Mustine Hydrochloride
A white or almost white, hygroscopic, vesicant, crystalline
powder or mass. Very soluble in water. A 0.2% solution in
water has a pH of 3 to 5. Solutions lose their activity very
rapidly particularly at neutral or alkaline pH.
Store ai a temperature of 8Β° to 15Β° in airtight containers. Pro-
tect from light.
CAUTION. Mustine hydrochloride is a strong vesicant: avoid
contact with skin and mucous membranes.
Stability. A study using an assay specific for mustine' found
that a 0.1% solution in Water for Injections or sodium chlo-
ride injection (0.9%) underwent a loss of approximately 10%
when stored for 6 hours at room temperature, and of approx-
imately 4 to 6% when stored for the same period at 4Β°; similar
results were obtained whether the solution was stored in glass
vials or plastic syringes. Solutions in 500 mL of sodium chlo-
ride or glucose (5%) injection and stored in PVC infusion
bags were still less stable, with 15% and 10% degradation re-
spectively after 6 hours at room temperature.
Adverse Effects, Treatment, and Precautions
Mustine hydrochloride is extremely toxic and its use
is invariably accompanied by side-effects. Severe
nausea and vomiting may commence within an hour
of injection of the drug and last for some hours:
antiemetics and sedatives should be given 10 to 30
minutes before a dose. It causes varying degrees of
bone-marrow depression depending on the dose. In
heavily pretreated patients, or when the total dose
for a single course exceeds 400 ng per kg body-
weight. there is a risk of severe and possibly fatal
depression with anaemia, lymphocytopenia, granu-
locytopenia, and thrombocytopenia with consequent
haemorrhage. Depression of lymphocytes may be
apparent within 24 hrs. of the administration of
mustine hydrochloride and maximum suppression
of granulocytes and platelets occurs within 7 to 21
days; haematological recovery may be adequate af-
ter 4 weeks.
Tinnitus, vertigo, deafness, headache, drowsiness.
and other neurological symptoms have been report-
ed, as have episodes of jaundice. Skin reactions to
mustine hydrochloride include maculopapular rash-
es. There is a high incidence of hypersensitivity
when topical preparations are used.
Mustine hydrochloride has a powerful vesicant ac-
tion on the skin and mucous membranes and great
care must be taken to avoid contact with the eyes.
Thrombophlebitis is a potential hazard of mustine
particularly if it is not sufficiently diluted. Extrava-
sation of the injection causes severe irritation and
even sloughing. If extravasation occurs during injec-
tion, the involved area should be infiltrated with an
isotonic 4% solution of sodium thiosulphate. fol-
lowed by the application of an ice compress inter-
mittently for 6 to 12 hours. A 1% lignocaine
solution may also be infiltrated.
Mustine hydrochloride may produce temporary or
permanent inhibition of fertility. There is some evi-
dence of teratogenicity and carcinogenicity.
Effects on the nervous system. Severe immediate neuro-
toxicity developed in 14 of 21 evaluable patients who under-
went bone-marrow transplantation after preparation with
cytotoxic regimens including mustine 0.3 to 2.0 mg per kg
body-weight. Symptoms, which developed a median of 4
days after treatment, included headache, hallucinations, con-
fusion, convulsions, paraplegia, and tremor. Symptoms re-
solved in most. although in some they had not done so before
their death. However, of the 13 patients who survived more
than 60 days. 6, all of whom had earlier recovered from acute
toxicity, developed a delayed neurotoxicity, beginning a me-
dian of 169 days after the first mustine injection and charac-
terised by symptoms including confusion, somnolence,
personality change, dementia, focal motor seizures, and hy-
drocephalus. Patients older than 21 years, those who had re-
ceived CNS irradiation, and those treated concomitantly with
other cytotoxic agents were at increased risk of neurotoxicity.
Handling and disposal. Urine produced for up to 48 hours
after a dose of mustine should be handled wearing protective
clothing.
The manufacturers state that unused injection solutions may
be neutralised by mixing with an equal volume of a solution
containing sodium thiosulphate 2.5% and sodium bicarbonate
2.5% and allowing to stand for 45 minutes. Equipment used
in the preparation and administration of mustine hydrochlo-
ride solutions may be treated similarly. Alternatively a solu-
tion containing sodium carbonate 2.5% or sodium hydroxide
in a mixture of industrial methylated spirit and water has been
suggested for the decontamination of equipment.
Pharmacokinetics
Following intravenous injection, mustine is rapidly
converted to a reactive ethyleneimmonium ion. It
usually disappears from the blood in a few minutes
A very small proportion is excreted unchanged in
the urine.
Uses and Administration
Mustine belongs to the group of antineoplastic drugs
described as alkylating agents. It also possesses
weak immunosuppressant properties.
Mustine hydrochloride is used in the treatment of
advanced Hodgkin's disease, usually in conjunction
with a vinca alkaloid, procarbazine, and prednisone
or prednisolone (the MOPP regimen). It may also be
used in other lymphomas and in tumours of the brail
and neuroblastoma, as indicated by the cross-refer
ences given below. Mustine has also been tried ii
some other malignancies including chronic leukae
mias. tumours of the breast, ovary, and lung, and in
polycythaemia vera. Mustine has been used in the
management of malignant effusions but is not the
agent of choice.
In the MOPP regimen mustine hydrochloride has
been given in doses of 6 mg per 2 body-surface
area. However, as a single agent, the usual dose of
mustine hydrochloride is 400 ng per kg body-
weight, preferably as a single dose, although it may
be divided into 2 or 4 equal doses on successive
days. It is given byintravenous injection in a
strength of I mg per mL in Water for Injections or
sodium chloride 0.9%. Injection over 2 minutes into
the tubing of a fast running intravenous infusion of
sodium chloride 0.9% or glucose 5% may reduce the
incidence of thrombophlebitis and the risk of ex-
travasation.
The response should be assessed by the trend of the
blood counts. Treatment with mustine may be re-
peated when the bone-marrow function has recov-
ered.
Intracavitary injections of 200 to 400 mcg per kg have
been given in the treatment of malignant, especially
pleural. effusions. In mycosis fungoides with exten-
sive skin involvement, very dilute solutions of mus-
tine (e.g. 200 mcg per mL) have been applied
topically.
Histeocytic syndromes. The value of
systemic chemotherapy for Langerhans cell histiocytosis is
uncertain: however dilute solutions of mustine (200 mcg per
mL) have been applied topically for the cutaneous symp-
toms.
Malignant neoplasm. Mustine plays a central role in the
MOPP regimen which was the first effective combination reg-
imen to be widely used for the treatment of Hodgkin's dis-
case. By extension this and similar
regimens have also been given in some forms of non-Hodg-
kin's lymphoma . Topical mustine is often used in
the treatment of mycosis fungoides . Because of rela-
tively good CNS penetration mustine has also been used in
the treatment of brain tumours and neuroblastoma .