Included as part of the PRECAUTIONS section.
Patient Counseling Information
Advise the patient to read the FDA-approved patient
labeling (Instructions for Use).
Impairment Of Fertility
In a 2-year dermal mouse
carcinogenicity study, ivermectin was administered to CD-1 mice at topical
doses of 1, 3, and10 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
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 9mg/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 vivogenotoxicity test (rat
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).
Use In Specific Populations
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 ivermectinwere 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.
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.
Safety and effectiveness of SOOLANTRA cream in pediatric
patients have not been established.
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