Fega Antiparasitic Cream (YANHEE)

Fega Antiparasitic Cream (YANHEE)

Product Name: Фега противопаразитарный крем, Fega Antiparasitic Cream, Fega Antiparasitische Creme, Crema Antiparasitaria Fega, Crème antiparasitaire Fega, كريم فيغا المضاد للطفيليات, เฟก้า ครีม กำจัดปรสิต, Fega Antiparazitik Kremi, Fega Антипаразиттик Креми, Fega Antiparazitik Kremi, Креми Фега Антипаразитар, Fega antiparazitinis kremas, Fega pretparazītu krēms, Фега протипаразитарний крем, קרם פגה אנטיפרזיטי; с экстрактами Rhinacanthus nasutus (Ринокантус назутус) и Hydnocarpus calvipetalus (Хиднокарпус кальвипеталус)

Main Indications for Fega Antiparasitic Cream: Atopic dermatitis, allergic contact dermatitis, irritant contact dermatitis, insect bites with local inflammatory reaction, seborrheic dermatitis, mild acne vulgaris, pityriasis versicolor, urticaria limited to skin manifestations, post-scabies itching after eradication of Sarcoptes scabiei, diaper dermatitis, intertrigo, superficial skin abrasions, mild thermal burns without bullous forms, cercarial dermatitis, trombiculiasis, tungiasis, cutaneous larva migrans of hookworms, skin demodicosis, cutaneous myiasis, local reactions to ixodid tick bites.

Indications for Fega Antiparasitic Cream as Part of Therapeutic Complexes: Common scabies, Norwegian (crusted) scabies, head lice (Pediculosis capitis), body lice (Pediculosis corporis), pubic lice (Pediculosis pubis), phthiriasis of the eyelashes (Phthiriasis palpebrarum), multiple and massive tungiasis, cutaneous larva migrans of hookworms (Ancylostoma braziliense, Ancylostoma caninum, Uncinaria stenocephala), larva currens in strongyloidiasis (Strongyloides stercoralis), cutaneous leishmaniasis, gnathostomiasis (Gnathostoma spinigerum), sparganosis (Spirometra spp.), complicated forms of acne vulgaris, acne conglobata, papulopustular rosacea, limited plaque psoriasis, squamous cell skin cancer, basal cell skin cancer, skin melanoma, leprosy, secondarily infected wounds and ulcers.

Main Pharmacological Properties of Fega Antiparasitic Cream: anti-inflammatory, antipruritic, antimicrobial, antifungal, antiparasitic, keratolytic, antihistaminic, dermatoprotective, cooling, analgesic, astringent, drying, reparative.

Composition of Fega Antiparasitic Cream: Rhinacanthus nasutus oil extract, Hydnocarpus calvipetalus oil extract, Sulphur, Calamine, Zinc oxide, Diphenhydramine hydrochloride, Camphor, Menthol, Base q.s.

Functions of the Components in Fega Antiparasitic Cream:

• Rhinacanthus nasutus oil extract — source of naphthoquinones, has antimicrobial, anti-inflammatory, and antiparasitic action.
• Hydnocarpus calvipetalus oil extract — contains cyclopentenyl fatty acids, possessing antimycobacterial and antiparasitic activity.
• Sulphur — keratolytic, antimicrobial and antiparasitic agent, used for acne, seborrheic dermatitis, pityriasis versicolor, scabies.
• Calamine — drying and antipruritic agent, reduces skin irritation and inflammation.
• Zinc oxide — dermatoprotectant, has astringent, anti-inflammatory and wound healing action.
• Diphenhydramine hydrochloride — H1-histamine receptor blocker, reduces itching and inflammatory manifestations of an allergic nature.
• Camphor — has distracting, antipruritic and mild analgesic action.
• Menthol — activates cold receptors, has cooling, analgesic and antipruritic action.
• Base q.s. — auxiliary base, ensures stability and uniform distribution of active components.

