Vaniqa Product Monograph

ACTION AND CLINICAL PHARMACOLOGY

VANIQA^® irreversibly inhibits ornithine decarboxylase in vitro and in vivo. This enzyme is integral in hair shaft production by the follicle. In preclinical and clinical studies, eflornithine administered topically has been shown to reduce the rate of hair growth.

Pharmacokinetics

The steady-state cutaneous penetration of eflornithine hydrochloride is minimal (less than 1%) after multiple-dose topical application of VANIQA^® to visibly intact facial skin of hirsute women. Absorption was determined under conditions of clinical use including shaving. Steady -state plasma levels are reached within four days of twice-daily application. The apparent plasma t_1/2 of eflornithine is approximately 8 hrs. The steady-state C_max , C_trough and AUC_{12 hr}, expressed in terms of the anhydrous free base, following twice-daily topical application of 0.5g of the VANIQA^® cream are approximately 10 ng/ml, 5 ng/ml, and 92 ng•hr/ml, respectively. Eflornithine is not known to be metabolized and is excreted unchanged in the urine.

INDICATIONS AND CLINICAL USE

VANIQA^® is indicated for slowing of the growth of unwanted facial hair in women. It is recommended as an adjunct to any hair removal technique.

VANIQA^® Cream has only been studied on the face and neck of affected women. Usage should be limited to those areas.

CONTRAINDICATIONS

Hypersensitivity to eflornithine or to any of the excipients of VANIQA^®.

WARNINGS

None.

PRECAUTIONS

General

VANIQA^® is for topical use only. Avoid contact with eyes or mucous membranes (e.g., nose or mouth). Discontinue use if hypersensitivity occurs. If skin irritation or intolerance develops, the patient should be directed to temporarily reduce the frequency of application to once per day. If irritation continues, the patient should discontinue use of VANIQA^® and consult their physician.

Transient stinging or burning may occur when applied to abraded or broken skin.

Use in the elderly: Of the total number of patients in clinical trials with VANIQA^® (n = 1370), approximately 6% were 65 years or older, while approximately 1% were 75 years or older. No overall differences in safety were observed between older and younger patients.

Use in children: The safety and effectiveness of this product in pediatric patients have not been established.

Adolescents: The safety and efficacy of this product in adolescent patients has not been established.

Nursing mothers: It is not known whether or not eflornithine hydrochloride is excreted in human milk. Caution should be exercised when VANIQA^® cream is administered to a nursing woman.

Use in pregnancy: There are no well-controlled studies of VANIQA^® Cream in pregnant women. Therefore, VANIQA^® should be used during pregnancy only if the physician considers the potential benefits to outweigh the potential risks to the fetus.

Hepatic and Renal Impairment: Safety and efficacy of VANIQA^® Cream in patients with hepatic or renal impairment have not been established. Considering the low systemic exposure after topical application, problems would not be expected.

Drug interaction: None known

INFORMATION FOR PATIENTS

Patients using VANIQA^® cream should receive the following information and instructions:

1. 1. This medication is not a depilatory, but rather appears to reduce hair growth to improve the condition and the patient's appearance. Patients will likely need to continue using a hair removal method (e.g. shaving, plucking, etc.) in conjunction with VANIQA^®.
2. 2. Onset of improvement may be seen after as little as 4-8 weeks of treatment. Further improvement may be seen with continued use. The condition may return to pretreatment levels 8 weeks after discontinuing treatment.
3. 3. If skin irritation or intolerance develops, direct the patient to temporarily reduce the frequency of application (e.g., once a day). If irritation continues, the patient should discontinue use of the product.

ADVERSE REACTIONS

Adverse reactions reported for most body systems occurred at similar frequencies in active and vehicle groups. The most frequent adverse reactions related to treatment with VANIQA^® Cream were skin related. The following table notes the skin-related adverse reactions that occurred in greater than 1% of patients treated with VANIQA^® or vehicle in controlled studies.

Incidence Attributed to Therapy

Percentage (%) of Patients

Treatment related skin adverse reactions that occurred in less than 1% of the subjects treated with VANIQA^® Cream are: bleeding skin, cheilitis, contact dermatitis, edema face, edema mouth, folliculitis, hair ingrown, herpes simplex, numbness and rosacea.

Adverse reactions were primarily mild in intensity and generally resolved without medical treatment or discontinuation of VANIQA^® Cream. No serious adverse reactions were related to treatment. Only 2% of subjects discontinued studies due to an adverse reaction related to use of VANIQA^® Cream. The drug was generally well tolerated.

Laboratory Test Abnormalities

No laboratory test abnormalities have been found to be associated with VANIQA^® Cream.

SYMPTOMS AND TREATMENT OF OVERDOSAGE

Dermal Administration

Given the minimal cutaneous penetration of this drug, overdosage via the topical route is not expected (see clinical pharmacology). However, should very high topical doses (e.g. multiple tubes per day) or oral ingestion be encountered (e.g., a 60 g tube contains 9 g of eflornithine HCI), the patient should be monitored, and appropriate supportive measures administered as necessary.

Intravenous Administration

Adverse effects and laboratory abnormalities have been noted with intravenous

administration of high doses of eflornithine hydrochloride (400 mg/kg/day or approximately 24 g/day) for the treatment of Trypanosoma brucei gambiense infection (African sleeping sickness). Adverse events have included hair loss, facial swelling, seizures, hearing impairment, stomach upset, loss of appetite, headache, weakness and dizziness. A variety of hematological toxicities, including anemia, thrombocytopenia and leukopenia have also been observed, but these were usually reversible upon discontinuation of treatment.

DOSAGE AND ADMINISTRATION

Apply a thin layer of VANIQA^® Cream to affected areas of the face and neck and rub in thoroughly. The treated area should not be washed for at least 4 hours after application. VANIQA^® should be used twice daily at least 8 hours apart. The product may be used alone or in conjunction with other hair removal techniques. VANIQA^® may be applied 5 minutes after shaving or other hair removal techniques. Cosmetics or sunscreens may be applied over treated areas after cream has dried.

Elderly: No dosage adjustment is necessary.

PHARMACEUTICAL INFORMATION

I. DRUG SUBSTANCE

Trade name:

VANIQA^®

Proper names: eflornithine HCI; difluoromethylornithine

Chemical Name:

2-(difluoromethyl)- DL-ornithine monohydrochloride monohydrate

Empirical Formula: C₆H₁₂F₂N₂O₂^.HCI^.H₂O

Structural Formula:

Molecular Weight: 236.65

Description: Eflornithine is a white crystalline solid. It is soluble in methanol and soluble in water up to 436 g/L. It is slightly soluble in ether, chloroform, acetone and ethanol.

II. COMPOSITION

In addition to the active ingredient, eflornithine hydrochloride, the cream contains: water, glyceryl stearate, PEG-100 stearate, cetearyl alcohol, ceteareth-20, mineral oil, stearyl alcohol, dimethicone, phenoxyethanol, methylparaben and propylparaben.

III. STORAGE

Store between 15 to 25°C.

AVAILABILITY OF DOSAGE FORM

VANIQA^® Cream is available in 15, 30 and 60 g plastic tubes. VANIQA^® is formulated as a smooth white to off-white, fragrance-free cream containing 13.9% (139 mg/g) of anhydrous eflornithine hydrochloride. See tube crimp and carton end for expiration date and lot number.