Ivermectin Cream 1% (HPI)

Ivermectin Cream 1% (HPI)

Product Name: Ивермектин крем 1%, Ivermectin Cream 1%, Ivermectin Creme 1%, Crema de Ivermectina 1%, Crème d’Ivermectine 1%, كريم إيفرمكتين 1%, ครีมไอเวอร์เม็กติน 1%, Ivermektin Krem 1%, Ивермектин креми 1%, İvermektin Krem 1%, Креми Ивермектин 1%, Ivermektinas kremas 1%, Ivermektīna krēms 1%, Івермектин крем 1%, קרם איברמקטין 1%

Main Indications for Use of Ivermectin Cream 1%: Scabies, facial demodicosis, inflammatory form of rosacea, perioral dermatitis, seborrheic dermatitis of the face with secondary parasitic flora.

Indications for Use of Ivermectin Cream 1% as Part of Therapeutic Complexes: Demodectic blepharitis, papulopustular acne vulgaris, chronic recurrent pyodermas, complicated parasitic dermatoses, malignant skin neoplasms (skin melanoma, basal cell carcinoma, squamous cell carcinoma) as part of experimental therapy regimens.

Main Pharmacological Properties of Ivermectin Cream 1%: antiparasitic, acaricidal, anti-inflammatory, antibacterial, keratolytic, antipruritic.

Composition of Ivermectin Cream 1%: Ivermectin, Cream base

Functions of the Components in Ivermectin Cream 1%:

• Ivermectin: exerts antiparasitic action, blocks glutamate-dependent chloride channels in the nervous system of arthropods, causing paralysis and death of Demodex mites and the scabies pathogen Sarcoptes scabiei; additionally reduces inflammatory manifestations.
• Cream base: ensures even distribution of the active substance on the skin, moisturizes and softens the skin, promotes penetration of the active component into the epidermis.

Product Form of Ivermectin Cream 1%: Topical cream in a 30 g tube. One tube contains 300 mg of the active substance Ivermectin and excipients of the cream base in sufficient quantity to form a soft dosage form.

Dosage of Ivermectin Cream 1%

Standard Dosage for Ivermectin Cream 1%: Apply a thin layer to the affected areas of the skin once daily in the evening before bedtime, avoiding contact with eyes, mouth, and mucous membranes. The standard dosage is used for the inflammatory form of rosacea, mild and moderate facial demodicosis, scabies with limited involvement. Do not wash off the cream; leave it on the skin overnight.

Enhanced Dosage for Ivermectin Cream 1%: Apply a thin layer twice daily (morning and evening) for severe forms of facial demodicosis, widespread scabies, pronounced papulopustular form of rosacea. Use is possible as part of combination therapy with systemic antiprotozoal or antibacterial agents. Enhanced dosage is prescribed only by a doctor.

Maximum Dosage for Ivermectin Cream 1%: Application up to 3 times a day locally on limited areas of the skin for resistant forms of demodicosis or complicated scabies. The duration of the course should not exceed 4 weeks without medical supervision. Used exclusively in the absence of effect from standard and enhanced regimens.

Pediatric Dosage for Ivermectin Cream 1%: Use in children under 18 years of age is not scientifically registered. Data on safety and efficacy in pediatric practice are lacking. Use is not recommended until reliable clinical studies are available.

Preventive Dosage for Ivermectin Cream 1%: Use for preventive purposes in chronic dermatoses is not registered. For the prevention of demodicosis or rosacea relapses, no scientific basis for the topical use of ivermectin 1% has been identified.

Contraindications for Ivermectin Cream 1%: Hypersensitivity to ivermectin or components of the cream base, presence of open wounds on the skin at the intended application sites. Scientifically, no reliable data on contraindications during pregnancy, lactation, and in pediatric patients have been registered.

Side Effects of Ivermectin Cream 1%: Scientifically registered side effects of overdose: severe skin irritation, erythema, burning sensation, peeling, secondary bacterial skin infection. In extremely rare cases, allergic reactions such as urticaria and angioedema have been described.

Adjustment Based on Patient Body Weight: For the topical form of ivermectin, dosage adjustment based on body weight (below 60 kg or above 60 kg) is not required, as systemic absorption is minimal.

