Mustargen (Mechlorethamine) is a chemotherapeutic drug that belongs to the class of drugs called the alkylating agents. It is used to treat patients with Hodgkin's lymphoma. 

Note: It is not available in the US.

Mustargen (Mechlorethamine) Uses:

• Hodgkin lymphoma:

  • Palliative treatment of Hodgkin lymphoma

• Off Label Use of Mechlorethamine in Adults:

  • Previously untreated Hodgkin lymphoma.

Mustargen (Mechlorethamine) Dose in Adults:

• Dosage should be based on ideal dry weight (evaluate the presence of edema or ascites so that dosage is based on actual weight unaugmented by edema/ascites).
• Mechlorethamine is associated with a high emetic potential
• Antiemetics are recommended to prevent nausea and vomiting.
• Dosing in the prescribing information does not reflect current clinical practice.

Mustargen (Mechlorethamine) Dose in the treatment of Hodgkin lymphoma, previously untreated (off-label use/dose): IV:

• Stanford V regimen:

  • Favorable/early-stage disease:

    • 6 mg/m² as a single dose on day 1 every 4 weeks (in combination with doxorubicin, vinblastine, vincristine, bleomycin, etoposide, prednisone, and radiation therapy) for a total of 2 cycles.

  • Unfavorable/advanced stage disease:

    • 6 mg/m² as a single dose on day 1 every 4 weeks (in combination with doxorubicin, vinblastine, vincristine, bleomycin, etoposide, prednisone, and radiation therapy) for a total of 3 cycles.

Mustargen (Mechlorethamine) Dose in Childrens:

Note:

• Dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol.
• Mechlorethamine is associated with high emetic potential.
• Antiemetics are recommended to prevent nausea and vomiting.

Mustargen (Mechlorethamine) Dose in the treatment of Hodgkin lymphoma:

• MOPP regimen:

Note:

• The MOPP (with or without ABVD) regimen is generally no longer used due to improved toxicity profiles with other combination regimens used in the treatment of Hodgkin lymphoma.
  • Children and Adolescents: IV: 6 mg/m² on days 1 and 8 of a 28-day cycle in combination with vincristine, procarbazine, and prednisone, may or may not alternate with doxorubicin, bleomycin, vinblastine, dacarbazine (MOPP/ABVD).

• Stanford V regimen:

  • Adolescents ≥16 years:
    • IV: 6 mg/m² as a single dose on day 1 in weeks 1, 5, and 9.

Pregnancy Risk Factor D

• [US Boxed Warning]
  • High levels of toxic chemicals in Mechlorethamine must be avoided. Both the solution and powder should be handled with extreme care.
  • Avoid inhaling dust and vapors as well as contact with skin or mucous membranes (especially the eyes).
  • Avoid pregnancy exposure
  • Special handling procedures are required due to the toxic nature of mechlorethamine (eg teratogenicity).
• It can cause harm to the fetus if administered to a pregnant woman.
• Mechlorethamine treatment is not recommended for females with reproductive potential.
• Female patients who have been treated with mechlorethamine may experience delayed menses, oligomenorrhea or temporary or permanent amenorrhea.
• Men may experience impaired spermatogenesis, total germinal aplasia and azoospermia when mechlorethamine is used with other chemotherapy agents.

Use of memorethamine while breastfeeding

• It is unknown if mechlorethamine can be found in breast milk.
• The potential for severe adverse reactions in breastfeeding infants should be considered.

Mustargen (Mechlorethamine) Dose in Kidney Disease:

• No dosage adjustments provided in the manufacturer's labeling.

Mustargen (Mechlorethamine) Dose in Liver disease:

• No dosage adjustments provided in the manufacturer's labeling.

• The following have also been reported:

  • Mild-to-moderate impairment:

    • No dosage adjustment is necessary.

  • Severe liver impairment:

    • No dosage adjustment is necessary.
    • Concomitant chemotherapy may require alteration until improvement in hepatic function.

Side effects of Mustargen (Mechlorethamine):

• Cardiovascular:

  • Local thrombophlebitis

• Central nervous system:

  • Brain disease (high dose)
  • Drowsiness
  • Headache
  • Lethargy
  • Metallic taste
  • Sedation
  • Vertigo

• Dermatologic:

  • Alopecia
  • Diaphoresis
  • Erythema multiforme
  • Maculopapular rash
  • Skin rash

• Endocrine & metabolic:

  • Amenorrhea
  • Hyperuricemia
  • Oligomenorrhea

• Gastrointestinal:

  • Anorexia
  • Diarrhea
  • Mucositis
  • Nausea
  • Vomiting

• Genitourinary:

  • Inhibition of spermatogenesis

• Hematologic & oncologic:

  • Agranulocytosis
  • Granulocytopenia
  • Hemolytic anemia
  • Leukopenia
  • Lymphocytopenia
  • Pancytopenia
  • Petechia
  • Thrombocytopenia

• Hepatic:

  • Jaundice

• Hypersensitivity:

  • Anaphylaxis
  • Hypersensitivity reaction

• Infection:

  • Herpes zoster

• Neuromuscular & skeletal:

  • Weakness

• Ophthalmic:

  • Lacrimation

• Otic:

  • Deafness
  • Tinnitus

• Miscellaneous:

  • Fever
  • Tissue necrosis (extravasation)

Contraindication to Mustargen (Mechlorethamine):

