Melphalan

Registered South African indications:

• Multiple myeloma
• Breast carcinoma
• Ovarian adenocarcinoma
• Neuroblastoma

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Severe myelosuppression (leukocytes <2000/mm³, thrombocytes <50 000/mm³)

Cautions

• Renal impairment
• Elderly
• Recent radiotherapy or chemotherapy
• Ovarian cancer
• Premenopausal women
• High doses
• Immunocompromised patients
• Child bearing potential
• Vaccinations (live organism)
• Patients who have undergone recent radiotherapy or chemotherapy
• Paediatric population

Forms avail. in SA and covered in this monograph: tab, inj

Used for the treatment of

Multiple myeloma
Breast carcinoma
Advanced ovarian adenocarcinoma

Consult specialist for dosages and regimens

Paed. forms avail. In SA and covered in this monograph: tab, inj

Used for the treatment of

Multiple myeloma
Breast carcinoma
Advanced ovarian adenocarcinoma
Neuroblastoma

Consult specialist for dosages and regimens

Pregnancy

• Contraindicated 
• Melphalan should not be used during pregnancy (especially during the first trimester)
• In the case of a vital indication for the treatment of a pregnant patient, medical advice should be given on the risk of harm to the child associated with the treatment
• As with chemotherapies containing cytostatics, appropriate contraceptive measures must be taken when one of the partners receive melphalan. If pregnancy occurs during treatment, the possibility of genetic counselling should be used
• Melphalan has a mutagenic effect on the development of an embryo

Breastfeeding 

• Contraindicated
• Women should not breastfeed during treatment with Melphalan

Fertility

• Melphalan causes suppression of ovarian function in premenopausal women resulting in amenorrhoea in a significant number of patients
• Melphalan has a mutagenic effect in animal models; in patients treated with the drug, chromosomal aberrations were observed. Therefore, men treated with melphalan are advised not to produce a child during treatment and up to 6 months afterward, and to consult a sperm reserve before the start of treatment because of the possibility of irreversible infertility caused by the treatment
• There is evidence from some animal studies that Melphalan can have an undesirable effect on speramtogenesis. Therefore, it is possible that Melphalan may cause temporary or permanent sterility in male patients

Renal Impairment

• Caution; dose adjustment recommended

Hepatic Impairment

• No dose adjustment recommended

Elderly            

• Caution; no information available

Porphyria Information

• Probably not porphyrinogenic (PNP)

Cardiovascular Disorders

• Cardiac arrest 

Respiratory Disorders

• Interstitial pneumonitis 
• Pulmonary fibrosis

Gastrointestinal Disorders

• Diarrhoea
• Stomatitis 
• Nausea and vomiting

Hepatobiliary Disorders

• Abnormal hepatic function tests
• Hepatitis 
• Jaundice

Genitourinary Disorders

• Increased blood urea 

Musculoskeletal Disorders

• Isolated limb perfusion
• Muscle atrophy
• Muscle fibrosis
• Myalgia
• Increased blood creatine phosphokinase
• Compartment syndrome
• Muscle necrosis
• Rhabdomyolysis

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Maculopapular rashes 
• Pruritus 
• Urticaria
• Oedema
• Skin rashes

Immune, Blood and Lymphatic System Disorders

• Bone marrow depression 
• Thrombocytopenia 
• Anaemia
• Haemolytic anaemia
• Allergic reactions 
• Anaphylactic shock  

Others

• Sensation of warmth 
• Sensation of tingling

• Live vaccines
• Nalidixic acid 
• Ciclosporin 

• Full blood count with differential
• Electrolytes
• Renal function
• Hepatic function
• Uric acid

Melphalan is a bifunctional alkylating agent. Formation of carbonium intermediates from each of the two bis-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.

Tablet 2mg

• Alkeran (Pharmacare) originator

Injection (per vial) 50mg

• Alkeran (Pharmacare) originator