Isotretinoin


Generic Medicine Info
Indications and Dosage
Oral
Acne
Adult: In severe cases such as nodular or conglobate acne, or acne at risk of permanent scarring, which are resistant to standard therapy including systemic antibiotics and topical therapy: As conventional cap: Initially, 0.5 mg/kg once daily or in 2 divided doses, may increase to 1 mg/kg daily. Continue until a total cumulative dose of 120-150 mg/kg is attained. Treatment duration may vary depending on individual daily dose; continue for 15-24 weeks or until the total cyst count has reduced by over 70%. In patients who have severe intolerance to the recommended dose, treatment may be continued at a lower dose for a longer duration. As lidose formulation: 0.5-1 mg/kg daily in 2 divided doses for 15-20 weeks. As micronised formulation: 0.4-0.8 mg/kg daily in 2 divided doses for 15-20 weeks. In patients with very severe disease with scarring or cases primarily manifested on the trunk, dose adjustment of up to 2 mg/kg daily (conventional/lidose) or 1.6 mg/kg daily (micronised) in divided doses may be required as tolerated. Doses may be adjusted according to patient response and tolerance. In case of relapse, may consider a 2nd course of treatment using the same daily dose and cumulative treatment dose; allow at least a 2-month drug-free period between treatments. Dosage or treatment recommendations may vary among countries or individual products (refer to specific product guidelines).
Child: ≥12 years Same as adult dose.

