Isotretinoin: Part I

Introduction

Isotretinoin is a drug most commonly used in patients suffering from severe cases of acne. Its also used as a chemotherapeutic agent in case of skin cancer (carcinoma). It is a retinoid, a derivative of vitamin A and is found in body in small quantities. It is sold as several brand names, viz.-

1)Accutane (Roche)
2)Amnesteem (Mylan)
3)Claravis (Barr)
4)Decutan (Actavis)
5)Isotane (Pacific Pharmaceuticals)
6)Sotret (Ranbaxy)
7)Oratane (Genepharm Australasia)
8)Roaccutane (Roche)
9)Isotrex or Isotrexin

Pharmacology

Isotretinoin mainly acts by altering DNA transcription; though this activity is unconfirmed. It acts by decreasing the size and secretion of sebacious glands; thereby secreting less of sebum. It further stabilizes keratin and also atropies sebacious glands. This greatly helps in reducing the formation of comedones. This distinguishes isotrtinoin from other conventional antibiotics therapy in acne treatment and gives it an added advantage of great efficacy.

Pharmacokinetics
Absorption-Isotretinoin is absorbed best orally when taken after a high fat meal owing to its lipophilic nature.
Distribution-It is about 99.9 % plasma bound to albumin in blood.
Metabolism-Isotretinoin is metabolized into 3 metabolites; viz.- 4-oxo-isotretinoin, retinoic acid and 4-oxo-retinoic acid
Excretion-It is primarily excreted through urine and faecus.

Clinical Use and Indications
Isotretinoin is used mainly in the treatment of severe acne vulgaris (http://en.wikipedia.org/wiki/Acne_vulgaris). It is also effective in treatment of:

hidradenitis suppurativa- http://en.wikipedia.org/wiki/Hidradenitis_suppurativa

acne rosacea- http://en.wikipedia.org/wiki/Acne_rosacea

harlequin ichthyosis- http://en.wikipedia.org/wiki/Harlequin_type_ichthyosis

Xeroderma pigmentosum- http://en.wikipedia.org/wiki/Xeroderma_pigmentosum

Adverse Effects
1) a)Common: Mild acne flare, dryness of skin, lips and mucous membranes, infection of the cuticles, cheilitis, itch, skin fragility, skin peeling, rash, flushing, photosensitivity, nose bleeds, dry eyes, eye irritation, conjunctivitis, reduced tolerance to contact lenses, hyperlipidaemia, raised liver enzymes, headaches, hair thinning, myalgia and/or arthralgia.
b)Infrequent: severe acne flare, raised blood glucose level, increased erythrocyte sedimentation rate, fatigue.
c)Rare: impaired night vision, cataracts, optic neuritis, menstrual disturbances, inflammatory bowel disease, pancreatitis, hepatitis, corneal opacities, papilloedema, idiopathic intracranial hypertension, skeletal hyperostosis, extraosseous calcification, psychosis, probably severe depression

2)Erectile Dysfunction; probably of psychiatric origin

3)Teratogenicity in neonates; hence pregnant women aren't given this medication.

4)Crohn's disease (http://en.wikipedia.org/wiki/Crohn%27s_Disease) and ulcerative colitis.

Drug-Drug Interactions
1)With Tetracycline- Concurrent use of isotretinoin with tetracycline may cause idiopathic intracranial hypertension (http://en.wikipedia.org/wiki/Idiopathic_intracranial_hypertension)
2)With Vitamin A- increases Vitamin A toxicity
3)with methotrexate-causes hepatotoxicity