CARMUSTINE

CARMUSTINE
(kar-mus'teen)
BiCNU, Gliadel
Classifications: antineoplastic; alkylating agent;
Therapeutic: antineoplastic

Prototype: Cyclophosphamide
Pregnancy Category: D

Availability

100 mg injection; 7.7 mg wafer

Action

Highly lipid-soluble nitrosourea derivative with cell-cycle-nonspecific activity against rapidly proliferating cells. Produces cross-linkage of DNA strands, thereby blocking DNA, RNA, and protein synthesis in tumor cells. Major toxic effect is bone marrow suppression.

Therapeutic Effect

Drug metabolites thought to be responsible for antineoplastic activities. Full or partial activity against a variety of cancers resulting in reduction or stabilization of tumor size and increased survival rates.

Uses

As single agent or with other antineoplastics in treatment of Hodgkin's disease and other lymphomas, melanoma, primary and metastatic tumors of brain, and GI tract malignancies.

Unlabeled Uses

Treatment of carcinomas of breast and lungs, Ewing's sarcoma, Burkitt's tumor, malignant melanoma, and topically for mycosis fungoides.

Contraindications

History of pulmonary function impairment; recent illness with or exposure to chickenpox or herpes zoster; infection; severe bone marrow depression, decreased circulating platelets, leukocytes, or erythrocytes; pregnancy (category D), lactation.

Cautious Use

Hepatic and renal insufficiency; patient with previous cytotoxic medication, or radiation therapy; history of herpes infections.

Route & Dosage

Previously Untreated Patients—Carcinoma
Adult: IV 150–200 mg/m2 q6wk in one dose or given over 2 d; adjust for hematologic toxicity

Mycosis Fungoides
Adult: Topical 0.05–0.4% solution in 30% alcohol to paint entire body (60 mLs) or ointment 1–2 times/d for 6–8 wk (10 mg/d) (must be specially compounded)

Administration

Note: When administering IV to infants and children, verify correct IV concentration and rate of infusion with physician.

Intravenous

PREPARE: IV Infusion: Wear disposable gloves; contact of drug with skin can cause burning, dermatitis, and hyperpigmentation. Add supplied diluent to the 100 mg vial. Further dilute with 27 mL of sterile water for injection to yield a concentration of 3.3 mg/mL. Each dose is then added to 100–500 mL of D5W or NS. If possible avoid using PVC IV tubing and bags.  

ADMINISTER: IV Infusion: Infuse a single dose over at least 1 h. Slow infusion over 1–2 h and adequate dilution will reduce pain of administration. Avoid starting infusion into dorsum of hand, wrist, or the antecubital veins; extravasation in these areas can damage underlying tendons and nerves leading to loss of mobility of entire limb.  

INCOMPATIBILITIES Solution/additive: Dextrose 5%, sodium bicarbonate. Y-site: Allopurinol.

  • Frequently check rate of flow and blood return; palpate injection site for extravasation. If there is any question about patency, line should be restarted.
  • Reconstituted solutions of carmustine are clear and colorless and may be stored at 2°–8° C (36°–46° F) for 8 h protected from light.
  • Store unopened vials at 2°–8° C (36°–46° F), protected from light, unless otherwise directed by manufacturer.
  • Signs of decomposition of carmustine in unopened vial: liquefaction and appearance of oil film at bottom of vial. Discard drug in this condition.

Adverse Effects (≥1%)

Hematologic: Delayed myelosuppression (dose-related); thrombocytopenia. CNS: Dizziness, ataxia. Respiratory: Pulmonary infiltration or fibrosis. Skin: Skin flushing and burning pain at injection site, hyperpigmentation of skin (from contact). Special Senses: (with high doses) Eye infarctions, retinal hemorrhage, suffusion of conjunctiva. GI: Stomatitis, nausea, vomiting.

Interactions

Drug: Cimetidine may potentiate neutropenia and thrombocytopenia.

Pharmacokinetics

Distribution: Readily crosses blood–brain barrier; CSF concentrations 15–70% of plasma concentrations. Metabolism: Rapidly metabolized. Elimination: 60–70% in urine in 96 h; 6% via lungs, 1% in feces; excreted in breast milk.

Nursing Implications

Assessment & Drug Effects

  • Frequently check rate of flow and blood return; palpate injection site for extravasation. If there is any question about patency, line should be restarted.
  • Monitor for nausea and vomiting (dose related), which may occur within 2 h after drug administration and persist for up to 6 h. Prior administration of an antiemetic may help to decrease or prevent these adverse effects.
  • Monitor for nausea and vomiting (dose related), which may occur within 2 h after drug administration and persist for up to 6 h. Prior administration of an antiemetic may help to decrease or prevent these adverse effects.
  • Lab tests: Baseline CBC with differential and platelet count, repeat blood studies following infusion at weekly intervals for at least 6 wk. Baseline and periodic tests of hepatic and renal function.
  • Platelet nadir usually occurs within 4–5 wk, and leukocyte nadir within 5–6 wk after therapy is terminated. Thrombocytopenia may be more severe than leukopenia; anemia is less severe.
  • Check temperature daily. Avoid use of rectal thermometer to prevent injury to mucosa. An elevation of 0.6° F or more above usual temperature warrants reporting.
  • Report symptoms of lung toxicity (cough, shortness of breath, fever) to the physician immediately.
  • Be alert to signs of hepatic toxicity (jaundice, dark urine, pruritus, light-colored stools) and renal insufficiency (dysuria, oliguria, hematuria, swelling of lower legs and feet).

Patient & Family Education

  • Report burning sensation immediately, as carmustine can cause burning discomfort even in the absence of extravasation. Infusion will be discontinued and restarted in another site. Ice application over the area may decrease the discomfort.
  • Intense flushing of skin may occur during IV infusion. This usually disappears in 2–4 h.
  • You will be highly susceptible to infection and to hemorrhagic disorders. Be alert to hazardous periods that occur 4–6 wk after a dose of carmustine. If possible, avoid invasive procedures (e.g., IM injections, enemas, rectal temperatures) during this period.
  • Report promptly the onset of sore throat, weakness, fever, chills, infection of any kind, or abnormal bleeding (ecchymosis, petechiae, epistaxis, bleeding gums, hematemesis, melena).

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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