Topical/Cutaneous
Acne vulgaris
Adult: For the treatment of mild to moderate cases with or without inflammation: As 0.05% gel: Apply sparingly on the affected area once daily or bid. Effect may be observed after 6-8 weeks of treatment.
Renal Impairment
Oral:
Severe: As conventional cap: Initiate at a lower dose (e.g. 10 mg daily) then increase up to 1 mg/kg daily or until the patient is receiving the Max tolerable dose.
Hepatic Impairment
Oral:
Contraindicated.
Administration
Standard Formulation: Should be taken with food. Administer w/ meals to increase absorption. Take w/ a full glass of liqd to minimise oesophageal irritation. Swallow whole, do not chew/suck.
Lidose &Amp; Micronised Formulations: May be taken with or without food. Take w/ a full glass of liqd to minimise oesophageal irritation. Swallow whole, do not chew/suck.
Contraindications
Hypervitaminosis A; hyperlipidaemia or excessively elevated blood lipid values. Hepatic impairment. Pregnancy and lactation. Concomitant use with tetracyclines and vitamin A (including dietary supplements).
Special Precautions
Patient with diabetes mellitus, existing or at high risk of hypertriglyceridaemia (e.g. family history of or those with lipid metabolism disorder, obesity, increased alcohol intake), dry eye syndrome; history of depression or psychiatric disorders; genetic predisposition for bone loss (e.g. history of childhood osteoporosis conditions, osteomalacia, other disorders of bone metabolism) including those with anorexia nervosa. Avoid blood donation during and for at least 1 month after treatment; aggressive chemical dermabrasion and cutaneous laser treatment during and for 5-6 months after treatment and wax depilation during and for at least 6 months after treatment. Patient taking medications that may cause drug-induced osteoporosis or osteomalacia and/or affect vitamin D metabolism (e.g. systemic corticosteroids, anticonvulsants). Avoid concurrent use with topical keratolytic or exfoliative anti-acne agents. Not indicated for prepubertal acne. Severe renal impairment. Children. Some oral products or formulations are not interchangeable; refer to specific product guideline for further information. Topical: Patient with history of photoallergy or photodermatitis, skin cancer (personal or family history); with concomitant rosacea or perioral dermatitis. Application to sensitive skin areas (e.g. neck). Delay therapy in patients with sunburn until resolved. Avoid application to eczematous skin.
Adverse Reactions
Significant: Hearing impairment, tinnitus; corneal opacities, dry eyes, keratitis, decreased tolerance to contact lenses, decreased night vision; decreased bone mineral density, osteoporosis, osteopenia, bone fractures, delay in healing of bone fractures, skeletal hyperostosis, premature epiphyseal closure, calcification of tendons and ligaments; photosensitivity, benign intracranial hypertension (pseudotumour cerebri), hypersensitivity reactions (e.g. anaphylactic reactions, allergic vasculitis often with purpura of the extremities and extracutaneous involvement), inflammatory bowel disease (including regional ileitis), severe (haemorrhagic) diarrhoea; arthralgia, myalgia, increased serum creatinine phosphokinase (particularly in patients undertaking vigorous physical activity); hepatitis, mild to moderate increase in liver enzymes, transient chest pain, acute pancreatitis, lipid abnormalities (e.g. increased serum triglycerides and cholesterol, decreased HDL), new onset or worsening of depression, psychosis, mood alterations, anxiety; dry skin and lips, neutropenia, impaired glucose control. Irritation, redness, peeling, or discomfort (topical). Rarely, agranulocytosis; suicidal ideation, aggressive and/or violent behaviours.
Blood and lymphatic system disorders: Anaemia, thrombocytopenia, thrombocytosis.
Eye disorders: Blepharitis, conjunctivitis, eye irritation.
General disorders and administration site conditions: Application site erythema, pruritus or irritation, localised tenderness (topical).
Investigations: Increased RBC sedimentation rate.
Musculoskeletal and connective tissue disorders: Back pain (particularly in adolescents).
Nervous system disorders: Headache.
Renal and urinary disorders: Haematuria, proteinuria.
Reproductive system and breast disorders: Rarely, sexual dysfunction including erectile dysfunction and decreased libido.
Respiratory, thoracic and mediastinal disorders: Nasopharyngitis, epistaxis, nasal dryness.
Skin and subcutaneous tissue disorders: Cheilitis, dermatitis, localised exfoliation, pruritus, rash erythematous, skin fragility, acute exacerbation of acne (during initial treatment); exfoliation, burning sensation or stinging of the skin, skin pain (topical).
Potentially Fatal: Severe skin reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme). Rarely, haemorrhagic pancreatitis, rhabdomyolysis, suicide attempts, suicide.
Patient Counseling Information
This drug may reduce your ability to see at night, be cautious when driving or operating machinery during night-time. Women of child-bearing potential must use proven contraceptive methods (1 or 2 methods) 1 month before starting treatment, during the entire course, and 1 month after stopping treatment. Avoid or minimise prolonged exposure to sunlight or UV rays, if exposure cannot be avoided, use sunscreen (with protection factor of at least SPF 15) or wear protective clothing.
Monitoring Parameters
Screen for pregnancy before starting (2 tests with sensitivity of ≥25 milliunits/mL), every month during treatment, at the end of the entire course and 1 month after discontinuation of treatment. Monitor LFTs and fasting lipid tests (before treatment and weekly or biweekly until treatment response is established), CBC with differential and platelet count, sedimentation rate (at baseline), blood glucose, creatine phosphokinase. Assess for signs and symptoms of depression, mood alteration, psychosis, aggression, severe skin reactions, and changes in vision.
Drug Interactions
May increase risk of local irritation with topical keratolytic or exfoliative anti-acne agents. Benzoyl peroxide may reduce the therapeutic efficacy of topical isotretinoin.
Potentially Fatal: Concomitant use with tetracyclines resulted in benign intracranial hypertension (pseudotumour cerebri). May increase risk of additive toxic effects with vitamin A.
Food Interaction
Increased bioavailability with food.
Action
Description: Isotretinoin is a retinoid and the cis configuration of tretinoin. The exact mechanism for the treatment of acne has not yet been fully elucidated, but it has been noted to be associated with the inhibition of the sebaceous gland activity and follicular keratinisation. It reduces sebum production reflecting a decrease in the size of sebaceous gland and inhibition of its differentiation. Topically, it stimulates epidermal mitosis, decreases intercellular cohesion in the stratum corneum, combats hyperkeratosis, aids in desquamation to prevent formation of lesions, and moderates an increase in production of less cohesive epidermal sebaceous cells to promote expulsion of comedones.
Pharmacokinetics:
Absorption: Absorbed from the gastrointestinal tract (oral); minimal systemic absorption after topical application. Increased bioavailability with food. Time to peak plasma concentration: Conventional cap: 5.3 hours (fed); 3.2 hours (fasting). Lidose formulation: 6.4 hours (fed); 2.9 hours (fasting). Micronised formulation: 5 hours (fed); 3.5 hours (fasting).
Distribution: Crosses the placenta. Plasma protein binding: 99-100%, mainly to albumin.
Metabolism: Metabolised in the liver by CYP2B6, 2C8, 2C9, and 3A4 into 4-oxo-isotretinoin (major active metabolite), retinoic acid (tretinoin), and 4-oxo-retinoic acid (4-oxo-tretinoin). Undergoes enterohepatic recycling (including its metabolites).
Excretion: Via urine and faeces (in equal amounts). Elimination half-life: Conventional cap: 21 ± 8.2 hours (isotretinoin); 24 ± 5.3 hours (active metabolite). Lidose formulation: 18 hours (isotretinoin); 38 hours (active metabolite). Micronised formulation: Approx 24 hours (isotretinoin); approx 38 hours (active metabolite).
Chemical Structure

