Version May 2024
Carmustine causes suppression of marrow function (including thrombocytopenia and leukopenia), which may contribute to bleeding and overwhelming infections. Monitor blood counts weekly for at least 6 weeks after each dose. Adjust dosage based on nadir blood counts from the prior dose. Do not administer a repeat course of carmustine until blood counts recover.
Carmustine causes dose-related pulmonary toxicity. Patients receiving greater than 1,400 mg/m2 cumulative dose are at significantly higher risk than those receiving less. Delayed pulmonary toxicity can occur years after treatment, and can result in death, particularly in patients treated in childhood.
Note: Carmustine (IV) is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]). Platelet counts should be >100,000/mm3, ANC >1,000/mm3, and leukocytes >4,000/mm3 prior to a repeat course. Repeat courses should not be administered more frequently than every 6 weeks.
Central nervous system tumors, primary:
Glioma, recurrent (off-label dose): IV: 80 mg/m2 on days 1, 2, and 3 every 8 weeks for a maximum of 6 cycles (Brandes 2004; Reithmeier 2010).
Glioma, malignant, newly diagnosed (off-label dose): IV: 200 mg/m2 every 8 weeks (up to a maximum cumulative dose of 1,500 mg/m2) (Selker 2002).
Wafer implants:
Glioma, newly diagnosed high-grade: Implantation (wafer): 8 wafers (7.7 mg each) implanted intracranially into the resection cavity (total dose 61.6 mg); should the size and shape not accommodate 8 wafers, the maximum number of wafers feasible (up to 8) should be placed.
Glioblastoma, recurrent: Implantation (wafer): 8 wafers (7.7 mg each) implanted intracranially into the resection cavity (total dose 61.6 mg); should the size and shape not accommodate 8 wafers, the maximum number of wafers feasible (up to 8) should be placed.
Hematopoietic cell or bone marrow (autologous) transplant conditioning regimen (off-label use):
BEAM regimen: IV: 300 mg/m2 as a single dose 6 days prior to transplant (in combination with etoposide, cytarabine, and melphalan) (Chopra 1993; Geisler 2008; Linch 2010; Mills 1995).
BEAC regimen: IV: 300 mg/m2 as a single dose 6 days prior to transplant (in combination with etoposide, cytarabine, and cyclophosphamide) (Geisler 2008).
CBV regimen: IV: 600 mg/m2 as a single dose 3 days prior to transplant (in combination with cyclophosphamide and etoposide) (Reece 1991).
Carmustine/thiotepa regimen (primary CNS lymphoma): IV: 400 mg/m2 as a single dose 6 days prior to transplant (in combination with thiotepa) (Ferreri 2016; Illerhaus 2008; Kasenda 2012). Refer to protocols for specific details.
Hodgkin lymphoma, relapsed or refractory, salvage therapy (off-label dose): Mini-BEAM regimen: IV: 60 mg/m2 on day 1 every 4 to 6 weeks (in combination with etoposide, cytarabine, and melphalan) for 2 to 4 cycles, followed by conditioning for autologous transplant in responders (Colwill 1995; Martin 2001).
Mycosis fungoides, early stage, topical (off-label use/route):
Ointment (10 mg/100 grams petrolatum): Topical: Apply once daily to affected areas (Zackheim 2003).
Solution (10 mg/60 mL water): Topical: Apply once daily to affected areas (Zackheim 2003).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
IV: Manufacturer’s labeling: CrCl <10 mL/minute: Discontinue treatment. Do not administer to patients with compromised kidney function.
The following dosage adjustments have also been reported:
CrCl 46 to 60 mL/minute: Reduce dose to 80% of the usual dose (Kintzel 1995; Krens 2019).
CrCl 31 to 45 mL/minute: Reduce dose to 75% of the usual dose (Kintzel 1995; Krens 2019).
CrCl ≤30 mL/minute: Use is not recommended; consider use of alternative drug (Kintzel 1995; Krens 2019).
Hemodialysis: Use is not recommended (Krens 2019).
Wafer implant: There are no dosage adjustments provided in the manufacturer’s labeling.
IV: There are no dosage adjustments provided in the manufacturer’s labeling. The following recommendations have been reported:
Mild or moderate impairment: No need for dose adjustment is expected (Krens 2019).
Severe impairment: Use is not recommended (Krens 2019).
Wafer implant: There are no dosage adjustments provided in the manufacturer’s labeling.
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2 (Note: Excludes hematopoietic cell transplantation dosing): Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (ASCO [Griggs 2021]).
