Solantra^® (Cream) Instructions for Use

Marketing Authorization Holder

Galderma, SA (Switzerland)

Manufactured By

Laboratoires Galderma (France)

Contact Information

GALDERMA SA (Switzerland)

ATC Code

D11AX22 (Ivermectin)

Active Substance

Ivermectin (Rec.INN registered by WHO)

Dosage Form

Solantra®

Cream for external use 1%: tubes 15 g or 30 g

Dosage Form, Packaging, and Composition

Cream for external use from white to light yellow in color.

Excipients: glycerol – 40 mg, isopropyl palmitate – 40 mg, carbomer copolymer type B – 2 mg, dimethicone 20 Cst – 5 mg, disodium edetate – 0.5 mg, citric acid monohydrate – 0.5 mg, cetyl alcohol – 35 mg, stearyl alcohol – 25 mg, peg cetostearyl ether – 30 mg, sorbitan stearate – 20 mg, methylparaben – 2 mg, propylparaben – 1 mg, phenoxyethanol – 10 mg, propylene glycol – 20 mg, oleyl alcohol – 20 mg, sodium hydroxide solution 10% – to pH 6.3±0.3, purified water – up to 1000 mg.

15 g – laminated tubes (1) – cardboard boxes.
30 g – laminated tubes (1) – cardboard boxes.

Clinical-Pharmacological Group

Drug for the treatment of inflammatory skin lesions in rosacea

Pharmacotherapeutic Group

Other dermatological preparations

Pharmacological Action

Ivermectin belongs to the avermectin group, which exerts an anti-inflammatory effect by suppressing the production of inflammatory cytokines induced by lipopolysaccharides.

The anti-inflammatory properties of topical ivermectin were observed in animal models of skin inflammatory processes. Ivermectin also causes parasite death, mainly through selective binding and high affinity to glutamate-regulated chloride channels located in the nerve and muscle cells of invertebrates.

The mechanism of action of Solantra^® in the treatment of inflammatory skin lesions in rosacea is unknown but may be associated with both the anti-inflammatory effects of ivermectin and the ability of ivermectin to cause the death of Demodex mites, which, in turn, are a factor causing skin inflammation.

Pharmacokinetics

Absorption

The absorption of ivermectin contained in Solantra^® was evaluated in a clinical study involving adult patients with severe papulopustular rosacea who applied the maximum allowable dose of the drug.

At steady state (after 2 weeks of treatment), the highest mean (± standard deviation) plasma concentrations of ivermectin were observed within 10±8 hours after drug application (C_max 2.1±1.0 ng/ml, range 0.7-4.0 ng/ml), and the highest mean (± standard deviation) AUC_{0-24 h} was 36±16 ng×h/ml, range 14-75 ng×h/ml).

Systemic exposure to ivermectin reached a plateau by the end of the second week of treatment under steady-state conditions. During longer-term treatment in phase 3 studies, the systemic exposure index of ivermectin remained the same as after two weeks of treatment.

Under steady-state concentration conditions, systemic exposure levels of ivermectin (AUC_{0-24 h} 36±16 ng×h/ml) were lower than after a single oral dose of 6 mg ivermectin in healthy volunteers (AUC_{0-24 h} 134 ±66 ng×h/ml).

Distribution

An in vitro study showed that the binding of ivermectin to plasma proteins (primarily albumin) is more than 99%. No significant binding of ivermectin to erythrocytes was observed.

Metabolism

In vitro studies using human liver microsomes and recombinant CYP450 enzymes noted that Ivermectin is metabolized mainly with the participation of CYP3A4 inhibitors.

In vitro studies have shown that Ivermectin does not inhibit the CYP450 isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, 4A11 or 2E1.

Ivermectin does not induce the expression of CYP450 enzymes (1A2, 2B6, 2C9 or 3A4) in human hepatocyte culture.

Two main metabolites of ivermectin (3"-O-demethyl Ivermectin and 4a-hydroxy Ivermectin) were identified during the clinical pharmacokinetic study using the maximum allowable dose of the drug and were studied during phase 2 clinical trials.

Similar to the parent compound, the metabolites reached steady state by the end of the second week of treatment, with no signs of accumulation observed for up to 12 weeks.

Furthermore, the systemic exposures of the metabolites (assessed using C_max and AUC), obtained at steady state, were much lower than those after oral administration of ivermectin.

Excretion

The terminal T_1/2 averaged 6 days (approximately 145 hours, range 92-238 hours) in patients who applied the drug to the skin once daily for 28 days during the clinical pharmacokinetic study using the maximum allowable dose of the drug.

Elimination from the body depends on the degree of absorption after topical application of Solantra^® cream.

The pharmacokinetics of ivermectin have not been studied in patients with impaired liver or kidney function.

Indications

• Treatment of inflammatory skin lesions in rosacea (papulopustular form) in adult patients.