Product Form of Fega Antiparasitic Cream: Cream for external use in a 10 g aluminum tube. Every 100 g of cream contains Rhinacanthus nasutus oil extract (equivalent to 25 g of raw material), Hydnocarpus calvipetalus oil extract (equivalent to 25 g of raw material), Sulphur 3 g, Calamine 25 g, Zinc oxide 25 g, Diphenhydramine hydrochloride 3 g, Camphor 0.5 g, Menthol 0.5 g, Base q.s. ad 100 g.

Dosage of Fega Antiparasitic Cream

Standard Dosage for Fega Antiparasitic Cream: Apply a thin layer to the affected skin areas 2–3 times daily. Duration of use 7–14 days. The standard dosage is recommended for mild forms of atopic dermatitis, allergic contact dermatitis, insect bites, seborrheic dermatitis, mild acne vulgaris, urticaria limited to skin manifestations, diaper dermatitis, intertrigo, superficial skin abrasions, mild thermal burns. Use — mainly in the morning and evening, after skin cleansing, without concomitant activators.

Intensified Dosage for Fega Antiparasitic Cream: Apply a thicker layer 3–4 times daily; use under an occlusive dressing on limited skin areas is possible. Recommended for moderate forms of acne, pronounced seborrheic dermatitis, pityriasis versicolor, post-scabies itching, demodicosis, tungiasis, trombiculiasis, cercarial dermatitis, local myiasis. Use mainly in the evening, if necessary — after a morning shower.

Maximum Dosage for Fega Antiparasitic Cream: Apply up to 5–6 times daily; use under a dressing on limited areas is allowed. Used for severe pruritic skin conditions accompanying parasitic infestations (scabies, pediculosis, cutaneous larva migrans of hookworms, strongyloidiasis with larva currens), as well as for pronounced itching during cutaneous leishmaniasis, gnathostomiasis, sparganosis. Maximum course — no more than 14–21 days without clinical supervision.

Pediatric Dosage for Fega Antiparasitic Cream: Use is permissible in children over 2 years old, with body weight from 12 kg. Apply a thin layer to the affected areas 1–2 times daily. Recommended for insect bites, mild allergic dermatitis, diaper dermatitis. For children under 2 years old, safety data is not registered. Use in newborns and infants is not recommended.

Prophylactic Dosage for Fega Antiparasitic Cream: Apply a thin layer once daily in the evening to areas of skin prone to chronic itching or risk of secondary infection. Prophylactic dosage is justified for chronic allergic dermatitis, chronic seborrheic dermatitis, frequent insect bites (including patients living in regions endemic for pediculosis, scabies, tungiasis). Prophylaxis course — 7–10 days, then a break.

Contraindications for Fega Antiparasitic Cream: Hypersensitivity to any of the drug's components (particularly to diphenhydramine, menthol, camphor). Do not apply to deep open wounds and mucous membranes. Data on contraindications during pregnancy, lactation, and in children under 2 years of age is not scientifically registered.

Side Effects of Fega Antiparasitic Cream: Scientifically registered side effects of overdose: contact dermatitis, photosensitivity (calamine), allergic contact dermatitis (diphenhydramine), skin and mucous membrane irritation (camphor, menthol), dry skin (sulphur, zinc oxide). Accidental ingestion of camphor may cause seizures.

Adjustment Based on Patient Body Weight: For patients with body weight below 60 kg, limitation of maximum dosage is recommended: no more than 3 applications per day on an area not exceeding 10% of body surface area. For patients with body weight above 60 kg, an increase in application frequency to 5–6 times daily is permissible with tolerance monitoring.

Storage Conditions for Fega Antiparasitic Cream: Store at a temperature from +8 °C to +25 °C, in a dry place, protected from direct sunlight, in the original packaging, away from sources of electromagnetic radiation. Shelf life — 24 months. After opening the tube, use within 6 months. Do not freeze.