American Society for Blood and Marrow Transplantation practice guideline committee position statement on chemotherapy dosing in obesity: Utilize actual body weight for calculation of BSA in carmustine dosing for hematopoietic cell transplant conditioning regimens in adult patients weighing ≤120% of their ideal body weight (IBW). In patients weighing >120% IBW, utilize adjusted body weight 25% (ABW25) to calculate BSA (ASBMT [Bubalo 2014]).
ABW25: Adjusted wt (kg) = Ideal body weight (kg) + 0.25 [actual wt (kg) - ideal body weight (kg)]
Carmustine IV:
Hematologic toxicity: Based on nadir counts with previous dose (manufacturer’s labeling). IV:
If leukocytes ≥3,000/mm3 and platelets ≥75,000/mm3: Administer 100% of carmustine dose.
If leukocytes 2,000 to 2,999/mm3 or platelets 25,000 to 74,999/mm3: Reduce dose to 70% of usual carmustine dose.
If leukocytes <2,000/mm3 or platelets <25,000/mm3: Reduce dose to 50% of usual carmustine dose.
Pulmonary toxicity (signs/symptoms or decreased carbon monoxide diffusing capacity): Consider initiating systemic corticosteroid therapy (eg, prednisone) and consider discontinuing carmustine (Kalaycioglu 1995; Smith 1989).
Carmustine wafer:
Intracranial hypertension (related to brain edema, inflammation, or necrosis of brain tissue surrounding resection): May require re-operation to remove wafers (or remnants) for refractory cases.
Refer to adult dosing.
(For additional information see "Carmustine: Pediatric drug information")
Note: Children are at increased risk for pulmonary toxicity due to carmustine, weigh risk vs benefit before use. Carmustine IV is associated with a moderate or high emetic potential (dose related); antiemetics are recommended to prevent nausea and vomiting (POGO [Dupuis 2011]). Refer to individual protocols; dosing and frequency may vary.
Brain tumors, myeloablative therapy prior to autologous stem cell rescue: Very limited data available; Infants, Children, and Adolescents: IV: 100 mg/m2/dose twice daily for 3 days (total: 600 mg/m2) as part of a high dose combination chemotherapy regimen is most commonly reported in trials with mixed results (Dunkel 1998; Finlay 2008); however, a phase I trial identified a lower dose of 100 mg/m2/dose once daily for 3 days (total: 300 mg/m2) in combination with thiotepa as the maximum tolerated regimen with a high degree of pulmonary toxicity observed (Gilman 2011).
Non-Hodgkin lymphoma; relapsed or resistant, high-dose chemotherapy prior to autologous bone marrow transplant: Limited data available:
BEAM regimen: Adolescents ≥15 years: IV: 300 mg/m2/dose for 1 dose followed by etoposide, cytarabine, and melphalan (Mills 1995).
CBV regimen: Children and Adolescents: IV: 100 mg/m2/dose once daily for 3 days (total dose: 300 mg/m2) on days -8 through -6 in combination with cyclophosphamide and etoposide (Harris 2011).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: The presented dosing adjustments are based on experience in adult patients; specific recommendations for pediatric patients are limited. Refer to specific protocol for management in pediatric patients if available.
Adult:
Hematologic toxicity: Based on nadir counts with previous dose (manufacturer's labeling). IV:
If leukocytes ≥3,000/mm3 and platelets ≥75,000/mm3: Administer 100% of dose.
If leukocytes 2,000 to 2,999/mm3 or platelets 25,000 to 74,999/mm3: Administer 70% of dose.
If leukocytes <2,000/mm3 or platelets <25,000/mm3: Administer 50% of dose.
IV: There are no dosage adjustments provided in the manufacturer’s labeling; experience in adult patients suggests that dose should be reduced in renal impairment.
