VALCHLOR

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VALCHLOR

Classes

Nitrogen Mustard Analogs
Other Topical Antineoplastics

Administration

For storage information, see specific product information within the How Supplied section.
Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Emetic Risk
High
Administer routine antiemetic prophylaxis prior to treatment.
Extravasation Risk
Vesicant
Administer drug through a central venous line.

Injectable Administration Intravenous Administration

Avoid inhalation of mechlorethamine dust or vapors, and contact with skin or mucous membranes, especially those of the eyes.
If eye exposure occurs, immediately rinse the affected area with copious amounts of water, normal saline, or a balanced salt ophthalmic irrigating solution for at least 15 minutes; promptly consult an ophthalmologist.
If skin contact occurs, immediately rinse the affected area with copious amounts of water for at least 15 minutes and then irrigate with a 2% sodium thiosulfate solution; remove and destroy contaminated clothing and shoes; promptly seek medical attention.
Neutralization (with a solution of equal volume of sodium thiosulfate 5% and sodium bicarbonate 5%) is required for equipment exposed to mechlorethamine (e.g, rubber gloves, tubing, glassware) and for unused mechlorethamine injection; allow solution to stand for 45 minutes.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
 
Reconstitution:
Add 10 ml of sterile water for injection or 0.9% sodium chloride injection into the 10 mg mechlorethamine powder vial for a final concentration of 1 mg/ml.
With the needle still in the rubber stopper (minimizes the risk of skin contact with mechlorethamine), shake the vial several times to ensure complete dissolution.
 
Direct intravenous injection:
Using a sterile needle, withdraw the dose from the vial containing the reconstituted solution.
Using another sterile needle, inject the reconstituted solution over a few minutes directly into any suitable vein.
 
Intravenous bolus injection:
Inject into the tubing or sidearm of a freely flowing IV infusion to reduce the risk of severe local reactions due to extravasation or high concentrations of the drug. Following administration, flush the vein with the running IV infusion for 2—5 minutes and/or inject 5—10 ml of IV solution into the sidearm to flush any remaining drug from the tubing.
For patients with elevated venous pressure due to mediastinal tumor compression of major blood vessels, mechlorethamine may be administered via an indwelling catheter inserted into the femoral vein.

Topical Administration Other Topical Formulations

Gel Formulation
Patients should wash hands thoroughly with soap and water after handling or applying mechlorethamine gel.
Caregivers must wear disposable nitrile gloves when applying mechlorethamine gel to patients and wash hands thoroughly with soap and water after glove removal. For accidental skin exposure, immediately wash exposed areas thoroughly with soap and water for at least 15 minutes and remove contaminated clothing.
If eye exposure occurs, immediately rinse the affected area with copious amounts of water, normal saline, or a balanced salt ophthalmic irrigating solution for at least 15 minutes; promptly consult an ophthalmologist.
Store mechlorethamine topical gel in the refrigerator at 2—8 degrees Celsius (36—46 degrees Fahrenheit); keep separated from food.
Discard unused product after 60 days.
Apply immediately or within 30 minutes after removal from the refrigerator; return mechlorethamine gel to the refrigerator immediately after each use.
Apply to completely dry skin at least 4 hours before or 30 minutes after showering or washing; allow treated areas to dry for 5—10 minutes after application before covering with clothing.
Emollients or moisturizers may be applied to the treated areas 2 hours before or 2 hours after application.
Do not use occlusive dressings on areas of the skin where mechlorethamine gel was applied.
Avoid fire, flame, and smoking until mechlorethamine gel has dried.

Extemporaneous Compounding-Topical

NOTE: Mechlorethamine 0.02% topical gel (Valchlor) is available and approved for use by the FDA. Other extemporaneous compounded formulations are not FDA approved.
 
Mechlorethamine topical solution:
Dissolve 10 mg of mechlorethamine in 50—60 ml of water.
Mechlorethamine topical ointment:
Dissolve mechlorethamine in dehydrated alcohol.
Filter the solution to remove the insoluble sodium chloride present in the commercial preparation.
Mix the mechlorethamine-alcohol solution into petrolatum or another anhydrous ointment base. The usual concentration is 0.01%.

Other Administration Route(s)

Intracavitary Administration
Specialized references should be consulted because techniques for intracavitary administration vary.
Further dilute the reconstituted solution in up to 100 ml of NS injection.
Before intrapleural or intraperitoneal instillation, paracentesis is performed to remove most of the fluid which facilitates contact of mechlorethamine with pleura or peritoneum.
 
