Soolantra Cream

Pregnancy

Pregnancy Category C.
There are no adequate and well-controlled studies in pregnant women. Soolantra Cream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Note: The animal multiples of human exposure calculations were based on AUC comparisons. The maximum topical human dose (MTHD) of Soolantra Cream is 1 g applied once daily.

Systemic embryofetal development studies were conducted in rats and rabbits. Oral doses of 1.5, 4, and 12 mg/kg/day ivermectin were administered during the period of organogenesis (gestational days 6–17) to pregnant female rats. Maternal death occurred at 12 mg/kg/day (1909X MTHD). Cleft palate occurred in the fetuses from the 12 mg/kg/day (1909X MTHD) group. No treatment related effects on embryofetal toxicity or teratogenicity were noted at 4 mg/kg/day (708X MTHD). Oral doses of 0.5, 1.5, 2.5, 3.5 and 4.5 mg/kg/day ivermectin were administered during the period of organogenesis (gestational days 7–20) to pregnant female rabbits. Maternal death occurred at doses >2.5 mg/kg/day (72X MTHD). Carpal flexure occurred in the fetuses from the 4.5 mg/kg/day (354X MTHD) group. Fetal weight decrease was noted at 3.5 mg/kg/day (146X MTHD). No treatment related effects on embryofetal toxicity were noted at 2.5 mg/kg/day (72X MTHD) and no treatment related effects on teratogenicity were noted at 3.5 mg/kg/day (146X MTHD).

A pre- and postnatal development study was conducted in rats. Oral doses of 1, 2 and 4 mg/kg/day ivermectin were administered to pregnant female rats during gestational days 6-20 and lactation days 2-20. Neonatal death occurred at doses >2 mg/kg/day. Behavior development of newborn rats was adversely affected at all doses.

Nursing Mothers

Following oral administration, ivermectin is excreted in human milk in low concentrations. Excretion in human milk following topical administration has not been evaluated. In oral studies in rats, ivermectin was excreted in the milk of nursing mothers and neonatal toxicity was observed in the litters. The blood-brain barrier in neonatal rats may not be fully developed at birth. Because of the potential for serious adverse reactions from Soolantra Cream in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness of Soolantra Cream in pediatric patients have not been established.

Geriatric Use

Of the 1371 subjects in the two pivotal clinical studies of Soolantra Cream, 170 (12.4%) were 65 and over, while 37 (2.7%) were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

In accidental or significant exposure to unknown quantities of veterinary formulations of ivermectin in humans, either by ingestion, inhalation, injection, or exposure to body surfaces, the following adverse effects have been reported most frequently: rash, edema, headache, dizziness, asthenia, nausea, vomiting, and diarrhea. Other adverse effects that have been reported include: seizure, ataxia, dyspnea, abdominal pain, paresthesia, urticaria, and contact dermatitis.

In case of accidental ingestion, supportive therapy, if indicated, should include parenteral fluids and electrolytes, respiratory support (oxygen and mechanical ventilation if necessary) and pressor agents if clinically significant hypotension is present. Induction of emesis and/or gastric lavage as soon as possible, followed by purgatives and other routine anti-poison measures, may be indicated if needed to prevent absorption of ingested material.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 2-year dermal mouse carcinogenicity study, ivermectin was administered to CD-1 mice at topical doses of 1, 3, and 10 mg/kg/day (0.1%, 0.3% and 1% ivermectin cream applied at 2 ml/kg/day). No drug-related tumors were noted in this study up to the highest dose evaluated in this study of 10 mg/kg/day (747X maximum topical human dose [MTHD]).

In a 2-year oral rat carcinogenicity study, ivermectin was administered to Wistar rats at gavage doses of 1, 3, and 9 mg/kg/day. A statistically significant increase in the incidence of hepatocellular adenoma was noted in males treated with 9 mg/kg/day (1766X MTHD) ivermectin. The clinical relevance of this finding is unknown. No drug-related tumors were noted in females up to the highest dose evaluated in this study of 9 mg/kg/day (1959X MTHD). No drug-related tumors were noted in males at doses ≤ 3 mg/kg/day (599X MTHD).

Ivermectin revealed no evidence of genotoxic potential based on the results of two in vitro genotoxicity tests (the Ames test and the L5178Y/TK+/- mouse lymphoma assay) and one in vivo genotoxicity test (rat micronucleus assay).

In a fertility study, oral doses of 0.1, 1 and 9 mg/kg/day ivermectin were administered to male and female rats. Mortality occurred at 9 mg/kg/day (1027X MTHD). The precoital period was generally prolonged at 9 mg/kg/day. No treatment-related effects on fertility or mating performance were noted at doses ≤ 1 mg/kg/day (68X MTHD).

Soolantra Cream applied once daily at bedtime was evaluated in the treatment of inflammatory lesions of rosacea in two randomized, double-blind, vehicle controlled clinical trials, which were identical in design. The trials were conducted in 1371 subjects aged 18 years and older who were treated once daily for 12 weeks with either Soolantra Cream or vehicle cream.

Overall, 96% of subjects were Caucasian and 67% were female. Using the 5-point Investigator Global Assessment (IGA) scale (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe), 79% of subjects were scored as moderate (IGA=3) and 21% scored as severe (IGA= 4) at baseline.

The co-primary efficacy endpoints in both pivotal trials were the success rate based on the IGA outcome (percentage of subjects “clear” and “almost clear”) and absolute change from baseline in inflammatory lesion counts at Week 12. Table 1 presents the co-primary efficacy results at Week 12. Soolantra Cream was more effective than vehicle cream on the co-primary efficacy endpoints starting from 4 weeks of treatment in both studies, see Figures 1 through 4.

Table 1: Co-Primary Efficacy Results at Week 12

Figures 1 and 2: IGA Success Rates Over Time

Figures 3 and 4: Mean Absolute Change in Inflammatory Lesion Counts from Baseline Over Time

SOOLANTRA (ivermectin) cream, 1% is a white to pale yellow cream, supplied in a laminated tube with a child resistant cap in the following sizes:
30 gram NDC 0299-3823-30
45 gram NDC 0299-3823-45
60 gram NDC 0299-3823-60

Storage
Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP Controlled Room Temperature].

Not for oral, ophthalmic, or intravaginal use.
To Open Tube: Push cap in and turn counterclockwise to remove cap.
Usual Dosage: Apply to the affected areas once daily. See package insert for complete prescribing information.
Each gram contains the active ingredient ivermectin 10 mg (1%) with the inactive ingredients carbomer copolymer type B, cetyl alcohol, citric acid monohydrate, dimethicone, edetate disodium, glycerin, isopropyl palmitate, methylparaben, oleyl alcohol, phenoxyethanol, polyoxyl 20 cetostearyl ether, propylene glycol, propylparaben, purified water, sodium hydroxide, sorbitan monostearate, and stearyl alcohol.
Storage: Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F).
[See USP Controlled Room Temperature].
See carton closure for lot number and expiration.

NDC 0299-3823-30

soolantra®

(ivermectin) cream, 1%

Rx only

For Topical Use Only

Keep Out of Reach of Children

NET WT. 30 g

GALDERMA

Lot No.:

Exp.:

Marketed by:

GALDERMA LABORATORIES, L.P.

Fort Worth, TX 76177 USA

Made in Canada

P52477-0 Rev.: 11/14