DOSAGE AND ADMINISTRATION
Not for oral administration
The dosage of MUSTARGEN varies with the clinical
situation, the therapeutic response and the magnitude of hematologic
depression. A total dose of 0.4 mg/kg of body weight for each course usually is
given either as a single dose or in divided doses of 0.1 to 0.2 mg/kg per day.
Dosage should be based on ideal dry body weight. The presence of edema or
ascites must be considered so that dosage will be based on actual weight
unaugmented by these conditions.
The margin of safety in therapy with MUSTARGEN is
narrow and considerable care must be exercised in the matter of dosage. Repeated
examinations of blood are mandatory as a guide to subsequent therapy. (See OVERDOSAGE.)
Within a few minutes after intravenous injection,
MUSTARGEN undergoes chemical transformation, combines with reactive compounds,
and is no longer present in its active form in the blood stream. Subsequent
courses should not be given until the patient has recovered hematologically
from the previous course; this is best determined by repeated studies of the
peripheral blood elements awaiting their return to normal levels. It is often
possible to give repeated courses of MUSTARGEN as early as three weeks after
Preparation of Solution for Intravenous Administration
This drug is HIGHLY TOXIC and both powder and
solution must be handled and administered with care. (See BOXED WARNING and
DOSAGE AND ADMINISTRATION, Special Handling.) Since MUSTARGEN is
a powerful vesicant, it is intended primarily for intravenous use, and in most
cases is given by this route. Inhalation of dust or vapors and contact with
skin or mucous membranes, especially those of the eyes, must be avoided.
Appropriate protective equipment should be worn when handling MUSTARGEN. Should
accidental eye contact occur, copious irrigation for at least 15 minutes with
water, normal saline or a balanced salt ophthalmic irrigating solution should
be instituted immediately, followed by prompt ophthalmologic consultation.
Should accidental skin contact occur, the affected part must be irrigated
immediately with copious amounts of water, for at least 15 minutes while
removing contaminated clothing and shoes, followed by 2% sodium thiosulfate
solution. Medical attention should be sought immediately. Contaminated clothing
should be destroyed. (See DOSAGE AND ADMINISTRATION, Special Handling.)
Each vial of MUSTARGEN contains 10 mg of mechlorethamine
hydrochloride triturated with sodium chloride q.s. 100 mg. In neutral or
alkaline aqueous solution it undergoes rapid chemical transformation and is
highly unstable. Although solutions prepared according to instructions are
acidic and do not decompose as rapidly, they should be prepared immediately
before each injection since they will decompose on standing. When
reconstituted, MUSTARGEN is a clear colorless solution. Do not use if the
solution is discolored or if droplets of water are visible within the vial
prior to reconstitution.
Using a sterile 10 mL syringe, inject 10 mL of Sterile
Water for Injection or 10 mL of 0.9% Sodium Chloride Injection into a vial of
MUSTARGEN. With the needle (syringe attached) still in the rubber stopper,
shake the vial several times to dissolve the drug completely. The resultant
solution contains 1 mg of mechlorethamine hydrochloride per mL.
Parenteral drug products should be inspected visually for
particulate matter and discoloration prior to administration whenever solution
and container permit.
Animal studies have shown mechlorethamine to be corrosive
to skin and eyes, a powerful vesicant, irritating to the mucous membranes of
the respiratory tract and highly toxic by the oral route. It has also been
shown to be carcinogenic, mutagenic and teratogenic. Due to the drug's toxic
properties, appropriate precautions including the use of appropriate safety
equipment are recommended for the preparation of MUSTARGEN for parenteral
administration. Inhalation of dust or vapors and contact with skin or mucous membranes,
especially those of the eyes, must be avoided. Avoid exposure during pregnancy.
The National Institutes of Health presently recommends that the preparation of
injectable antineoplastic drugs should be performed in a Class II laminar flow
biological safety cabinet.17 Personnel preparing drugs of this class
should wear chemical resistant, impervious gloves, safety goggles, outer
garments and shoe covers. Additional body garments should be used based upon
the task being performed (e.g., sleevelets, apron, gauntlets, disposable suits)
to avoid exposed skin surfaces and inhalation of vapors and dust. Appropriate
techniques should be used to remove potentially contaminated clothing.
Several other guidelines for proper handling and disposal
of antineoplastic drugs have been published and should be considered.18-
Accidental Contact Measures
Should accidental eye contact occur, copious irrigation
for at least 15 minutes with water, normal saline or a balanced salt ophthalmic
irrigating solution should be instituted immediately, followed by prompt
ophthalmologic consultation. Should accidental skin contact occur, the affected
part must be irrigated immediately with copious amounts of water, for at least
15 minutes, followed by 2% sodium thiosulfate solution. Medical attention
should be sought immediately. Contaminated clothing should be destroyed. (See PRECAUTIONS,
General and DOSAGE AND ADMINISTRATION, Preparation of Solution
for Intravenous Administration.)
