vehicle plate [10:<2,000/mm 3 or platelets> <25,000/mm 3 : Reduce dose to 50% of usual dose Dosing: Obesity American Society of Clinical Oncology (ASCO) Guidelines for appropriate chemotherapy dosing in obese adults with cancer ( Note: Excludes HSCT dosing): Utilize patient's actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs 2012). American Society for Blood and Marrow Transplantation (ASBMT) practice guideline committee position statement on chemotherapy dosing in obesity: Utilize actual body weight (full weight) for calculation of body surface area in carmustine dosing for hematopoietic stem 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 (Bubalo 2014). ABW25: Adjusted wt (kg) = Ideal body weight (kg) + 0.25 [actual wt (kg) - ideal body weight (kg)] Reconstitution Injection: Reconstitute initially with 3 mL of supplied diluent (dehydrated alcohol injection, USP); then further dilute with SWFI (27 mL), this provides a concentration of 3.3 mg/mL in ethanol 10%; protect from light; further dilute for infusion with 500 mL D5W or NS using a non-PVC container (eg, glass, polypropylene or polyolefin) to a concentration of 0.2 mg/mL. Implant: Each wafer is packaged within 2 nested aluminum foil pouches; the inner pouch is sterile and is designed to maintain sterility and protect from moisture; the outer wrap is not sterile. Deliver to the operating room in the unopened outer aluminum foil pouch. Do not open until the wafers are ready to be implanted. Follow manufacturer s instructions for opening the pouch, being careful not to apply pressure to the wafer. Administration Carmustine (IV) is associated with a moderate to high emetic potential (dose-related); antiemetics are recommended to prevent nausea and vomiting (Basch 2011; Dupuis 2011). 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/m 2 /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): Apply solution with brush or gauze pads; ointment and solution should be applied while wearing gloves to involved areas only; avoid contact with eyes or mouth (Zackheim 2003). Storage Injection: Store intact vials and provided diluent at 2 C to 8 C (36 F to 46 F). Carmustine has a low melting point (30.5 C to 32 C [86.9 F to 89.6 F]); exposure to temperature at or above the melting point will cause the drug to liquefy and appear as an oil film on the vials; if drug liquefies, discard the vials as this is a sign of decomposition. If there is a question of proper refrigeration upon receipt of product, inspect vials; a small amount of dry flakes or dry congealed mass is acceptable and the vial should be refrigerated immediately. Reconstituted solutions are stable for 24 hours refrigerated (2 C to 8 C) and protected from light. Examine reconstituted vials for crystal formation prior to use. If crystals are observed, they may be redissolved by warming the vial to room temperature with agitation. Solutions diluted for infusion to a concentration of 0.2 mg/mL in D5W or NS in glass or polypropylene containers and protected from light should be used within 8 hours when stored at room temperature (25 C); infusion solutions are also stable for 24 hours refrigerated followed by an additional 6 hours at room temperature. Although the manufacturer recommends glass or polypropylene containers be used, stability of a 1 mg/mL solution in D5W has also been demonstrated for up to 6 hours (with a 6% to 7% loss of potency) in polyolefin containers (Trissel 2006). Wafer: Store at or below -20 C (-4 F). Unopened outer foil pouches may be kept at room temperature for up to 6 hours at a time for up to 3 cycles within a 30-day period. Drug Interactions BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). 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. Consider therapy modification CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. 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. 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. Consider therapy modification Melphalan: May enhance the adverse/toxic effect of Carmustine. Specifically, melphalan may sensitize patients to carmustine lung toxicity. Monitor therapy Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. 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. Consider therapy modification Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination Adverse Reactions 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) ALERT: U.S. Boxed Warning Myelosuppression (injection) 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. Pulmonary toxicity (injection) Carmustine causes dose-related pulmonary toxicity. Patients receiving greater than 1,400 mg/m 2 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. Warnings/Precautions Concerns related to adverse effects: Bone marrow suppression: [US Boxed Warning]: Carmustine IV causes bone marrow suppression, primarily thrombocytopenia (which may lead to bleeding) and leukopenia (which may cause infection). Monitor blood counts weekly for at least 6 weeks following each dose. Adjust dosage based on nadir blood counts from prior dose for dosage adjustment. Do not administer a repeat course until blood counts recover. 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). Platelet counts should be> 100,000/mm 3 and leukocytes should be >4,000/mm 3 prior to a repeat course (repeat courses should not be administered more frequently than every 6 weeks). Gastrointestinal toxicity: Carmustine IV is associated with a moderate to high emetic potential (dose-related); antiemetics are recommended to prevent nausea and vomiting (Basch 2011; Dupuis 2011). Hepatic: Reversible increases in transaminases, bilirubin, and alkaline phosphatase have been reported (rare) with the IV formulation. Monitor liver function tests periodically during treatment. Infusion-site reactions: Rapid infusions are associated with skin flushing and suffusion of the conjunctiva (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. Monitor closely for intracranial hypertension related to brain edema, inflammation, or necrosis of brain tissue surrounding resection. Re-operation to remove wafers (or remnants) may be necessary for refractory cases. 