CARBOPLATIN

CARBOPLATIN
(car-bo-pla'tin)
Paraplatin
Classifications: antineoplastic; alkylating agent;
Therapeutic: antineoplastic
Prototype: Cyclophosphamide
Pregnancy Category: D

Availability

50 mg, 150 mg, 450 mg vials

Action

Carboplatin is a platinum compound that is a chemotherapeutic agent. It produces interstrand DNA cross-linkages, thus interfering with DNA, RNA, and protein synthesis. Carboplatin is cell-cycle nonspecific (i.e., effective throughout the entire cell life cycle) it induces programmed cell death.

Therapeutic Effect

Full or partial activity against a variety of cancers resulting in reduction or stabilization of tumor size and useful in patients with impaired renal function, patients unable to accommodate high-volume hydration, or patients at high risk for neurotoxicity and/or ototoxicity.

Uses

Monotherapy or combination therapy for ovarian cancer.

Unlabeled Uses

Combination therapy for breast, cervical, colon, endometrial, head and neck, and lung cancer; leukemia, lymphoma, and melanoma.

Contraindications

History of severe reactions to carboplatin or other platinum compounds, severe bone marrow depression; significant bleeding; impaired renal function; pregnancy (category D), and lactation.

Cautious Use

Use with other nephrotoxic drugs; coagulapathy; previous radiation therapy; renal impairment.

Route & Dosage

Ovarian Cancer
Adult: IV 360 mg/m² once q4wk. May be repeated when neutrophil count is at least 2000 mm³ and platelet count is at least 100,000 mm³. If neutrophil and platelet counts are lower, dose of carboplatin should be reduced by 50–75% of initial dose. Alternatively, 400 mg/m² as a 24-h infusion for 2 consecutive d can be used.

Renal Impairment
Cl_cr 41–59 mL/min: dose 250 mg/m²; 16–40 mL/min: dose 200 mg/m²
Hemodialysis: Initial dose not to exceed 150 mg/m²

Administration

Intravenous

PREPARE: IV Infusion: Do not use needles or IV sets containing aluminum. Immediately before use, reconstitute with either sterile water for injection or D5W or NS as follows: 50-mg vial plus 5 mL diluent; 150-mg vial plus 15 mL diluent; 450-mg vial plus 45 mL diluent. All dilutions yield 10 mg/mL. May be further diluted to a concentration as low as 0.5 mg/mL with D5W or NS.

ADMINISTER: IV Infusion: Give IV solution over 15 min or longer, depending on total amount of solution and patient tolerance. Lengthening duration of administration may decrease nausea and vomiting.

INCOMPATIBILITIES Solution/additive: Sodium bicarbonate, fluorouracil, mesna. Y-site: Amphotericin B cholesteryl complex, lansoprazole.

Premedication with a parenteral antiemetic ? h before and on a scheduled basis thereafter is normally used.
Do not repeat doses until the neutrophil count is at least 2000/mm³ and platelet count at least 100,000/mm³.

Protect from light. Reconstituted solutions are stable for 8 h at room temperature; discard solutions 8 h after dilution.

Adverse Effects (≥1%)

Body as a Whole: Hypersensitivity reactions. GI: Mild to moderate nausea and vomiting, anorexia, hypogeusia, dysgeusia, mucositis, diarrhea, constipation, elevated liver enzymes. Hematologic: Thrombocytopenia, leukopenia, neutropenia, anemia. Metabolic: Mild hyponatremia, hypomagnesemia, hypocalcemia, and hypokalemia. CNS: Peripheral neuropathy. Skin: Rash, alopecia. Special Senses: Tinnitus. Urogenital: Nephrotoxicity.

Diagnostic Test Interference

Decreased calcium levels; mild increases in liver function tests; decreased levels of magnesium, potassium, and sodium.

Interactions

Drug: aminoglycosides may increase the risk of ototoxicity and nephrotoxicity. May decrease phenytoin levels.

Pharmacokinetics

Onset: 8 wk (2 cycles). Duration: 2–16 mo. Distribution: Highest concentration in the liver, lung, kidney, skin, and tumors. Not bound to plasma proteins. Metabolism: Hydrolyzed in the serum. Elimination: Primarily by the kidneys; 60–80% excreted in urine within 24 h. Half-Life: 3 h.

Nursing Implications

Assessment & Drug Effects

Monitor closely during first 15 min of infusion, since allergic reactions have occurred within minutes of carboplatin administration.
Lab tests: Baseline and periodic CBC with differential, platelet count, Hgb and Hct. Monitor kidney function periodically with creatinine clearance tests and serum electrolytes.
Monitor results of peripheral blood counts. Median nadir occurs at day 21. Leukopenia, neutropenia, and thrombocytopenia are dose related and may produce dose-limiting toxicity.
Monitor for peripheral neuropathy (e.g., paresthesias), ototoxicity, and visual disturbances.
Monitor serum electrolyte studies, because carboplatin has been associated with decreases in sodium, potassium, calcium, and magnesium. Special precautions may be warranted for patients on diuretic therapy.

Patient & Family Education

Learn about the range of potential adverse effects. Strategies for nausea prevention should receive special attention.
During therapy you are at risk for infection and hemorrhagic complications related to bone marrow suppression. Avoid unnecessary exposure to crowds or infected persons during the nadir period.
Report paresthesias (numbness, tingling), visual disturbances, or symptoms of ototoxicity (hearing loss and/or tinnitus).

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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