Ivermectin (Topical)
Soolantra (cream 1%), Sklice (lotion 0.5%)
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Inflammatory lesions of rosacea (papules and pustules) | Adults (≥18 years) | Monotherapy (topical, once daily) | FDA Approved |
| Head lice infestation (Pediculus humanus capitis) | ≥6 months | Single-application pediculicide | FDA Approved |
Topical ivermectin occupies two distinct therapeutic niches. The 1% cream (Soolantra) was approved in December 2014 for papulopustular rosacea and has demonstrated superiority over topical metronidazole 0.75% in head-to-head trials. The 0.5% lotion (Sklice) was originally approved in 2012 as a prescription pediculicide and was switched to over-the-counter status in October 2020. A key advantage of the ivermectin lotion is that only a single application is needed without mandatory nit combing, distinguishing it from most other pediculicides that require retreatment.
Demodicosis (non-rosacea Demodex infestations): Topical ivermectin 1% cream has been used for demodicosis presenting as blepharitis, pityriasis folliculorum, and demodicidosis beyond typical rosacea. Evidence quality: Low (case series)
Scabies (topical adjunct): Topical ivermectin 1% has been explored as adjunctive treatment for localised scabies in combination with oral ivermectin or permethrin, particularly in crusted scabies. Evidence quality: Low (case reports)
Perioral dermatitis with Demodex involvement: Case reports suggest efficacy where standard therapy has failed. Evidence quality: Very low (case reports)
Dosing
Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Papulopustular rosacea — moderate to severe (cream 1%) | Pea-sized amount per facial zone, once daily | Once daily to affected areas indefinitely | ~1 g/day total (5 pea-sized amounts) | Apply at bedtime to forehead, chin, nose, and each cheek. Spread as thin layer. Avoid eyes and lips. Initial improvement expected by week 4. FDA PI (Soolantra); long-term data to 52 weeks |
| Head lice — active infestation (lotion 0.5%) | Single application to dry hair/scalp | N/A (single use) | One 4 oz (117 g) tube | Apply sufficient amount (up to entire tube) to coat hair and scalp. Leave on 10 minutes, rinse with water. Wait 24 h before shampooing. Nit combing not required. FDA PI (Sklice); do not retreat without clinician guidance |
| Rosacea — combination with oral doxycycline for severe disease (off-label protocol) | Cream 1% QD + doxycycline 40 mg MR QD | Combination for 12 weeks, then step down to ivermectin cream alone | As above | Phase 3b/4 data suggest faster onset and greater lesion reduction with combination vs monotherapy in severe (IGA 4) rosacea. Taieb et al. JAAD 2019 |
Use a pea-sized amount for each of five facial zones (forehead, nose, chin, each cheek). Evening application is preferred as it avoids cosmetic interference during the day and allows overnight contact time. Do not apply to erythematotelangiectatic areas alone, as the cream addresses papulopustular inflammation rather than fixed telangiectases. Patients typically notice improvement by week 4, with maximal benefit by week 12, though continued use beyond 12 weeks maintains remission. In the ATTRACT extension study, patients on ivermectin had fewer relapses than those on metronidazole during a 36-week follow-up.
