Tretinoin


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Acute promyelocytic leukaemia Induction of remission in previously untreated patients and those who have relapsed from or refractory to standard chemotherapy: 45 mg/m2 daily in 2 equally divided doses, continued until complete remission. Max treatment duration: 90 days. Dose reduction, dosing interruption or re-initiation may be required according to individual safety and tolerability (refer to detailed product guideline). Topical Acne vulgaris As 0.01-0.05% gel/cream/lotion: Apply enough to the entire affected area once daily at night or before bedtime. Therapeutic effects may be observed after 2-3 weeks but may require >6 weeks of treatment to see consistent beneficial effects. Mottled hyperpigmentation, roughness and fine wrinkling of photodamaged skin As 0.02% or 0.05% cream: Apply a pea-sized amount onto the face once daily at night or before bedtime, to cover the entire affected area lightly. Therapeutic effects may be observed after 6 months.
Dosage Details
Oral
Acute promyelocytic leukaemia
Adult: Induction of remission in previously untreated patients and those who have relapsed from or refractory to standard chemotherapy: 45 mg/m2 daily in 2 equally divided doses, continued until complete remission. Max treatment duration: 90 days. Dose reduction, dosing interruption or re-initiation may be required according to individual safety and tolerability (refer to detailed product guideline).
Child: 1-16 years Same as adult dose. Consider dose reduction to 25 mg/m2 if toxicity symptoms (e.g. intractable headache) occur.

Topical/Cutaneous
Mottled hyperpigmentation, roughness and fine wrinkling of photodamaged skin
Adult: As 0.02% or 0.05% cream: Apply a pea-sized amount onto the face once daily at night or before bedtime, to cover the entire affected area lightly. Therapeutic effects may be observed after 6 months.

