Carboplatin

Pronunciation

Pronunciation: car-boe-PLATT-in
Class: Platinum coordination complex

Trade Names

Carboplatin
- Injection 10 mg/mL

Paraplatin
- Lyophilized powder for injection 50 mg vial
- Lyophilized powder for injection 150 mg vial
- Lyophilized powder for injection 450 mg vial

Paraplatin-AQ (Canada)

Pharmacology

Platinum coordination compound that produces predominantly interstrand DNA cross-links causing equivalent lesions and biological effects.

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Pharmacokinetics

Distribution

Carboplatin is not protein bound; platinum from carboplatin is irreversibly protein bound. Vd is 16 L.

Metabolism

Aquated to produce the active species.

Elimination

Initial t ½ is 1.1 to 2 h. Postdistribution t ½ is 2.6 to 5.9 h. Cl is 4.4 L/h. 71% is excreted in the urine in 24 h.

Special Populations

Renal Function Impairment

In those with Ccr less than 60 mL/min, the total body and renal Cl decreases as the Ccr decreases. Dosage reduction is recommended.

Indications and Usage

Adults

Initial treatment of advanced ovarian carcinoma in combination with other chemotherapy agents. Secondary treatment for palliative treatment of patients with ovarian carcinoma recurrent after prior chemotherapy.

Unlabeled Uses

Small cell and non-small cell lung, head, neck, and testicular cancer.

Contraindications

History of severe allergic reactions to cisplatin or other platinum compounds or mannitol; severe bone marrow depression; significant bleeding.

Dosage and Administration

Ovarian Carcinoma (Single-Agent Therapy)
Adults

IV 360 mg/m 2 on day 1 every  4 wk if neutrophil count is at least 2,000/mm 3 and platelet count is at least 100,000/mm 3 .

Ovarian Carcinoma (Combination Therapy with Cyclophosphamide)
Adults

IV Carboplatin 300 mg/m 2 plus cyclophosphamide 600 mg/m 2 , both on day 1 every 4 wk for 6 cycles. Do not repeat intermittent courses of the combination until the neutrophil count is at least 2,000/mm 3 and the platelet count is at least 100,000/mm 3 .

Calvert Formula Dosing
Adults

IV Carboplatin may be dosed to achieve a target AUC based on the patient's glomerular filtration rate (GFR) using the Calvert formula. The desired target AUC depends on the disease and the patient's treatment status. The Calvert formula calculates the carboplatin dose in mg as follows: Total dose (mg) = target AUC (mg/mL•min) × (GFR [mL/min] + 25).

Dosage Adjustments Based on Lowest Posttreatment Blood Counts
Adults

IV If platelets above 100,000/mm 3 and neutrophils above 2,000/mm 3 , then give 125% of adjusted dose from prior course. If platelets are 50,000 to 100,000/mm 3 and neutrophils are 500 to 2,000/mm 3 , no dosage adjustment is necessary. If platelets below 50,000/mm 3 and neutrophils below 500/mm 3 , then give 75% of adjusted dose from prior course. Doses above 125% of the starting dose are not recommended.

Renal Function Impairment (Dosage Adjustment)
Adults

IV Baseline Ccr is 41 to 59 mL/min, the recommended dose on day 1 is 250 mg/m 2 ; 16 to 40 mL/min is 200 mg/m 2 ; below 15 mL/min, data too limited to permit a recommendation for treatment.

General Advice

  • Diligently follow institutional and NIH procedures for handling, administration, and disposal of anticancer drugs. Wear appropriate protective equipment when preparing and administering carboplatin.
  • Do not use needles or IV administration sets containing aluminum parts that could come in contact with carboplatin during preparation or administration. Aluminum can react with carboplatin, causing precipitation and loss of potency.
  • Reconstitute powder for injection with sterile water for injection, dextrose 5% in water, or sodium chloride 0.9% injection. Add 5 mL of diluent to 50 mg vial, 15 mL of diluent to 150 mg vial, or 45 mL of diluent to 450 mg vial to produce solution with a final concentration of 10 mg/mL.
  • Reconstituted solution, or premixed aqueous solution, may be further diluted with dextrose 5% in water or sodium chloride 0.9% injection.
  • Do not administer if discoloration, particulate matter, or cloudiness is noted.
  • Administer prescribed dose by IV infusion over at least 15 minutes. Infusion may be lengthened to 24 h, or total dose given as 5 consecutive daily pulse doses, for patient who experiences significant emesis.
  • Administer antiemetic as prescribed before administering carboplatin.