Special Populations
| Population | Recommendation | Key Consideration |
|---|---|---|
| Paediatric (cream 1%) | Safety and efficacy not established | No paediatric rosacea trials conducted with topical ivermectin |
| Paediatric (lotion 0.5%) | Approved ≥6 months | Not recommended <6 months due to higher surface-area-to-body-mass ratio and immature skin barrier increasing systemic absorption risk |
| Elderly (≥65 years) | No dose adjustment | In pivotal rosacea trials, 12.4% of subjects were ≥65 years; no safety or efficacy differences observed |
| Pregnancy | Use only if clearly needed | Insufficient human data. Animal studies showed cleft palate (rats, 1909× MRHD) and carpal flexure (rabbits, 354× MRHD) only at maternally toxic doses. Topical absorption is far lower than oral |
Pharmacology
Mechanism of Action
The precise mechanism by which topical ivermectin improves rosacea lesions is not fully established (FDA PI). Ivermectin is a semi-synthetic macrocyclic lactone derived from fermentation of Streptomyces avermitilis. Its therapeutic effect in rosacea is attributed to a dual mechanism: an antiparasitic action against Demodex folliculorum and D. brevis mites, which are found in increased density in rosacea-affected skin, and an anti-inflammatory effect through downregulation of inflammatory mediators including TLR-2 pathway activation, cathelicidin (LL-37) overexpression, and NF-κB signalling. For head lice, ivermectin acts by binding to glutamate-gated chloride channels in invertebrate nerve and muscle cells, causing hyperpolarisation, paralysis, and death. Importantly, lice hatching from eggs on treated hair die within 48 hours of exposure, which is why retreatment is typically unnecessary.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Cream 1% (steady state, 1 g/day): Cmax 2.10 ± 1.04 ng/mL; AUC0-24 36.14 ± 15.56 ng·h/mL; Tmax ~10 h. Lotion 0.5% (single use): Cmax 0.24 ± 0.23 ng/mL. No plasma accumulation over 52 weeks. | Plasma levels from topical use are far below those from oral dosing (Cmax 30–47 ng/mL oral); systemic toxicity risk is negligible at approved topical doses |
| Distribution | Protein binding >99%, primarily to human serum albumin; no significant erythrocyte binding | High protein binding limits free drug systemically; tissue distribution from topical application is primarily local |
| Metabolism | Primarily hepatic via CYP3A4 (based on in vitro studies); does not inhibit or induce CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4, or 4A11 at therapeutic topical concentrations | Clean CYP interaction profile at topical doses; systemic drug interactions are not expected |
| Elimination | Apparent terminal t½ ~6.5 days (155 ± 40 h, range 92–238 h) after 28 days of once-daily topical application of 1% cream | Long apparent half-life reflects slow dermal absorption rather than slow systemic clearance; supports once-daily dosing for rosacea |
Side Effects
Topical ivermectin has an exceptionally favourable tolerability profile. In the pivotal rosacea trials (N=2,047 treated subjects, including 519 treated for approximately one year), adverse reactions were reported in ≤1% of subjects. For head lice, adverse events from the lotion were reported in <1% of subjects in controlled trials.
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Skin burning sensation | ≤1% | Most commonly reported event; typically mild, transient, and self-limiting with continued use |
| Skin irritation | ≤1% | Rosacea-prone skin is inherently sensitive; distinguish drug-related irritation from underlying disease flare |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Conjunctivitis / ocular hyperaemia | ~0.5% | From accidental eye contact; emphasise keeping eyes closed during application and rinsing |
| Eye irritation | <1% | Rinse thoroughly with water if contact occurs; typically self-resolving |
| Dandruff / dry skin | <1% | Mild scalp dryness after use; may be related to vehicle formulation |
| Skin burning sensation | ~0.3% | Transient scalp burning during 10-minute application; resolves after rinsing |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Contact dermatitis / allergic dermatitis | Very rare (postmarketing) | Days to weeks | Discontinue ivermectin cream; topical corticosteroid for acute dermatitis; consider patch testing before rechallenge |
| Accidental ingestion toxicity (paediatric, lotion) | Very rare | Within hours of ingestion | Seek emergency care; supportive therapy including fluids and respiratory support; potential signs include rash, nausea, vomiting, dizziness, seizure, hypotension |
| Initial rosacea flare (Demodex die-off reaction) | Uncommon | First 1–2 weeks of treatment | Counsel patient this may be a positive sign of mite killing; continue treatment unless severe; consider short-course topical steroid if significantly symptomatic |
The remarkably low side effect rate (≤1% for all events) is clinically significant in a population with inherently reactive skin. In the ATTRACT head-to-head trial, ivermectin 1% once daily demonstrated a comparable safety profile to metronidazole 0.75% twice daily, with the additional advantage of once-daily dosing and superior efficacy. Patients with rosacea often discontinue treatments due to irritation, making ivermectin’s gentle profile a meaningful clinical advantage.
Drug Interactions
Topical ivermectin has a very clean interaction profile. In vitro studies confirm that ivermectin at topical therapeutic concentrations neither inhibits nor induces CYP450 enzymes. Systemic plasma levels from topical use are far below those achieved with oral ivermectin, making clinically relevant systemic drug interactions extremely unlikely. The following considerations are primarily related to concomitant topical use or theoretical concerns.