ICD codes

Dosage Regimen

For external use only.

Apply Solantra^® cream once daily throughout the entire course of treatment – up to 4 months. If necessary, the course of treatment can be repeated.

If there is no improvement after 3 months of using the drug, treatment should be discontinued.

A small amount of cream (the size of a pea) should be applied to the skin of each of the five facial areas: forehead, chin, nose, and cheeks. Spread the drug in a thin layer over the entire face, avoiding contact with eyes, lips, and mucous membranes.

Solantra^® should be applied only to the face.

No dose adjustment is required in patients with impaired renal function or in elderly patients.

Adverse Reactions

In clinical trials, the most common (<1%) adverse reactions observed in patients treated with the drug were burning sensation, skin irritation, itching, and dry skin.

These reactions are generally mild or moderate and usually subside with continued therapy.

No significant differences in the safety profile were noted between patients aged 18 to 65 years and patients over 65 years of age.

Adverse reactions obtained during clinical trials of Solantra^® are presented in Table 1.

These reactions are classified by organ system and frequency of occurrence as follows: very common (≥1/10), common (from ≥1/100 to <1/10), uncommon (from ≥1/1000 to <1/100), rare (from ≥1/10000 to <1/1000), very rare (<1/10000), unknown (cannot be estimated from the available data).

Table 1

* Data from post-marketing surveillance.

If any of the mentioned side effects worsen or any other side effects not listed in the instructions are noted, you should immediately inform your doctor.

Contraindications

• Hypersensitivity to the active substance or any other component of the drug;
• Pregnancy;
• Breastfeeding period;
• Children under 18 years of age (safety and efficacy of the drug for this age category have not been studied).

With caution impaired liver function.

Use in Pregnancy and Lactation

Pregnancy

Data on the use of ivermectin in pregnant women are limited or absent.

Reproductive toxicity studies with oral ivermectin have shown that the drug has teratogenic potential in rats and rabbits; however, due to low systemic exposure with topical application at the recommended dose, the drug has a low risk of fetotoxicity in humans.

The use of Solantra^® during pregnancy is not recommended.

Breastfeeding period

After oral administration, low concentrations of ivermectin are excreted in breast milk.

The excretion of ivermectin in breast milk with topical application of the drug has not been studied.

Pharmacokinetic and toxicological data obtained from animal studies also indicate the excretion of ivermectin in breast milk.

The risk to the breastfed infant cannot be excluded. If it is necessary to use the drug, you should consult your doctor to decide on discontinuing breastfeeding.

Use in Hepatic Impairment

The drug should be prescribed with caution in case of impaired liver function.

Use in Renal Impairment

No dose adjustment is required in patients with impaired renal function.

Pediatric Use

Contraindicated for use in children under 18 years of age.

Geriatric Use

No dose adjustment is required in elderly patients.

Special Precautions

Patients may experience a temporary exacerbation of rosacea, which is a reaction to the death of Demodex mites, and which usually resolves within 1 week with continued treatment.

In case of severe exacerbation with a severe skin reaction, treatment should be discontinued.

Solantra^® contains: cetyl alcohol and stearyl alcohol, which may cause local skin reactions (e.g., contact dermatitis); methylparaben (E218) and propylparaben (E216), which may cause allergic reactions (including delayed-type); propylene glycol, which may cause skin irritation.

After applying the drug, wash your hands.

After the drug has dried, cosmetic products can be applied.

Effect on ability to drive vehicles and operate machinery

Solantra^® does not affect or insignificantly affects the ability to drive vehicles and operate machinery.

Overdose

No cases of overdose with Solantra^® have been reported.

In cases of accidental or significant exposure of humans to unknown quantities of veterinary dosage forms of ivermectin (ingestion, inhalation, parenteral administration, or contact with the body surface), the following symptoms were most frequently noted: skin rash, facial edema, eyelid edema, headache, dizziness, asthenia, nausea, vomiting, and diarrhea.

Other reported adverse reactions include: seizures, ataxia, dyspnea, abdominal pain, paresthesia, urticaria, and contact dermatitis.

Treatment to prevent absorption of the ingested drug may include inducing vomiting and/or urgent gastric lavage, followed by the use of laxatives and other detoxification measures.

In case of accidental ingestion of the drug, symptomatic therapy is carried out, including parenteral administration of fluids and electrolytes, respiratory support (providing oxygen and, if necessary, mechanical ventilation) and vasopressors (in the presence of a pronounced decrease in blood pressure).

Drug Interactions

No studies on the interaction of the drug with other medicinal products have been conducted.

The concomitant use of Solantra^® cream with other topical and systemic drugs for the treatment of rosacea has not been studied.

Caution should be exercised when using ivermectin concomitantly with potent CYP3A4 inhibitors, as the plasma concentration of the drug may increase significantly.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

Shelf life – 2 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.