Mustargen

Before taking Mustargen, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to Mustargen or to any of its ingredients
• have an infection
• have previously received or will be receiving radiation (x-ray) therapy or other chemotherapy
• are pregnant, plan to become pregnant, or are breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Call your doctor for instructions if you miss a dose of mechlorethamine.

Other drugs may interact with mechlorethamine, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Mechlorethamine is sometimes given together with certain other medicines. If you are using a combination of medicines, it is important that you receive each one at the proper time. If you are taking some of these medicines by mouth, ask your health care professional to help you plan a way to take them at the right times.

While you are using this medicine, your doctor may want you to drink extra fluids so that you will pass more urine. This will help prevent kidney problems and keep your kidneys working well.

Mechlorethamine often causes nausea and vomiting, which usually last only 8 to 24 hours. It is very important that you continue to receive the medicine, even if you begin to feel ill. Ask your health care professional for ways to lessen these effects.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• It is used to treat cancer.
• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Loose stools (diarrhea).
• Not hungry.
• Upset stomach or throwing up.
• Feeling tired or weak.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Mechlorethamine, a biologic alkylating agent, has a cytotoxic action which inhibits rapidly proliferating cells.

Pharmacokinetics and Metabolism:

In water or body fluids, mechlorethamine undergoes rapid chemical transformation and combines with water or reactive compounds of cells, so that the drug is no longer present in active form a few minutes after administration.[1]

Clinical use of Mustargen usually is accompanied by toxic manifestations.

Local Toxicity: Thrombosis and thrombophlebitis may result from direct contact of the drug with the intima of the injected vein. Avoid high concentration and prolonged contact with the drug, especially in cases of elevated pressure in the antebrachial vein (e.g., in mediastinal tumor compression from severe vena cava syndrome).

Systemic Toxicity
General: Hypersensitivity reactions, including anaphylaxis, have been reported. Nausea, vomiting and depression of formed elements in the circulating blood are dose-limiting side effects and usually occur with the use of full doses of Mustargen. Jaundice, alopecia, vertigo, tinnitus and diminished hearing may occur infrequently. Rarely, hemolytic anemia associated with such diseases as the lymphomas and chronic lymphocytic leukemia may be precipitated by treatment with alkylating agents including Mustargen. Also, various chromosomal abnormalities have been reported in association with nitrogen mustard therapy.

Mustargen is given preferably at night in case sedation for side effects is required. Nausea and vomiting usually occur 1 to 3 hours after use of the drug. Emesis may disappear in the first 8 hours, but nausea may persist for 24 hours. Nausea and vomiting may be so severe as to precipitate vascular accidents in patients with a hemorrhagic tendency. Premedication with antiemetics, in addition to sedatives, may help control severe nausea and vomiting. Anorexia, weakness and diarrhea may also occur.

Hematologic: The usual course of Mustargen (total dose of 0.4 mg/kg either given as a single intravenous dose or divided into two or four daily doses of 0.2 or 0.1 mg/kg, respectively) generally produces a lymphocytopenia within 24 hours after the first injection; significant granulocytopenia occurs within 6 to 8 days and lasts for 10 days to 3 weeks. Agranulocytosis appears to be relatively infrequent and recovery from leukopenia in most cases is complete within two weeks of the maximum reduction. Thrombocytopenia is variable but the time course of the appearance and recovery from reduced platelet counts generally parallels the sequence of granulocyte levels. In some cases severe thrombocytopenia may lead to bleeding from the gums and gastrointestinal tract, petechiae, and small subcutaneous hemorrhages; these symptoms appear to be transient and in most cases disappear with return to a normal platelet count. However, a severe and even uncontrollable depression of the hematopoietic system occasionally may follow the usual dose of Mustargen, particularly in patients with widespread disease and debility and in patients previously treated with other antineoplastic agents or x-ray. Persistent pancytopenia has been reported. In rare instances, hemorrhagic complications may be due to hyperheparinemia. Erythrocyte and hemoglobin levels may decline during the first 2 weeks after therapy but rarely significantly. Depression of the hematopoietic system may be found up to 50 days or more after starting therapy.

Integumentary: Occasionally, a maculopapular skin eruption occurs, but this may be idiosyncratic and does not necessarily recur with subsequent courses of the drug. Erythema multiforme has been observed. Herpes zoster, a common complicating infection in patients with lymphomas, may first appear after therapy is instituted and on occasion may be precipitated by treatment. Further treatment should be discontinued during the acute phase of this illness to avoid progression to generalized herpes zoster.

Reproductive: Since the gonads are susceptible to Mustargen, treatment may be followed by delayed catamenia, oligomenorrhea, or temporary or permanent amenorrhea. Impaired spermatogenesis, azoospermia, and total germinal aplasia have been reported in male patients treated with alkylating agents, especially in combination with other drugs. In some instances spermatogenesis may return in patients in remission, but this may occur only several years after intensive chemotherapy has been discontinued. Patients should be warned of the potential risk to their reproductive capacity.

To report suspected adverse reactions, contact Recordati Rare Diseases Inc. at 1-888-575-8344 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.

NDC 55292-911-51

Storage
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 before use.

NDC 55292-911-51 4 Vials

Trituration of Mustargen®
(mechlorethamine HCI for injection)

10 mg

A Nitrogen Mustard – POISON

RECORDATI RARE DISEASES GROUP

Rx only

Each vial contains:
Mechlorethamine Hydrochloride..... 10 mg
Sodium Chloride q.s.................... 100 mg

Usual Adult Dosage: 0.1 mg/kg of body weight daily. See accompanying package insert.

PRIMARILY FOR INTRAVENOUS INJECTION

PREPARE SOLUTION IMMEDIATELY BEFORE USE.

The reconstituted solution is clear, colorless, and essentially free from visible particles.

DANGER: Contact Poison. Avoid contact with skin, mucous membranes, or eyes. Do not inhale the dust or vapor. In case of skin contact, wash with copious amounts of water for at least 15 minutes, followed by 2% sodium thiosulfate solution. See PRECAUTIONS and DOSAGE AND ADMINISTRATION in accompanying package insert.

After contact with Mustargen (mechlorethamine HCI for injection), soak equipment in an aqueous solution containing equal volumes of sodium thiosulfate (5%) and sodium bicarbonate (5%) for 45 minutes.

Store at controlled room temperature, 15-30°C (59-86°F). Protect from light and humidity.

Manufactured by: Baxter Oncology GmbH
33790 Halle/Westfalen, Germany

For: Recordati Rare Diseases Inc.
Lebanon, NJ 08833, U.S.A.

® Trademark of Recordati Rare Diseases Inc.

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