Monitoring
-
Clinical Response (Rosacea)
Week 4, then week 12
Routine Assess inflammatory lesion counts (papules and pustules) using a standardised assessment such as the IGA. Improvement typically begins by week 4; if no response by week 12, reconsider diagnosis or add systemic therapy. Long-term use (>12 weeks) maintains remission. -
Local Tolerability
First 2–4 weeks
Routine Rosacea patients have sensitive skin. Ask about burning, stinging, or irritation at follow-up. An initial worsening in the first 1–2 weeks may represent a Demodex die-off reaction and does not necessarily require discontinuation. -
Head Lice Eradication
Day 7–14 post-treatment
Routine Check for live lice at 7–14 days after application. In pivotal trials, 74–95% of patients were lice-free on day 2 through day 15. If live lice are present at follow-up, consult a clinician before retreating. -
Contact Dermatitis
If new dermatitis pattern emerges
Trigger-based Allergic contact dermatitis has been reported in postmarketing experience. Distinguish from rosacea flare: contact dermatitis often extends beyond the rosacea distribution, is intensely pruritic, and may show vesiculation. -
Accidental Ingestion (Paediatric)
At each prescription fill
Routine Remind caregivers that the lotion must be applied under direct adult supervision in children. If accidentally ingested, signs may include nausea, vomiting, dizziness, and in severe cases seizures or hypotension. Seek emergency care.
Contraindications & Cautions
Absolute Contraindications
- None listed in the FDA prescribing information for either formulation. This is notable and reflects the excellent safety margin of topical ivermectin at approved doses.
Relative Contraindications (Specialist Input Recommended)
- Known hypersensitivity to ivermectin or any excipient: Although no formal contraindication section exists in the PI, prior allergic reaction to ivermectin (any formulation) or to the cream/lotion excipients should preclude use. Postmarketing reports include contact dermatitis and allergic dermatitis.
- Infants <6 months (lotion 0.5%): Higher surface-area-to-body-mass ratio and immature skin barrier may lead to disproportionate systemic absorption.
Use with Caution
- Eyes, lips, and mucosal surfaces: Not for ophthalmic, oral, or intravaginal use. If cream contacts eyes, rinse immediately with water.
- Pregnancy: Insufficient human data for topical use. Use only if the benefit clearly justifies the potential risk to the foetus. Systemic exposure from topical application is substantially lower than from oral dosing.
- Lactation: Topical ivermectin exposure to breast milk has not been studied. Oral ivermectin has been detected in human breast milk. Avoid applying the cream to the breast or nipple area to minimise infant exposure.
- Erythematotelangiectatic rosacea without papulopustular lesions: The cream is indicated for inflammatory lesions (papules, pustules); it has not been shown to treat persistent erythema or telangiectases alone.
The FDA label for the 0.5% lotion includes a warning about accidental ingestion in paediatric patients. The lotion should only be administered under direct adult supervision. Symptoms of ivermectin toxicity after oral exposure include rash, oedema, headache, dizziness, weakness, nausea, vomiting, diarrhoea, and in severe cases seizures, ataxia, and hypotension. Emergency care should be sought if ingestion is suspected.
Patient Counselling
Purpose of Therapy
For rosacea: Ivermectin cream is a once-daily treatment applied to the face to reduce the red bumps and pimples (papules and pustules) caused by rosacea. It is not an antibiotic, so it does not contribute to antibiotic resistance. Results are typically visible within 4 weeks, with maximal improvement by 12 weeks. Continued use maintains the improvement. For head lice: Ivermectin lotion is a single-use treatment applied to dry hair for 10 minutes to kill lice. Unlike many other treatments, it kills newly hatched lice from treated eggs, so a second application is usually not needed.
How to Apply
Rosacea cream: Apply a pea-sized amount to each affected area of the face (forehead, nose, chin, each cheek) once daily, preferably at bedtime. Spread in a thin layer and avoid the eyes and lips. Head lice lotion: Apply to dry hair starting at the scalp and working outwards to the tips. Use enough to coat all hair completely (up to the full tube). Leave on for exactly 10 minutes, then rinse off with water only. Wait at least 24 hours before shampooing.
Sources
- SOOLANTRA (ivermectin) Cream, 1% — Full Prescribing Information. Galderma Laboratories (revised October 2022). accessdata.fda.gov Primary regulatory source for the 1% cream; provides approved indication for rosacea, dosing, adverse reactions, pharmacokinetic data, and clinical trial results.
- Ivermectin Lotion, 0.5% (Sklice) — Full Prescribing Information. FDA label (revised 2017). accessdata.fda.gov Regulatory source for the 0.5% lotion; covers head lice indication, paediatric dosing from 6 months, and pharmacokinetic data in young children.
