mechlorethamine (Mustargen, mechlorethamine hcl, Nitrogen Mustard)

Dosing and uses of Mustargen, mechlorethamine hcl (mechlorethamine)

• Adult
• Pediatric
• Geriatric

 

Adult dosage forms and strengths

powder for injection

• 10mg/vial

 

Cancers

Leukemia/Lymphomas/Polycythemia Vera/Mycosis Fungoides/Bronchogenic Carcinoma

0.4 mg/kg IV divided over 2 or 4 days

Combo treatment (MOPP regimen): 6 mg/m²/day IV days 1 and 8 q4Weeks

Do not repeat course until WBC >1000/mm³ & plateletes >50 k/mm³

 

Metastatic Carcinoma

Intracavitary: 0.4 mg/kg once

Intrapericardial: 0.2 mg/kg once

 

Mycosis Fungoides (Orphan)

Orphan indication sponsor

• Yaupon Therapeutics, Inc; 259 Radnor Chester Road; Radnor, PA 19087

 

Administration

Monitor

• CBC, renal, hepatic, & bone marrow functions
• Adjust subsequent dose based on WBC, platelete counts

 

Other Indication & Uses

Intrapleural, intraperitoneal, intrapericardiaL

Off-label: Cutaneous mycosis fungoides (topical application)

 

Pediatric dosage forms and strengths

Safety & efficacy not established

 

Geriatric dosage forms and strengths

 

Cancers

Leukemia/Lymphomas/Polycythemia Vera/Mycosis Fungoides/Bronchogenic Carcinoma

0.4 mg/kg IV divided over 2 or 4 days

Combo treatment (MOPP regimen): 6 mg/m²/day IV days 1 and 8 q4Weeks

Do not repeat course until WBC >1000/mm³ & plateletes >50 k/mm³

 

Metastatic Carcinoma

Intracavitary: 0.4 mg/kg once

Intrapericardial: 0.2 mg/kg once  

 

Mustargen, mechlorethamine hcl (mechlorethamine) adverse (side) effects

> 10%

Severe nausea/vomiting (90%)

 

Frequency not defined

Vertigo

Chills

Fever

Tinnitus

Thrombosis

Angioedema

Dyspnea

Hemolytic anemia

Hyperuricemia

Myelosuppression

Jaundice

IV site pain

Skin rash

Dermatitis

Erythema multiforme

Urticaria

Fertility impairment

Amenorrhea

Oligomenorrhea

Azoospermia

Oligozoospermia

Allergic reactions

Anaphylaxis

Alopecia

Aggravation of amyloidosis

 

Warnings

Black box warnings

Caution in handling and disposing of the drug

The drug should be administered under the supervision of an experienced cancer chemotherapy physician

If extravasation occurs, it may cause severe tissue damage, leading to ulceration and necrosis

Avoid exposure during pregnancy

 

Contraindications

Hypersensitivity, history of anaphylaxis

Active infection

 

Cautions

Amyloidosis

Blood coagulation disorder may occur

Bone marrow depression (leukopenia, thrombocytopenia, anemia)-potential contraindication in CLL

Risk of hyperuricemia

Bone & nervous tissue tumors have responded poorly to therapy

Vesicant (avoid extravasation)

Avoid pregnancy

 

Pregnancy and lactation

Pregnancy category: d

Lactation: not known if excreted in breast milk, do not nurse

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Mustargen, mechlorethamine hcl (mechlorethamine)

Mechanism of action

Inhibits DNA & RNA synthesis, via formation of carbonium ions; cross links DNA strands (interstrand and intrastrand crosslinking) causing miscoding breakage and subsequently DNA replication failure

 

Pharmacokinetics

Half-life elimination: <1 min

Metabolism: Extensive (within minutes; rapid demethylation and hydrolysis)

Excretion: Urine

 

Administration

IV Incompatibilities

Solution: D5W, Ns

• However only 10% drug loss in both fluids

Additive: methohexitaL

Y-site: allopurinol, cefepime

 

IV Compatibilities

Y-site: amifostine, aztreonam, filgrastim, fludarabine, granisetron, melphalan, ondansetron, sargramostim, teniposide, vinorelbine

 

IV Preparation

Must be used fresh, solution is stable for only 1 hr after dilution & must be administered within 1 hr

Do not use if solution is discolored or if water droplets visible prior to reconstitution

Dilute powder with 10 mL SWI to a final concentration of 1 mg/mL; may be diluted in up to 100 mL NS for intracavitary administration

Standard dilution

• IV push: dose/syringe (concentration: 1 mg/mL)
• Maximum syringe for IVP is 30 mL & syringe should be <75% full

 

IV Administration

Vesicant, do not give IM/SC

Margin of error is very slight

Administer IVP through sidearm of free flowing IV (preferred) or direct injection into vein over a few min

Flush with 5-10 mL Ns

 

Extravasation Management

Sodium thiosulfate1/6 M is specific antidote for nitrogen mustard extravasations

• Mix 4 mL of 10% sodium thiosulfate with 6 mL SWI (or 1.6 mL 25% Na-thiosulfate with 8.4 mL SWI)
• Aspirate residual drug & remove needle
• Inject antidote (2 mL for every 1 mg of drug extravasated) into SC tissue clockwise into infiltrated area using 25 gauge needle
• Time is essential in treating extravasation
• Heat & cold not proven effective

 

Storage

Store intact vials at room temp