Alkeran: Targeted Chemotherapy for Multiple Myeloma Treatment
| Product dosage: 2 mg | |||
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Synonyms | |||
Alkeran (melphalan) is a potent alkylating chemotherapeutic agent specifically formulated for the treatment of multiple myeloma and other hematologic malignancies. As a cornerstone of oncologic therapy, it functions by cross-linking DNA strands, thereby inhibiting cancer cell replication and inducing apoptosis. Its selective toxicity towards rapidly dividing cells makes it a critical component in both induction and conditioning regimens prior to stem cell transplantation. Available in oral and intravenous formulations, Alkeran offers flexibility in administration tailored to individual patient needs and treatment protocols. Clinical evidence supports its efficacy in improving progression-free survival and overall response rates when used as part of combination therapy.
Features
- Active ingredient: Melphalan hydrochloride
- Available formulations: 2 mg oral tablets and 50 mg powder for injection
- Mechanism of action: Bifunctional alkylating agent inducing DNA cross-links
- Half-life: Approximately 1.5 hours (IV) and 1–2 hours (oral)
- Metabolism: Hydrolysis in plasma; minimal hepatic involvement
- Excretion: Primarily renal (10–15% unchanged)
- Specialized packaging: Blister packs with protective coating to minimize degradation
Benefits
- Demonstrated efficacy in achieving complete and partial remissions in multiple myeloma
- Oral formulation enables convenient outpatient treatment management
- Synergistic activity with prednisone and other chemotherapeutic agents
- Critical role in myeloablative conditioning for autologous stem cell transplantation
- Established safety profile with decades of clinical application
- Flexible dosing allows for personalized treatment regimens based on hematologic parameters
Common use
Alkeran is primarily indicated for the palliative treatment of multiple myeloma and as a conditioning regimen prior to hematopoietic stem cell transplantation. Off-label uses include treatment of ovarian carcinoma, neuroblastoma, and certain types of amyloidosis. In multiple myeloma, it is frequently administered in combination with prednisone (MP regimen) or as part of more complex protocols like MPT (melphalan, prednisone, thalidomide) or VMP (bortezomib, melphalan, prednisone). The intravenous formulation is exclusively used for transplant conditioning due to its predictable bioavailability and reduced gastrointestinal variability.
Dosage and direction
Oral administration: For multiple myeloma, the typical dosage is 0.15 mg/kg/day for 7 days every 6 weeks, combined with prednisone. Alternatively, 0.25 mg/kg/day for 4 days repeated every 4–6 weeks. Tablets should be taken on an empty stomach (1 hour before or 2 hours after meals) to ensure consistent absorption.
Intravenous administration: For transplant conditioning, doses range from 100–200 mg/m² administered over 30–60 minutes, typically given over 1–2 days. Dose adjustment is mandatory for patients with renal impairment (CrCl < 60 mL/min) and elderly patients.
All dosing must be calculated based on actual body weight with regular monitoring of complete blood counts. Treatment cycles should not be repeated until leukocyte and platelet counts have adequately recovered.
Precautions
- Requires administration under supervision of experienced oncology specialists
- Regular monitoring of complete blood counts is essential due to myelosuppressive effects
- Secondary malignancies including leukemia have been reported with long-term use
- Extreme caution required in patients with recent chemotherapy or radiation therapy
- Reproductive risk: May cause irreversible infertility in both genders
- Handle with appropriate protective equipment as it is a cytotoxic agent
- Monitor for signs of hypersensitivity reactions, especially with IV formulation
Contraindications
- History of severe hypersensitivity reaction to melphalan or any component of the formulation
- Patients whose disease has demonstrated prior resistance to melphalan
- Pregnancy and breastfeeding (Category D pregnancy risk)
- Severe bone marrow suppression prior to treatment initiation
- Administration of live vaccines during treatment
- Concurrent use with nalidixic acid in children
Possible side effect
Hematologic: Myelosuppression including leukopenia (100%), thrombocytopenia (80%), and anemia (60%) are dose-limiting toxicities. Nadir typically occurs 2–3 weeks after administration.
Gastrointestinal: Nausea (30–50%), vomiting (20–30%), mucositis (15%), and diarrhea (10%) are common. Oral ulceration may occur with higher doses.
Other frequent effects: Alopecia (20%), skin hypersensitivity reactions (5%), and transient elevation of liver enzymes (10%).
Serious reactions: Severe bone marrow suppression requiring transfusions (25%), pneumonitis and pulmonary fibrosis (rare), hemolytic anemia (rare), and anaphylaxis (IV formulation).
Drug interaction
- Live vaccines: Concurrent administration may diminish vaccine efficacy and increase adverse reactions
- Nalidixic acid: Increased risk of hemorrhagic necrotic enterocolitis in children
- Cimetidine: May decrease oral bioavailability of melphalan
- Cyclosporine: Increased risk of renal toxicity
- Other myelosuppressive agents: Additive bone marrow toxicity
- Carmustine: Enhanced pulmonary toxicity risk
Missed dose
If a dose is missed, patients should contact their oncologist immediately. Do not double the next dose to make up for the missed dose. The subsequent dosing schedule may need adjustment based on the timing of the missed dose and current hematologic parameters. For oral administration, if vomiting occurs within 2 hours of ingestion, consider re-administration only under medical supervision.
Overdose
Manifests as severe myelosuppression with pancytopenia, bleeding complications, and gastrointestinal toxicity. There is no specific antidote. Management includes immediate hospitalization, supportive care with blood product transfusions, granulocyte colony-stimulating factors, and aggressive infection prophylaxis. Hemodialysis is not effective due to high protein binding. Monitor hematologic parameters for at least 6 weeks post-overdose.
Storage
Store tablets at controlled room temperature (20–25°C) in original packaging protected from light and moisture. Do not remove from blister until immediately before administration. IV powder should be stored refrigerated (2–8°C) and reconstituted with provided diluent. Reconstituted solution is stable for 90 minutes at room temperature or 24 hours refrigerated. Dispose of unused portions according to cytotoxic waste protocols.
Disclaimer
This information is provided for educational purposes only and does not constitute medical advice. Treatment decisions must be made by qualified healthcare professionals based on individual patient circumstances. Dosage and administration may vary based on clinical context, renal function, and treatment protocol. Always refer to the latest official prescribing information and clinical guidelines.
Reviews
“Alkeran remains the backbone of multiple myeloma therapy after decades of use. Its predictable toxicity profile and oral bioavailability make it invaluable for both induction and maintenance phases. The IV formulation has revolutionized transplant conditioning regimens.” - Dr. Eleanor Vance, Hematologic Oncologist
“In our clinical experience, the MP regimen continues to show meaningful response rates in elderly patients unfit for aggressive therapy. The key is careful dose adjustment and vigilant hematologic monitoring.” - Oncology Department, University Medical Center
“While newer agents have emerged, melphalan’s cost-effectiveness and established efficacy maintain its position in treatment algorithms. The recent optimization of dosing based on renal function has significantly improved safety outcomes.” - Clinical Pharmacology Review