Akno

Approved Indications:

• Severe Nodular Acne (Cystic Acne): Primarily indicated for patients with severe recalcitrant nodular acne unresponsive to conventional therapy (e.g., systemic antibiotics and topical agents).
• Acne Conglobata: A severe form of acne with interconnected nodules and abscesses.
• Acne with High Risk of Scarring or Psychological Impact: May be used even in moderate acne if the psychosocial burden or risk of permanent scarring is significant.

Clinically Accepted Off-label Uses:

• Rosacea (Severe Refractory Cases)
• Hidradenitis Suppurativa (Moderate to Severe)
• Seborrheic Dermatitis (Resistant Cases)
• Photoaging and Actinic Keratosis (Low-dose regimens)
• Dissecting Cellulitis of the Scalp
• Folliculitis Decalvans
• Harlequin Ichthyosis (Adjunct Therapy)

General Principles:

• Isotretinoin dosing is weight-based and cumulative total dose-based.
• Administer orally with food for optimal absorption.

Adults (including Adolescents ≥12 years):

• Initial dose: 0.5 mg/kg/day, divided into two doses.
• Maintenance dose: 0.5–1.0 mg/kg/day depending on response and tolerance.
• Cumulative dose target: 120–150 mg/kg over 15–20 weeks to reduce relapse risk.
• Duration: Typically 16–20 weeks; may extend in severe cases.

Pediatrics (<12 years):

• Use not routinely recommended; reserved for severe cases with specialist oversight.

Elderly:

• Similar dosing as adults; monitor hepatic function closely.

Renal Impairment:

• Start at lower doses (e.g., 0.2–0.4 mg/kg/day); titrate based on tolerance.

Hepatic Impairment:

• Contraindicated in significant hepatic dysfunction. Monitor liver enzymes closely if initiated in mild cases.

Administration Notes:

• Capsules should not be chewed or crushed.
• Take with a high-fat meal to enhance bioavailability.
• Do not donate blood during therapy and for at least 1 month after stopping treatment.
• Pregnancy prevention program (iPLEDGE or equivalent) must be followed strictly.

Isotretinoin, a synthetic oral retinoid (13-cis-retinoic acid), works by modulating gene expression through activation of retinoic acid receptors (RARs). It significantly reduces sebaceous gland size and sebum production, inhibits Propionibacterium acnes colonization, and normalizes follicular keratinization. Additionally, it exerts potent anti-inflammatory activity. These combined effects make isotretinoin highly effective in severe acne resistant to conventional therapies.

• Absorption: Variable; enhanced 2-fold when taken with high-fat meals.
• Bioavailability: ~20–50%
• Distribution: Highly lipophilic; extensively distributed in fatty tissues.
• Protein Binding: ≥99.9%
• Metabolism: Hepatic; undergoes isomerization to all-trans-retinoic acid and oxidation via CYP enzymes (CYP2C8, CYP2C9, CYP3A4).
• Active Metabolites: 4-oxo-isotretinoin (major active metabolite).
• Half-life:
• Isotretinoin: 10–20 hours
• 4-oxo-isotretinoin: 25 hours
• Elimination: Primarily in feces (~65%) and urine (~35%)

Pregnancy:

• FDA Category X (Contraindicated)
• Causes severe teratogenic effects: craniofacial, cardiac, thymic, and CNS malformations.
• Absolute contraindication in women who are pregnant or planning pregnancy.
• Mandatory enrollment in risk mitigation program (e.g., iPLEDGE).

Lactation:

• Excreted into human breast milk in small amounts.
• Breastfeeding is contraindicated due to potential adverse effects on the infant.

• Primary Class: Retinoid (Systemic)
• Subclass: Oral Vitamin A derivative; 1st Generation Retinoid

• Hypersensitivity to isotretinoin or its excipients
• Pregnancy or suspected pregnancy
• Lactation
• Hepatic insufficiency or significantly elevated liver enzymes
• Chronic hyperlipidemia (uncontrolled)
• Vitamin A toxicity
• Concomitant use of tetracyclines (risk of pseudotumor cerebri)

• Teratogenicity: Requires strict pregnancy prevention measures.
• Psychiatric Risks: Monitor for depression, mood changes, and suicidal ideation.
• Hepatic Effects: Monitor liver function tests (LFTs) regularly.
• Lipid Elevation: Triglycerides and cholesterol should be monitored.
• Ocular Effects: May cause dry eyes, blurred vision, and intolerance to contact lenses.
• Skeletal Effects: Potential for premature epiphyseal closure in growing children.
• Pseudotumor Cerebri: Avoid co-administration with tetracyclines.
• IBD & Pancreatitis: Rare but serious events; discontinue if suspected.
• Wound Healing: Avoid elective surgery, dermabrasion, or waxing during and for 6 months post-therapy.

Common:

• Dermatologic: Dry skin, cheilitis (dry lips), photosensitivity, skin fragility
• Ophthalmic: Dry eyes, conjunctivitis, blepharitis, decreased night vision
• Musculoskeletal: Arthralgia, myalgia, back pain
• GI: Nausea, inflammatory bowel symptoms (rare)

Serious/Rare:

• Psychiatric: Depression, suicidal thoughts
• Hepatic: Elevated transaminases
• Lipid: Hypertriglyceridemia, pancreatitis
• Neurologic: Benign intracranial hypertension
• Hematologic: Neutropenia, anemia (rare)

Timing/Onset:

• Most effects occur within 2–4 weeks of initiation and are dose-dependent.

Major Interactions:

• Tetracyclines: Increased risk of intracranial hypertension
• Vitamin A Supplements: Additive toxicity
• Phenytoin: May worsen bone loss
• Corticosteroids: Additive risk of osteoporosis
• Alcohol: Increases risk of hypertriglyceridemia

Enzyme Systems:

• Metabolized by CYP3A4, CYP2C8, CYP2C9—monitor if used with other CYP substrates or inhibitors.

Food Interactions:

• Fat-rich meals enhance absorption; recommend dosing with meals.

Alcohol Interaction:

• Avoid alcohol due to hepatotoxicity and hyperlipidemia risks.

• iPLEDGE Program Changes: Updated in the U.S. to include gender-neutral risk categories rather than sex-specific labels.
• European Guidelines (2023): Reaffirmed isotretinoin as first-line for severe acne and an option for moderate acne with psychological burden or scarring risk.
• Dosage Updates: Low-dose regimens (e.g., 0.1–0.3 mg/kg/day) gaining acceptance for moderate acne with fewer side effects and relapse.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Humidity: Store in a dry place; avoid excessive moisture.
• Light: Protect from light.
• Handling: Do not crush or split capsules.
• Disposal: Follow special disposal procedures to prevent environmental contamination.
• Refrigeration: Not required.