Aspen Asia


Full Prescribing Info
Alkeran Tablet is a cytotoxic drug which falls into the general class of alkylating agents.
Pharmacology: Mode of Action: Melphalan is a bifunctional alkylating agent. Formation of carbonium intermediates from each of the two bis-2-chloroethyl groups enables alkylation through covalent-binding with the 7-nitrogen of guanine on DNA, cross-linking two DNA strands and thereby preventing cell replication.
Treatment of multiple myeloma and advanced ovarian adenocarcinoma.
Treatment of Breast Carcinoma: Alkeran Tablet, either alone or in combination with other drugs, has a significant therapeutic effect in a proportion of patients suffering from advanced breast carcinoma; Alkeran Tablet has also been used as an adjuvant to surgery in the management of breast carcinoma.
Treatment of Polycythaemia Rubra Vera: Alkeran Tablet is effective in the treatment of a proportion of patients suffering from polycythaemia vera.
Dosage/Direction for Use
Alkeran Tablet should be prescribed only by physicians experienced in the management of malignant disease with such agents.
Since Alkeran Tablet is myelosuppressive, frequent blood counts are essential during therapy and the dosage should be delayed or adjusted if necessary (see Precautions).
The absorption of Alkeran Tablet after oral administration is variable. Dosage may need to be cautiously increased until myelosuppression is seen, in order to ensure that potentially therapeutic levels have been reached.
Multiple Myeloma: A typical oral dosage schedule is 0.15 mg/kg body weight/day in divided doses for 4 days repeated at intervals of 6 weeks.
Numerous regimens have, however, been used and the scientific literature should be consulted for details.
The administration of oral Alkeran and prednisone may be more effective than Alkeran Tablet alone. The combination is usually given on an intermittent basis.
Prolonging treatment beyond 1 year in responders does not appear to improve results.
Advanced Ovarian Adenocarcinoma: A typical regimen is 0.2 mg/kg body weight/day orally for 5 days. This is repeated every 4-8 weeks, or as soon as the peripheral blood count has recovered.
Carcinoma of the Breast: Alkeran Tablet has been given orally at a dose of 0.15 mg/kg body weight or 6 mg/m2 body surface area/day for 5 days and repeated every 6 weeks. The dose was decreased if bone marrow toxicity was observed.
Polycythaemia Rubra Vera: For remission induction, doses of 6-10 mg daily for 5-7 days have been used, after which 2-4 mg daily were given until satisfactory disease control was achieved.
A dose of 2-6 mg once per week has been used for maintenance therapy.
In view of the possibility of severe myelosuppression if Alkeran Tablet is given on a continuous basis, it is essential that frequent blood counts are taken throughout therapy, with dosage adjustment or breaks in treatment, as appropriate, to maintain careful haematological control.
Children: Alkeran Tablet, within the conventional dosage range, is only rarely indicated in children and absolute dosage guidelines cannot be provided.
Renal Impairment: (See Precautions).
Alkeran Tablet clearance, though variable, is decreased in renal impairment. Currently available pharmacokinetic data do not justify an absolute recommendation on dosage reduction when administering Alkeran Tablet to patients with renal impairment, but it may be prudent to use a reduced dosage initially until tolerance is established.
Symptoms: Gastrointestinal effects, including nausea, vomiting and diarrhoea are the most likely early signs of acute oral overdosage.
The principal toxic effect is bone marrow suppression, leading to leucopenia, thrombocytopenia and anaemia.
Treatment: General supportive measures, together with appropriate blood and platelet transfusions, should be instituted if necessary, and consideration given to hospitalisation, cover with anti-infective agents, and the use of haematological growth factors.
There is no specific antidote. The blood picture should be closely monitored for at least 4 weeks following overdosage until there is evidence of recovery.
Patients who have suffered a previous hypersensitivity reaction to melphalan.
Special Precautions
Alkeran Tablet is an active cytotoxic agent for use under the direction of physicians experienced in the administration of such agents.
Safe Handling of Alkeran Tablet: See Cautions for Usage.
Monitoring: Since Alkeran Tablet is a potent myelosuppressive agent, it is essential that careful attention should be paid to the monitoring of blood counts to avoid the possibility of excessive myelosuppression and the risk of irreversible bone marrow aplasia.
Blood counts may continue to fall after treatment is stopped, so at the first sign of an abnormally large fall in leukocyte or platelet counts, treatment should be temporarily interrupted.
Alkeran Tablet should be used with caution in patients who have undergone recent radiotherapy or chemotherapy in view of increased bone marrow toxicity.
Renal Impairment: Alkeran Tablet clearance may be reduced in patients with renal impairment who may also have uraemic bone marrow suppression. Dose reduction may therefore be necessary (see Dosage & Administration) and these patients should be closely observed.
Mutagenicity: Chromosome aberrations have been observed in patients being treated with Alkeran Tablet.
