Vesanoid

Newly diagnosed, relapsed or refractory to chemotherapy acute promyelocytic leukaemia (APL) in combination w/ arsenic trioxide or chemotherapy.

Adult & elderly APL 45 mg/m² daily in 2 equally divided doses (approx 8 cap daily/patient). Childn (w/ toxicity symptoms eg, intractable headache) Reduce daily dose to 25 mg/m². Patient w/ hepatic &/or renal impairment 25 mg/m². Induction therapy should be continued until complete remission has been achieved or up to max 90 days.

Should be taken with food: Take w/ meal or shortly thereafter. Swallow whole w/ water. Do not chew.

Hypersensitivity to tretinoin, other retinoids, soya, peanut. Combination w/ vit A, tetracyclines & retinoids. Pregnancy & in nursing mothers.

Hyperleukocytosis, sometimes associated w/ differentiation syndrome (DS). Consider temporary interruption of therapy in severe DS cases. May cause intracranial HTN/pseudotumour cerebri (higher incidence in paed patient). Reports of QTc prolongation (might lead to torsade de pointes arrhythmias); increased hepatotoxicity (liver toxicity has occurred predominantly during induction therapy) in combination therapy w/ arsenic trioxide. Reports of depression, aggravated depression, anxiety & mood alterations; caution in patients w/ history of depression & monitor for signs of depression. Cases of Sweet's syndrome or acute febrile neutrophilic dermatitis; risk of venous & arterial thrombosis during 1st mth of treatment. Monitor serum Ca levels due to risk of hypercalcaemia. Supportive care should be maintained during therapy (eg, prophylaxis of bleeding & prompt therapy for infection); frequently monitor haematologic & coagulation profile, LFT results, triglyceride & cholesterol levels. Maintain & monitor daily the values (eg, platelet count >30-50 x 10⁹/L & fibrinogen level >100-150 mg/dL) & continue supportive care during entire induction phase until disappearance of clinical & lab signs of coagulopathy. Closely monitor patients w/ increased BMI during therapy (in terms of resp functions, diuresis & creatinine levels). Monitor ECG prior to & during the course of therapy for the management of QTc prolongation especially for patients w/ existing risk factors. Should not be taken by patients w/ fructose intolerance. May impair ability to drive or operate machinery as dizziness or severe headache may be experienced. Women of childbearing potential must use reliable contraception method & perform pregnancy tests before treatment & at mthly intervals during therapy. Micro-dosed progestagene prep are inadequate contraception methods during tretinoin treatment. High risk of severe malformation of foetus particularly when given during 1st trimester of pregnancy. Discontinue nursing if therapy is initiated. Optimal paed dose has not yet been established.

Decreased appetite; confusional state, anxiety, depression, insomnia; headache, increased ICP & pseudotumour cerebri, dizziness, paraesthesia; visual disturbances, conjunctival disorders; impaired hearing; arrhythmia; flushing; resp failure, nasal dryness, asthma; dry mouth, nausea, vomiting, abdominal pain, diarrhoea, constipation, pancreatitis, cheilitis; erythema, rash, pruritus, alopecia, hyperhidrosis; bone pain; chest pain, chills, malaise; increased blood triglyceride, creatinine & cholesterol, increased transaminases.

May potentially alter pharmacokinetics parameters w/ hepatic P450 inducers (including rifampicin, glucocorticoids, phenobarb, pentobarbital) & hepatic P450 inhibitors (including ketoconazole, cimetidine, erythromycin, verapamil, diltiazem & ciclosporin). Increased toxicity w/ azole antifungals (eg, fluconazole, voriconazole, posaconazole). Combination w/ other strong CYP3A4 inhibitors (PIs or macrolides eg, clarithromycin) may trigger tretinoin toxicity. Cases of fatal thrombotic complications in concomitant use w/ antifibrinolytics eg, tranexamic acid, aminocaproic acid & aprotinin. Concomitant use of agents known to cause intracranial HTN/pseudotumour cerebri eg, tetracyclines (might increase risk of this condition). Symptoms of hypervitaminosis A could be aggravated w/ vit A.

Cytotoxic Chemotherapy

L01XF01 - tretinoin ; Belongs to the class of retinoids for cancer treatment. Used in the treatment of cancer.

Rx