carmustine: clinical use

Prescribing considerations

• Intravenous carmustine should be supervised by clinicians experienced in chemotherapy; account for prior marrow suppression, cumulative pulmonary toxicity, renal function, thoracic irradiation and other lung-toxic treatments.
• The implant is restricted to intralesional placement during resection. Avoid placement adjacent to large cerebral vessels and prevent communication between the cavity and ventricular system.
• Discuss reproductive risk, contraception and possible fertility preservation before treatment where relevant.
• The infusion solvent contains a clinically relevant quantity of ethanol.

Contraindications and cautions

• Infusion: hypersensitivity to carmustine, another nitrosourea or an excipient; severe marrow depression; end-stage renal impairment; childhood or adolescence; breastfeeding.
• Implant: hypersensitivity to carmustine or an implant excipient. It is not recommended during pregnancy; breastfeeding is contraindicated.

Monitoring

• Infusion: frequent full blood counts because marrow suppression is delayed and cumulative; assess renal and hepatic function.
• Obtain baseline chest imaging and pulmonary-function tests, with ongoing pulmonary assessment during intravenous treatment.
• Monitor the infusion site for pain, burning or extravasation.
• Implant: monitor for seizures, cerebral oedema or intracranial hypertension, infection, cerebrospinal-fluid leak, abnormal wound healing, hydrocephalus and neurological deterioration. Interpret postoperative imaging with awareness that inflammation and oedema may resemble progression.

Clinical pharmacology

Carmustine is a cell-cycle-nonspecific, lipophilic nitrosourea. Reactive intermediates alkylate nucleoproteins and form interstrand DNA cross-links; carbamoylation may additionally inhibit DNA-repair enzymes. Intravenous carmustine is rapidly degraded and crosses the blood–brain barrier. The implant releases carmustine locally as its polifeprosan matrix biodegrades.

Formulation and product differences

• The intravenous product is a powder with an ethanol-containing solvent. It requires aseptic reconstitution, further dilution, light protection and compatible glass or polypropylene equipment.
• The implant is a biodegradable carmustine-containing wafer placed in the surgical resection cavity. It requires cytotoxic handling precautions and is not interchangeable with intravenous carmustine.
• Systemic contraindications, interaction evidence, monitoring requirements and contraceptive advice differ from those for the implant.

Implant

Route: Implant

Strengths: 7.7 mg

Solution for infusion

Route: Intravenous

Strengths: 100 mg