Carcinogenicity: Melphalan, in common with other alkylating agents, may be leukaemogenic in man. There have been reports of acute leukaemia occurring after prolonged melphalan treatment for diseases eg, amyloid, malignant melanoma, multiple myeloma, macroglobulinaemia, cold agglutinin sydrome and ovarian cancer.
A comparison of patients with ovarian cancer who received alkylating agents with those who did not showed that the use of alkylating agents, including melphalan, significantly increased the incidence of acute leukaemia.
The leukaemogenic risk must be balanced against the potential therapeutic benefit when considering the use of melphalan.
Teratogenicity: The teratogenic potential of Alkeran Tablet has not been studied. In view of its mutagenic properties and structural similarity to known teratogenic compounds, it is possible that melphalan could cause congenital defects in the offspring of patients treated with the drug.
Impairment of Fertility: Alkeran causes suppression of ovarian function in premenopausal women resulting in amenorrhoea in a significant number of patients.
There is evidence from some animal studies that Alkeran can have an adverse effect on spermatogenesis. Therefore, it is possible that Alkeran may cause temporary or permanent sterility in male patients.
Use in pregnancy & lactation: As with all cytotoxic chemotherapy, adequate contraceptive precautions should be practised when either partner is receiving Alkeran Tablet.
The use of melphalan should be avoided whenever possible during pregnancy, particularly during the 1st trimester. In any individual case, the potential hazard to the foetus must be balanced against the expected benefit to the mother.
Mothers receiving Alkeran Tablet should not breastfeed.
Use in the elderly: Although Alkeran Tablet is frequently used at conventional dosage in the elderly, there is no specific information available relating to its administration to this patient subgroup.
Experience in the use of high-dose Alkeran Tablet in elderly patients is limited. Consideration should therefore be given to ensure adequate performance status and organ function before using high-dose Alkeran Injection in elderly patients.
Use In Pregnancy & Lactation
Use in pregnancy & lactation: As with all cytotoxic chemotherapy, adequate contraceptive precautions should be practised when either partner is receiving Alkeran Tablet.
The use of melphalan should be avoided whenever possible during pregnancy, particularly during the 1st trimester. In any individual case, the potential hazard to the foetus must be balanced against the expected benefit to the mother.
Mothers receiving Alkeran Tablet should not breastfeed.
Adverse Reactions
For Alkeran Tablet, there is no modern clinical documentation which can be used as support for determining the frequency of undesirable effects.
Undesirable effects may vary in their incidence depending on the indication and dose received and also when given in combination with other therapeutic agents.
The following convention has been utilised for the classification of frequency: Very common ≥1/10; common ≥1/100 and <1/10; uncommon ≥1/1000 and <1/100; rare ≥1/10,000 and <1/1000; very rare <1/10,000.
Blood and Lymphatic System Disorders: Very Common: Bone marrow depression leading to leucopenia, thrombocytopenia.
Rare: Haemolytic anaemia.
Immune System Disorders: Rare: Allergic reactions (see Skin and Subcutaneous Tissue Disorders).
Allergic reactions to melphalan eg, urticaria, oedema, skin rashes and anaphylactic shock have been reported uncommonly following initial or subsequent dosing, particularly after IV administration. Cardiac arrest has also been reported rarely in association with such events.
Respiratory, Thoracic and Mediastinal Disorders: Rare: Interstitial pneumonitis and pulmonary fibrosis (including fatal reports).
Gastrointestinal Disorders: Very Common: Nausea, vomiting and diarrhoea; stomatitis at high dose.
Rare: Stomatitis at conventional dose.
Gastrointestinal effects eg, nausea and vomiting have been reported in up to 30% of patients receiving conventional oral doses of melphalan.
Hepatobiliary Disorders: Rare: Hepatic disorders ranging from abnormal liver function tests to clinical manifestations eg, hepatitis and jaundice.
Skin and Subcutaneous Tissue Disorders: Very Common: Alopecia at high dose.
Common: Alopecia at conventional dose.
Rare: Maculopapular rashes and pruritus (see Immune System Disorders).
Renal and Urinary Disorders: Common: Temporary significant elevation of the blood urea has been seen in the early stages of melphalan therapy in myeloma patients with renal damage.
Drug Interactions
Nalidixic acid together with high-dose IV melphalan has caused deaths in children due to haemorrhagic enterocolitis.
Impaired renal function has been described in bone marrow transplant patients who were conditioned with high-dose IV melphalan and who subsequently received cyclosporin to prevent graft-versus-host disease.
Caution For Usage
Safe Handling: The handling of Alkeran Tablet should follow guidelines for the handling of cytotoxic drugs according to prevailing local recommendations and/or regulations.
Provided the outer coating of the tablet is intact, there is no risk in handling Alkeran Tablet.
Alkeran Tablet should not be divided.
Disposal: Alkeran Tablet should be destroyed in accordance with relevant local regulatory requirements concerning the disposal of cytotoxic drugs.
Store between 2-8°C.
ATC Classification
L01AA03 - melphalan ; Belongs to the class of alkylating agents, nitrogen mustard analogues. Used in the treatment of cancer.
Tab 2 mg (film-coated) x 25's.
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