Method of injection:
Inject slowly with frequent aspiration to ensure that a free flow of fluid is present; if fluid cannot be aspirated, injection outside the cavity may occur, resulting in pain and necrosis. Free flow of fluid prevents injection into a pocket and ensures adequate dissemination of mechlorethamine.
Change the position of patient every 5—10 minutes for 1 hour following injection to uniformly distribute mechlorethamine throughout the body cavity.
Remaining fluid may be removed from the pleural or peritoneal cavity by paracentesis 24—36 hours later.
 
Intrapleural or intrapericardial injection
Administer directly through the thoracentesis needle.
 
Intraperitoneal injection
Administer through a rubber catheter inserted into the trocar used for paracentesis or through an 18-gauge needle inserted at another site.

Adverse Reactions
Severe

exfoliative dermatitis / Delayed / 56.0-56.0
pruritus / Rapid / 4.0-4.0
skin ulcer / Delayed / 3.0-3.0
new primary malignancy / Delayed / 2.0-2.0
infection / Delayed / 2.0-2.0
thrombosis / Delayed / Incidence not known
tissue necrosis / Early / Incidence not known
hemolytic anemia / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
hearing loss / Delayed / Incidence not known

Moderate

anemia / Delayed / 0-13.0
thrombocytopenia / Delayed / 0-13.0
neutropenia / Delayed / 0-13.0
phlebitis / Rapid / Incidence not known
lymphopenia / Delayed / Incidence not known
bleeding / Early / Incidence not known
leukopenia / Delayed / Incidence not known
hyperuricemia / Delayed / Incidence not known
infertility / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
immunosuppression / Delayed / Incidence not known

Mild

skin hyperpigmentation / Delayed / 5.0-5.0
injection site reaction / Rapid / Incidence not known
petechiae / Delayed / Incidence not known
diarrhea / Early / Incidence not known
vomiting / Early / Incidence not known
anorexia / Delayed / Incidence not known
nausea / Early / Incidence not known
gonadal suppression / Delayed / Incidence not known
oligomenorrhea / Delayed / Incidence not known
amenorrhea / Delayed / Incidence not known
azoospermia / Delayed / Incidence not known
spermatogenesis inhibition / Delayed / Incidence not known
maculopapular rash / Early / Incidence not known
alopecia / Delayed / Incidence not known
weakness / Early / Incidence not known
vertigo / Early / Incidence not known
tinnitus / Delayed / Incidence not known

Boxed Warning
Anemia, bleeding, bone marrow suppression, herpes infection, immunosuppression, infection, leukopenia, neutropenia, radiation therapy, requires an experienced clinician, thrombocytopenia, varicella, viral infection

Hematologic toxicity (e.g., anemia, neutropenia, leukopenia, and thrombocytopenia) has been reported with mechlorethamine therapy. This drug requires an experienced clinician knowledgeable in the use of cancer chemotherapy. Infection and bleeding may occur as a result of bone marrow suppression. Intravenous (IV) mechlorethamine should be used cautiously in patients receiving other myelosuppressive therapy (e.g., radiation therapy). Monitor hematologic parameters (e.g., complete blood count panel) frequently during therapy. Bone morrow function should be recovered prior to administering IV mechlorethamine and/or radiation therapy. Use of IV mechlorethamine is contraindicated in patients who have an infectious disease. Immunosuppression has been reported with IV mechlorethamine therapy and bacterial, fungal, or viral infection (e.g., varicella, herpes infection) may occur. Herpes zoster infection may occur during or be precipitated by mechlorethamine treatment. Discontinue therapy in patients with herpes zoster infection.

Extravasation

Extravasation resulting in severe tissue damage (e.g., inflammation, induration, or sloughing of tissue) has been reported with mechlorethamine therapy. If extravasation or signs of drug leakage occur, promptly treat with sterile isotonic sodium thiosulfate (1/6 molar) and apply an ice compress for 6 to 12 hours. For a 1/6 molar solution of sodium thiosulfate, use 4.14 g of sodium thiosulfate per 100 mL of Sterile Water for Injection or 2.64 g of anhydrous sodium thiosulfate per 100 mL. Alternatively, dilute 4 mL of 10% sodium thiosulfate injection with 6 mL of Sterile Water for Injection.