Topical/Cutaneous
Acne vulgaris
Adult: As 0.01-0.05% gel/cream/lotion: Apply enough to the entire affected area once daily at night or before bedtime. Exacerbation of inflammatory lesions may occur in early weeks of treatment. Therapeutic effects may be observed after 2-3 weeks but may require >6 weeks of treatment to see consistent beneficial effects.
Renal Impairment
Oral:
Reduce dose to 25 mg/mdaily.
Hepatic Impairment
Oral:
Reduce dose to 25 mg/mdaily.
Administration
Should be taken with food.
Contraindications
Pregnancy and lactation (oral). Concomitant use with tetracyclines, vitamin A, retinoids and anti-fibrinolytic agents (e.g. tranexamic acid, aminocaproic acid, aprotinin).
Special Precautions
Patient with history of depression; eczema, sunburn, personal or family history of skin cancer, considerable sun exposure (e.g. due to occupation, inherent sensitivity to sunlight), fish allergies (topical). Avoid application to eyes, mouth and nose (topical). Lactation (topical). Children. Renal and hepatic impairment.
Adverse Reactions
Significant: Venous thrombosis, MI, pseudotumor cerebri/benign intracranial hypertension (children), hypercholesterolaemia or hypertriglyceridaemia (reversible), hypercalcaemia, psychiatric disorders (e.g. depression, anxiety, mood alterations), elevated LFT, Sweet’s syndrome (acute febrile neutrophilic dermatosis); hypersensitivity reactions, photosensitivity (topical), skin irritation (e.g. excessive dryness, redness, swollen, blistered), application site reactions (e.g. feeling of warmth, dry skin, peeling, burning, stinging, pain).
Blood and lymphatic system disorders: Thrombocytosis, basophilia.
Cardiac disorders: Arrhythmia, chest pain.
Ear and labyrinth disorders: Impaired hearing.
Eye disorders: Visual disturbances, conjunctival disorders.
Gastrointestinal disorders: Dry mouth, nausea, vomiting, diarrhoea, abdominal pain, constipation, pancreatitis, cheilitis.
General disorders and administration site conditions: Chills, malaise.
Investigations: Increased blood creatinine.
Metabolism and nutrition disorders: Decreased appetite.
Musculoskeletal and connective tissue disorders: Bone pain.
Nervous system disorders: Headache, dizziness, paraesthesia.
Psychiatric disorders: Confusional state, insomnia.
Respiratory, thoracic and mediastinal disorders: Nasal dryness, asthma, respiratory failure.
Skin and subcutaneous tissue disorders: Rash, pruritus, hyperhidrosis, erythema, alopecia, hypo-/hyperpigmentation (temporary).
Vascular disorders: Flushing.
Potentially Fatal: APL differentiation syndrome/retinoic acid syndrome, leukocytosis, QTc prolongation leading to torsade de pointes.
Topical: C; PO: D
Patient Counseling Information
Oral: This drug may cause dizziness or severe headache, if affected, do not drive or operate machinery. Topical: Avoid or minimise exposure to sunlight (including sunlamps), if exposure cannot be avoided, use sunscreens or protective clothing over treated areas.
MonitoringParameters
Perform bone marrow cytology to confirm t(15;17) translocation or presence of PML/RARα fusion protein; pregnancy test 1 week prior to therapy and every month during treatment. Monitor CBC with differential, coagulation profile, LFTs, triglycerides and cholesterol levels frequently. Closely monitor cardiac, CNS, and respiratory status frequently during treatment; signs of depression, and acute promyelocytic leukaemia (APL) differentiation syndrome (e.g. monitor volume and pulmonary status, temperature, respiration).
Overdosage
Symptoms: Oral: Reversible signs of hypervitaminosis A (e.g. headache, nausea, vomiting, mucocutaneous symptoms), transient headache, facial flushing, cheilosis, abdominal pain, dizziness, and ataxia. Topical: Marked skin redness, peeling, blistering, or discomfort. Management: Oral: Treat patient in a special haematological unit. Topical: Discontinue use and apply cold compress and a bland cream. If ingested, promote rapid gastric emptying by inducing emesis, gastric lavage and/or forced fluids.
Drug Interactions
Oral: May potentially alter pharmacokinetics with CYP450 inducers (e.g. rifampicin, glucocorticoids, phenobarbital, pentobarbital) and CYP450 inhibitors (e.g. ketoconazole, cimetidine, erythromycin, verapamil, diltiazem, ciclosporin). Topical: May increase risk of skin irritation with topical medications, medicated or abrasive soaps, shampoos, cleansers, permanent wave solutions, electrolysis, hair depilatories or waxes, cosmetics with strong drying effect, products with high concentrations of alcohol, astringents, spices or lime, and preparations containing sulfur, resorcinol, benzoyl peroxide or salicylic acid.
Potentially Fatal: Oral: Increased risk of pseudotumour cerebri/intracranial hypertension with tetracyclines. Increased risk of symptoms suggestive of hypervitaminosis A with other retinoids and vitamin A. Increased risk of thrombotic complications with antifibrinolytic agents (e.g. tranexamic acid, aminocaproic acid, aprotinin).
Food Interaction
Enhanced absorption with food. Rarely, may increase risk of vitamin A toxicity with cod liver oil or halibut fish oil.
Action
Description: Tretinoin is a retinoid and an acid from of vitamin A. Topically, it modifies epithelial growth and differentiation; in acne treatment, it decreases the cohesiveness of follicular epithelial cells and microcomedo formation, stimulates mitotic activity, and increases the turnover of follicular epithelial cells resulting in the extrusion of comedones. Systemically, tretinoin specifically binds to 1 or more nuclear retinoic acid receptors (RAR), induces cellular differentiation, and decreases proliferation of acute promyelocytic leukaemia (APL) cells.
Synonym: All-trans retinoic acid (ATRA).
Onset: Acne: ≥2 weeks, may take ≥7 weeks. Facial wrinkles: Up to 6 months.
Pharmacokinetics:
Absorption: Well absorbed from the gastrointestinal tract (oral); minimally absorbed from the skin (topical). Enhanced absorption with food (oral). Bioavailability: Approx 50% (oral). Time to peak plasma concentration: 1-2 hours (oral).
Distribution: Plasma protein binding: >95%, mainly to albumin.
Metabolism: Metabolised in the liver by CYP450 enzymes to form 4-oxo-trans-retinoic acid (primary metabolite); displays auto-metabolism.
Excretion: Via urine (63%); faeces (30%). Terminal elimination half-life: 0.5-2 hours (oral).
Chemical Structure

Chemical Structure Image
Tretinoin

Source: National Center for Biotechnology Information. PubChem Database. Tretinoin, CID=444795, https://pubchem.ncbi.nlm.nih.gov/compound/Tretinoin (accessed on Jan. 23, 2020)

Storage
Cap: Store between 20-25°C. Protect from light and moisture. Cream/gel/lotion: Store between 20-25°C. Do not freeze.
ATC Classification
D10AD01 - tretinoin ; Belongs to the class of topical retinoid preparations used in the treatment of acne.
References
Altreno Lotion (Bausch Health US LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/01/2020.

Anon. Tretinoin (Systemic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/01/2020.

Anon. Tretinoin (Topical). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/01/2020.

Atralin 0.05% w/w Gel (Generics Ltd t/a Mylan). MHRA. https://products.mhra.gov.uk/. Accessed 13/03/2020.

Avita Cream (Mylan Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/01/2020.

Buckingham R (ed). Tretinoin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/01/2020.

Joint Formulary Committee. Tretinoin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 18/03/2020.

Refissa Cream (Suneva Medical, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/01/2020.

Renova Cream (Bausch Health US LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/01/2020.

Tretinoin Capsule, Liquid Filled (Teva Pharmaceuticals USA, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/01/2020.

Vesanoid 10 mg Soft Capsules (Cheplapharm Arzneimittel GmbH). MHRA. https://products.mhra.gov.uk/. Accessed 13/03/2020.

Disclaimer: This information is independently developed by MIMS based on Tretinoin 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 © 2020 MIMS. All rights reserved. Powered by MIMS.com
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