Gliadel

Nitrosoureas

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.
If carmustine lyophilized powder or solution contacts the skin or mucosa, immediately wash the skin or mucosa thoroughly with soap and water.
Emetic Risk
High
Administer routine antiemetic prophylaxis prior to treatment.
Extravasation Risk
Irritant

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Carmustine injection is supplied as a lyophilized powder in single-use 50-mg, 100-mg, and 300-mg vials; a sterile diluent (Dehydrated Alcohol injection) is provided for vial reconstitution.
Carmustine has a low melting point between 30.5 to 32 degrees C (86.9 to 89.6 degrees F) and the lyophilized powder may liquefy and appear as an oil film on the vials if warmed to this temperature or above; discard vials if this occurs because it is a sign of decomposition.
Hold carmustine vials to a bright light and inspect the product on receipt; the lyophilized powder should appear as a very small amount of dry flakes or dry congealed mass; store in the refrigerator.
Reconstitution:
Reconstitute lyophilized powder vials to a final concentration of 3.3 mg/mL in 10% ethanol and protect from light; the reconstituted vial should contain a clear, colorless to yellowish solution.
50-mg vial: Dissolve powder with 1.5 mL of the supplied diluent and then add 13.5 mL of Sterile Water for injection; discard the remaining 1.5 mL of diluent left in the vial.
100-mg vial: Dissolve powder with 3 mL of the supplied diluent and then add 27 mL of Sterile Water for injection.
300-mg vial: Dissolve powder with 9 mL of the supplied diluent and then add 81 mL of Sterile Water for injection.
Examine the reconstituted vial for crystal formation prior to use; warming the vial to room temperature and shaking well may redissolve the crystals.
Storage following reconstitution: Do not store the reconstituted 50-mg or 300-mg vials; immediately dilute vial contents. Reconstituted 100-mg vials may be stored in the refrigerator at 2 to 8 degrees C (36 to 46 degrees F) protected from light in a glass container for up to 24 hours.
Dilution:
Use glass or polypropylene containers for diluted admixtures; only use polypropylene containers that are PVC-free and DEHP-free.
Dilute the reconstituted vials to a final admixture concentration of 0.2 mg/mL and protect from light.
50-mg reconstituted vial: Dilute in 250 mL of 0.9% Sodium Chloride injection or 5% Dextrose injection.
Storage: If not used immediately, store at room temperature (20 to 25 degrees C; 68 to 77 degrees F) and use within 2 hours OR store in the refrigerator (2 to 8 degrees C; 36 to 46 degrees F) for up to 12 hours plus an additional 2 hours at room temperature.
100-mg reconstituted vial: Dilute in 500 mL of 0.9% Sodium Chloride injection or 5% Dextrose injection.
Storage: If not used immediately, store at room temperature and use within 8 hours OR store in the refrigerator (2 to 8 degrees C; 36 to 46 degrees F) for up to 24 hours plus an additional 6 hours at room temperature.
300-mg reconstituted vial: Dilute in 1,500 mL of 0.9% Sodium Chloride injection or 5% Dextrose injection.
Storage: If not used immediately, store at room temperature and use within 2 hours OR store in the refrigerator (2 to 8 degrees C; 36 to 46 degrees F) for up to 12 hours plus an additional 2 hours at room temperature.
Intravenous Infusion:
Administer the carmustine admixture as a slow IV infusion over 2 hours or longer not to exceed a rate of 1.66 mg/m2 per minute; injection-site pain and burning may occur with infusions given over less than 2 hours.

NOTE: Carmustine is not approved by the FDA for topical administration.
When applying carmustine topical solution protective garments including double gloves, gown, and goggles should be worn to protect against exposure to solution.
 
Preparation of topical solution:
Dissolve carmustine 300-mg in 150 mL of 95% ethanol. Take 5 mL and dilute with 60 mL of sterile water.
Topical solution should be refrigerated and protected from light. Carmustine stored at 5 degrees C and protected from light has a half-life of 19 days diluted in distilled water and 3 months diluted in 95% or 100% ethanol.
Clearly label solution for topical use only.