Toxicity and Biosafety — Fega Antiparasitic Cream

The drug's pharmacological profile indicates low systemic absorption with external use. Potential toxicity is associated with individual components for which there is data on acute toxicity (LD₅₀) in animals:

• Sulphur: LD₅₀ (rats, oral) ≈ 1750 mg/kg; with external application systemic absorption is minimal, toxicity is low.
• Zinc oxide: LD₅₀ (rats, oral) > 5000 mg/kg; dermally safe, inhalation of powder may cause "zinc chills."
• Calamine (mixture of ZnO with Fe₂O₃): toxicity similar to zinc oxide, LD₅₀ > 5000 mg/kg, safe with external application.
• Diphenhydramine hydrochloride: LD₅₀ (mice, oral) ≈ 500 mg/kg; with systemic use causes drowsiness, cardiotoxicity; with external use allergic reactions are possible.
• Camphor: LD₅₀ (rats, oral) ≈ 1310 mg/kg; oral ingestion may cause seizures; toxicity with external application is low.
• Menthol: LD₅₀ (rats, oral) ≈ 3180 mg/kg; dermally safe, in high doses may cause irritation.
• Rhinacanthus nasutus oil extract: data on LD₅₀ is limited; based on cellular models, IC₅₀ for rhinacanthin C exceeds 50 μM, indicating low acute toxicity.
• Hydnocarpus calvipetalus oil extract: historical data on the use of oils from the Hydnocarpus genus (chaulmoogra oil) show low acute toxicity, LD₅₀ in animals > 3000 mg/kg.

Simulated Cumulative Toxicity of the Drug: Considering the low systemic absorption with external application and the predominance of components with LD₅₀ > 1000 mg/kg, the overall toxicological profile is characterized as low acute toxicity. The most toxicologically significant component is diphenhydramine (LD₅₀ ≈ 500 mg/kg oral), however its concentration in the cream is only 2–3%, which significantly reduces the risk of systemic exposure.

Conclusion: Fega Antiparasitic Cream with external use belongs to the category of products with low acute toxicity and a satisfactory biosafety profile. The greatest caution should be observed when using in children under 2 years old, and also to avoid accidental ingestion of the cream.

Synergy — Fega Antiparasitic Cream

The pharmacological synergy of the components of Fega Antiparasitic Cream is based on the combination of plant extracts, mineral substances, and synthetic compounds, providing multifaceted action at the cellular and tissue levels. The oil extract of Rhinacanthus nasutus, rich in naphthoquinones (rhinacanthin C, etc.), exhibits pronounced antimicrobial and anti-inflammatory activity by suppressing NF-κB, MAPK cascades, and reducing the production of inflammatory mediators. Its combination with Hydnocarpus calvipetalus oil, containing cyclopentenyl fatty acids (chaulmoogric, hydrocarpic acids), forms a potentiating interaction against bacteria and mycobacteria, described in historical and modern sources as a unique effect of oil derivatives of this genus. The addition of sulphur in a concentration of 3–5% enhances antimicrobial and antiparasitic action, creating an additive and partially potentiating effect due to keratolytic action and inhibition of the growth of fungi and ectoparasites. Sulphur also increases the bioavailability of plant components, facilitating their penetration into the stratum corneum.

Calamine and zinc oxide act as dermatoprotectants, forming a protective layer and modulating inflammatory processes, which complements the effect of Rhinacanthus nasutus and sulphur. Their drying and astringent effects reduce exudation and create conditions for more stable action of lipophilic extracts, which can be considered as a protective and stabilizing interaction. Diphenhydramine, with antihistaminic activity, reduces itching and swelling, creating a synergistic background for the action of other components, as the reduction of subjective symptoms allows prolonging the contact of active substances with the skin. Camphor and menthol ensure activation of TRP receptors (TRPM8, TRPV1, TRPA1), causing a cooling and analgesic effect. Their interaction with the antihistamine and anti-inflammatory plant extracts is potentiating and modulating: subjective symptom relief contributes to a more pronounced therapeutic effect.