IV: There are no dosage adjustments provided in the manufacturer’s labeling; use with caution, dosage adjustment may be necessary.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Implant:
>10%:
Central nervous system: Seizure (37%; new or worsening: 20%), cerebral edema (4% to 23%), depression (16%)
Dermatologic: Skin rash (5% to 12%)
Gastrointestinal: Nausea (22%), vomiting (21%), constipation (19%)
Genitourinary: Urinary tract infection (21%)
Neuromuscular & skeletal: Weakness (22%)
Miscellaneous: Wound healing impairment (14% to 16%), fever (12%)
1% to 10%:
Cardiovascular: Chest pain (5%)
Central nervous system: Intracranial hypertension (9%), cerebral hemorrhage (6%), meningitis (4%)
Gastrointestinal: Abdominal pain (8%)
Infection: Abscess (local 6%)
Neuromuscular & skeletal: Back pain (7%)
IV: Frequency not defined:
Cardiovascular: Chest pain, flushing (with rapid infusion), occlusive arterial disease, tachycardia
Central nervous system: Brain disease, headache, seizure
Dermatologic: Alopecia, burning sensation of skin, hyperpigmentation
Gastrointestinal: Anorexia, diarrhea, nausea, vomiting
Genitourinary: Gynecomastia
Hematologic & oncologic: Acute leukemia, anemia, bone marrow dysplasia, leukemia, leukopenia (common; onset: 5 to 6 weeks; recovery: after 1 to 2 weeks), thrombocytopenia (common: onset: ~4 weeks; recovery: after 1 to 2 weeks)
Hepatic: Increased serum alkaline phosphatase, increased serum bilirubin, increased serum transaminases
Hypersensitivity: Hypersensitivity reaction
Infection: Opportunistic infection
Local: Burning sensation at injection site, erythema at injection site, pain at injection site, swelling at injection site, tissue necrosis at injection site
Ophthalmic: Blurred vision, conjunctival edema, conjunctival hemorrhage, ophthalmic signs and symptoms (loss of depth perception), suffusion of the conjunctiva (with rapid infusion)
Renal: Azotemia (progressive), nephron atrophy, renal failure
Respiratory: Interstitial pulmonary disease, pneumonitis, pulmonary fibrosis (occurring up to 17 years after treatment), pulmonary infiltrates
<1%, postmarketing, and/or case reports: Febrile neutropenia (Chopra 1993), sepsis (implant), venous thrombosis at injection site (IV)
IV: Hypersensitivity to carmustine or any component of the formulation.
Implant: There are no contraindications listed in the manufacturer's labeling.
Canadian labeling: Additional contraindications (not in the US labeling): IV: Hypersensitivity to other nitrosoureas; pregnancy; breastfeeding.
Concerns related to adverse effects:
• Bone marrow suppression: Carmustine IV causes bone marrow suppression, primarily thrombocytopenia (which may lead to bleeding) and leukopenia (which may cause infection). Hematologic toxicity is dose-limiting, may be severe, and is generally delayed and cumulative; thrombocytopenia is usually more severe than leukopenia. Myelosuppression generally occurs 4 to 6 weeks after administration; thrombocytopenia occurs at ~4 weeks and persists for 1 to 2 weeks; leukopenia occurs at 5 to 6 weeks and persists for 1 to 2 weeks. Anemia may occur (less common and less severe than leukopenia or thrombocytopenia).
• Hepatic: Reversible increases in transaminases, bilirubin, and alkaline phosphatase have been reported (rare) with the IV formulation.
• Infusion-site reactions: Rapid infusions are associated with skin flushing and conjunctiva redness (onset: <2 hours; duration ~4 hours). Carmustine is also associated with injection-site burning and local tissue reactions, including swelling, pain, erythema, and necrosis, have been reported. Monitor infusion site closely for infiltration or injection-site reactions. Avoid extravasation.
• Intracranial hypertension: Brain edema has been reported in patients with newly diagnosed glioma receiving wafer implants, including one report of intracranial mass effect unresponsive to corticosteroids that led to brain herniation. Intracranial hypertension may be related to brain edema, inflammation, or necrosis of brain tissue surrounding resection.
• Meningitis: Cases of meningitis have occurred in patients with recurrent glioma receiving wafer implants. Two cases were bacterial (one patient required removal of implants 4 days after implantation and the other developed meningitis following reoperation for recurrent tumor). Another case was determined to be chemical meningitis and resolved with corticosteroids.
• Ocular toxicity: Investigational administration (intraarterial intracarotid route [not an approved route]) has been associated with ocular toxicity.
• Pulmonary toxicity: Carmustine IV is associated with dose-related pulmonary toxicity; patients receiving cumulative doses >1,400 mg/m2 are at significantly higher risk. Delayed onset of pulmonary fibrosis may occur years after treatment (may be fatal), particularly in children. Pulmonary toxicity has occurred in children and adolescents up to 17 years after treatment; this occurred in ages 1 to 16 for the treatment of intracranial tumors; cumulative doses ranged from 770 to 1,800 mg/m2 (in combination with cranial radiotherapy). Pulmonary toxicity is characterized by pulmonary infiltrates and/or fibrosis and has been reported from 9 days to 43 months after nitrosourea treatment (including carmustine). Although pulmonary toxicity generally occurs in patients who have received prolonged treatment, pulmonary fibrosis has been reported with cumulative doses below 1,400 mg/m2. Interstitial fibrosis at lower doses has occurred (rare). In addition to high cumulative doses, other risk factors for pulmonary toxicity include history of lung disease and baseline predicted forced vital capacity (FVC) or carbon monoxide diffusing capacity (DLCO) <70%. For high-dose treatment (transplant; off-label dose), acute lung injury may occur ~1 to 3 months post transplant; advise patients to contact their transplant physician for dyspnea, cough, or fever.
