Sklice

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The data described below reflect exposure to a single 10 minute treatment of SKLICE Lotion in 379 patients, ages 6 months and older, in placebo-controlled trials. Of these subjects, 47 subjects were age 6 months to 4 years, 179 subjects were age 4 to 12 years, 56 subjects were age 12 to 16 years and 97 subjects were age 16 or older. Adverse reactions, reported in less than 1% of subjects treated with SKLICE Lotion, include conjunctivitis, ocular hyperemia, eye irritation, dandruff, dry skin, and skin burning sensation.

Included as part of the PRECAUTIONS section.

Oral:

Before taking ivermectin,

• tell your doctor and pharmacist if you are allergic to ivermectin or any other medications.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.
• tell your doctor if you have or have ever had meningitis, human African trypanosomiasis (African sleeping sickness; an infection that is spread by the bite of the tsetse fly in certain African countries), or conditions that affect your immune system, such as human immunodeficiency virus (HIV).
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant during your treatment with ivermectin, call your doctor.
• ask your doctor about the safe use of alcoholic beverages while you are taking ivermectin.
• if you have had loiasis (Loa loa infection with a type of worm that causes skin and eye problems) or if you have ever lived in or traveled to areas of West or Central Africa where loiasis is common.

Topical:

Before using ivermectin lotion, tell your healthcare provider if you or your child:

• have any skin conditions or sensitivities
• have any other medical conditions
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed
• are taking any prescription and/or nonprescription medications, vitamins, nutritional supplements, and herbal products

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Burning, itching, redness, or stinging of the skin
• burning, dry, or itching eyes
• dandruff
• discharge or excessive tearing
• dry skin
• redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Use Sklice as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Follow how to use as you have been told by the doctor or read the package insert.
• Do not take this medicine by mouth. Use on your scalp and hair only. Keep out of your mouth, nose, ears, and eyes (may burn).
• If you get Sklice in any of these areas, rinse well with water.
• Do not wet hair before putting on lotion.
• Rub into dry hair and scalp all the way.
• Wash your hands after use.
• Leave on your hair and scalp for 10 minutes.
• After 10 minutes, fully rinse hair and scalp with water only.
• Throw away any part not used after use.
• After using this medicine, wait 24 hours before using shampoo on hair and scalp.
• Use special nit comb or tweezers to get rid of dead nits (lice eggs) from hair.
• Wash all bedding, towels, and recently worn clothes in hot water or have them dry cleaned.
• Wash all combs, brushes, and hair clips in hot water.

What do I do if I miss a dose?

• Most of the time, only one dose of Sklice is needed. If you forget to put on the dose, put it on as soon as you think about it.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Irritation where Sklice is used.
• Burning.
• Dry skin.
• Eye irritation.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

None.

Pregnancy

Risk Summary

There are no studies with the use of Sklice Lotion in pregnant women. Epidemiologic studies with the use of oral ivermectin during pregnancy are insufficient to inform a drug-associated risk of adverse developmental outcomes, because either the timing of administration during gestation was not accurately ascertained or the administration occurred only during the second trimester (see Data). However, systemic exposure from topical use of ivermectin is much lower than that from oral use [see Clinical Pharmacology (12.3)]. In animal reproduction studies, ivermectin induced adverse developmental outcomes when orally administered to pregnant mice, rats and rabbits during the period of organogenesis only at or near doses that were maternally toxic to the pregnant females [see Data].

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Human Data

Four published epidemiology studies, all performed in rural Africa to treat soil-transmitted helminths, evaluated pregnancy outcomes in a total of 744 women exposed to oral ivermectin in various stages of pregnancy. In the largest of these studies, 397 women in their second trimester of pregnancy were treated open-label with single doses of oral ivermectin, or ivermectin plus albendazole, for soil-transmitted helminths and compared with a pregnant, non-treated population. No differences in pregnancy outcomes were observed between treated and untreated populations. These studies cannot definitively establish or exclude the absence of any drug-associated risk during pregnancy, because either the timing of administration during gestation was not accurately ascertained or the administration occurred only during the second trimester.

