Solantra, cream 1% 30 g

An antimicrobial and antiprotozoal agent.

Pharmacodynamics

Ivermectin belongs to the group of avermectin. which has an anti-inflammatory effect by inhibiting the production of inflammatory cytokines induced by lipopolysaccharides.

The anti-inflammatory properties of ivermectin for external use have been observed in models of inflammatory skin processes in animals. Ivermectin also causes death of parasites, mainly through selective binding and high affinity for glutamate-regulated chlorine channels found in nerve and muscle cells of invertebrates.

The mechanism of action of Solantra in treating inflammatory skin lesions in rosacea is not known, but may be related both to the anti-inflammatory effects of ivermectin and to the ability of ivermectin to induce Demodex mites, which in turn cause skin inflammation.

Pharmacokinetics

Ivermectin in Solantra was evaluated in a clinical study in adult patients with severe papulopustular rosacea using the maximum tolerated dose of the drug.

At equilibrium (after 2 weeks of treatment), the highest mean (± standard deviation) plasma ivermectin concentrations were observed within 10 ± 8 hours of drug administration (Cmax 2.1 ± 1.0 ng/mL, range: 0.7-4.0 ng/mL), and the highest mean (± standard deviation) AUC0-244 was 36 ± 16 ng/mL, range: 14-75 ng/mL).

The systemic exposure of ivermectin reached a plateau by the end of the second week of equilibrium treatment. For longer treatments in phase 3 studies, the systemic exposure rate of ivermectin remained the same as after two weeks of treatment.

The systemic exposure levels of ivermectin (AUC0-244: 36 ± 16 ng h/mL) were lower under equilibrium concentration conditions than after a single oral dose of 6 mg of ivermectin in healthy volunteers (AUC0-244: 134 ± 66 ng h/mL).

Distribution

In vitro studies have shown that the binding of ivermectin to plasma proteins (predominantly to albumin) is over 99%. Significant binding of ivermectin to erythrocytes was not observed.

Metabolism

In in vitro studies using human liver microsomes and recombinant CYP450 enzymes it was noted that ivermectin is metabolized mainly through CYP3A4 inhibitors.

In vitro studies have shown that ivermectin does not inhibit the CYP450 isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, WA4, 4A11 or 2E1.

Ivermectin does not induce the expression of CYP450 enzymes (1A2, 2B6, 2C9 or WA4) in human hepatocyte culture. The 2 major metabolites of ivermectin (3″-0-demethyl ivermectin and 4a-hydroxy ivermectin) were identified in a clinical pharmacokinetic study of the maximum tolerated dose of the drug and were studied in a phase 2 clinical trial.

Similar to the parent compound, metabolites reached equilibrium by the end of the second week of treatment, with no evidence of accumulation noted for up to 12 weeks. In addition, systemic metabolite exposures (assessed using Cmax and AUC) obtained at equilibrium were much lower than those after oral administration of ivermectin.

Elimination

The final half-life, on average, was 6 days (approximately 145 hours, range: 92-238 hours) in patients who applied the drug to the skin once daily for 28 days in a clinical pharmacokinetic study using the maximum tolerated dose of the drug.

Extraction from the body depends on the degree of absorption after external application of Solantra cream. The pharmacokinetics of ivermectin have not been studied in patients with impaired hepatic or renal function.

Indications

Active ingredient

Composition

1 g of the cream contains:

The active ingredient:

Ivermectin 10.0 mg.

Excipients:

Glycerol 40.0 mg,

Isopropylpalmitate 40.0 mg,

Carbomer copolymer type B 2.0 mg,

Dimethicone 20 Cst 5.0 mg,

Dinatrium edetate 0.5 mg,

How to take, the dosage

For external use only.

Apply Solantra cream once a day every day for the entire course of treatment – up to 4 months. The treatment can be repeated if necessary.

If there is no improvement after 3 months of application, treatment should be discontinued.

Please apply a small amount of cream (pea-sized) to each of the five areas of the face: forehead, chin, nose and cheeks. Spread the product sparingly over the entire face, avoiding contact with eyes, lips and mucous membranes.

Solantra should only be applied to the face.

In patients with impaired renal function and elderly patients, no dose adjustment is necessary.

Interaction

There have been no studies of drug interactions with other medicinal products.

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

Cautions must be taken when using ivermectin concomitantly with potent CYP3A4 inhibitors, because plasma concentrations of the drug may increase significantly.

Special Instructions

The medicinal product contains:

– cetyl alcohol and stearyl alcohol, which may cause local skin reactions (e.g., contact dermatitis),

– methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216), which can cause allergic reactions (including delayed type),

propylene glycol, which can cause skin irritation.

Wash hands after applying the medication.

Cosmetics can be applied after the medication has dried.

Contraindications

– Hypersensitivity to the active substance or any other component of the drug;

– pregnancy;

– period of breast-feeding;

– childhood under 18 years (the safety and effectiveness of the drug for this age group has not been studied).

With caution:

Liver function disorders.

Side effects

The most common adverse reactions, such as burning sensation, skin irritation, itching and dry skin, have been reported in less than 1% of patients treated with the drug in clinical trials.

In general, these reactions are mild to moderate and usually subside with continued therapy.

There were no significant differences in the safety profile between patients aged 18 to 65 years and patients over 65 years.

Overdose

No cases of overdose of Solantra have been reported.

When accidental or significant exposure to unknown amounts of veterinary dosage forms of ivermectin in humans (ingestion, inhalation, parenteral administration or contact with the body surface), the following symptoms were most frequently reported: skin rash, facial edema, swelling of the eyelids, headache, dizziness, asthenia, nausea, vomiting and diarrhea.

Other reported adverse reactions include: seizures, ataxia, shortness of breath, abdominal pain, paresthesias, urticaria, and contact dermatitis.

In case of accidental ingestion of the drug, symptomatic therapy including parenteral administration of fluids and electrolytes, respiratory support (ensuring oxygen supply and, if necessary, artificial lung ventilation) and vasopressors (if there is a marked decrease in blood pressure) are provided.

In order to prevent absorption of the ingested drug, inducing vomiting and/or urgent gastric lavage may be indicated, followed by the use of laxatives and other measures to eliminate intoxication.

Pregnancy use

Pregnancy

There are limited or no data on the use of ivermectin in pregnant women. Studies of reproductive toxicity with oral administration of ivermectin have shown that the drug has teratogenic potential in rats and rabbits, but because of its low systemic effects when used topically at the recommended dose, the drug has a low risk of fetotoxicity in humans.

The use of Solantra during pregnancy is not recommended.

Breastfeeding

Low concentrations of ivermectin are excreted into breast milk after oral administration. Excretion of ivermectin into breast milk has not been studied when the drug is used externally.

Pharmacokinetic and toxicological data from animal studies also indicate excretion of ivermectin into breast milk. The risk to the infant cannot be excluded. If it is necessary to use the drug, the attending physician should be consulted to decide whether to stop breastfeeding.

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