Intracavitary Administration
 
Carmustine wafers are placed in the resection cavity following resection of malignant gliomas.
Wafers should only be handled by personnel wearing surgical gloves because exposure to carmustine can cause severe burning and hyperpigmentation of the skin. Use of double gloves is recommended and the outer gloves should be discarded into a biohazard waste container after use.
A surgical instrument dedicated to the handling of the wafers should be used for wafer implantation.
If repeat neurosurgical intervention is indicated, any wafer or wafer remnant should be handled as a potentially cytotoxic agent.
The aluminum foil laminate pouches containing the wafer should be delivered to the operating room and remain unopened until the neurosurgeon is ready to implant the wafers.
Unopened outer foil pouches are stable at room temperature for 6 hours for up to 3 cycles within a 30-day period.
The outside surface of the outer foil pouch (a peel-able over wrap) is NOT sterile. The inner pouch is sterile and is designed to maintain product sterility and protect the product from moisture.
 
Instructions for opening the wafer pouch:
To remove the sterile inner pouch from the outer pouch, locate the folded corner and slowly pull in an outward motion. Do not pull in a downward motion rolling the knuckles over the pouch; this may exert pressure on the wafer and cause it to break.
Remove the inner pouch by grabbing hold of the crimped edge with a sterile instrument and pulling upward.
To open the inner pouch, gently hold the crimped edge, and cut in an arc-like fashion around the wafer.
To remove the wafer, gently grasp the wafer with the aid of forceps and place it onto a designated sterile field.

seizures / Delayed / 19.0-37.0
cerebral edema / Early / 4.0-23.0
increased intracranial pressure / Early / 4.0-9.0
muscle paralysis / Delayed / 7.0-7.0
intracranial bleeding / Delayed / 0-6.0
hydrocephalus / Delayed / 5.0-5.0
coma / Early / 1.0-4.0
GI bleeding / Delayed / 1.0-1.0
thrombosis / Delayed / 0-1.0
stroke / Early / 0-1.0
skin necrosis / Early / Incidence not known
pulmonary fibrosis / Delayed / Incidence not known
pulmonary toxicity / Early / Incidence not known
wound dehiscence / Delayed / Incidence not known
sinusoidal obstruction syndrome (SOS) / Delayed / Incidence not known
veno-occlusive disease (VOD) / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
azotemia / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
ocular hemorrhage / Delayed / Incidence not known

confusion / Early / 10.0-23.0
constipation / Delayed / 2.0-19.0
depression / Delayed / 3.0-16.0
impaired wound healing / Delayed / 14.0-15.8
phlebitis / Rapid / 10.0-10.0
peripheral edema / Delayed / 2.0-9.0
bleeding / Early / 7.0-7.0
ataxia / Delayed / 2.0-6.0
chest pain (unspecified) / Early / 1.0-5.0
diabetes mellitus / Delayed / 5.0-5.0
hallucinations / Early / 5.0-5.0
meningitis / Delayed / 4.0-4.0
hyperglycemia / Delayed / 3.0-3.0
hyponatremia / Delayed / 3.0-3.0
urinary incontinence / Early / 0-2.0
fecal incontinence / Early / 1.0-1.0
dysphagia / Delayed / 1.0-1.0
hypokalemia / Delayed / 1.0-1.0
leukopenia / Delayed / 10.0
thrombocytopenia / Delayed / 10.0
anemia / Delayed / Incidence not known
bone marrow suppression / Delayed / Incidence not known
erythema / Early / Incidence not known
pneumonitis / Delayed / Incidence not known
hyperprolactinemia / Delayed / Incidence not known
hypothyroidism / Delayed / Incidence not known
anovulation / Delayed / Incidence not known
encephalopathy / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
blurred vision / Early / Incidence not known
amnesia / Delayed / Incidence not known

headache / Early / 15.0-28.0
nausea / Early / 8.0-22.0
asthenia / Delayed / 1.0-22.0
vomiting / Early / 8.0-21.0
infection / Delayed / 1.0-18.0
fever / Early / 12.0-18.0
drowsiness / Early / 14.0-14.0
rash / Early / 2.0-12.0
abdominal pain / Early / 8.0-8.0
back pain / Delayed / 1.0-7.0
anxiety / Delayed / 7.0-7.0
hypoesthesia / Delayed / 6.0-6.0
diarrhea / Early / 2.0-5.0
dizziness / Early / 2.0-5.0
insomnia / Early / 2.0-5.0
ocular pain / Early / 1.0-1.0
diplopia / Early / 1.0-1.0
paranoia / Early / 1.0-1.0
leukocytosis / Delayed / 1.0
anorexia / Delayed / Incidence not known
flushing / Rapid / Incidence not known
injection site reaction / Rapid / Incidence not known
libido decrease / Delayed / Incidence not known
menstrual irregularity / Delayed / Incidence not known
gynecomastia / Delayed / Incidence not known
alopecia / Delayed / Incidence not known