Animal Data

No comparisons of animal exposure with human exposure are made due to the low systemic exposure noted in the clinical pharmacokinetic study [see Clinical Pharmacology (12.3)].

Systemic embryofetal development studies were conducted in mice, rats and rabbits. Oral doses of ivermectin at 0.1, 0.2, 0.4, 0.8, and 1.6 mg/kg/day were administered during the period of organogenesis to pregnant female mice. Maternal death occurred at 0.4 mg/kg/day and above. Cleft palate occurred in the fetuses from the 0.4, 0.8, and 1.6 mg/kg/day groups. Exencephaly was seen in the fetuses from the 0.8 mg/kg group. Oral doses of ivermectin at 2.5, 5, and 10 mg/kg/day were administered during the period of organogenesis to pregnant female rats. Maternal death and pre-implantation loss occurred at 10 mg/kg/day. Cleft palate and wavy ribs were seen in fetuses from the 10 mg/kg/day group. Oral doses of ivermectin at 1.5, 3, and 6 mg/kg/day were administered during the period of organogenesis to pregnant female rabbits. Maternal toxicity and abortion occurred at 6 mg/kg/day. Cleft palate and clubbed forepaws occurred in the fetuses from the 3 and 6 mg/kg groups. These teratogenic effects were found only at or near doses that were maternally toxic to the pregnant female. Therefore, ivermectin does not appear to be selectively fetotoxic to the developing fetus.

Lactation

Risk Summary

There is information available on the presence of ivermectin in human milk in 4 lactating women after a single 150 mcg/kg oral dose of ivermectin. However, there is insufficient information from this study to determine the effects of ivermectin on the breastfed infant or the effects of ivermectin on milk production.

Topical ivermectin systemic exposure is much lower than that for oral ivermectin [see Clinical Pharmacology (12.3)]. Furthermore, the amount of ivermectin present in human milk after topical application of Sklice to lactating women has not been studied.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Sklice Lotion and any potential adverse effects on the breastfed infant from Sklice Lotion or from the underlying maternal condition.

Clinical Considerations

Advise a lactating woman to avoid accidental transfer of Sklice Lotion to breast area where the infant might directly ingest the drug.

Pediatric Use

The safety and effectiveness of Sklice Lotion have been established for pediatric patients 6 months of age and older [see Clinical Pharmacology (12.3) and Clinical Studies (14)].

The safety of Sklice Lotion has not been established in pediatric patients below the age of 6 months. Sklice Lotion is not recommended in pediatric patients under 6 months of age because of the potential increased systemic absorption due to a high ratio of skin surface area to body mass and the potential for an immature skin barrier and risk of ivermectin toxicity.

Geriatric Use

Clinical studies of Sklice Lotion did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Sklice Lotion or ivermectin.

Ivermectin was not genotoxic in vitro in the Ames test, the mouse lymphoma assay, or the unscheduled DNA synthesis assay in human fibroblasts.

Ivermectin had no adverse effects on fertility in rats at repeated oral doses of up to 3.6 mg/kg/day.

Two identical multi-center, randomized, double-blind, vehicle-controlled studies were conducted in subjects 6 months of age and older with head lice infestation. All subjects received a single application of either Sklice Lotion or vehicle control with instructions not to use a nit comb. For the evaluation of efficacy, the youngest subject from each household was considered to be the index subject of the household (N=289). Other enrolled infested household members received the same treatment as the youngest subject and were evaluated for all safety parameters [see Adverse Reactions (6.1)].

The primary efficacy was assessed as the proportion of index subjects who were free of live lice at day 2 and through day 8 to the final evaluation 14 (+2) days following a single application. Subjects with live lice present at any time up to the final evaluation were considered treatment failures. Table 1 contains the proportion of subjects who were free of live lice in each of the two trials.