Technique for Intravenous Administration
Withdraw into the syringe the calculated volume of
solution required for a single injection. Dispose of any remaining solution
after neutralization (see below). Although the drug may be injected
directly into any suitable vein, it is injected preferably into the rubber or
plastic tubing of a flowing intravenous infusion set. This reduces the possibility
of severe local reactions due to extravasation or high concentration of the
drug. Injecting the drug into the tubing rather than adding it to the entire
volume of the infusion fluid minimizes a chemical reaction between the drug and
the solution. The rate of injection apparently is not critical provided it is
completed within a few minutes.
Nitrogen mustard has been used by intracavitary
administration with varying success in certain malignant conditions for the
control of pleural,4-13 peritoneal,5,6,9,11-16 and
pericardial,5,11-13 effusions caused by malignant cells.
The technique and the dose used by any of these routes
varies. Therefore, if MUSTARGEN is given by the intracavitary route, the
published articles concerning such use should be consulted. Because of the
inherent risks involved, the physician should be experienced in the appropriate
injection techniques, and be thoroughly aware of the indications, dosages,
hazards, and precautions as set forth in the published literature. When using MUSTARGEN
by the intracavitary route, the general precautions concerning this agent
should be borne in mind.
As a general guide, reference is made especially to the
techniques of Weisberger et al.5,11-13 Intracavitary use is indicated
in the presence of pleural, peritoneal, or pericardial effusion due to
metastatic tumors. Local therapy with nitrogen mustard is used only when
malignant cells are demonstrated in the effusion. Intracavitary injection is not
recommended when the accumulated fluid is chylous in nature, since results are
likely to be poor.
Paracentesis is first performed with most of the fluid
being removed from the pleural or peritoneal cavity. The intracavitary use of
MUSTARGEN may exert at least some of its effect through production of a
chemical poudrage. Therefore, the removal of excess fluid allows the drug to
more easily contact the peritoneal and pleural linings. For intrapleural or
intrapericardial injection nitrogen mustard is introduced directly through the
thoracentesis needle. For intraperitoneal injection it is given through a
rubber catheter inserted into the trocar used for paracentesis or through a No.
18 gauge needle inserted at another site. This drug should be injected slowly,
with frequent aspiration to ensure that a free flow of fluid is present. If
fluid cannot be aspirated, pain and necrosis due to injection of solution
outside the cavity may occur.5,11-13 Free flow of fluid also is
necessary to prevent injection into a loculated pocket and to ensure adequate
dissemination of nitrogen mustard.
The usual dose of nitrogen mustard for intracavitary
injection is 0.4 mg/kg of body weight, though 0.2 mg/kg (or 10 to 20 mg) has
been used by the intrapericardial route.5,11-13 The solution is prepared, as
previously described for intravenous injection, by adding 10 mL of Sterile
Water for Injection or 10 mL of 0.9% Sodium Chloride Injection to the vial
containing 10 mg of mechlorethamine hydrochloride. (Amounts of diluent of 50 to
100 mL of normal saline have also been used.4, 5) The position of
the patient should be changed every 5 to 10 minutes for an hour after injection
to obtain more uniform distribution of the drug throughout the serous cavity.
The remaining fluid may be removed from the pleural or peritoneal cavity by
paracentesis 24 to 36 hours later. The patient should be followed carefully by
clinical and x-ray examination to detect reaccumulation of fluid.
Pain occurs rarely with intrapleural use; it is common
with intraperitoneal injection and is often associated with nausea, vomiting,
and diarrhea of 2 to 3 days duration. Transient cardiac irregularities may
occur with intrapericardial injection. Death, possibly accelerated by nitrogen
mustard, has been reported following the use of this agent by the intracavitary
route.9 Although absorption of MUSTARGEN when given by the
intracavitary route is probably not complete because of its rapid deactivation
by body fluids, the systemic effect is unpredictable. The acute side effects
such as nausea and vomiting are usually mild. Bone marrow depression is
generally milder than when the drug is given intravenously. Care should be
taken to avoid use by the intracavitary route when other agents which may
suppress bone marrow function are being used systemically.
Neutralization of Equipment and Unused Solution
To clean rubber gloves, tubing, glassware, etc., after
giving MUSTARGEN, soak them in an aqueous solution containing equal volumes of
sodium thiosulfate (5%) and sodium bicarbonate (5%) for 45 minutes. Excess
reagents and reaction products are washed away easily with water. Any unused
injection solution should be neutralized by mixing with an equal volume of
sodium thiosulfate/sodium bicarbonate solution. Allow the mixture to stand for
45 minutes. Vials that have contained MUSTARGEN should be treated in the same
way with thiosulfate/bicarbonate solution before disposal.