- Stein Gold L, Kircik L, Fowler J, et al. Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies. J Drugs Dermatol. 2014;13(3):316–323. Two pivotal phase 3 trials (N=1,371) establishing superiority of ivermectin 1% cream over vehicle for inflammatory lesions of rosacea, with IGA success rates of 38.4% and 40.1% vs 11.6% and 18.8%.
- Taieb A, Ortonne JP, Ruzicka T, et al. Superiority of ivermectin 1% cream over metronidazole 0.75% cream in treating inflammatory lesions of rosacea: a randomized, investigator-blinded trial. Br J Dermatol. 2015;172(4):1103–1110. doi:10.1111/bjd.13408 The ATTRACT study (N=962): ivermectin 1% QD achieved 83.0% inflammatory lesion reduction vs 73.7% for metronidazole 0.75% BID at week 16, with superior IGA success rates.
- Taieb A, Khemis A, Ruzicka T, et al. Maintenance of remission following successful treatment of papulopustular rosacea with ivermectin 1% cream vs. metronidazole 0.75% cream: 36-week extension of the ATTRACT randomized study. J Eur Acad Dermatol Venereol. 2016;30(5):829–836. doi:10.1111/jdv.13537 Extension study demonstrating that ivermectin-treated patients had longer remission duration and fewer relapses than metronidazole-treated patients over 36 weeks after discontinuation.
- Pariser DM, Meinking TL, Bell M, Ryan WG. Topical 0.5% ivermectin lotion for treatment of head lice. N Engl J Med. 2012;367(18):1687–1693. doi:10.1056/NEJMoa1200107 Two pivotal double-blind RCTs (N=765) demonstrating that single-application ivermectin 0.5% lotion without nit combing achieved 95% louse-free rate at day 2 and 74% at day 15 vs 31% and 18% for vehicle.
- van Zuuren EJ, Fedorowicz Z, Carter B, et al. Interventions for rosacea. Cochrane Database Syst Rev. 2015;(4):CD003262. doi:10.1002/14651858.CD003262.pub5 Cochrane systematic review of rosacea interventions; provides the evidence framework within which ivermectin 1% cream is positioned as an effective topical therapy.
- Two JL, Wu W, Gallo RL, et al. Rosacea: part II. Topical and systemic therapies in the treatment of rosacea. J Am Acad Dermatol. 2015;72(5):761–770. doi:10.1016/j.jaad.2014.08.027 JAAD review of rosacea therapeutics providing clinical context for positioning ivermectin among topical and systemic treatment options.
- Forton FMN. The pathogenic role of Demodex mites in rosacea: a potential therapeutic target already in erythematotelangiectatic rosacea? Dermatol Ther (Heidelb). 2020;10(6):1229–1253. doi:10.1007/s13555-020-00458-9 Comprehensive review of the role of Demodex mites in rosacea pathogenesis, providing the mechanistic rationale for ivermectin’s antiparasitic contribution to clinical efficacy.
- Zhang X, Song Y, Ci X, et al. Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice. Inflamm Res. 2008;57(11):524–529. doi:10.1007/s00011-008-8007-8 Preclinical evidence for ivermectin’s anti-inflammatory properties via suppression of inflammatory cytokine production and NF-κB signalling, relevant to its dual mechanism in rosacea.
- Schaller M, Dirschka T, Kemény L, et al. Superior efficacy with ivermectin 1% cream compared to metronidazole 0.75% cream contributes to a better quality of life in patients with severe papulopustular rosacea: a subanalysis of the randomized, investigator-blinded ATTRACT study. Dermatol Ther (Heidelb). 2016;6(3):427–436. doi:10.1007/s13555-016-0133-6 Subanalysis of severe rosacea patients (IGA 4) from the ATTRACT trial showing ivermectin achieved 85.1% lesion reduction vs 75.2% for metronidazole, with improved quality-of-life scores.
- Cardwell LA, Alinia H, Moradi Tuchayi S, Feldman SR. New developments in the treatment of rosacea — role of once-daily ivermectin cream. Clin Cosmet Investig Dermatol. 2016;9:71–77. doi:10.2147/CCID.S98091 Clinical review consolidating efficacy, safety, and pharmacologic data for ivermectin 1% cream, placing it in the context of existing rosacea treatment options.