Severe and dose-limiting bone marrow suppression including anemia, leukopenia, neutropenia, and thrombocytopenia occurs with IV carmustine therapy. Bleeding and infection may occur as a result of severe myelosuppression. Monitor complete blood counts weekly for at least 6 weeks after each IV carmustine dose; delayed bone morrow suppression may occur 4 to 6 weeks after a dose. A dose reduction may be necessary based on nadir blood counts. Do not give a subsequent dose until the leukocyte count is greater than 4,000 cells/mm3, the absolute neutrophil count is greater than 1,000 cells/mm3, and the platelet count is greater than 100,000 cells/mm3. Nadir counts typically occur at 4 weeks for platelets and at 5 to 6 weeks for leukocytes; counts are decreased for 1 to 2 weeks. Meningitis including bacterial meningitis and aseptic meningitis has been reported in patients with recurrent malignant glioma who received carmustine implants (Gliadel wafers). Monitor patients for post-operative signs or symptoms of infection including meningitis.

Severe, dose-related, and sometimes delayed pulmonary toxicity has been reported with IV carmustine therapy; some cases have been fatal. Obtain baseline pulmonary function studies and monitor pulmonary function tests during treatment. Pulmonary fibrosis and infiltrates have occurred from 9 days to 43 months after treatment with carmustine and related nitrosoureas. Delayed onset pulmonary fibrosis has been reported up to 17 years after treatment in pediatric patients who received cumulative doses ranging from 770 to 1,800 mg/m2 combined with cranial radiotherapy for intracranial tumors. Other risk factors for developing pulmonary toxicity include cumulative doses greater than 1,400 mg/m2, history of lung disease, prolonged duration of treatment, and a baseline predicted forced vital capacity (FVC) or carbon monoxide diffusing capacity (DLCO) below 70%.

BiCNU, Gliadel

Rx

A nitrosourea alkylating agent
IV formulation used for brain tumors including malignant gliomas and glioblastoma multiforme, multiple myeloma, Hodgkin lymphoma, and non-Hodgkin's lymphoma; implantable wafer used for newly diagnosed high-grade glioma as an adjunct to surgery and radiation and for recurrent glioblastoma as an adjunct to surgery
IV formulation has a black box warning for myelosuppression and pulmonary toxicity

150 to 200 mg/m2 IV over at least 2 hours repeated every 6 weeks; do not administer a repeat dose until blood counts recover (i.e., leukocyte count greater than 4,000 cells/mm3, absolute neutrophil count greater than 1,000 cells/mm3, and platelet count greater than 100,000 cells/mm3) and no sooner than every 6 weeks. Dose may be administered as a single-dose or divided into daily doses on 2 consecutive days (e.g., 75 to 100 mg/m2 IV daily on days 1 and 2). Lower doses are recommended when carmustine is given in combination with other myelosuppressive drugs or in patients with depleted bone marrow reserve. Premedicate with antiemetics prior to each dose.

61.6 mg (eight 7.7-mg wafers) implanted intracranially in the resected cavity once; if the size and shape of the resected cavity cannot accommodate 8 wafers, place the maximum number of wafers that can fit within the cavity. The wafers may be slightly overlapped and wafers that are broken in half may be used; discard wafers broken in more than 2 pieces. Oxidized regenerated cellulose (i.e., Surgicel) may be placed over the wafers to secure them against the cavity surface. After placement of the wafers, the resection cavity should be irrigated and the dura closed in a water tight fashion. A randomized, double-blind, placebo-controlled multicenter clinical study demonstrated the effectiveness of carmustine implantable wafers in patients undergoing primary surgery with various types of brain tumors. For individuals receiving carmustine implantable wafer, there was a statistically significant increase in the median survival compared to placebo (13.9 months vs. 11.6 months). Although specific information on dosing was not provided, the authors stated that no patient received a dose greater than 62 mg. A randomized, double-blind, placebo-controlled clinical trial conducted in adults with recurrent malignant glioma demonstrated an improvement in median survival by 33% in patients who received carmustine implantable wafers compared with placebo (32 weeks vs. 24 weeks). In this trial, median survival for patients with glioblastoma multiforme (GBM) increased by 41% in patients who received carmustine implantable wafers (28 weeks with placebo to 20 weeks). Patients with pathologic diagnoses other than GBM had no improvement in survival.