Accidental exposure, ocular exposure

Mechlorethamine is highly toxic and the powder, solution must be handled and administered with care; all injectable forms contain a boxed warning against accidental exposure. Review and diligently follow special handling procedures before and during mechlorethamine handling because of the toxic properties of the drug such as corrosivity, carcinogenicity, mutagenicity, and teratogenicity. Appropriate protective equipment should be worn to avoid accidental exposure to mechlorethamine during preparation, handling, and administration. Avoid exposure to the eyes, avoid inhalation of dust or vapors, and avoid accidental contact with the skin or mucous membranes. Contaminated clothing should be destroyed. To clean gloves, tubing, surfaces, etc., after contact with mechlorethamine, soak in aqueous solution containing equal parts sodium thiosulfate 5% and sodium bicarbonate 5% for 45 minutes. Any unused solution and vials should be neutralized by mixing with an equal volume of sodium thiosulfate/sodium bicarbonate solution prior to disposal. Accidental skin contact with parenteral mechlorethamine should be treated with thorough rinsing of the area with water for at least 15 minutes, while removing contaminated clothing and shoes, followed by rinsing with 2% sodium thiosulfate solution. Medical attention should be sought immediately. Ocular exposure to mechlorethamine in any formulation causes pain, burns, inflammation, photophobia, and blurred vision. Blindness and severe irreversible anterior eye injury may occur. The topical gel does not contain a boxed warning regarding accidental exposure, but should only be applied to the skin, and several warnings regarding proper application and need for care in handling during administration apply. If accidental eye contact occurs to mechlorethamine topical gel or other dosage forms, rinse the exposed eye(s) with copious amounts of water, normal saline, or a balanced salt solution for at least 15 minutes; promptly seek emergency care, which should include consult of an ophthalmologist. If oral mucous membrane exposure occurs with topical mechlorethamine gel use, immediately rinse the area for at least 15 minutes with water and promptly seek medical attention. Individuals other than the patient should avoid direct skin contact with mechlorethamine gel due to the risks of secondary exposure including dermatitis, mucosal injury, and secondary cancers.

New primary malignancy

The risk of a new primary malignancy is increased with the use of alkylating agents such as mechlorethamine, particularly when alkylating agents are used in combination with other antineoplastic agents or radiation therapy. Thymic lymphomas, pulmonary adenomas, and squamous cell tumors have been observed in the animal studies. Additionally, non-melanoma skin cancer has been reported in patients who received mechlorethamine topical gel. Some non-melanoma skin cancers occurred in patients who had received prior therapies known to cause non-melanoma skin cancer. Monitor patients for non-melanoma skin cancers during and after treatment with mechlorethamine topical gel.

Pregnancy

Mechlorethamine may cause fetal harm when administered during pregnancy based on its mechanism of action, data from animal studies, genotoxicity findings, and case reports in humans. Females of reproductive potential should avoid pregnancy during mechlorethamine therapy. Congenital malformations have been reported in newborns following systemic mechlorethamine use in pregnant women; however, there have been no reports of these malformations with mechlorethamine topical gel based on limited data in pregnant women. Pregnant patients should be apprised of the potential hazard to the fetus. Fetal malformations including fetal death and growth retardation occurred in animals after a single subcutaneous 1 mg/kg dose.

Common Brand Names

VALCHLOR

Dea Class

Rx

Description

Bifunctional alkylating agent
Topical gel approved to treat recurrent mycosis fungoides; IV formulation used in the palliative treatment of many malignancies including Hodgkin lymphoma, chronic lymphocytic leukemia, chronic myelogenous leukemia, and mycosis fungoides;
Strong adherence to cytotoxic handling, administration, and disposal procedures is advised due to corrosive, carcinogenic, mutagenic, and teratogenic properties of mechlorethamine

Dosage And Indications
For the treatment of chronic lymphocytic leukemia (CLL). Intravenous dosage Adults

6 mg/m2 IV every 4 weeks as a part of the ProMACE-MOPP regimen.

For the treatment of chronic myelogenous leukemia (CML). Intravenous dosage Adults

0.4 mg/kg or 6 mg/m2 as a single IV dose monthly or as necessary to lower the white blood cell count.