• Hypersensitivity (prior anaphylactic response) to mechlorethamine and any component of the formulation/
• Existence of known infectious diseases

Warnings and precautions

• Suppression of bone marrow

  • Hematologic toxicities may include leukopenia and neutropenia as well as thrombocytopenia and anemia.
  • The onsets of neutropenia or thrombocytopenia usually occur in 6-8 days. They last 10-21 days.
  • Anemia usually begins within two weeks. It is usually mild.
  • Within one day, lymphocytopenia begins.
  • Rarely, hemolytic anemia or granulocytopenia may occur.
  • Patients with severe hematologic toxicities may have poor performance, widespread disease and/or patients who have been treated with radiation therapy or other antineoplastic agents.
  • The duration of bone marrow suppression can be prolonged (upto 50 days or more); persistent pancytopenia may also be reported.
  • Keep track of your blood pressure.
  • Severe thrombocytopenia can cause bleeding.
  • Patients with anemia, thrombocytopenia, leukopenia or tumor invasion of bone marrow should be cautious.
  • Treatment response, as defined by the absence or improvement in bone marrow function, may include the treatment of any tumors.
  • In non-responders and heavily pretreated patients, however, the hematopoietic functions may be further compromised.
  • This could lead to severe (and possibly fatal) leukopenia, anemia, and thrombocytopenia.
  • Before starting radiation therapy or any other chemotherapy, bone marrow function must be rehabilitated after mechlorethamine has been administered.

• Extravasation

  • Mechlorethamine can be used as a vesicant.
  • [US Boxed Warning]
    • Extravasation can cause painful inflammation, induration, and sloughing.
    • Extravasation should be treated immediately. To minimize the damage, infiltrate the area with 1/6 molar sodiumthiosulfate solution.
    • Dry cold compresses are then applied for 6 to 12 hours.
    • Use 4.14 g sodium thiosulfate for a 1/6-molar solution in 100 mL sterile drinking water or 2.64 grams anhydrous sodiumthiosulfate for 100 mL. Or, dilute 4mL sodium thiosulfate injection (10%) in 6 mL sterile drinking water for injection.
  • Before and during infusion, ensure proper placement of the needle or catheter.
  • Avoid excessive use.

• Toxicities to the gastrointestinal tract:

  • Mechlorethamine has a high emetic potency.
  • To prevent nausea and vomiting, antiemetics should be used.
  • You may experience nausea for as long as 24 hours.

• Hypersensitivity

  • Reports of hypersensitivity reactions including anaphylaxis have been made.

• Immunosuppression

  • Mechlorethamine is an immunosuppressant.
  • Patients may be more susceptible to fungal, viral or bacterial infections.

• Secondary malignancies

  • Secondary malignancies are more common when secondary alkylating agents (such as mechlorethamine) are used.
  • Risks may be increased by concurrent radiation therapy and combination chemotherapy.

• Tumor lysis syndrome

  • Hyperuricemia can occur with lymphomas and other forms of hyperuricemia.
  • Make sure you get enough water
  • If necessary, consider antihyperuricemic treatment.

• Amyloidosis

  • The rapid/extensive development of amyloidosis may be facilitated by nitrogen mustards.
  • Only use memorethamine if there are no foci of acute or chronic suppurative inflammation.

• Nonresponding Tumors

  • Mechlorethamine is not well-suited for treating bone and nerve tumors.
  • In widely disseminated cancers, it is not recommended to use mechlorethamine routinely.

Mechlorethamine (systemic) (United States: Not available): Drug Interaction

Monitoring parameters:

• CBC with differential and platelet count
• Renal function.
• Hepatic function.
• Monitor for signs/symptoms of hypersensitivity reactions and infection.
• Monitor the infusion site for extravasation.

How to administer Mustargen (Mechlorethamine)?

• IV:
  • Assist with a slow IV push for a few minutes before transferring to a faster-flowing IV solution.
  • Mechlorethamine has a high emetic potency.
  • To prevent nausea and vomiting, antiemetics should be used.
  • Before administering, prepare immediately.
  • It is a vesicant.
  • Before and during infusion, ensure proper placement of the needle or catheter
  • Avoid excessive use.

Extravasation management:

• Extravasation can be prevented by stopping infusion immediately.
• Extravasated solution can be gently aspirated (do not flush the line).
• Take out needle/cannula
• Elevate extremes

Sodium Thiosulfate 1/6M solution:

• Subcutaneously inject 2 mL of mechlorethamine into the extravasation area.
• After sodium thiosulfate administration, apply ice for 6-12 hours. Dry cold compresses may be applied for 20 minutes QID for up to 2 days.

Mechanism of action of Mustargen (Mechlorethamine):

• Bifunctional alkylating agent, mechlorethamine inhibits DNA andRNA synthesis by forming carbonium ions
• Interstrand and intrastrand crosslinks in DNA can cause miscoding, breakage and failure to reproduce.
• The mechlorethamine effects are not cell-phase specific, but they are most evident in the S phase. Cell proliferation is stopped in the G phase.

Metabolism:

• Rapid hydrolysis in the plasma to active metabolites.

Half-life elimination:

• 15 to 20 minutes.

International Brands of Mechlorethamine:

• Mustargen
• Caryolysine

Mechlorethamine Brand Names in Pakistan:

No Brands Available in Pakistan.