Ivermectin (ROSIVER)

1. Health Canada Product Monograph — Ivermectin

• Ivermectin cream 1% (ROSIVER) is indicated for the topical treatment of inflammatory lesions of rosacea, including papules and pustules, in adults 18 years of age or older.
• It is intended for use only on the skin of the face and is not for oral, ophthalmic, or intravaginal use.

• Ivermectin cream is not recommended during pregnancy because there are no adequate, well-controlled studies of topical use in pregnant women.
• Oral ivermectin has been shown to be teratogenic in rats and rabbits at doses well above the exposure produced by topical use.
• Use during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

• Ivermectin is excreted into human breast milk after oral dosing, though excretion into milk after topical application specifically has not been studied.
• In animal studies, oral ivermectin reached higher concentrations in milk than in maternal plasma and caused toxic effects in nursing offspring.
• Because of the potential for serious reactions in a nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account its importance to the mother.

• Efficacy and safety in patients 65 years of age and older were comparable to those in younger adults in clinical trials.
• No dose adjustment is required based on age alone.

• Safety and effectiveness in patients under 18 years of age have not been established, and ivermectin cream is not recommended in this age group.

• Wash the affected area with a mild cleanser and dry it before application.
• Apply a pea-sized amount to each of five areas of the face (forehead, chin, nose, and each cheek) once daily at bedtime, spreading it as a thin, even layer across the entire face.
• Avoid contact with the eyes and lips, and wash the hands after each application.
• Do not apply cosmetics until the applied cream has dried.
• Apply only to facial skin; do not use on other parts of the body, and do not swallow the product.
• Do not cover treated areas with dressings or bandages.
• No dose adjustment has been established for hepatic or renal impairment, since systemic exposure from topical use is very low.
• If a dose is missed, resume the regular bedtime application at the next scheduled time; do not apply a double amount to make up for a missed dose.
• Improvement is usually noticed after about 4 weeks of treatment; if there is no improvement after 3 months, treatment should be discontinued and the patient reassessed.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• No cases of overdose have been reported with this topical 1% ivermectin cream itself.
• Accidental or significant exposure to veterinary ivermectin formulations in humans (by ingestion, inhalation, injection, or skin contact) has been associated with rash, swelling, headache, dizziness, weakness, nausea, vomiting, and diarrhea.
• Less commonly reported effects from veterinary-formulation exposure include seizures, unsteady gait, difficulty breathing, abdominal pain, tingling or numbness, hives, and contact dermatitis.

• A burning sensation of the skin may occur.
• Skin irritation may occur.
• Itching (pruritus) may occur.
• Dry skin may occur.
• Redness (erythema) at the application site may occur.
• Contact dermatitis, allergic or irritant, may occur.
• Worsening of underlying rosacea may occur.
• Swelling of the face may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Severe worsening of rosacea can occur; treatment should be discontinued if this happens.
• Hypersensitivity reactions, including significant swelling of the face, can occur and require discontinuation.
• Elevated liver enzyme levels have been reported rarely after use.
• Accidental ingestion or significant systemic exposure to ivermectin, as reported with non-topical formulations, can cause rash, swelling, headache, dizziness, weakness, nausea, vomiting, and diarrhea, and rarely seizures, an unsteady gait, difficulty breathing, abdominal pain, tingling, and hives.
• Seek urgent medical attention for a severe allergic reaction, significant facial swelling, or marked worsening of skin symptoms that does not improve with discontinuation.

• Use with caution in patients with known sensitivity to cetyl alcohol or stearyl alcohol, which can cause local contact dermatitis.
• Use with caution in patients with known sensitivity to the methylparaben or propylparaben preservatives, which can cause delayed allergic reactions.
• Use with caution in patients sensitive to propylene glycol, which can cause skin irritation.
• Avoid alcohol-based cleansers, astringents, abrasives, peeling agents, and other potentially irritating topical products or procedures at the same time, since their interaction with ivermectin cream has not been studied.
• Avoid excessive sun exposure, which can aggravate rosacea.
• Animal studies suggest a potential for delayed skin sensitization and photoallergic reactions; photosafety has not been specifically evaluated in humans.
• In case of accidental ingestion of the product, contact a regional Poison Control Centre; supportive treatment may include fluids, respiratory support, and gastrointestinal decontamination if needed.

• Contraindicated in patients with known hypersensitivity to ivermectin or to any ingredient in the formulation or component of the container.

• No clinical drug interaction studies have been conducted with ivermectin cream.
• Ivermectin is metabolized in the liver primarily by the CYP3A4 enzyme, but at the very low systemic concentrations reached with topical use, it neither inhibits nor induces cytochrome P450 (CYP450) enzymes.
• Based on the very low systemic exposure with topical application, no clinically relevant systemic drug-drug interactions are expected.
• Interactions with known skin irritants or photo-enhancing products have not been studied, so concurrent use of such products should be avoided.

• Food timing does not apply to this topical cream, as it is applied to the skin of the face rather than taken by mouth.

• Apply once daily at bedtime; timing is not related to meals since this is a topical product.

• Store at room temperature (15°C to 25°C).
• Keep out of reach and sight of children and pets.

• Ivermectin cream (ROSIVER) is a once-daily topical treatment for the inflammatory bumps and pimples of rosacea in adults.
• Apply a pea-sized amount to each of five facial areas at bedtime, avoiding the eyes and lips, and wash your hands afterward.
• Visible improvement usually takes about 4 weeks; tell your doctor if there is no improvement after 3 months.
• Skin burning, irritation, itching, and dryness are the most common effects; stop use and contact your doctor if your rosacea or skin reaction worsens significantly, or if you develop signs of an allergic reaction.