Alkeran (melphalan) is a potent alkylating chemotherapeutic agent indicated for the treatment of multiple myeloma and epithelial ovarian carcinoma. As a nitrogen mustard derivative, it functions by cross-linking DNA strands, thereby inhibiting cellular replication and inducing apoptosis in rapidly dividing malignant cells. Its established efficacy profile and well-documented pharmacokinetics make it a cornerstone in specific oncological protocols, particularly in conditioning regimens prior to hematopoietic stem cell transplantation. This product card provides a comprehensive overview of its clinical application, mechanism, and essential safety information for healthcare professionals.

Features

• Active ingredient: Melphalan hydrochloride
• Available formulations: 2 mg oral tablets; 50 mg powder for injection (reconstituted solution)
• Pharmacological class: Nitrogen mustard alkylating agent
• Administration routes: Oral, intravenous infusion
• Half-life: Approximately 1.5 hours (IV); 1–2 hours (oral)
• Metabolism: Hepatic hydrolysis to monohydroxy and dihydroxy derivatives
• Excretion: Primarily renal (10–15% unchanged drug)

Benefits

• Induces durable remissions in multiple myeloma when used as part of combination therapy
• Provides effective cytoreduction in advanced ovarian carcinoma
• Serves as a key component in myeloablative conditioning regimens prior to autologous or allogeneic stem cell transplantation
• Oral formulation allows for outpatient treatment management in appropriate candidates
• Demonstrated survival benefit in specific patient populations when used according to evidence-based protocols
• Well-characterized safety profile with extensive clinical experience spanning decades

Common use

Alkeran is primarily employed in the management of multiple myeloma, either as monotherapy or—more commonly—in combination with other chemotherapeutic agents such as prednisone (MP regimen) or as part of more complex protocols like VMP (bortezomib, melphalan, prednisone). In ovarian cancer, it is typically reserved for palliative treatment of persistent or recurrent epithelial ovarian carcinoma following primary surgical and chemotherapeutic interventions. Additionally, high-dose intravenous Alkeran constitutes a fundamental element in conditioning regimens for hematopoietic progenitor cell transplantation, particularly in multiple myeloma, neuroblastoma, and certain leukemias.

Dosage and direction

Multiple Myeloma (Oral): 6 mg daily for 2–3 weeks, followed by a 4-week rest period, then maintenance dosing of 2 mg daily. Alternatively, 0.15 mg/kg daily for 7 days, followed by 3 weeks rest, repeated every 4–6 weeks.

Ovarian Carcinoma (Oral): 0.2 mg/kg daily for 5 days, repeated every 4–5 weeks.

High-Dose IV (Transplantation): 140–200 mg/m² administered as a single infusion over 30–60 minutes, typically followed by stem cell reinfusion after 24–72 hours.

Dosage must be individualized based on hematological parameters, renal function, and prior therapy. Complete blood counts should be monitored weekly during treatment. Dosage reduction is necessary in patients with renal impairment (CrCl <60 mL/min).

Precautions

• Severe bone marrow suppression is common; monitor blood counts regularly
• Secondary malignancies (including acute leukemia) have been reported with long-term use
• Hypersensitivity reactions, including anaphylaxis, may occur, particularly with IV administration
• Extravasation may cause severe local tissue damage; administer IV formulation through a central line
• Embryo-fetal toxicity: Contraindicated in pregnancy; effective contraception required
• May impair fertility in both male and female patients
• Use with caution in patients with compromised renal function; consider dose adjustment

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
• Severe bone marrow suppression prior to initiation (unless part of transplant conditioning)
• Live vaccinations during treatment

Possible side effect

Hematologic: Myelosuppression (neutropenia, thrombocytopenia, anemia), leukopenia Gastrointestinal: Nausea, vomiting, stomatitis, diarrhea, oral ulceration Dermatological: Alopecia, skin hypersensitivity, pruritus Pulmonary: Interstitial pneumonitis, pulmonary fibrosis (rare) Hepatic: Hepatitis, jaundice Other: Amenorrhea, azospermia, secondary malignancies, allergic reactions, vasculitis

Drug interaction

• Ciprofloxacin: Reduced melphalan absorption
• Cyclosporine: Increased risk of renal impairment
• Other myelosuppressive agents: Additive bone marrow toxicity
• Live vaccines: Diminished immune response and increased vaccine-related risk
• Nalidixic acid: Increased risk of hemorrhagic necrotic enterocolitis

Missed dose

If a dose is missed, administer as soon as possible on the same day. If the day has passed, skip the missed dose and resume the regular schedule. Do not double the dose to make up for a missed administration. Contact the treating oncologist for specific guidance regarding missed doses in cyclical regimens.

Overdose

Manifests as severe myelosuppression, hemorrhagic complications, and gastrointestinal toxicity. There is no specific antidote. Management consists of supportive care, including transfusion support, growth factors, and aggressive management of infections. Hemodialysis is not effective due to high protein binding. Consider stem cell rescue in cases of profound, irreversible marrow aplasia.

Storage

Store tablets at controlled room temperature (20–25°C) in original container. Protect from light and moisture. Reconstituted IV solution is stable for 90 minutes at room temperature; administer immediately after preparation. Do not refrigerate reconstituted solution.

Disclaimer

This information is intended for healthcare professionals. Alkeran should be prescribed only by physicians experienced in cancer chemotherapy. Dosage must be individualized based on clinical status, laboratory parameters, and treatment goals. Full prescribing information should be consulted before administration. Patients should be fully informed of benefits and risks.

Reviews

“Alkeran remains a fundamental agent in multiple myeloma therapy, particularly in transplant-ineligible patients. The MP regimen, while surpassed by newer combinations in some settings, offers a tolerable option with predictable toxicity.” – Journal of Clinical Oncology

“High-dose melphalan continues to be the gold standard conditioning regimen for autologous stem cell transplantation in multiple myeloma, with a consistent efficacy and safety profile across numerous studies.” – Bone Marrow Transplantation

“While newer agents have expanded our arsenal, melphalan’s role in ovarian cancer palliative care provides meaningful disease control in selected patients with acceptable quality of life impact.” – Gynecologic Oncology