Retin-A (Cream) Instructions for Use

Marketing Authorization Holder

Cilag, AG (Switzerland)

ATC Code

D10AD01 (Tretinoin)

Active Substance

Tretinoin (Rec.INN registered by WHO)

Dosage Form

Retin-A

Cream 0.05%: tube 30 g

Dosage Form, Packaging, and Composition

30 g – aluminum tubes (1) – cardboard packs.

Clinical-Pharmacological Group

Acne treatment drug. Retinoid

Pharmacotherapeutic Group

Acne treatment agent

Pharmacological Action

Retinoid. Structurally related to vitamin A, it is a natural metabolite of retinol. When taken orally, it suppresses the differentiation and growth of the clone of altered blood cells, including human myeloleukemic cells. The mechanism of action in acute promyelocytic leukemia is probably due to damage caused by the binding of tretinoin to nuclear retinoic acid receptors.

When applied topically, it enhances cell proliferation in the papillary layer of the skin, reduces the adhesion of cells involved in the formation of acne vulgaris. When treating open comedones, it helps to even out the skin surface without signs of inflammation. When treating closed comedones, it promotes their transition to open comedones or papules, which then heal without scarring after removal of the keratin plug. Prevents the formation of new comedones.

Pharmacokinetics

Tretinoin is a natural metabolite of retinol, which is normally present in plasma. After oral administration, Tretinoin is absorbed from the gastrointestinal tract. Plasma concentration returns to the initial endogenous level 7-12 hours after a single 40 mg dose.

Plasma protein binding is high. Does not accumulate.

T_1/2 is 0.7 hours. After oral administration of radioactively labeled tretinoin, about 60% is excreted in the urine and about 30% in the feces. Metabolites are formed by oxidation and glucuronidation.

With prolonged use of tretinoin, a decrease in its plasma concentration is observed, which may be due to the induction of CYP system isoenzymes.

Indications

For oral administration: acute promyelocytic leukemia (for induction of remission) both in patients who have not previously received therapy, and in cases of relapse or refractoriness to standard therapy (daunorubicin or cytarabine).

For topical application: acne vulgaris (including with the formation of comedones, papules, pustules), conglobate acne. Favre-Racouchot disease (nodular cystic elastosis of the skin with comedones).

ICD codes

Dosage Regimen

Determine the dosage regimen individually based on the indication, disease stage, and concurrent anticancer therapy.

For acute promyelocytic leukemia, administer orally. The typical daily dose is 45 mg/m² divided into two equal doses. Continue therapy until complete remission is achieved, for a maximum of 90 days.

For acne vulgaris, apply topically. Prior to application, cleanse the affected skin area and dry thoroughly. Apply a thin layer of the cream to cover the entire affected area once daily, preferably in the evening.

Avoid contact with eyes, eyelids, mouth, angles of the nose, and mucous membranes. If contact occurs, rinse thoroughly with water.

During the initial weeks of topical treatment, expect a local skin reaction, including erythema, peeling, and a sensation of warmth or stinging. This indicates an initial therapeutic effect.

If excessive irritation occurs, reduce the frequency of application to once every other day or temporarily discontinue use. Once the skin tolerates the treatment, resume daily application.

For patients with hepatic or renal impairment, a dose reduction is necessary. Adjust the dose based on clinical tolerance and laboratory parameters.

Monitor patients on oral therapy for signs of retinoic acid syndrome (fever, dyspnea, weight gain). Initiate high-dose corticosteroid therapy immediately upon the earliest signs.

Concomitant use with drugs that cause skin desquamation or dryness is not recommended. During therapy, minimize exposure to sunlight and UV rays and consistently use sunscreen.

Adverse Reactions

Retinoic acid syndrome – often: fever, dyspnea, shortness of breath, acute respiratory distress syndrome, pulmonary infiltrate, hyperleukocytosis, arterial hypotension, pleural effusion, renal and hepatic failure.

Dermatological reactions – possible: xeroderma, rash, cheilitis; rarely: erythema, itching, increased sweating, cellulitis, alopecia, exfoliative dermatitis, dryness of mucous membranes, xerophthalmia.

From the digestive system – possible: dry mouth, nausea, vomiting, increased activity of liver transaminases; rarely: abdominal pain, diarrhea, constipation, bullous stomatitis.

From the CNS – rarely: dizziness, impaired consciousness, increased intracranial pressure, anxiety, depression, visual and hearing impairment.

From metabolism – possible: increased plasma triglycerides, cholesterol, changes in body weight.

From the respiratory system – rarely: cough, pleural effusion, swelling of the nasal mucosa, shortness of breath, pharyngitis, pulmonary wheezing, stridor breathing.

From the cardiovascular system – rarely: arrhythmias.

From the musculoskeletal system – rarely: muscle and bone pain.

From the hematopoietic system – rarely: increased bleeding.

Other – possible: edema; rarely: fever, chills, associated infections (including pneumonia, septicemia), general weakness and drowsiness, chest and back pain.

With topical application – possible: redness, burning sensation, peeling of the skin at the application site; in isolated cases: swelling, blistering or crusting, photosensitivity.

Contraindications

Hypersensitivity to tretinoin; pregnancy, breastfeeding period (for oral administration), history of skin epithelioma (including family history).

For topical application: acute inflammatory (including eczematous) skin lesions, wounds, burns.

Use in Pregnancy and Lactation

Contraindicated during pregnancy. Women of childbearing potential must use effective methods of contraception for at least 1 month before starting treatment, during therapy, and for 1 month after discontinuation of tretinoin. Treatment should be started on the 2nd-3rd day of a normal menstrual cycle. The absence of pregnancy should be confirmed by laboratory tests 2 weeks before starting treatment. Such tests should be performed once a month.

If oral administration is necessary during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

Should be used with caution in patients with hepatic insufficiency. The dose should be reduced in this category of patients.

Use in Renal Impairment

Should be used with caution in patients with renal insufficiency. The dose should be reduced in this category of patients.

Pediatric Use

Should be used with caution in children.

Special Precautions

Oral Tretinoin should be prescribed only by a physician experienced in the treatment of hematological/oncological diseases.

To prevent retinoic acid syndrome with a significant increase in the number of leukocytes or the appearance of other signs of this syndrome, full-dose chemotherapy is prescribed. At the earliest signs, a course of treatment with dexamethasone should be started immediately.

When applied topically, avoid contact of tretinoin with the eyes, mouth, mucous membranes; in case of contact, rinse immediately with water.

During treatment, it is recommended to avoid sun exposure. Treatment of sun-tanned skin can be started after the tan fades.

During the first week of treatment, an exacerbation of acne may occur.

Tretinoin should not be used simultaneously with drugs that cause skin desquamation, as well as with cosmetic and hygiene products that cause dryness and skin irritation.

Drug Interactions

Tretinoin is metabolized in the liver with the participation of CYP450 system isoenzymes. Therefore, when used concomitantly with drugs that affect these enzymes, a change in pharmacokinetic parameters cannot be excluded.

Tretinoin reduces the contraceptive effect of progestogens.

When used concomitantly with tetracyclines, an increase in intracranial pressure is possible.

When used concomitantly with vitamin A, symptoms of hypervitaminosis are observed.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.