Trituration of MUSTARGEN is a light yellow brown
crystalline powder, each vial containing 10 mg of mechlorethamine hydrochloride
with sodium chloride q.s. 100 mg, and is supplied in treatment sets of 4 vials.
Store at controlled room temperature 15-30°C (59-86°F).
Protect from light and humidity. Solutions of mechlorethamine HCl decompose on
standing; therefore, solutions of the drug should be prepared immediately
4. Bass, B.H.: Nitrogen mustard in the palliation of lung
cancer, Brit. Med. J. 1: 617-620, Feb. 27, 1960.
5. Bonte, F.J.; Storaasli, J.P.; Weisberger, A.S.:
Comparative evaluation of radioactive colloidal gold and nitrogen mustard in
the treatment of serous effusions of neoplastic origin, Radiol. 67: 63-66, July
6. Fullerton, C.W.; Reed, P.I.: Nitrogen mustard in
treatment of pleural and peritoneal effusions, Can. Med. Ass. J. 79: 190-191,
Aug. 1, 1958.
7. Harris, M.S.: The use of chemotherapy for carcinoma of
the lung, J. Int. Coll. Surg. 34: 666-673, Nov. 1960.
8. Hepper, N.G.G.; Carr, D.T.: Intrapleural use of
nitrogen mustard in malignant pleural effusion, Minn.Med. 43: 374-376, June
9. Levison, V.B.: Nitrogen mustard in palliation of
malignant effusions, Brit. Med. J. 1:1143-1145, Apr. 22, 1961.
10.Taylor, L.: A technique for intrapleural
administration of nitrogen mustard compounds, Amer. J. Med. Sci. 233: 538-541,
11.Weisberger, A.S.: Direct instillation of nitrogen
mustard in the management of malignant effusions, Ann. N.Y. Acad. Sci. 68:
1091-1096, Apr. 24, 1958.
12.Weisberger, A.S.; Bonte, F.J.; Suhrland, L.G.:
Management of malignant serous effusions, Geriat. 11: 23-30, Jan. 1956.
13. Weisberger, A.S.; Levine, B.; Storaasli, J.P.: Use of
nitrogen mustard in treatment of serous effusions of neoplastic origin, J.
Amer. Med. Ass. 159: 1704-1707, Dec. 31, 1958.
14. Brown, F.E.; Wright, H.K.: Hypovolemia following
intraperitoneal nitrogen mustard therapy, Surg. Gynecol. & Obstet. 121:
528-530, Sept. 1965.
15. Greenwald, E.S.: Cancer chemotherapy, N.Y. Med. J. 66:
2532-2548, Oct. 1, 1966.
16. Rohn, R.J.; Bond, W.H.: Some indications for the use
of chemotherapy in neoplastic disorders, J. Ind. Med. Ass. 50: 417-428, Apr.
17. Recommendations for the Safe Handling of Parenteral
Antineoplastic Drugs, NIH Publication No. 83-2621. For sale by the
Superintendent of Documents, U.S. Government Printing Office, Washington, DC
18. AMA Council Report: Guidelines for Handling
Parenteral Antineoplastics, JAMA 253: 1590-1592, 1985.
19. National Study Commission on Cytotoxic
Exposure-Recommendations for Handling Cytotoxic Agents. Available from Louis P.
Jeffrey, Sc. D., Chairman, National Study Commission on Cytotoxic Exposure,
Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood
Avenue, Boston, Massachusetts 02115.
20. Clinical Oncological Society of Australia: Guidelines
and recommendations for safe handling of antineoplastic agents, Med. J.
Australia 1: 426-428, 1983.
21. Jones, R.B., et al: Safe handling of chemotherapeutic
agents: A report from the Mount Sinai Medical Center, Ca - A Cancer Journal for
Clinicians Sept/Oct, 258-263, 1983.
22. American Society of Hospital Pharmacists: Technical
assistance bulletin on handling cytotoxic and hazardous drugs, Am. J. Hosp.
Pharm. 47: 1033-1049, 1995.
23. Controlling Occupational Exposure to Hazardous Drugs
(OSHA Work-Practice Guidelines), Am. J. Health-Syst. Pharm. 53: 1669-1685,
Manufactured by: Baxter Oncology GmbH, 33790
Halle/Westfalen, Germany. For: Recordati Rare Diseases Inc., Lebanon, NJ 08833,
U.S.A. Revised: February 2013