Tretinoin

Indications
 Oral
Acute promyelocytic leukaemia
Adult: A daily dose of 45 mg/m2 daily in 2 divided doses, continue treatment until 30 days after complete remission or 90 days of treatment given, whichever occurs first. To increase duration of remission, consolidation therapy, usually with an anthracycline- and cytarabine-based regimen, is given concurrently or subsequently, depending on the leukocyte count.
Child: A daily dose of 45 mg/m2 daily in 2 divided doses, continue treatment until 30 days after complete remission or 90 days of treatment given, whichever occurs first. To increase duration of remission, consolidation therapy, usually with an anthracycline- and cytarabine-based regimen, is given concurrently or subsequently, depending on the leukocyte count. Reduce dose if serious or intolerable drug toxicity. However, the safety and efficacy < 45 mg/m2 daily in paediatric patients have not been established.
Renal impairment: Decrease to 25 mg/m2 daily.
Hepatic impairment: Decrease to 25 mg/m2 daily.
Topical/Cutaneous
Acne
Adult: Apply a 0.01-0.1% cream/gel/alcoholic solution once or bid onto affected area which has been previously cleansed to remove excessive oiliness and dried 15-30 min prior to application. Therapeutic response may be seen after 6-8 wk.
Topical/Cutaneous
Mottled hyperpigmentation, roughness and fine wrinkling of photodamaged skin
Adult: Wash face with mild soap, pat dry and wait for 20-30 min before applying 0.02-0.05% preparation once daily at night. Therapeutic response may be seen after 6 mth.
Contraindications
 Hypersensitivity to retinoids. Application to eczematous, sunburnt or abraded skin. Pregnancy, lactation.
Warnings / Precautions
 Topical: avoid concomitant topical applications, esp keratolytic agents. Avoid exposure to sunlight, UV light and weather extremes (e.g. cold). Keep away from eyes, mouth, angles of nose, mucous membranes or open wounds. In case of severe local erythema, oedema, blistering or crusting, use less frequently or discontinue. Avoid medicated or drying soaps, abrasive soaps and cleansers, frequent washing and harsh scrubbing. Avoid use of topical preparations with high concentrations of alcohol, menthol, spices or lime. Oral: Children, hepatic or renal impairment. Reduce dose if intractable headache occurs. Discontinue temporarily if LFT exceed 5 times upper limit of normal. Monitor closely for leukocytosis or respiratory compromise. Monitor haematologic profile, coagulation parameters, LFT, serum triglyceride and cholesterol concentrations regularly.
Adverse Reactions
 Initial exacerbation of symptoms, skin irritation, stinging on application, oedema, blistering, crusting of the skin, erythema, scaling, photosensitivity, temporary hypo/hyperpigmentation. Oral: Haemorrhage, reversible hypercholesterolemia and/or hypertriglyceridemia, acidosis, hypothermia, pseudotumour cerebri, infection, dizziness, paresthesias, anxiety, dryness of skin and mucous membranes, nausea, vomiting, GI haemorrhage, mucositis, decreased appetite, rash, pruritus, increased sweating, alopecia, bone pain, peripheral oedema, renal insufficiency, earache, visual disturbances, neurotoxicity.
Potentially Fatal: Retinoic acid syndrome, cardiac arrthythmia, disseminated intravascular coagulation, blood dyscrasias, cardiac arrest, cerebral haemorrhage.
Overdose Reactions
 Symptoms: transient headache, facial flushing, cheilosis, abdominal pain, dizziness and ataxia.
Drug Interactions
 Enhances percutaneous absorption of minoxidil. Increased risk of fatal thrombotic complications with antifibrinolytic. Increased tretinoin concentrations with azole antifungals. Enhances peeling action of sulphur, resorcinol, benzoyl peroxide, salicylic acid. Increased photosensitivity with photosensitising medications eg, thiazides, tetracyclines, fluoroquinolones, phenothiazines and sulfonamides.
Potentially Fatal: Increased risk of intracranial pressure with tetracyclines.
See Below for More tretinoin Drug Interactions
Food Interactions
 Dong quai and St. John's wort may potentiate photosensitisation. Increased risk of vitamin A toxicity with vit A supplements or food/preparations rich in vit A eg, cod liver oil and halibut fish oil.
Mechanism of Actions
 Tretinoin is a trans-retinoic acid form of vitimin A. It stimulates mitosis and turnover of follicular epithelial cells and reduce their cohesiveness. This facilitates extrusion of existing comedones and prevents formation of new comedone. It also exhibits thinning effect on the stratum corneum. In acute promyelocytic leukaemia, it induces cellular differentiation and decreases proliferations.
Absorption: Well absorbed from the GIT, peak plasma concentrations after 1-2 hrs (oral). Oral bioavilability: 50%.
Distribution: Highly bound to plasma proteins.
Metabolism: Hepatic by cytochrome P450 isoenzyme; converted to isotretinoin, 4-oxo-trans-retinoic acid and 4-oxo-cis-retinoic acid.
Excretion: Urine and faeces; 0.5-2 hrs (terminal elimination half-life).
Administration
 Should be taken with food.
Storage Conditions
 Oral: Store 15-30°C (59-86°F). Topical/Cutaneous: Solution / gel: Store below 30°C (86°F). Cream: Store below 80°F.
ATC Classification
 D10AD01 - tretinoin ; Belongs to the class of topical retinoid preparations used in the treatment of acne.
L01XX14 - tretinoin ; Belongs to the class of other antineoplastic agents. Used in the treatment of cancer.
Storage
 Oral: Store 15-30°C (59-86°F). Topical/Cutaneous: Solution / gel: Store below 30°C (86°F). Cream: Store below 80°F.
Available As
  • Tretinoin 0.012% w/w
  • Tretinoin 0.025%
  • Tretinoin 0.025% w/w
  • Tretinoin 0.03%
  • Tretinoin 0.03% w/w
  • Tretinoin 0.04%
  • Tretinoin 0.05%
  • Tretinoin 0.05% w/w
  • Tretinoin 0.1%
  • Tretinoin 0.25%
  • Tretinoin 2.5% w/w
  • Tretinoin 5%

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