Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

ALKYLATING AGENTS
Mechlorethamine
Other names
Mechlorethamine hydrochloride, chloromethine
hydrochloride, mustargen hydrochloride, chlorethazine
hydrochloride, chlormethine (mustine) hydrochloride,
nitrogen mustard, HN 2
Clinical applications
The major use of mechlorethamine is in the treatment
of relapsed drug-resistant canine and feline lymphoma
as part of the MOPP protocol (mechlorethamine, vincristine,
procarbazine, prednisolone (or prednisone)).
Mechlorethamine has been used topically in humans to
treat mycosis fungoides and related cutaneous diseases.
Due to the difficulties associated with drug handling, we
cannot recommend topical therapy for veterinary
patients with mycosis fungoides.
Formulations and dose rates
Preparation: 1 mg/mL in 0.9% w/v sodium chloride or 5% w/v
glucose. Solutions decompose quickly and should be discarded if not
used within 4 h (room temperature) or 6 h (4°C). Solutions should not
be mixed with other drugs
DOGS AND CATS
• 3–6 mg/m 2 IV. The higher end of the dose range may be
severely myelotoxic in both cats and dogs. 3 mg/m 2 IV on days
0 and 7 is recommended for use in the MOPP protocol
• Administer into injection port of rapidly running infusion of 0.9%
sodium chloride at a rate of 60 drops per min
Pharmacokinetics
Mechlorethamine is the prototype drug in the nitrogen
mustard group of alkylating agents. Nitrogen mustard
undergoes rapid spontaneous hydrolysis after intravenous
injection, disappearing from blood within approximately
10 min. In addition, it undergoes considerable
enzymatic degradation. Less than 0.01% is excreted
unchanged in urine.
Adverse effects
● Mechlorethamine is markedly vesicant and causes
severe local reaction if extravasated.
● Nausea and emesis are common, usually lasting less
than 12 h in humans. Consider pretreatment with
antiemetic agents.
● Myelosuppression, with nadir at approximately
7 d.
● Other – diarrhea, oral ulcers, pulmonary infiltrates
and fibrosis, leukemia, alopecia.
● Contraindications to use of mechlorethamine are
severe neutropenia, thrombocytopenia, anemia and
coexisting infection.
Known drug interactions
● Mechlorethamine is incompatible with methohexital
sodium.
● As with other cytotoxics, the myelosuppressive
effects of mechlorethamine may be enhanced by
other myelosuppressive drugs.
Melphalan
Other names
L-PAM, L-phenylalanine mustard, L-sarcolysin, Alkeran
Clinical applications
Melphalan, in combination with prednisone, is the standard
first-line treatment for canine multiple myeloma
and has also been used in cats with multiple myeloma.
In combination with actinomycin D, cytosine arabinoside
and dexamethasone (D-MAC protocol), it has
shown efficacy for canine lymphoma rescue therapy.
Melphalan has been used to treat canine ovarian,
mammary, pulmonary and apocrine gland carcinomas
and adenocarcinomas and osteosarcoma and is reported
to be effective against feline chronic lymphocytic
leukemia.
Formulations and dose rates
A number of different dosing regimens have been described for use
in different protocols.
DOGS
• 0.63 mg/kg IV every 2–4 weeks
• 0.1 mg/kg PO daily for 10 d then 0.05 mg/kg/d
• 1.5–2 mg/m 2 PO daily for 7–10 d, repeat every 2–3 weeks if
needed
• 20 mg/m 2 PO once weekly
CATS
• 10 mg/m 2 PO once weekly
For human patients, some authorities recommend
adjusting the oral dose rate or duration until myelosuppression
is detected in order to ensure that an effective
dose has been administered. It is not known whether
this recommendation might apply to companion
animals. Anecdotal evidence suggests that cats may be
more susceptible to melphalan-induced myelosuppression
than dogs.
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