Isotretinoin gel (Isotrex)

Generic Name

Isotretinoin

Brand Name (Topical Gel)

Isotrex

Other international brands include Isotrex Gel, Isotrexin (isotretinoin + erythromycin), and Retino-A Micro (region-specific)

Dosage Forms and Strengths

Topical gel

Available strengths:

– 0.05% isotretinoin

Formulated in alcohol-based gel vehicle for enhanced skin penetration

Drug Class

Topical retinoid

Derivative of vitamin A (13-cis-retinoic acid)

Keratolytic and comedolytic agent

Mechanism of Action

Isotretinoin is a synthetic retinoid that regulates epithelial cell growth and differentiation

Reduces hyperkeratinization of follicular epithelium, promoting normal desquamation and preventing comedone formation

Suppresses sebaceous gland activity and decreases sebum production locally

Reduces inflammation through modulation of Toll-like receptors and inhibition of pro-inflammatory cytokines

Enhances penetration of other topical agents (e.g., antibiotics) when used in combination

Indications (Topical Formulation)

Acne vulgaris (mild to moderate inflammatory and comedonal acne)

May be used in combination with topical antibiotics for enhanced efficacy

Isotrexin (isotretinoin + erythromycin) indicated in moderate inflammatory acne

Off-Label Uses

Rosacea (select cases under supervision)

Hyperkeratotic disorders (e.g., keratosis pilaris, sebaceous hyperplasia)

Skin texture improvement in photodamage (limited evidence)

Dosage and Administration

Apply a thin film once or twice daily to clean, dry skin

Initiate with once-daily application at bedtime to reduce irritation

Amount: pea-sized quantity sufficient for the entire face

Avoid application to mucous membranes, eyes, angles of nose, and broken skin

Allow skin to dry fully (10–15 minutes) after washing before application

Moisturizer may be used to reduce irritation, ideally 30 minutes after retinoid application

Treatment Duration

Initial response seen in 6–8 weeks

Optimal results in 10–12 weeks

May continue for up to 3–6 months based on clinical response

Storage and Handling

Store at room temperature below 25°C

Avoid exposure to sunlight and heat

Alcohol-based vehicle is flammable – keep away from open flame

Pharmacokinetics (Topical)

Minimal systemic absorption (<1% of applied dose)

Local action on skin

Plasma isotretinoin levels remain negligible compared to oral administration

No systemic accumulation expected

Contraindications

Hypersensitivity to isotretinoin or formulation excipients

Pregnancy (contraindicated due to teratogenicity, even with minimal absorption)

Breastfeeding (avoid use on or near the breast area)

Children under 12 years unless directed by specialist

Warnings and Precautions

Pregnancy (Category X)

Teratogenicity is a class effect for retinoids

Although systemic absorption is negligible, topical isotretinoin is contraindicated in pregnancy

Ensure effective contraception for women of childbearing age

Avoid if planning pregnancy

Use pregnancy test if indicated

Photosensitivity

Increases susceptibility to UV-induced erythema and damage

Avoid excessive sunlight and tanning beds

Use broad-spectrum sunscreen (SPF ≥30) daily and wear protective clothing

Irritation

May cause dryness, scaling, erythema, burning, stinging

Initial irritation common in first 2–4 weeks

Recommend bland moisturizers and reducing application frequency if needed

Eczema, Dermatitis, Rosacea

Use with caution in patients with sensitive skin or active dermatitis

May worsen rosacea or perioral dermatitis

Bleaching Potential

May bleach hair, fabrics, and pillowcases

Advise handwashing after application and avoiding contact with colored materials

Use in Pediatrics

Not generally used under 12 years

If used, under dermatological supervision

Use in Elderly

No specific restrictions but limited data

Skin sensitivity may increase

Adverse Effects (Topical Use)

Very Common (≥10%)

Skin dryness

Erythema

Peeling

Burning or stinging sensation

Photosensitivity

Common (1–10%)

Pruritus

Scaling

Sunburn reaction

Temporary acne flare (early weeks)

Uncommon (<1%)

Contact dermatitis

Hyperpigmentation or hypopigmentation

Skin blistering or ulceration

Allergic reaction to formulation base

Systemic Side Effects

Not expected due to low absorption

No teratogenicity reported with topical use but theoretical risk remains

Pregnancy and Lactation

Pregnancy

Topical isotretinoin is contraindicated in pregnancy

Even with minimal absorption, systemic retinoid risk profile applies

Avoid use in women planning to conceive

Lactation

Safety not established

Minimal absorption suggests low risk, but avoid applying to chest or areas where infant may contact

Prefer alternative treatments with known safety in breastfeeding

Drug Interactions

Topical Products

Avoid concomitant use with:

– Abrasive cleansers or soaps

– Topical keratolytics (e.g., salicylic acid, benzoyl peroxide) unless directed by a physician

– Topical antibiotics (may be combined but monitor for irritation)

– Astringents, alcohol-based solutions

– Other topical retinoids (increased irritation risk)

Oral Medications

Oral tetracyclines: potential additive photosensitivity

Avoid oral isotretinoin + topical retinoids due to cumulative irritation

No known significant systemic interactions

Monitoring Parameters

Clinical improvement in acne lesions

Irritation, erythema, or dermatitis

Pigmentary changes or photosensitivity reactions

No routine laboratory monitoring required for topical use

Comparative Pharmacology

Topical Isotretinoin vs Tretinoin

Isotretinoin is 13-cis-retinoic acid; tretinoin is all-trans-retinoic acid

Isotretinoin is generally less irritating and may be better tolerated

Tretinoin has more robust evidence base and widespread clinical use

Both work through retinoid receptors but have different receptor affinity profiles

Isotretinoin Gel vs Oral Isotretinoin

Topical: local effect, limited systemic absorption, mild to moderate acne

Oral: systemic, severe nodulocystic acne, teratogenicity, monitored under strict pregnancy prevention programs

Topical form avoids systemic toxicity and hepatotoxicity risks

Isotretinoin vs Adapalene

Adapalene is more photostable and less irritating

Adapalene is preferred for sensitive skin

Isotretinoin may offer deeper penetration for sebaceous gland-rich areas

Clinical Notes

Often used as part of multi-agent acne regimens

Topical antibiotics (e.g., clindamycin) may be used concurrently for inflammatory acne

In cases of antibiotic resistance or nonresponse, dermatological referral is advised

Legal and Regulatory Status

Prescription-only medication

Topical isotretinoin not available in all countries

Not regulated under iPLEDGE (US pregnancy prevention program) unlike oral form