For the treatment of Hodgkin lymphoma. For the treatment of Hodgkin lymphoma as part of the Stanford V regimen. Intravenous dosage Adults and Adolescents >= 15 years

6 mg/m2 IV on weeks 1, 5, and 9 in combination with doxorubicin (25 mg/m2 IV on weeks 1, 3, 5, 7, 9, and 11), vinblastine (6 mg/m2 IV on weeks 1, 3, 5, 7, 9, and 11), vincristine (1.4 mg/m2 (max: 2 mg) IV on weeks 2, 4, 6, 8, 10, and 12), bleomycin (5 units/m2 IV on weeks 2, 4, 6, 8, 10, and 12), etoposide (60 mg/m2/day IV on 2 consecutive days in weeks 3, 7, and 11), and prednisone (40 mg/m2 PO every other day for 10 weeks then tapered by 10 mg PO every other day between weeks 10 and 12). Total duration of Stanford V regimen is 12 weeks; three 4-week cycles. Doses of mechlorethamine, doxorubicin, vinblastine, and etoposide have been reduced to 65% if ANC less than 1,000 cells/mm3 (treatment delayed if ANC less than 500 cells/mm3). Prophylactic sulfamethoxazole-trimethoprim, acyclovir, and a H2-blocker were given throughout the treatment period. G-CSF has also been used to maintain dose intensity as needed after the first dose reduction. Alternative prophylactic medications have also been used.

As a single agent or as part of a regimen. Intravenous dosage Adults

0.2 mg/kg or 6 mg/m2 given as a single IV dose on day 1 or on days 1 and 8 of a regimen. Alternatively, it may be given as 0.1 mg/kg IV once daily for 4 successive days every 3 to 6 weeks. This dosage should be reduced to 0.2 to 0.4 mg/kg in those patients who have received prior radiation or chemotherapy.

Children† and Adolescents†

As part of the MOPP regimen, 6 mg/m2 IV on days 1 and 8 of a 28 day cycle.

For the treatment of lung cancer. Intravenous dosage Adults

6 mg/m2 IV every 2 weeks in combination with doxorubicin and methotrexate or every 4 weeks with doxorubicin, methotrexate, fluorouracil, hydroxyurea, and procarbazine.

For intracavitary administration for neoplastic effusions including pericardial effusion, pleural effusion, and peritoneal effusion. Intracavitary dosage Adults

0.2—0.4 mg/kg as a single, intracavitary injection. Pericardial effusions are usually treated with 0.2 mg/kg. Pleural effusions are sometimes treated with fixed doses of 10, 15, 20 or 30 mg.

For the treatment of polycythemia vera (PCV). Intravenous dosage Adults

0.4 mg/kg or 6 mg/m2 as a single IV dose monthly or as necessary to lower the red blood cell count.

For the treatment of cutaneous T-cell lymphoma (CTCL), including mycosis fungoides. For the palliative treatment of mycosis fungoides. Intravenous dosage Adults

0.2 mg/kg or 6 mg/m2 given as a single IV dose on day 1 or on days 1 and 8 of a regimen. Alternatively, it may be given as 0.1 mg/kg IV once daily for 4 successive days every 3—6 weeks. This dosage should be reduced to 0.2—0.4 mg/kg in those patients who have received prior radiation or chemotherapy.

For the treatment of of stage IA and IB mycosis fungoides in patients who have received prior skin directed therapy. Topical dosage Adults

Apply a thin film of mechlorethamine topical gel once daily to affected skin. If skin ulceration, blistering, or moderate to severe or severe dermatitis occurs, interrupt treatment and restart at a reduced application frequency of every 3 days when symptoms improve. If the reduced frequency schedule is tolerated for 1 week, increase the application frequency to once every other day for 1 week and then to once daily as tolerated. Once-daily application of mechlorethamine 0.02% topical gel (Valchlor; n = 130) or a compounded, petrolatum-based mechlorethamine 0.02% topical ointment (n = 130) for 12 months was evaluated in patients who had recurrent stage IA, IB, or IIA mycosis fungoides following at least 1 prior therapy (median of 2 prior therapies; range, 1—12 therapies) in a multicenter, randomized, phase II non-inferiority trial. Patients who had previously received topical carmustine, topical mechlorethamine within 2 years, or radiation therapy within 1 year were excluded from this trial. Valchlor gel was noninferior to compounded mechlorethamine ointment for the primary endpoint of Composite Assessment of Index Lesion Severity (CAILS) response rate in the intention-to-treat population (59% vs 48%; response ratio = 1.23; 95% CI, 0.97—1.55; lower limit of CI met criteria of >= 0.75) and the per-protocol population (77% vs 59%; response ratio = 1.3; 95% CI, 1.06—1.61). The CAILS evaluated the response in up to 5 index lesions identified at baseline. The CAILS complete response rates for patients who received Valchlor gel were 14% in the ITT population and 19% in the per-protocol population. The modified Severity Weighted Assessment Tool (mSWAT) response rate (secondary endpoint) was similar with Valchlor and compounded mechlorethamine ointment (47% vs 46%).