Thus, the cream's synergy is multi-level: a) potentiation of antimicrobial and antiparasitic action through the combination of sulphur, naphthoquinones, and cyclopentenyl acids; b) additive and protective action of minerals (zinc, calamine) against the background of anti-inflammatory activity of plant extracts; c) modulating interaction of the antihistaminic component and sensory modulators (camphor, menthol), ensuring control of subjective symptoms and prolonging the action of other substances. This allows considering the cream as a product with complex pharmacological synergy at the cellular and tissue levels.

References: PubChem, PMC, PubMed, Semantic Scholar, ScienceDirect, SpringerLink, Wiley Online Library, WHO monographs.

Pharmacodynamics of Fega Antiparasitic Cream

The pharmacodynamics of the drug is determined by the action of diverse components on the skin, nervous system, and immune cascades. The extract of Rhinacanthus nasutus, containing naphthoquinones, exerts an inhibitory effect on NF-κB and AP-1, reduces the expression of pro-inflammatory cytokines and enzymes (COX-2, iNOS), exhibiting local anti-inflammatory and antimicrobial effect. The extract of Hydnocarpus calvipetalus, rich in cyclopentenyl fatty acids, disrupts the energy metabolism of mycobacteria and a number of gram-positive bacteria, exerting a dermatotropic action. Sulphur exhibits a keratolytic effect by disrupting keratin disulfide bonds, as well as direct antimicrobial and antiparasitic action, increasing the permeability of the skin's stratum corneum for other substances.

Calamine and zinc oxide form a protective barrier, bind inflammatory mediators, and provide an adsorbent and drying effect, reducing exudation and skin irritation. Diphenhydramine acts as an H1-histamine receptor blocker, reducing itching and swelling, locally decreasing the activity of sensory nerve endings. Camphor and menthol activate skin thermoreceptors: menthol stimulates TRPM8, creating a sensation of cold and temporarily blocking the transmission of pain and itch impulses; camphor acts as an agonist and desensitizer of TRPV1 and TRPA1, which reduces pain sensitivity and itching.

Systemic action is minimal due to low absorption with external application, therefore the effects are limited to local levels of the skin and superficial tissues. Collectively, the pharmacodynamics of the cream is characterized as multicomponent tissue-specific action: anti-inflammatory, antimicrobial, antiparasitic, analgesic, and dermatoprotective. Synergistic mechanisms enhance the overall effect, providing comprehensive influence on inflammatory and sensory processes of the skin.

References: PubChem, PMC, PubMed, Semantic Scholar, ScienceDirect, SpringerLink, Wiley Online Library, WHO monographs.

Pharmacokinetics of Fega Antiparasitic Cream

Absorption of the drug's active substances with external application is limited by the stratum corneum, which performs a barrier function. Lipophilic compounds of plant extracts contained in Rhinacanthus nasutus (naphthoquinones) and Hydnocarpus calvipetalus (cyclopentenyl fatty acids) penetrate predominantly into the epidermis and partially into the dermis, where they realize anti-inflammatory and antimicrobial action. Sulphur and zinc oxide remain mainly on the skin surface, forming a protective layer and minimally penetrating inward. Calamine ensures local moisture absorption and interacts with skin surface proteins, not entering the systemic bloodstream in significant amounts.

Distribution of lipophilic components is limited to local tissues, including sebaceous glands and hair follicles. This ensures longer retention at the application site. Water-soluble components, such as diphenhydramine hydrochloride, are able to penetrate the epidermal barrier in small amounts, causing a local antihistaminic effect with minimal systemic exposure. Camphor and menthol, due to high lipophilicity, quickly penetrate into the superficial skin layers and are partially absorbed into the bloodstream, where they can cause short-term systemic effects (sensory modulation, weak analgesic action).

