Carmustine

Name: Carmustine

Carmustine Overview

Carmustine is a prescription medication used to treat certain types of brain tumors, multiple myeloma (cancer of the bone marrow), and Hodgkin's and non-Hodgkin's lymphoma (cancers of the immune system). Carmustine belongs to a group of drugs called alkylating agents, which prevent cancer cells from growing and multiplying.

This medication comes in injectable form that is slowly injected into a vein (IV) by a healthcare provider once every 6 weeks.

This medication also comes in a wafer form that is implanted within the cranium (skull) via surgical procedure.

Common side effects of carmustine include nausea, vomiting, and headache.

Carmustine Food Interactions

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of carmustine there are no specific foods that you must exclude from your diet when receiving carmustine.

Carmustine and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category D. It is not known if carmustine will harm your unborn baby. Talk to your doctor about birth control methods, as it is important to prevent pregnancy while on this medication. If you become pregnant, tell your doctor right away.

Interactions for Carmustine

Intracranial Wafer

No formal drug interaction studies to date.124 In clinical trials, chemotherapy was withheld for at least 4 weeks (6 weeks for nitrosoureas) prior to and 2 weeks after surgery.124 Implantation in conjunction with radiotherapy does not appear to have any short-term or chronic toxicities;124 in clinical trials, external beam radiation therapy was administered >3 weeks after surgery.124

Specific Drugs

Drug

Interaction

Comments

Cimetidine

Potentiation of neutropenic and thrombocytopenic effect of carmustined

Mitomycin

Possible changes in tear films, with subsequent damage of corneal and conjunctival epithelium146

Phenytoin

Possible decreased serum phenytoin concentrations147

Monitor serum phenytoin concentrations carefully and adjust dosage accordingly147

Pronunciation

(kar MUS teen)

Off Label Uses

Mycosis fungoides (topical)

Data from a nonrandomized observational study of patients with mycosis fungoides treated with topical carmustine suggests that topical carmustine is beneficial for the treatment of patients with this condition [Zackheim 2003]. Additional data may be necessary to further define the role of topical carmustine in the treatment of this condition.

Stem cell or bone marrow transplant (autologous) conditioning regimen

Data from a nonrandomized clinical study in patients with poor-risk Hodgkin lymphoma, a randomized active comparator study in patients with poor prognosis histologically aggressive non-Hodgkin lymphoma, and a nonrandomized study in relapsed or refractory non-Hodgkin lymphoma support the use of carmustine (in combination with etoposide, cytarabine, and melphalan [BEAM regimen]) administered prior to stem cell or bone marrow transplantation [Chopra 1993], [Linch 2010], [Mills 1995]. Data from a nonrandomized clinical study in patients with advanced Hodgkin lymphoma also supports the use of carmustine (in combination with cyclophosphamide and etoposide [CBV regimen]) administered prior to stem cell or bone marrow transplantation [Reece 1991]. Data from a study in pediatric patients with either relapsed or refractory Hodgkin or non-Hodgkin lymphomas supports the use of carmustine (in combination with cyclophosphamide and etoposide [CBV regimen]) as a myeloablative conditioning regimen prior to stem cell transplant ([Harris 2011]).

Dosing Renal Impairment

IV: Manufacturer’s labeling: CrCl <10 mL/minute: Discontinue treatment.

The following dosage adjustments have also been reported (Kintzel 1995):

CrCl 46 to 60 mL/minute: Reduce dose to 80% of the usual dose

CrCl 31 to 45 mL/minute: Reduce dose to 75% of the usual dose

CrCl ≤30 mL/minute: Consider use of alternative drug.

Wafer implant: There are no dosage adjustments provided in the manufacturer’s labeling.

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. 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

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)

Liver Dose Adjustments

Data not available

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