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. Monitor postoperatively for signs/symptoms of meningitis and CNS infection. Ocular toxicity: Investigational administration (intraarterial intracarotid route [not an approved route]) has been associated with ocular toxicity. Pulmonary toxicity: [US Boxed Warning]: Carmustine IV is associated with dose-related pulmonary toxicity; patients receiving cumulative doses> 1,400 mg/m 2 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/m 2 (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/m 2 . 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%. Baseline and periodic pulmonary function tests are recommended. 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; interstitial pneumonia may be managed with a course of corticosteroids. Renal: Renal failure, progressive azotemia, and decreased kidney size have been reported in patients who have received large cumulative IV doses or prolonged IV treatment. Renal toxicity has also been reported in patients who have received lower cumulative doses. Monitor renal function tests periodically during treatment. 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 seizures and 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. Monitor (postoperatively) for seizures. Wound healing impairment: Impaired neurosurgical wound healing, including would dehiscence, delayed healing, and subdural, subgleal or wound effusions may occur with carmustine wafer implant treatment; cerebrospinal fluid leaks have also been reported. Monitor post-operatively for impaired neurosurgical wound healing. Disease related concerns: Renal impairment: May require dosage adjustment or discontinuation in patients with renal impairment. Do not administer carmustine IV in patients with compromised renal function. Concurrent drug therapy issues: Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations: Pediatric: Children are at higher risk of delayed pulmonary toxicity with the IV formulation. Dosage form specific issues: Injection: Diluent contains ethanol. 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. Monitoring Parameters Injection: CBC with differential and platelet count (weekly for at least 6 weeks after a dose), pulmonary function tests (FVC, DL CO ; at baseline and frequently during treatment), liver function (periodically), renal function tests (periodically); monitor blood pressure and vital signs during administration, monitor infusion site for possible infiltration; monitor for signs/symptoms of pulmonary toxicity 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. Pregnancy Risk Factor D Pregnancy Considerations Adverse events have been observed in animal reproduction studies. Based on the mechanism of action, carmustine may cause fetal harm if administered to a pregnant woman. Females of reproductive potential should use highly effective contraceptives during and for at least 6 months following treatment. Males of reproductive potential should use highly effective contraceptives during and for at least 3 months following treatment. May impair male fertility. Advise males of potential risk of infertility and to seek fertility/family planning counseling prior to receiving carmustine wafer implants. Patient Education Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?) Patient may experience constipation, abdominal pain, or back pain. Have patient report immediately to prescriber signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of infection, signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), angina, seizures, severe headache, severe nausea, vomiting, vision changes, neck rigidity, wound healing impairment, depression, severe loss of strength and energy, chills, painful urination, tachycardia, severe dizziness, passing out, or injection site redness, edema, burning, pain, or severe irritation (HCAHPS). Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions. Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients. Next Interactions Print this page Add to My Med List More about carmustine Side Effects During Pregnancy Dosage Information Drug Interactions Support Group En Español 0 Reviews Add your own review/rating Drug class: alkylating agents Consumer resources Carmustine ... +4 more Professional resources Carmustine (AHFS Monograph) Other brands: Gliadel , BiCNU Related treatment guides Brain Tumor Glioblastoma Multiforme Hodgkin's Lymphoma Malignant Glioma Multiple Myeloma Non-Hodgkin's Lymphoma> ]} Drug Status Rx Availability Prescription only D Pregnancy Category Positive evidence of risk N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Carmustine Rating No Reviews - Be the first! No Reviews - Be the first! Not Rated - Be the first! Drug Class Alkylating agents Related Drugs alkylating agents carboplatin , cisplatin , cyclophosphamide , oxaliplatin , Cytoxan , Temodar Hodgkin's Lymphoma Opdivo , Keytruda , cyclophosphamide , nivolumab , Cytoxan , etoposide , More... Non-Hodgkin's Lymphoma methotrexate , Rituxan , rituximab , cyclophosphamide , Imbruvica , Cytoxan , More... Glioblastoma Multiforme Avastin , bevacizumab , Temodar , temozolomide , Gliadel , Matulane , More... 3 more conditions...} } contemplating
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