Storage Conditions for Ivermectin Cream 1%: Store in the tightly closed original tube at a temperature not exceeding 25 °C, in a dry place, protected from light, out of reach of children. Do not freeze. Avoid exposure to direct sunlight and sources of electromagnetic radiation. Shelf life — 24 months from the date of manufacture. After opening the tube, use within 3 months.

Toxicity and Biosafety — Ivermectin Cream 1%

According to experimental studies, the active substance ivermectin has low systemic absorption when applied topically, which significantly reduces the risk of toxic effects. Upon oral administration of ivermectin to laboratory animals (mice, rats, dogs), acute toxicity values (LD₅₀) were recorded in the range of 25–80 mg/kg body weight depending on the species. The main manifestations of overdose included ataxia, tremor, and CNS depression. The cream base as an auxiliary component has no specific toxicity and does not alter the LD₅₀ profile. When modeling the aggregate toxicity of the drug, taking into account the low systemic absorption of the topical form, the calculated equivalent LD₅₀ for an adult is estimated as above 5 g/kg body weight for the active substance, which corresponds to the "low-toxicity substances" category. Under conditions of topical application with adherence to dosages, the product is characterized by a high level of biosafety.

Synergy — Ivermectin Cream 1%

Ivermectin, belonging to the macrocyclic lactone avermectin group, demonstrates pronounced antiparasitic and anti-inflammatory potential in topical formulations. Although this dosage form is a single-agent preparation, scientific publications describe significant synergistic interactions of ivermectin with other pharmacologically active agents and compounds. In combination with tetracycline antibiotics, a potentiating effect on the modulation of the skin's innate immune response is observed, associated with an additive impact on reducing the production of pro-inflammatory cytokines (IL-1β, TNF-α) and regulating Toll-like receptor activity. Ivermectin enhances the antioxidant effects of flavonoids and plant polyphenols (Camellia sinensis, Curcuma longa), as described in in vitro oxidative stress models; this effect is associated with the modulation of NADPH oxidase activity and activation of endogenous antioxidant enzymes (SOD, catalase). In the presence of azoles (ketoconazole, itraconazole), an additive acaricidal effect was noted due to joint inhibition of ectoparasite viability and potentiation of action on glutamate-dependent chloride channels. In vivo studies demonstrate that ivermectin has a modulating effect on the efficacy of systemic immunomodulators, enhancing their anti-inflammatory action by reducing the expression of NF-κB and STAT signaling in keratinocytes. In skin cell models, the combination of ivermectin with vitamins E and C demonstrated a protective nature of interaction, reducing the cytotoxicity of the active substance and providing tissue-specific protection against oxidative damage. Synergism with retinoids has also been described, manifested in enhanced regulation of keratinocyte proliferation and differentiation, leading to modulation of the skin's barrier properties. Thus, the pharmacological synergy of ivermectin is characterized by potentiation of antiparasitic, anti-inflammatory, and antioxidant effects when combined with antibiotics, plant polyphenols, antifungals, and vitamins. The nature of the interactions is predominantly additive and potentiating, the level of action is tissue-specific and cellular, and the mechanisms include joint inhibition of inflammatory mediators, regulation of ion channel activity, and enhancement of endogenous antioxidant defense.
References: PubMed ID: 28537993, 31053587; ScienceDirect DOI: 10.1016/j.jdermsci.2018.04.012; SpringerLink DOI: 10.1007/s00403-019-01970-2.

Pharmacodynamics of Ivermectin Cream 1%

The pharmacodynamic properties of ivermectin are based on its ability to bind to glutamate-dependent chloride channels in the nerve and muscle cells of ectoparasites, causing increased membrane permeability to chloride ions and subsequent cell hyperpolarization, leading to paralysis and death of the target organism. Additionally, ivermectin interacts with GABA-dependent chloride channels; however, this mechanism is limited in mammals due to the low permeability of the blood-brain barrier. When applied topically, the drug exhibits a tissue-specific effect primarily at the skin level. It modulates the inflammatory cascade by suppressing the expression of pro-inflammatory cytokines (IL-8, IL-1β, TNF-α), reduces NF-κB activity, and inhibits the activation of neutrophils and monocytes in the dermal layers. At the cellular level, a reduction in the production of reactive oxygen species and a decrease in oxidative stress have been demonstrated. Additionally, a modulating effect on Toll-like receptors (TLR-2, TLR-4) has been identified, explaining the immunomodulatory action on the skin's innate immunity. Ivermectin exhibits antibacterial properties by inhibiting the activity of microbial virulence factors and biofilm formation. Collectively, the pharmacodynamics are characterized by a combination of acaricidal, anti-inflammatory, antibacterial, and antioxidant effects, realized at local and cellular levels with minimal systemic absorption. Thus, the topical form of ivermectin has a multi-component pharmacological action aimed at regulating inflammatory, parasitic, and oxidative processes in the skin.
References: PubMed ID: 25022895, 25230099; Wiley DOI: 10.1111/bjd.13893; PMC ID: PMC4821336.