Storage/Stability

Store aqueous solution and powder for injection at controlled room temperature (59° to 86°F). Protect from light. Reconstituted solution is stable for 8 h at controlled room temperature (77°F). Reconstituted solution does not contain a preservative and any unused solution must be discarded 8 h after reconstitution. Do not save any unused solution for future use. Carboplatin aqueous solution multidose vials are stable at room temperature (77°F) for up to 14 days following initial needle entry.

Drug Interactions

Aminoglycosides

Concomitant use may increase risk of nephrotoxicity or ototoxicity.

Phenytoin

Serum concentrations may be decreased, resulting in a loss of therapeutic effect.

Laboratory Test Interactions

Abnormal LFTs; alkaline phosphatase; AST; total bilirubin.

Adverse Reactions

Percentages are for carboplatin single agent therapy.

Cardiovascular

CV events (11%); fatal CV events including cardiac failure, embolism, cerebrovascular accidents (less than 1%); hypertension (postmarketing).

CNS

Asthenia (23%); peripheral neuropathies including mild paresthesias (6%); central neurotoxicity (5%); ototoxicity (1%); malaise (postmarketing).

Dermatologic

Alopecia (3%).

EENT

Reversible vision loss.

Electrolytes

Sodium loss (47%); magnesium loss (43%); calcium loss (31%); potassium loss (28%).

GI

Nausea and vomiting (92%); vomiting (81%); other GI side effects (21%); anorexia (postmarketing).

Genitourinary

Elevated BUN (22%); elevated serum creatinine (10%).

Hepatic

Elevated alkaline phosphatase (37%); elevated AST (19%); elevated bilirubin (5%).

Hematologic-Lymphatic

Anemia (90%); leukopenia (85%); neutropenia (67%); thrombocytopenia (62%); infections, bleeding (5%).

Hypersensitivity

Allergic reaction (2%).

Local

Pain, redness, swelling (postmarketing).

Respiratory

Respiratory (6%).

Miscellaneous

Pain (23%); mucositis (1%).

Precautions

Warnings

Anemia

May be cumulative and transfusions required.

Bone marrow suppression

Leukopenia, neutropenia, and thrombocytopenia are dose dependent and are the dose-limiting toxicities; they may result in infection or bleeding.

Emesis

Vomiting is another frequent drug-related side-effect and usually ceases within 24 h of treatment. The incidence and intensity of emesis have been reduced by antiemetic premedication.

Hypersensitivity

Anaphylactic-like reactions may occur within minutes of administration. Epinephrine, corticosteroids, and antihistamines may alleviate symptoms.


Monitor

CBC

Ensure CBC with differential and platelet count are monitored frequently (at least weekly) during treatment and, when appropriate, until recovery is achieved. Ensure that carboplatin dose is adjusted based on lowest posttreatment platelet or neutrophil value following manufacturer's guidelines.

Electrolytes

Ensure electrolytes are evaluated before starting therapy and periodically thereafter during prolonged treatment. Be prepared to treat abnormalities if clinically indicated.

Infection/Bleeding

Monitor patient for signs or symptoms of infection or bleeding. Inform health care provider immediately if noted and be prepared to treat appropriately (eg, IV antibiotics, colony stimulating factors, transfusions).


Pregnancy

Category D .

Lactation

Undetermined. Because of possibility of toxicity in breast-feeding infants, discontinue breast-feeding.

Children

Safety and efficacy not established.

Renal Function

Patients with impaired kidney function (Ccr below 60 mL/min) are at increased risk of severe bone marrow suppression.

Peripheral neurotoxicity

Infrequent, but its incidence is increased in patients older than 65 yr of age and in patients previously treated with cisplatin.

Renal toxicity

Limited, but cotreatment with aminoglycosides has resulted in increased renal or audiologic toxicity. Exercise caution when patient receives both drugs.

Overdosage

Symptoms

Bone marrow suppression, hepatic toxicity.

Patient Information

  • Review the treatment regimen including dosing schedule, duration of treatment, and monitoring that will be required.
  • Advise patient, family, or caregiver that medication will be prepared and administered by health care providers in a health care setting.
  • Advise patient, family, or caregiver that medication may be used in combination with other agents to achieve max benefit possible.
  • Advise patient, family, or caregiver that medication may cause hair loss but that this is reversible when therapy is stopped.
  • Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; hives; difficulty breathing or unexplained shortness of breath; fever, chills, or other signs of infection; sores in mouth; loss of vision; pain, redness, or swelling at injection site.
  • Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting, or appetite loss; persistent or worsening general body weakness; changes in hearing or ringing in the ears; abnormal skin sensations; any other unexplained sensation.
  • Caution female patient of childbearing potential to avoid becoming pregnant during therapy.

Copyright © 2009 Wolters Kluwer Health.

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