Mechlorethamine

MECHLORETHAMINE

Complete information including dosage, side effects, interactions and pregnancy & breast feeding warnings for patient and professional use.

Overview and uses

Mechlorethamine is a very slow acting alkylating agent used for the treatment of cancer.

Indication (uses):

For the palliative treatment of:

  • Hodgkin’s disease (stage III and stage IV)
  • Lymphosarcoma
  • Chronic myelocytic leukemia
  • Chronic lymphocytic leukemia
  • Polycythemia vera
  • Mycosis fungoides
  • Bronchogenic carcinoma
  • Metastatic carcinoma in effusion (intrapleural, intraperitoneal and intrapericardial use)
  • Stage IA and stage IB mycosis fungoides – type cutaneous T cell lymphoma (topical use)

Pharmacological classification

Alkylating agent used for the treatment of cancer.

Brand names

MUSTINE, MUSTARGEN, VALCHLOR

Dosage form

  • Supplied in a tube containing 60 g of 0.016 %w/w Mechlorethamine (equivalent to 0.02% Mechlorethamine HCl).
  • Supplied in vials – each vial containing 10 mg of Mechlorethamine with sodium chloride q.s. 100 mg.

Mechanism of action:

Alkylating agents produce highly reactive carbonium ion intermediates which transfer alkyl groups to cellular macromolecules by forming covalent bonds. These intermediates may react with carboxyl, hydroxyl, amino, sulfhydryl and phosphate groups of biomacromolecules. Alkylation results in cross linking/abnormal base pairing/scission of DNA strand. Cross linking of nucleic acids with proteins can also take place.

Dosage

  • Intravenous use
    • The dosage of Mechlorethamine varies on the basis of therapeutic response and the magnitude of hematologic depression.
    • 4 mg/kg of the body weight for each course given either as a single dose or in divided doses of 0.1 to 0.2 mg/kg per day.
    • Dose should be calculated on the basis of dry body weight. Presence of edema and/or ascites should be considered.
    • Subsequent courses should not be given until the patient has recovered hematologically from the previous course.
    • Mechlorethamine is a highly toxic drug. Both powder as well as the solution must be handled with care and only with appropriate protective equipments.
    • Utmost care should be taken to avoid contact of the drug with eye and skin.
  • Intracavitary use
    • 4 mg/kg of the body weight per day.
    • Intracavitary use is indicated in the presence of pleural, peritoneal or pericardial effusion due to metastatic tumors.
    • Intracavitary use is not recommended if the accumulated fluid is chylous in nature.

Renal dose adjustments

  • Data not available.

Hepatic dose adjustments

  • Data not available.

Geriatric dose adjustments

  • Data not available.

Pediatric use

  • Data not available.

Overdosage

  • No specific antidote is known.
  • Symptoms of Overdosage includes
  • Severe leukopenia
  • Anemia
  • Thrombocytopenia
  • Hemorrhagic diathesis
  • Treatment of overdosage involves
  • General supportive measures.
  • Repeated blood product transfusion.
  • Antibiotic treatment of complicating infections.

