comparable to that of younger patients.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Pregnancy
Teratogenic Effects:
No evidence of impaired fertility or harm to the fetus due to docosanol administered in oral doses of 10, 500, 1000, or 2000 mg/kg/day was observed in reproduction studies performed in rat and rabbits. Based on the lack of absorption of topically applied docosanol, these tested doses are a thousand-fold higher than the human dose. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, ABREVA(r) should be used during pregnancy only if clearly needed.
Nursing Mothers
It is not known whether docosanol is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ABREVA(r) is administered to a nursing woman.
ABREVA(r) (docosanol cream 10%) is contraindicated in patients with known hypersensitivity to the product or any of its components. For a complete listing of the product composition, please refer to the section on Dosage Forms, Composition and Packaging.
ABREVA(r) should only be used to treat cold sores on the lips and face. Care should be taken to avoid application in or near the eyes since it may cause irritation; if contact occurs, rinse thoroughly with water. If excessive skin irritation develops or increases, discontinue use and consult a doctor. It should not be taken orally. Ophthalmic, penile, and vaginal irritation studies in rabbits demonstrate minimal irritation when ABREVA(r) is placed on these tissues.
In clinical trials for the treatment of recurrent oral-facial herpes simplex, a total of 1008 patients were treated with ABREVA(r) (docosanol cream 10%) and 989 with placebo. The most frequently reported adverse event was headache, which occurred in 10.4% of the patients treated with ABREVA(r) and 10.7% of the patients treated with placebo. One or more local adverse reactions were reported by 4.4% of patients treated with ABREVA(r) and 3.2% of placebo treated patients (Table 1). No evidence of contact sensitization or photoallergy was observed.
Table 1: Local Adverse Reactions Reported in North American Phase 2/3 Clinical Trials
| Description | ABREVA(r)(N=1008) % | Placebo (N=989) % |
| Application site reaction | 2.9 | 2.3 |
| Rash | 0.5 | 0.8 |
| Pruritis | 0.4 | 0.2 |
| Dry skin | 0.4 | 0.2 |
| Acne | 0.3 | 0.0 |
Interactions with other drugs, foods and herbal products have not been established.
ABREVA(r) (docosanol cream 10%) should be applied topically 5 times/day as soon as possible, preferably at the prodrome or erythema stages, until the lesion is healed, up to a maximum of 10 days. Treatment is most effective if applied at the first symptoms (pain, itching, burning or tingling) or sign, (redness), prior to the formation of a papule (bump) or a blister.
Adverse reactions related to overdosage by topical application of ABREVA(r) (docosanol cream 10%) are unlikely because of limited transcutaneous absorption. Similarly, poor oral absorption makes the occurrence of adverse reactions unlikely following ingestion of docosanol.
Mechanism of Action
The predominant mechanism for the anti-HSV activity of docosanol appears to be inhibition of fusion between the plasma membrane and the HSV envelope and, as a result, the blocking of entry and subsequent viral replication. This is in contrast to the mode of action of currently available antiviral agents. This mechanism of action explains the effectiveness of docosanol against all tested lipid- enveloped viruses that employ fusion as the sole or major means of entry into the cell and contrasts its mode of action to other antiviral agents that target a single viral protein.
Pharmacokinetics
Under conditions reflecting normal clinical use of ABREVA(r) (docosanol cream 10%), the active ingredient could not be quantified (LOQ=10 ng/mL) in the plasma of treated patients. Ten women with active oral-facial herpes simplex lesions were treated with ABREVA(tm), applied as a single dose (Day 1), and as multiple topical doses (five times daily, Days 2 and 3). Blood samples were withdrawn up to 24 hours after treatment and analyzed for docosanol. Of the 209 plasma samples analyzed, the docosanol level was below the limit of quantitation in 208 and exactly 10 ng/mL in the other.
n
-Docosanoic acid, the major metabolite of docosanol, is an endogenous component of cell membranes in man, particularly in erythrocytes, brain, nerve myelin sheath, lung and kidney.
Store between 15oC - 25oC. Do not freeze.
ABREVA(r) (docosanol cream 10%) is available in a 2g tube or a 2g pump. Each gram of cream contains: docosanol 100 mg (10%). Nonmedicinal ingredients: sucrose stearate (and) sucrose distearate, light mineral oil, propylene glycol, benzyl alcohol, and purified water.