MECHLORETHAMINE HCL

Chemistry - A bifunctional alkylating agent, mechlorethamine occurs as a hygroscopic, white, crystalline powder that is very soluble in water. After reconstitution with sterile water or sterilesaline, the resultant solution is clear and has a pH of 3-5.

Storage, Stability, Compatibility

Store the powder for injection at room temperature.
Mechlorethamine is highly unstable in neutral or alkaline aqueous solutions and rapidly degrades.
While more stable in an acidic environment, the drug should be administered immediately afterpreparation. Mechlorethamine may also be known as nitrogen mustard, mustine or HN2.

Pharmacology - MECHLORETHAMINE HCL

Mechlorethamine is an alkylating agent, thereby interfering with DNA replication,
RNA transcription, and protein synthesis. It is cell cycle-phase nonspecific.
With intracavitary administration, mechlorethamine causes sclerosing and an inflammatory response on serous membranes, thereby causing adherence of serosal surfaces.

Uses, Indications

In small animals, mechlorethamine may be useful for the adjunctive treatmentof lymphoreticular neoplasms or with intracavitary administration, for treating pleural and peritonealeffusions.

Pharmacokinetics - MECHLORETHAMINE HCL

Because mechlorethamine is so irritating to tissues it must be given IV forsystemic use. It is incompletely absorbed after intracavitary administration. After injection, mechlorethamine is rapidly (within minutes) inactivated.

Contraindications, Precautions, Reproductive Safety

Mechlorethamine should be used onlywhen its potential benefits outweigh its risks with the following conditions: anemia, bone marrowdepression, tumor cel infiltration into bone marrow, current infection, sensitivity tomechlorethamine or patients who have received previous chemotherapy or radiotherapy.
Mechlorethamine is a teratogen in lab animals. Use only during pregnancy when the benefits tothe mother outweigh the risks to the offspring. Mechlorethamine can suppress gonadal function.
While it is unknown whether mechlorethamine enters maternal milk, nursing puppies or kittensshould receive milk replacer when the bitch or queen is receiving mechlorethamine.

Adverse Effects, Warnings

Bone marrow depression, GI effects (vomiting, nausea) are quitecommon and can be serious and therapy halting. Ototoxicity may occur with either high dosages orregional perfusions. Other potential effects include alopecia, hyperuricemia, hepatotoxicity, peripheral neuropathy and GI ulcers.
Because severe tissue sloughing may occur; avoid extravasation.
Overdosage, Acute Toxicity - Because of the toxic potential of this agent, overdoses must beavoided. Determine dosages carefully.

Drug Interactions

Use extreme caution when used concurrently with other drugs that are alsomyelosuppressive, including many of the other antineoplastics and other bone marrow depressant drugs (e.g., chloramphenicol, flucytosine, amphotericin B, or colchicine). Bonemarrow depression may be additive. Use with other immunosuppressant drugs (e.g., azathioprine, cyclophosphamide, corticosteroids) may increase the risk of infection. Live virus vaccines should be used with caution if at all during therapy.
Laboratory Considerations - Mechlorethamine may raise serum uric acid levels. Drugs such asallopurinol may be required to control hyperuricemia.