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Drug Interactions

Acetaminophen; Ibuprofen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Amlodipine; Celecoxib: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Bupivacaine; Meloxicam: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Celecoxib: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Celecoxib; Tramadol: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Diclofenac: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diclofenac; Misoprostol: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diflunisal: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Diphenhydramine; Ibuprofen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diphenhydramine; Naproxen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Etodolac: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Febuxostat: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
Fenoprofen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Flurbiprofen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Hydrocodone; Ibuprofen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Famotidine: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Oxycodone: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Pseudoephedrine: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Indomethacin: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ketoprofen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ketorolac: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Live Vaccines: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Meclofenamate Sodium: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Mefenamic Acid: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Meloxicam: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Nabumetone: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen; Esomeprazole: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen; Pseudoephedrine: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Nonsteroidal antiinflammatory drugs: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Oxaprozin: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Piroxicam: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Sulindac: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Sumatriptan; Naproxen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Tolmetin: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Valdecoxib: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.

How Supplied

Mustargen Intra-Articular Inj Pwd F/Sol: 10mg
Mustargen Intracavitary Inj Pwd F/Sol: 10mg
Mustargen Intravenous Inj Pwd F/Sol: 10mg
VALCHLOR Topical Gel: 0.016%

Maximum Dosage
Adults

IV: 0.4 mg/kg/dose or 6 mg/m2/dose.
Intracavitary: 0.4 mg/kg/dose.
Topical gel: 1 application/day to affected area(s).

Geriatric

IV: 0.4 mg/kg/dose or 6 mg/m2/dose.
Intracavitary: 0.4 mg/kg/dose.
Topical gel: 1 application/day to affected area(s).

Adolescents

IV: Safety and efficacy have not been established, although 6 mg/m2/dose has been used off-label for Hodgkin's disease.
Topical gel: Safety and efficacy have not been established.

Children

IV: Safety and efficacy have not been established, although 6 mg/m2/dose has been used off-label for Hodgkin's disease.
Topical gel: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism Of Action

Mechanism of Action: Mechlorethamine is a bifunctional alkylating agent and exerts its chemotherapeutic effects by substituting alkyl groups for hydrogen ions in a number of organic compounds. Mechlorethamine reacts readily with phosphate, amino, hydroxyl, sulfhydryl, carboxyl, and imidazole groups on amino acids. DNA-DNA interstrand and DNA-protein crosslinking occur, leading to DNA strand breakage and interference in DNA replication, transcription of RNA, and nucleic acid function. Cellular functions such as protein synthesis and glycolysis are impaired. Besides being an antineoplastic, mechlorethamine also is a mutagen and radiomimetic.

Pharmacokinetics

Mechlorethamine is administered via intravenous, intracavitary and topical administration. The active form of mechlorethamine reacts with various components of the cell before becoming inactivated by the body fluids. Metabolites of the drug are excreted in the urine.

Intravenous Route

Following IV administration, mechlorethamine is rapidly transformed to its active form; unchanged drug is undetectable in the blood a few minutes after administration.

Topical Route

Systemic exposure was undetectable in 16 patients who received mechlorethamine 0.016% topical gel (equivalent to mechlorethamine hydrochloride 0.02%). In these patients, no detectable plasma mechlorethamine concentrations were found in blood samples obtained after 1 day and 1 month of topical use.

Other Route(s)

Intracavitary Route
Intracavitary injection results in incomplete absorption of mechlorethamine, probably due to rapid inactivation of the drug by the body fluids.

Pregnancy And Lactation
Pregnancy

Mechlorethamine may cause fetal harm when administered during pregnancy based on its mechanism of action, data from animal studies, genotoxicity findings, and case reports in humans. Females of reproductive potential should avoid pregnancy during mechlorethamine therapy. Congenital malformations have been reported in newborns following systemic mechlorethamine use in pregnant women; however, there have been no reports of these malformations with mechlorethamine topical gel based on limited data in pregnant women. Pregnant patients should be apprised of the potential hazard to the fetus. Fetal malformations including fetal death and growth retardation occurred in animals after a single subcutaneous 1 mg/kg dose.

Advise patients that breast-feeding is not recommended during mechlorethamine treatment due to the potential for serious adverse reactions in the breastfed child. There are no data on the presence of mechlorethamine or its metabolites in human milk, the effects on the breast-fed child, or the effects on milk production.