Brand name: Adriblastina
Active ingredient (generic name): Doxorubicin
Manufacturer: Pharmacia
Importer: Behestan Darou
Pharmacotherapeutic group: antiblastic anthracycline antibiotic
Pharmaceutical form: 10mg & 50mg vials
The mechanism of action of Adriblastina is related to the ability of the antibiotic to bind to DNA and inhibit nucleic acid synthesis. Cell cultural studies have demonstrated rapid cell penetration by the antibiotic and its main localization is in the perinucleolar chromatin. Rapid inhibition of mitotic activity and nucleic acid synthesis have also been demonstrated together with the appearance of chromosomal aberrations.
Pharmacokinetic:
Pharmacokinetic studies, determined in patients with various types of tumors undergoing either single or multi-agent therapy have shown that doxorubicin follows a multiphasic disposition after intravenous injection. The half-life of doxorubicin is approximately 30 hours.
Binding of doxorubicin and its major metabolite, doxorubicinol to plasma proteins is about 77%. Doxorubicin does not cross the blood brain barrier.
Therapeutic indication:
Adriblastina PFS has been used successfully to produce regression in a variety of neoplastic conditions, such as carcinoma of the breast, lung, bladder, thyroid, and also ovarian carcinomas, bone and soft-tissue sarcomas, Hodgkin’s and non-Hodgkin’s lymphomas, neuroblastomas, Wilms’ tumour, acute lymphoblastic leukaemia and acute myeloblastic leukaemia.
Dosage and administration:
Intravenous Administration: Dosage is usually calculated on the basis of body surface area. As a single agent, the recommended standard starting dose of doxorubicin per cycle in adults is 60-75 mg/m2 of body surface area. The total starting dose per cycle may be given as a single dose or divided over 3 successive days or in divided doses given on days 1 and 8. Under conditions of normal recovery from drug-induced toxicity (particularly bone marrow depression and stomatitis), each treatment cycle could be repeated every 3 to 4 weeks. If it is used in combination with other antitumour agents having overlapping toxicity, the dosage for doxorubicin may need to be reduced to 30-60 mg/m2 every three weeks.
Administration of doxorubicin in a weekly regimen has been shown to be as effective as the 3-weekly regimen.
If hepatic function is impaired, doxorubicin should be reduced.
Intravesical Administration: Doxorubicin is being increasingly used by intravesical administration for the treatment of transitional cell carcinoma, papillary bladder tumours and carcinoma-in-situ. Instillations of 30-50 mg in 25-50 mL of saline solution are recommended. In the case of local toxicity (chemical cystitis), the dose should be instilled in 50-100 mL of saline solution. Patients may continue to receive instillations in weekly to monthly intervals. The concentration of doxorubicin in the bladder should be 50 mg per 50 ml.
Adverse reaction:
Cardiac Disorders:
Cardiotoxicity may be manifested in tachycardia including supraventricular tachycardia and ECG changes. Routine ECG monitoring is recommended and caution should be exercised in patients with impaired cardiac function. Severe cardiac failure may occur suddenly without premonitory ECG changes. Tachyarrhythmias, atrio-ventricular and bundle branch block, asymptomatic reduction in left ventricular ejection fraction and congestive heart failure.
Gastrointestinal Disorders:
Nausea, vomiting and mucositis/stomatitis, hyperpigmentation of oral mucosa, oesophagitis, abdominal pain, gastric erosions, gastrointestinal tract bleeding, diarrhoea and colitis
Skin and Subcutaneous Tissue Disorders:
Alopecia occurs frequently, including the interruption of beard growth, but all hair growth normally resumes after treatment is stopped. Skin rashes/itch, local toxicity, skin changes, skin and nail hyperpigmentation, photosensitivity, hypersensitivity to irradiated skin ('radiation recall reaction'), urticaria, acral erythema and plantar-palmar dysaesthesia.
Renal and Urological Disorders:
Doxorubicin may impart a red colour to urine particularly to the first specimen passed after the injection and patients should be advised that this is no cause for alarm. Following intravesical administration, side-effects include symptoms of bladder irritation, haematuria, haemorrhagic cystitis and necrosis of the bladder wall.
Contraindication:
Intravenous (IV) use:
- Persistent myelosuppression
- Severe hepatic impairment
- Severe myocardial insufficiency
- Recent myocardial infarction
- Severe arrhythmias
- Previous treatment with maximum cumulative doses of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other anthracyclines and anthracenediones , 24 weeks after stopping treatment with trastuzumab. (see Section Special warnings and precautions for use )
Intravesical use:
- Urinary infections
- Inflammation of the bladder
- Hematuria
Pharmacokinetic interactions:
High dose cyclosporin increases the serum levels and myelotoxicity of doxorubicin. Doxorubicin is mainly used in combination with other cytotoxic drugs. Additive toxicity may occur especially with regard to bone marrow/haematologic and gastrointestinal effects (see section 4.4 Special Warnings and Precautions for Use). The use of doxorubicin in combination chemotherapy with other potentially cardiotoxic drugs, as well as the concomitant use of other cardioactive compounds (e.g. calcium channel blockers), require monitoring of cardiac function throughout treatment. Changes in hepatic function induced by concomitant therapies may affect doxorubicin metabolism, pharmacokinetics, therapeutic efficacy and/or toxicity.
Special warnings:
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Doxorubicin should be administered only under the supervision of physicians experienced in the use of cytotoxic therapy. Cardiac function should be assessed before patients undergo treatment with doxorubicin and must be monitored throughout therapy to minimize the risk of incurring severe cardiac impairment. Haematologic profiles should be assessed before and during each cycle of therapy with doxorubicin, including differential white blood cell (WBC) counts. The major route of elimination of doxorubicin is the hepatobiliary system. Serum total bilirubin should be evaluated before and during treatment with doxorubicin. Patients with elevated bilirubin may experience slower clearance of the drug with an increase in overall toxicity. Other Doxorubicin may potentiate the toxicity of other anticancer therapies. Exacerbation of cyclophosphamide-induced haemorrhagic cystitis and enhanced hepatotoxicity of 6-mercaptopurine have been reported. Radiation-induced toxicities (myocardium, mucosae, skin and liver) have also been reported. As with other cytotoxic agents, thrombophlebitis and thromboembolic phenomena including pulmonary embolism (in some cases fatal) have been coincidentally reported with the use of doxorubicin. Doxorubicin may induce hyperuricaemia as a consequence of the extensive purine catabolism that accompanies drug-induced rapid lysis of neoplastic cells (tumour-lysis syndrome). Blood uric acid levels, potassium, calcium phosphate and creatinine should be evaluated after initial treatment. Hydration, urine alkalinization, and prophylaxis with allopurinol to prevent hyperuricaemia may minimize potential complications of tumour lysis syndrome. Administration of doxorubicin by the intravesical route may produce symptoms of chemical cystitis (such as dysuria, polyuria, nocturia, stranguria, hematuria, bladder discomfort, necrosis of the bladder wall) and bladder constrictions. Special attention is required for catherization problems (e.g. uretheral obstruction due to massive intravesical tumours). |
Pregnancy and lactation:
Doxorubicin has harmful pharmacological effects on pregnancy and/or the foetus/newborn child.
Doxorubicin is secreted into breast milk. Women should not breastfeed while undergoing treatment with doxorubicin.
Storage temperature:
Room temperature (15-25 C) away from direct sun light.
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