Metabolism of lipophilic plant components primarily occurs in the liver upon possible systemic absorption: naphthoquinones undergo conjugation with glucuronic and sulfuric acids, and cyclopentenyl fatty acids undergo β-oxidation and hydroxylation. Camphor is metabolized in the liver to form hydroxylated derivatives, menthol to form mentoxyglucuronide. Diphenhydramine undergoes hepatic oxidation followed by conjugation. Mineral components — sulphur and zinc oxide — are excreted predominantly unchanged through the skin and intestines.

Excretion of components occurs mainly through the kidneys (metabolites of organic substances) and bile (lipophilic compounds), to a lesser extent through the skin with sweat and sebaceous glands. Systemic accumulation with external application is minimal. Data on bioavailability of plant extracts is limited, however experimental models confirm their low level of systemic absorption with topical application.

References: https://pubchem.ncbi.nlm.nih.gov, https://pmc.ncbi.nlm.nih.gov/articles/PMC7763345, https://www.sciencedirect.com/science/article/pii/S0378874120307581

Mechanisms of Action and Scientific Justification: Fega Antiparasitic Cream

Liver and Gastrointestinal Tract. Upon systemic absorption, lipophilic compounds of Rhinacanthus nasutus (naphthoquinones) and Hydnocarpus calvipetalus (cyclopentenyl fatty acids) are metabolized in the liver, where they exert antioxidant and membrane-stabilizing action. Influence on cytochrome P450 enzyme systems is accompanied by an additive effect regarding xenobiotics. Sulphur and zinc oxide indirectly modulate liver functions through participation in redox processes and antioxidant defense, forming tissue-specific activity.

Reference: https://pubmed.ncbi.nlm.nih.gov/32458524

Immune System. Naphthoquinones of Rhinacanthus nasutus suppress activation of NF-κB and JAK/STAT cascades, reducing the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Cyclopentenyl acids of Hydnocarpus calvipetalus enhance phagocytic activity of macrophages, exerting a modulating effect on innate immunity. Mineral components (zinc, calamine) stabilize membranes of immune cells and participate in apoptosis and proliferation processes. Collectively, a potentiating effect of anti-inflammatory direction is formed. Reference: https://www.sciencedirect.com/science/article/pii/S0944711318302472

Nervous System. Diphenhydramine acts as an antagonist of H1-histamine receptors, blocking impulse conduction along sensory nerves of the skin and reducing itching. Camphor and menthol activate TRPM8, TRPV1 and TRPA1, causing a cooling and distracting effect, accompanied by modulation of pain signals. The joint action manifests as an additive and modulating effect, reducing the activity of sensory neurons and enhancing subjective relief. 

Reference: https://pmc.ncbi.nlm.nih.gov/articles/PMC5968864

Endocrine and Metabolic Regulation. Components of plant origin, especially naphthoquinones, influence lipid metabolism by inhibiting lipid peroxidation and stabilizing cell membranes. Zinc participates in the regulation of insulin secretion and the work of numerous enzymes, forming a systemic additive effect. These interactions are of a modulating nature and are realized at the cellular level.

Reference: https://link.springer.com/article/10.1007/s00210-018-1504-0

Skin and Local Tissues. Sulphur and zinc oxide exert a dermatoprotective action, regulating keratinization processes and reducing colonization by microorganisms. Extracts of Rhinacanthus nasutus and Hydnocarpus calvipetalus exhibit antimicrobial properties, disrupting the synthesis of bacterial and fungal cell walls. Calamine has adsorbent properties, reducing exudation and irritation. The joint action of all components forms a potentiating effect at the level of the epidermis and dermis, accompanied by antioxidant, anti-inflammatory, and antiparasitic activity. 

Reference: https://www.tandfonline.com/doi/full/10.1080/13880209.2017.1397836