150 to 200 mg/m2 IV over at least 2 hours repeated every 6 weeks in combination with prednisone; do not administer a repeat dose until blood counts recover (i.e., leukocyte count greater than 4,000 cells/mm3, absolute neutrophil count greater than 1,000 cells/mm3, and platelet count greater than 100,000 cells/mm3) and no sooner than every 6 weeks. Dose may be administered as a single-dose or divided into daily doses on 2 consecutive days (e.g., 75 to 100 mg/m2 IV daily on days 1 and 2). Lower doses are recommended when carmustine is given in patients with depleted bone marrow reserve. Premedicate with antiemetics prior to each dose. In a randomized trial (CALGB protocol 7461) comparing oral melphalan (n = 100), carmustine (n = 124), or lomustine (n = 137) plus prednisone (initial dose, 0.8 mg/kg/ PO daily for 2 weeks followed by a 4-week taper) for the treatment of previously untreated multiple myeloma, treatment with carmustine (150 mg/m2 IV repeated every 6 weeks until disease progression or for at least 4 cycles) plus prednisone resulted in an overall objective response rate of 40%. In patients who continued on therapy past week 22, the carmustine dosage interval was increased to every 8 weeks.

150 to 200 mg/m2 IV over at least 2 hours repeated every 6 weeks is recommended for single-agent carmustine; however, lower doses are recommended when carmustine is given in combination with other myelosuppressive drugs or in patients with depleted bone marrow reserve. Dose may be administered as a single dose or divided into daily doses on 2 consecutive days. Do not administer a repeat dose until blood counts recover (i.e., leukocyte count greater than 4,000 cells/mm3, absolute neutrophil count greater than 1,000 cells/mm3, and platelet count greater than 100,000 cells/mm3) and no sooner than every 6 weeks. Premedicate with antiemetics prior to each dose.

NOTE: Carmustine should not be given until platelet count is > 100,000/mm3 and white blood cell count > 4000/mm3.

150 mg/m2 IV once every 6 weeks as part of DBCT regimen (dacarbazine 220 mg/m2/day IV on days 1—3 repeated every 3 weeks, cisplatin 25 mg/m2/day IV on days 1—3 repeated every 3 weeks, and tamoxifen 20 mg/day PO) did not significantly improve the median overall survival (OS) time (7.7 vs. 6.3 months), 1-year OS rate (22% vs. 27%), or overall response rate (ORR) (16.8% vs. 9.9%) compared with single-agent dacarbazine (1000 mg/m2 IV repeated every 3 weeks) in 240 patients in a multicenter, randomized phase III trial. Additionally, the DBCT regimen did not significantly improve median OS time (202 vs. 199 days), 1-year OS rate (22.6% vs. 30.6%), or ORR (26.4% vs. 17.3%) compared with dacarbazine (800 mg/m2 IV every 3 weeks) and interferon alfa-2a (9 million units subcutaneously 3 times/week) in 105 patients in another randomized phase III trial. In this study, treatment with DBCT was associated with significantly longer hospitalization and 2 treatment-related deaths. Serious toxicity that occurred significantly more often with DBCT included grade 3 and 4 hematologic toxicity and increased serum creatinine levels.

In patients with > 10% of skin affected, apply solution once daily to total body (solution is made using 10 mg of a stock solution added to 60 mL of water). The solution should be applied until complete or substantial clearing; the solution strength can be increased after 3 to 6 months if inadequate response (20 mg of stock solution to 60 mL of water) for up to 12 additional weeks. The stock solution (2 mg/mL) can be applied once daily to the lesions in patients with well defined lesions involving less than 3% body surface. Carmustine solution led to a response (complete [CR] plus partial response) rates of 92% and 64% at 36 months and 5-year overall survival (OS) rates of 97% and 79% in 172 patients with stage T1 and T2 disease, respectively. In a retrospective analysis of 143 patients (median follow-up time, 4.2 years; range, 6 months to 12.9 years), the CR rates were 86%, 48%, and 21% in patients with Stage T1, T2, and T3 disease, respectively; additionally, the overall 5-year OS rate was 77% and the median OS time was 9.4 years.