Chemical Structure Image
Isotretinoin

Source: National Center for Biotechnology Information. PubChem Database. Isotretinoin, CID=5282379, https://pubchem.ncbi.nlm.nih.gov/compound/Isotretinoin (accessed on Jan. 21, 2020)

Storage
Store below 30°C. Protect from light. Topical gel: Keep away from fire, flame, or heat. Storage recommendations may vary among individual products. Refer to specific product guideline.
MIMS Class
Acne Treatment Preparations
ATC Classification
D10BA01 - isotretinoin ; Belongs to the class of systemic retinoid preparations used in the treatment of acne.
D10AD04 - isotretinoin ; Belongs to the class of topical retinoid preparations used in the treatment of acne.
References
Absorica/Absorica LD Capsule (Sun Pharmaceuticals Industries, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 22/06/2021.

Accutane Capsule, Gelatin Coated (JG Pharma Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 22/06/2021.

Acnoin 500 mcg/g (0.05% w/w) Gel (Zee Laboratories Limited). MIMS Philippines. http://www.mims.com/philippines. Accessed 28/05/2021.

Anon. Isotretinoin (Systemic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 28/05/2021.

Anon. Isotretinoin (Topical). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 28/05/2021.

Anon. Isotretinoin. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 28/05/2021.

Buckingham R (ed). Isotretinoin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 28/05/2021.

Isotretinoin 10 mg Capsules, Soft (Ennogen Healthcare Limited). MHRA. https://products.mhra.gov.uk. Accessed 28/05/2021.

Isotretinoin 20 mg Soft Capsules (Sun Pharmaceutical Industries Europe B.V.). MHRA. https://products.mhra.gov.uk. Accessed 28/05/2021.

Isotretinoin 40 mg Soft Capsules (Generics [UK] Limited t/a Mylan). MHRA. https://products.mhra.gov.uk. Accessed 28/05/2021.

Isotretinoin 5 mg Capsules (Ennogen Healthcare Limited). MHRA. https://products.mhra.gov.uk. Accessed 28/05/2021.

Isotretinoin Capsule (Actavis Pharma, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 28/05/2021.

Joint Formulary Committee. Isotretinoin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 28/05/2021.

Roaccutane (Roche [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 28/05/2021.

Disclaimer: This information is independently developed by MIMS based on Isotretinoin from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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