Systemic Therapy Program
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Disease Group

Cancer Type

Document Type

Drug Monographs
Treatment Regimens
Scientific Name:
MELPHALAN TABLETS (see also Melphalan IV)
Brand Name(s):

Drug Monograph


Mechanism of Action

Alkylating Agent which is a derivative of mechlorethamine that inhibits DNA and RNA synthesis via formation of carbonium ions; cross-links strands of DNA.


Oral Absorption:
incomplete, variable, 25-89% post oral dose; AUC decreased by 39% when taken with food.
rapid distribution into total body water; excretion in breast-milk unknown
cross blood brain barrier? no information
Vd:  0.5-0.6 L/kg; 14.6±5.1 L/m2
PPB: 90±5%
not actively metabolised, spontaneously degrades to mono and dihydroxy products; primary means of elimination
metabolite(s): active- no inactive- no
mainly feces (20-50% within 6 days) and urine
feces: 20-50% within 6 days
Urine: 10-30% as intact drug in 24 hours
Cl:  5.2±2.9 mL/min/kg; 0.438±0.178 L/min/m2

Side Effects

IMMEDIATE ONSET (hours to days)
* anaphylaxis (rare)
   nausea and vomiting (rare with chronic low doses)
* hyperuricemia- may indicate early stages of renal damage
EARLY ONSET (days to weeks)
* low WBC, RBC, platelets (myelosuppression nadir 10-21 days, recovery 18-40 days)
   mouth sores (stomatitis)
* liver toxicity- hepatitis, jaundice, hepatic veno-occlusive disease
   darkening of skin (hyperpigmentation)
   skin rash
   hair loss (alopecia, BMT doses)
DELAYED/LATE ONSET (weeks to years)
   loss of menstruation (amenorrhea)
* lung problems (pulmonary fibrosis, interstitial pneumonitis- rare)
* acute leukemia


Approved Indications

• Multiple myeloma
• Ovarian cancer

Acute lymphoblastic leukemia (ALL)
Breast cancer       
Ewing’s sarcoma       
Hodgkin’s disease
Malignant melanoma       
Non-Hodgkin’s lymphomas


Oral (on an empty stomach).


• q4w: 9 mg/m²/day po x 4 days, escalate to 12 mg/m²/day
• q4-5w: 2 mg/kg/day po x 5 days
• daily: 4 mg/m² po
• single daily dose, on empty stomach preferable
Adequate trial:
• response may be gradual over many months

• q3-4w: 30-45 mg/m²

Dose Adjustment Criteria

Renal failure
Reduce to 75% dose if CrCl = 0.2-0.8mL/sec;
Reduce to 50% dose if CrCl < 0.2mL/sec (intravenous doses only)
 (Suggested action)

Antiemetic Risk

Oral Doses- LOW RISK (Less than 10% of patients)
• No routine antiemetic pre-chemotherapy or post-chemotherapy


• Known hypersensitivity to melphalan • Pregnancy and breast feeding • Low WBC, RBC, platelets (myelosuppression)


Clinical Monitoring

• Complete blood count including differential, platelets and hemoglobin (CBC), serum electrolytes and serum uric acid levels before each cycle of treatment

• Baseline renal function tests- intravenous doses only [serum creatinine, electrolytes & BUN]

Significant Interactions

• CloZAPine: may increase the toxicity of Clozapine (specifically, agranulocytosis) • Cyclosporine (systemic): may increase nephrotoxic effect of Cyclosporine • Digoxin: may decrease absorption of Digoxin. • Echinacea: may decrease the therapeutic effect of Melphalan • Leflunomide: may increase toxicity of Leflunomide (specifically, the risk of hematologic toxicity). Consider not using a leflunomide loading dose in patients receiving Melphalan. Monitor patient for bone marrow suppression at least monthly if using these drugs concurrently. • Nalidixic Acid: may increase the toxicity of Melphalan (avoid combination) • Tacrolimus (topical): may increase the toxicity of Melphalan (avoid combination) • Vaccines (inactivated, live): may increase toxicity and decrease therapeutic effect of vaccines (avoid combination) • Vitamin K Antagonists (e.g. Warfarin): may increase/decrease the anticoagulant effect of Vitamin K Antagonists

Product Information

Commercial Product Description

White tablets with 2mg.

Pharmaceutical Considerations

Tablets:  2 mg; store in refrigerator (4°C); protect from light and moisture. The manufacturer recommends that melphalan be dispensed in glass. Tablets contain lactose, sucrose, potato starch, povidone, and magnesium stearate

Handling Risk Level

Pregnancy D/Carcinogen 1KNOWN HAZARDOUS DRUG
FDA Pregnancy Risk Factor D
IARC Carcinogen Risk Group 1 (Known Carcinogen)

  • This drug must be handled using precautions outlined in CCNS Policies for Occupational Safety, Preparing Cancer Chemotherapy and Administering Cancer Chemotherapy


FDA Pregnancy Risk Factor D
IARC Carcinogen Risk Group 1 (Known Carcinogen)
• This drug must be handled using precautions outlined in CCNS Policies for Preparing Cancer Chemotherapy and Administering Cancer Chemotherapy and the CCNS Standard for Oral Systemic Therapy for Cancer
• Go to "Additional Information" tab (above) for links to CCNS Policies

Availability & Funding

Administrative Information (Nova Scotia)

• CCNS Provincial Formulary Status- Oral- Basic Level for ordering on preprinted Physician Standing Order; Community Level for Prescription Filling • Go to "Additional Information" tab (above) for links to Provincial Formulary of Cancer Drugs • Pharmacare Formulary Status- Formulary • NOTE: It is recommended to limit ordering of this medication to standard preprinted order forms, for patient safety.