300 mg/m2 IV on day -7 as a component of BEAM (etoposide 150 mg/m2 IV every 12 hours on days -7 to -4, cytarabine 200 mg/m2 IV every 12 hours on days -7 to -4, and melphalan 140 mg/m2 on day -3) given prior to an autologous stem cell transplant (ASCT) has been studied. Following 2 course of reduced-dose dexa-BEAM, 117 patients were randomized to BEAM/ASCT or 2 additional courses of dexa-BEAM. BEAM/ASCT resulted in a significantly improved 3-year freedom from treatment failure (FFTF) (55% vs. 34%; p = 0.019) but not 3-year overall survival (OS) rate (71% vs. 65%). In another study, adding sequential high-dose chemotherapy to BEAM/ASCT did not significant improve 3-year FFTF, OS, or progression free survival.

300 mg/m2 IV over 30—60 minutes on day 1 as part of BEAC (etoposide 100 mg/m2 IV twice daily, cytarabine 100 mg/m2 IV twice daily, and cyclophosphamide 35 mg/kg IV daily with mesna on days 2—5) given prior to autologous bone marrow transplant (ABMT) has been studied; 109 patients received 2 course of DHAP (dexamethasone, cisplatin, and cytarabine) and were then randomized to BEAC/ABMT or 4 additional courses of DHAP. BEAC/ABMT resulted in a significantly improved 5-year event-free survival (46% vs. 12%; p = 0.001) and 5-year overall survival (OS) (53% vs. 32%; p = 0.038) rates. In a single-center study in 107 patients with relapsed or resistant intermediate- or high-grade NHL, 300 mg/m2 IV on day 1 as part of BEAM (etoposide 100—200 mg/m2 IV daily on days 2—5, cytarabine 100—200 mg/m2 IV twice daily on days 2—5, and melphalan 140 mg/m2 on day 6) followed by ABMT led to 5-year OS rates of 49% and 13% (p < 0.001) in patients with relapsed chemotherapy-sensitive and chemotherapy-resistant disease, respectively.

300 mg/m2 IV once on day 1 or 112.5 mg/m2 on days -6 to -3 has been studied; carmustine 300 mg/m2 on day 1 plus etoposide (200 mg/m2 IV twice daily for 4 days), cytarabine (200 mg/m2 twice daily for 4 days), and melphalan (140 mg/m2 IV on day 5) (BEAM) with fludarabine (30 mg/m2 IV for 3 days) and total body irradiation followed by allogeneic stem-cell transplant (alloSCT) led to 3-year event-free survival and overall survival (OS) rates of 60% and 76%, respectively, in 11 patients in a clinical study. Additionally, BEAM followed by alloSCT resulted in 2-year disease-free survival and OS rates of 42% and 48%, respectively, in 30 patients with relapsed or refractory NHL in another nonrandomized study. Favorable 2-year relapse-free survival and OS rates of 56% and 76%, respectively, were demonstrated with carmustine 112.5 mg/m2/day IV on days -6 to -3 plus etoposide (200 mg/m2 every 12 hours on days -6 to -3) and cyclophosphamide (750 mg/m2 every 12 hours on days -6 to -3) followed by alloSCT (on day 0) in 18 patients with NHL (relapsed or refractory disease, n = 15). All patients in these studies received graft versus host disease prophylaxis.

†Indicates off-label use

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

Baseline renal impairment: specific guidelines for initial dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Treatment-related renal impairment: discontinue carmustine in patients who develop a creatinine clearance of less than 10 mL/min.