Side effects or adverse effects

  • Local side effects
    • Thrombophlebitis and thrombosis at the site of injection.
  • Hypersensitivity reactions
    • Anaphylaxis has been reported with Mechlorethamine use.
    • Pain in chest or abdomen, skin rash, difficulty in breathing, rapid breathing, shortness of breath, dizziness, fainting, low blood pressure are some of the symptoms.
    • Consult your doctor as soon as possible.
  • Other systemic side effects
    • Jaundice
    • Vertigo
    • Tinnitus
    • Diminished hearing
    • Occurrence/precipitation of hemolytic anemia
  • Bone marrow depression
    • Bone marrow depression is the most serious side effect/toxicity. It is also a limiting factor for the dose. Infections and bleeding are the common complications.
    • Bone marrow depression results in granulocytopenia, agranulocytosis, thrombocytopenia and aplastic anemia.
    • Consult your doctor as soon as possible if you observe any of the below mentioned symptoms:
      • Sore throat
      • Chills
      • Sudden fever
      • Weakness in limbs
      • Mouth ulcers
      • Bleeding gums
      • Sore mouth
      • Fast heart rate
      • Low blood pressure
      • Sore gums
      • Skin abscesses
      • Rapid breathing
      • Rapid progression of infection of any organ
      • Rapid progression of Septicemia
    • Gastrointestinal side effects
      • Nausea and vomiting are commonly observed with anti-cancer medicines.
      • Mucositis – painful inflammation and ulceration of mucus membrane lining the digestive tract.
      • Diarrhea, shredding of mucosa and haemorrhage due to decreased rate of renewal of gastrointestinal mucosa lining.
    • Skin
      • Alopecia or hair loss.
      • Dermatitis
    • Oral side effects
      • Breaches during chewing.
      • Depression of immunity due to reduction in number of WBCs largely increases the risk of oral infections.
      • Bleeding gums
      • Rapid progression of dental caries.
    • Gonadal side effects
      • Infertility due to Oligozoospermia in males.
      • Impotence in males.
      • Loss or reduces sex drive.
      • Inhibition of ovulation in females
      • Amenorrhea in females.
      • Damage to germinal cells may lead to mutagenesis.
    • Lymphoreticular tissue
      • Lymphocytopenia (reduced number of lymphocytes)
      • Inhibition of lymphocyte function.
      • Suppression of immunity due to bone marrow depression and reduced lymphocyte function highly increases the risk of opportunistic infections like:
        • Candida and other infections causing deep mycosis.
        • Cytomegalo virus
        • Herpes zoster
        • Pneumocystis jiroveci
        • Toxoplasma
      • Fetal side effects
        • Use of anti-cancer medicines in pregnant women may cause fetal damage leading to:
          • Fetal death
          • Abortion
          • Teratogenesis
        • Renal side effects
          • Renal failure, Gout and Urate stones may develop in urinary tract.
        • Hyperuricemia
          • An elevated level of uric acid is common in leukemia and bulky lymphomas.
        • Please note: The side effects mentioned above are from the reported cases. However, side effects are not limited to above mentioned conditions and symptoms. Consult your doctor as soon as possible if you feel or observe any symptoms that you relate to your treatment.

Warnings & Precautions

  • Contra-indicated in patients with known hypersensitivity to Mechlorethamine.
  • Contra-indicated in patients with known infectious disease.
  • Hematologic status of the patient must be determined before starting Mechlorethamine therapy.

Contraindications

  • Contraindicated in presence of known infectious disease.
  • Contraindicated in patients with a history of anaphylactic reaction with Mechlorethamine.

Pregnancy & breast feeding warnings

  • Pregnancy
    • Category D, which means there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
  • Nursing:
    • It is not known whether Mechlorethamine is excreted in human breast milk or not.
    • Since many drugs are excreted in milk and because of the potential for side effects in nursing infants, a decision should be made whether to discontinue drug or to discontinue nursing.

Interactions

Drug – drug interactions

  • Concomitant use of Mechlorethamine with following drugs/medicines should be strictly avoided.
    • Leflunomide as it increases the risk of infections.
    • Adalimumab as it increases the risk of infections.
    • Teriflunomide as it increases the risk of infections.
    • Certolizumab as it increases the risk of infections.
    • Clozapine as it may lower the WBC count.
    • Deferiprone as it may lower the WBC count.
    • Etanercept as it increases the risk of infections.
    • Fingolimod as it increases the risk of infections.
    • Golimumab as it increases the risk of infections.
    • Infliximab as it increases the risk of infections.
    • Talimogene as it increases the risk of herpes infections.
    • Nalidixic acid as the combination may cause unusual bruising or bleeding, nausea, stomach pain, unusual weakness, low fever and loss of appetite.
    • Natalizumab as it increases the risk of infections.
    • Tofacitinib as it increases the risk of infections.

Click here to go to Mechlorethamine forums.

Reference

  • “Product information. MUSTARGEN® (Mechlorethamine HCl).” Merck & Co., INC., NJ, USA.
  • “Product information. VALCHLOR™ (Mechlorethamine HCl).” Merck & Co., INC., NJ, USA.
By |2018-12-29T07:02:02+00:00May 2nd, 2017|medicines|Comments Off on Mechlorethamine

About the Author:

B. Pharm (K.L.E. society's S.V.V. Patil College of Pharmacy, Bengaluru) M. Pharm (Maharishi Arvind Institute of Pharmacy, Jaipur)

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