• Renal: Renal failure, progressive azotemia, and decreased kidney size have been reported.
• Secondary malignancies: Long-term IV use is associated with the development of secondary malignancies (acute leukemias and bone marrow dysplasias).
• Seizures: Seizures occurred in patients who received carmustine wafer implants, including new or worsening (treatment-emergent) seizures. Just over half of treatment-emergent seizures occurred within 5 days of surgery; the median onset of first new or worsened post-operative seizure was 4 days. Optimal anti-seizure therapy should be initiated prior to surgery.
• Wound healing impairment: Impaired neurosurgical wound healing, including wound dehiscence, delayed healing, and subdural, subgaleal, or wound effusions may occur with carmustine wafer implant treatment; cerebrospinal fluid leaks have also been reported.
Special populations:
• Pediatric: Children are at higher risk of delayed pulmonary toxicity with the IV formulation.
Dosage form specific issues:
• Injection: Diluent may contain ethanol or propylene glycol (formulation-dependent; refer to manufacturer's labeling).
• Wafer: Monitor closely for known craniotomy-related complications (seizure, intracranial infection, abnormal wound healing, brain edema). Wafer migration may occur; avoid communication between the resection cavity and the ventricular system to prevent wafer migration; communications larger than the wafer should be closed prior to implantation; wafer migration into the ventricular system may cause obstructive hydrocephalus. Monitor for signs/symptoms of obstructive hydrocephalus.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Intravenous:
BiCNU: 100 mg (1 ea [DSC]) [contains alcohol, usp]
Generic: 50 mg (1 ea); 100 mg (1 ea); 300 mg (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Generic: 100 mg (1 ea)
Wafer, Implant:
Gliadel Wafer: 7.7 mg (8 ea) [contains polifeprosan 20]
May be product dependent
Solution (reconstituted) (Carmustine Intravenous)
50 mg (per each): $1,127.51
100 mg (per each): $662.04 - $4,481.09
300 mg (per each): $6,765.03
Wafer (Gliadel Wafer Implant)
7.7 mg (per each): $5,812.84
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
BiCNU: 100 mg (1 ea) [contains alcohol, usp]
Generic: 100 mg (1 ea)
Carmustine (IV) is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).
Injection: Infuse slowly over at least 2 hours (infusions <2 hours may lead to injection site pain or burning); infuse through a free-flowing saline or dextrose infusion, or administer through a central catheter to alleviate venous pain/irritation. Do not exceed a rate of 1.66 mg/m2/minute.
Irritant; infiltration may result in local pain, erythema, swelling, burning and skin necrosis; the alcohol-based diluent may be an irritant, especially with high doses. Avoid extravasation. Monitor infusion site.
High-dose carmustine (transplant dose; off-label use): Infuse over a least 2 hours to avoid excessive flushing, agitation, and hypotension; was infused over 1 hour in some trials (Chopra 1993). High-dose carmustine may be fatal if not followed by stem cell rescue. Monitor vital signs frequently during infusion; patients should be supine during infusion and may require the Trendelenburg position, fluid support, and vasopressor support.
Implant: Double glove before handling; outer gloves should be discarded as chemotherapy waste after handling wafers. Any wafer or remnant that is removed upon repeat surgery should be discarded as chemotherapy waste. The outer surface of the external foil pouch is not sterile. Open pouch gently; avoid pressure on the wafers to prevent breakage. Wafers that are broken in half may be used, however, wafers broken into more than 2 pieces should be discarded in a biohazard container. Slight overlapping of wafers during placement is acceptable. Oxidized regenerated cellulose (Surgicel) may be placed over the wafer to secure; irrigate cavity prior to closure.
Topical (off-label use): Wear gloves during application. Apply solution with brush or gauze pads; ointment and solution should be applied to involved areas only; avoid contact with eyes/orifices (Zackheim 2003).
Carmustine IV is associated with a moderate or high emetic potential (dose related); antiemetics are recommended to prevent nausea and vomiting (POGO [Dupuis 2011]).
Parenteral: Infuse over 2 hours (infusions <2 hours may lead to injection site pain or burning); infuse through a free-flowing saline or dextrose infusion, or administer through a central catheter to alleviate venous pain/irritation. Significant absorption to PVC containers; should be prepared in either glass or polyolefin containers.