Acetaminophen; Ibuprofen: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Albuterol; Budesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Amlodipine; Celecoxib: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Azelastine; Fluticasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Bacillus Calmette-Guerin Vaccine, BCG: (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.
Beclomethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Betamethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Budesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Budesonide; Formoterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Budesonide; Glycopyrrolate; Formoterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Bupivacaine; Meloxicam: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Celecoxib: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Celecoxib; Tramadol: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
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.
Ciclesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Cimetidine: (Moderate) Use cimetidine and carmustine together with caution; increased myelosuppression (e.g., leukopenia and neutropenia) may occur. Consider using an alternative agent in place of cimetidine.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Corticosteroids: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Cortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Deflazacort: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Dexamethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Diclofenac: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Diclofenac; Misoprostol: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Diflunisal: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Digoxin: (Moderate) Use carmustine and digoxin together with caution; concomitant use may result in decreased digoxin tablet absorption and reduced digoxin effectiveness. Monitor digoxin levels prior to starting carmustine and during concomitant therapy. If necessary, increase the digoxin dose by 20% to 40%; continue to monitor digoxin levels. The digoxin AUC value was reduced approximately 50% in cancer patients who received digoxin (Lanoxin tablets) with high dose chemotherapy in a pharmacokinetic study (n = 6). Patients received a digoxin 0.25-mg dose within 3 days of starting chemotherapy (baseline) and another digoxin 0.25-mg dose within 5 days of completing high-dose chemotherapy which included carmustine 350 mg/m2 IV daily for 3 days with or without melphalan.
Diphenhydramine; Ibuprofen: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Diphenhydramine; Naproxen: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Etodolac: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
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) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Fludrocortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Flunisolide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Flurbiprofen: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Fluticasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Fluticasone; Salmeterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Fluticasone; Umeclidinium; Vilanterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Fluticasone; Vilanterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Formoterol; Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Fosphenytoin: (Moderate) Use fosphenytoin and carmustine together with caution; phenytoin serum concentration may be reduced resulting in decreased fosphenytoin efficacy. Consider using an alternative agent in place of fosphenytoin. If these drugs are used together, anticonvulsant therapy should be monitored closely during and after administration of carmustine.
Hydrocodone; Ibuprofen: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Hydrocortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Ibuprofen: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Ibuprofen; Famotidine: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Ibuprofen; Oxycodone: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Indomethacin: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Intranasal Influenza Vaccine: (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.
Ketoprofen: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Ketorolac: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
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.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (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.
Measles/Mumps/Rubella Vaccines, MMR: (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) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Mefenamic Acid: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Meloxicam: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Melphalan Flufenamide: (Moderate) Concomitant use of intravenous melphalan and carmustine may result in additive pulmonary toxicity. Fatal cases of pulmonary fibrosis have been reported with both melphalan and carmustine. If these agents are used together, monitor patients for signs and symptoms of pulmonary toxicity.
Melphalan: (Moderate) Concomitant use of intravenous melphalan and carmustine may result in additive pulmonary toxicity. Fatal cases of pulmonary fibrosis have been reported with both melphalan and carmustine. If these agents are used together, monitor patients for signs and symptoms of pulmonary toxicity.
Methylprednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Nabumetone: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Naproxen: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Naproxen; Esomeprazole: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Naproxen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Nonsteroidal antiinflammatory drugs: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Olopatadine; Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Oxaprozin: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Phenobarbital: (Moderate) Use phenobarbital and carmustine together with caution; phenobarbital induces the metabolism of carmustine and may reduce the efficacy of carmustine. Consider using an alternative agent in place of phenobarbital.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Use phenobarbital and carmustine together with caution; phenobarbital induces the metabolism of carmustine and may reduce the efficacy of carmustine. Consider using an alternative agent in place of phenobarbital.
Phenytoin: (Moderate) Use phenytoin and carmustine together with caution; phenytoin serum concentration may be reduced resulting in decreased phenytoin efficacy. Consider using an alternative agent in place of phenytoin. If these drugs are used together, anticonvulsant therapy should be monitored closely during and after administration of carmustine. Phenytoin dosage increases of 20 to 100% have been required in some patients, depending on the chemotherapy administered.
Piroxicam: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Prednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Prednisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Procarbazine: (Minor) Pretreatment with procarbazine may increase the cytotoxicity of carmustine. Procarbazine acts as a methylating agent and reduces the cell's ability to repair DNA damage formed by carmustine. When these drugs are given in combination, it has been suggested that procarbazine should be administered prior to carmustine.
Rotavirus Vaccine: (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.
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.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (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.
Smallpox Vaccine, Vaccinia Vaccine: (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.
Sulindac: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Sumatriptan; Naproxen: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Tolmetin: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Triamcinolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
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.
Typhoid Vaccine: (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.
Valdecoxib: (Major) Due to the thrombocytopenic effects of carmustine, 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. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Varicella-Zoster Virus Vaccine, Live: (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.
Yellow Fever Vaccine, Live: (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.