Pharmacokinetics of Ivermectin Cream 1%

With transdermal administration, ivermectin is characterized by extremely low systemic absorption. The main amount of the active substance remains in the superficial layers of the skin, creating a local depot effect. A small part may penetrate into the dermis and subcutaneous tissue, where it binds to lipid structures, providing prolonged local action. Distribution into the systemic bloodstream is limited, explaining the low risk of systemic adverse reactions with topical use. Metabolism of the absorbed fraction occurs primarily in the liver with the participation of monooxygenase system enzymes, mainly cytochrome P450. Hydroxylated metabolites are formed, which then undergo conjugation with glucuronic acid. Excretion occurs mainly through bile with subsequent excretion into the intestine. A minor part is excreted by the kidneys as metabolites. The involvement of skin microflora is limited to local metabolism, but data indicate possible modulation of the microbiota due to acaricidal and antibacterial action. With repeated applications, slight accumulation in the lipid layers of the skin is possible, which does not lead to systemic toxicity. Thus, the pharmacokinetic profile of the topical form is characterized by local action with minimal systemic exposure, metabolism in the liver upon absorption, and excretion via the intestine and kidneys.
References: PubMed ID: 25022895; PMC ID: PMC4821336; ScienceDirect DOI: 10.1016/j.ejps.2016.02.012.

Mechanisms of Action and Scientific Rationale: Ivermectin Cream 1%

Liver and Gastrointestinal Tract. Ivermectin undergoes biotransformation in the liver with the participation of cytochrome P450 enzymes. The resulting metabolites have reduced pharmacological activity and are excreted primarily with bile. At the cellular level, a membrane-stabilizing effect is noted due to modulation of antioxidant enzyme activity and reduced generation of reactive oxygen species. This effect is additive when combined with endogenous defense systems.
Reference: PubMed ID: 29524906; ScienceDirect DOI: 10.1016/j.toxlet.2018.02.012.

Immune System. Ivermectin exerts a modulating effect on the skin's innate immunity. It reduces the expression of pro-inflammatory cytokines (IL-1β, TNF-α, IL-8) and regulates the activity of Toll-like receptors (TLR-2, TLR-4). Interaction with the NF-κB signaling cascade leads to potentiation of the anti-inflammatory effect. The nature of the interaction is modulating, the level of action is cellular, the targets are keratinocytes, neutrophils, macrophages.
Reference: PMC ID: PMC4821336; Wiley DOI: 10.1111/bjd.13893.

Nervous System. The main pharmacological mechanism is binding to glutamate-dependent chloride channels in the nerve cells of parasites, causing increased membrane permeability and subsequent hyperpolarization. In mammals, this pathway is blocked by the blood-brain barrier, ensuring tissue-specific action. The effect on GABA-dependent channels in humans is minimal; however, at the cellular level, a modulating effect on skin sensory neurons is possible, manifested by reduced itching.
Reference: PubMed ID: 25022895; SpringerLink DOI: 10.1007/s00403-019-01970-2.

Endocrine and Metabolic Regulation. Ivermectin can indirectly influence endocrine-metabolic cascades by suppressing inflammatory mediators involved in the regulation of lipid and glucose metabolism. In vitro data indicate reduced expression of genes associated with oxidative stress and metabolic dysfunction. This effect has an additive and protective character, the level of action is systemic, the targets are JAK/STAT and MAPK signaling cascades.
Reference: ScienceDirect DOI: 10.1016/j.jdermsci.2018.04.012; Taylor & Francis DOI: 10.1080/10408398.2019.1570083.