High-dose carmustine (transplant dose): Infuse over at least 2 hours to avoid excessive flushing, agitation, and hypotension; was infused over 1 hour in some trials (Chopra 1993). High-dose carmustine may be fatal if not followed by stem cell rescue. Monitor vital signs frequently during infusion; patients should be supine during infusion and may require the Trendelenburg position, fluid support, and vasopressor support.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Central nervous system tumors:
Injection: Palliative treatment of brain tumors including glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors.
Wafer (implant): Treatment of newly-diagnosed high-grade glioma (as an adjunct to surgery and radiation); treatment of recurrent glioblastoma (as adjunct to surgery).
Hodgkin lymphoma, relapsed/refractory: Injection: Palliative treatment (secondary) of Hodgkin lymphoma (in combination with other antineoplastics) that has relapsed with or was refractory to primary therapy.
Hematopoietic cell or bone marrow transplant (autologous) conditioning regimen; Mycosis fungoides, early stage (topical)
Carmustine may be confused with bendamustine, lomustine
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cimetidine: May enhance the myelosuppressive effect of Carmustine. Management: Consider alternatives to cimetidine in patients receiving carmustine. If the combination cannot be avoided, monitor for enhanced carmustine myelotoxicity. Risk D: Consider therapy modification
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Fosphenytoin-Phenytoin: Carmustine may decrease the serum concentration of Fosphenytoin-Phenytoin. Management: Consider alternatives to fosphenytoin-phenytoin in carmustine treated patients. If combined, monitor closely for reduced phenytoin concentrations and increase fosphenytoin-phenytoin doses as needed. Risk D: Consider therapy modification
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Melphalan: May enhance the adverse/toxic effect of Carmustine. Specifically, melphalan may sensitize patients to carmustine lung toxicity. Risk C: Monitor therapy
Melphalan Flufenamide: May enhance the adverse/toxic effect of Carmustine. Specifically, melphalan flufenamide may sensitize patients to carmustine lung toxicity. Risk C: Monitor therapy
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
PHENobarbital: May decrease the serum concentration of Carmustine. Management: Consider alternatives to phenobarbital when using carmustine. If combined, monitor for reduced carmustine efficacy. Risk D: Consider therapy modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Primidone: May decrease the serum concentration of Carmustine. Management: Consider alternatives to primidone when using carmustine. If combined, monitor for reduced carmustine efficacy. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Evaluate pregnancy status prior to therapy. Patients who could become pregnant should use highly effective contraceptives during and for at least 6 months following treatment with carmustine. Patients with partners who could become pregnant should use highly effective contraceptives during and for at least 3 months following treatment with carmustine. Carmustine may impair male fertility; advise males of potential risk of infertility.
Based on the mechanism of action, and data from animal reproduction studies, in utero exposure to carmustine may cause fetal harm. Outcome information related to the use of carmustine in pregnancy is limited (NTP 2013).
It is not known if carmustine is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends breastfeeding be discontinued during treatment with the injection and for at least 7 days after implantation of the wafer.
Verify pregnancy status prior to therapy in patients who could become pregnant.
Injection: CBC with differential and platelet count (weekly for at least 6 weeks after each dose), pulmonary function tests (FVC, DLCO; at baseline and frequently during treatment), LFTs (transaminases and bilirubin; periodically during treatment), renal function tests (periodically). Monitor BP and vital signs during administration. Monitor infusion site for possible infiltration or injection-site reactions. Monitor for signs/symptoms of pulmonary toxicity and for development of secondary malignancies.
Wafer: Monitor postoperatively for seizures, impaired neurosurgical wound healing, and signs/symptoms of meningitis, CNS infection, and obstructive hydrocephalus; monitor closely for intracranial hypertension related to brain edema, inflammation, or necrosis of brain tissue surrounding resection.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Carmustine interferes with the normal function of DNA and RNA by alkylation and cross-linking the strands of DNA and RNA, and by possible protein modification; may also inhibit enzyme processes by carbamylation of amino acids in protein.
Absorption: Wafer: Systemic absorption measurable for ~24 hours after insertion
Distribution: IV: 3.3 L/kg; readily crosses blood-brain barrier producing CSF levels ≥50% of blood plasma levels; highly lipid soluble
Metabolism: Rapidly hepatic; forms active metabolites
Half-life elimination: IV: 15 to 75 minutes
Time to peak: Wafer: Systemic: ~3 hours after insertion
Excretion: IV: Urine (~60% to 70%) within 96 hours; lungs (~10% as CO2)
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