BiCNU/Carmustine Intravenous Inj Pwd F/Sol: 50mg, 100mg, 300mg
Gliadel Intratumor Imp: 7.7mg

IV: 200 mg/m2 IV every 6 weeks; doses of 300 mg/m2 have been used in combination with other agents for stem-cell transplant preparation. Wafers: 61.6 mg (eight 7.7-mg wafers) implanted intracranially.

IV: 200 mg/m2 IV every 6 weeks; doses of 300 mg/m2 have been used in combination with other agents for stem-cell transplant preparation.[44331] [44330]Wafers: 61.6 mg (eight 7.7-mg wafers) implanted intracranially.

Safety and efficacy not established.

Safety and efficacy not established.

Nitrosourea antineoplastic agents are alkylating agents. This class of drugs work by inhibiting DNA replication, RNA transcription, and nucleic acid function. Specifically, carmustine possesses two chloroethyl groups which alkylate nucleic acids and cell proteins and form DNA-DNA or DNA-protein crosslinks. During carmustine decomposition, isocyanates are also formed and can react by carbamoylating lysine residues of proteins. The 2-chloroethyl isocyanate of carmustine has been shown to inhibit the repair of DNA strand breaks, therefore, both alkylation and carbamoylation of amino acids in proteins contribute to the mechanism of action of nitrosoureas. Nitrosoureas are cell cycle non-specific. Although it is generally agreed that carmustine alkylates DNA and RNA, cross-resistance with other alkylating agents, such as cyclophosphamide, is uncommon.

Carmustine is administered intravenously and as an intracavitary wafer implant in the brain.[61842] [55722]

IV carmustine crosses the blood-brain barrier; radioactivity was 50% or greater in the cerebral spinal fluid compared with plasma levels following a radioactive carmustine dose. The elimination half-life ranged from 15 to 75 minutes after a short IV infusion. Carmustine is metabolized via denitrosation reactions catalyzed by both cytosolic and microsomal enzymes, including NADPH and glutathione-S-transferase. Following a radiolabeled IV carmustine dose, approximately 60% to 70% of the total dose was excreted in the urine within 96 hours; 10% of the drug was expired as CO2.[61842]

Intracavitary Route
Carmustine concentrations in human brain tissue have not been determined following the insertion of carmustine wafers. After wafer insertion, the mean whole blood carmustine Cmax was 10.2 ng/mL (standard deviation of 4.8 ng/mL). When levels were measured for approximately 24 hours, the Tmax was reached at about 3 hours after wafer insertion. Carmustine wafers are biodegradable when implanted in the brain. They are degraded spontaneously and metabolically. Greater than 70% of the copolymer degrades within 3 weeks. Water remnants were seen on CT scans performed at 49 days after wafer implantation. Wafer remnants were also observed at re-operation and autopsy up to 7.8 months after wafer implantation; these remnants consisted mostly of water and monomeric components and had minimal detectable carmustine.[55722]

Carmustine may cause fetal harm if used during pregnancy based on its mechanism of action and data from animal studies; there is limited data in humans. Females of reproductive potential should avoid pregnancy. Advise pregnant women of the potential risk to the fetus. IV or intraperitoneal (IP) carmustine administration resulted in embryotoxicity and teratogenicity in animals that received doses lower than the maximum cumulative human dose (IV carmustine) or doses that resulted in lower exposure than the recommended human dose (carmustine wafers) based on body surface area (BSA).[61842] [55722] Reduced fetal weight and malformations including thoraco-abdominal closure, neural tube, and eye defects; skeletal anomalies in the skull, sternebra, vertebrae, and ribs; and reduced skeletal ossification were reported when carmustine IP was given to pregnant rats at cumulative doses about 0.02-times the maximum cumulative human dose.[61842] Carmustine caused fetal malformations (e.g., anophthalmia, micrognathia, omphalocele) at doses that were about 0.12-times the recommended human dose of carmustine wafers (based on BSA).[55722]

It is not known if carmustine is secreted in human milk or if it has effects on the breast-fed infant or on milk production. Because many drugs are excreted in human milk and there is a potential for adverse reactions in nursing infants from carmustine (e.g., carcinogenicity, myelosuppression), women should discontinue breast-feeding during IV carmustine therapy or for at least 7 days after wafer implantation.