CISPLATIN (CIS-DDP, CIS-PLATINUM II)

CISPLATIN (cis-DDP, cis-PLATINUM II)
(sis'pla-tin)
Abiplatin , Platinol
Classifications: antineoplastic; alkylating agent;
Therapeutic: antineoplastic
; alkylating agent
Prototype: Cyclophosphamide
Pregnancy Category: D

Availability

1 mg/mL injection

Action

A heavy metal complex with platinum as central atom surrounded by 2 chloride atoms and 2 ammonia molecules in the cis chemical position. Biochemical properties similar to those of other alkylating agents. Produces interstrand and intrastrand cross linkage in DNA of rapidly dividing cells, thus preventing DNA, RNA, and protein synthesis.

Therapeutic Effect

Cell cycle-nonspecific (i.e., effective throughout the entire cell life cycle).

Uses

Established combination therapy (cisplatin, vinblastine, bleomycin) in patient with metastatic testicular tumors and with doxorubicin for metastatic ovarian tumors following appropriate surgical or radiation therapy.

Unlabeled Uses

Carcinoma of endometrium, bladder, head, and neck.

Contraindications

History of hypersensitivity to cisplatin or other platinum-containing compounds; impaired renal function; severe myelosuppression; impaired hearing; active infection; history of gout and urate renal stones, renal failure; hypomagnesia; concurrent administration with loop diuretics; Raynaud syndrome; pregnancy (category D). Safe use in children not established, although experimental regimens have been used.

Cautious Use

Previous cytotoxic drug or radiation therapy with other ototoxic and nephrotoxic drugs; peripheral neuropathy; hyperuricemia; electrolyte imbalances, moderate renal impairment; hepatic impairment; history of circulatory disorders.

Route & Dosage

Testicular Neoplasms
Adult: IV 20 mg/m2/d for 5 d q3–4wk for 3 courses

Ovarian Neoplasms
Adult: IV With cyclophosphamide: 75–100 mg/m2 once q4wk; Single agent: 100 mg/m2 once q4wk

Advanced Bladder Cancer
Adult: IV 50–75 mg/m2 q3–4 wk

Administration

  • Administered only under supervision of a qualified physician experienced in the use of antineoplastics.
  • Usually a parenteral antiemetic agent is administered ? h before cisplatin therapy is instituted and given on a scheduled basis throughout day and night as long as necessary.
  • Before the initial dose is given, hydration is started with 1–2 L IV infusion fluid to reduce risk of nephrotoxicity and ototoxicity.
Intravenous

PREPARE: IV Infusion: Use disposable gloves when preparing cisplatin solutions. If drug accidentally contacts skin or mucosa, wash immediately and thoroughly with soap and water. Do not use any equipment containing aluminum. Withdraw required dose and dilute in 2 L D5W 5% dextrose in ? or 1/3 normal saline containing 37.5 g mannitol.  

ADMINISTER: IV Infusion: Give 2 L over 6–8 h  

INCOMPATIBILITIES Solution/additive: 5% dextrose, fluorouracil, mesna, metoclopramide, sodium bicarbonate, thiotepa. Y-site: Amifostine, amphotericin B, cholesteryl, cefepime, lansoprazole, piperacillin/tazobactam, thiotepa, TPN.

  • Hydration and forced diuresis are continued for at least 24 h after drug administration to ensure adequate urinary output.
  • Store at 15°–30° C (59°–86° F). Do not refrigerate. Protect from light. Once vial is opened, solution is stable for 28 d protected from light or 7 d in fluorescent light.

Adverse Effects (≥1%)

Body as a Whole: Anaphylactic-like reactions. CV: Cardiac abnormalities. GI: Marked nausea, vomiting, anorexia, stomatitis, xerostomia, diarrhea, constipation. Hematologic: Myelosuppression (25–30% patients): leukopenia, thrombocytopenia; hemolytic anemia, hemolysis. Metabolic: Hypocalcemia, hypomagnesemia, hyperuricemia, elevated AST, SIADH. CNS: Seizures, headache; peripheral neuropathies (may be irreversible): paresthesia, unsteady gait, clumsiness of hands and feet, exacerbation of neuropathy with exercise, loss of taste. Special Senses: Ototoxicity (may be irreversible): tinnitus, hearing loss, deafness, vertigo, blurred vision, changes in ability to see colors (optic neuritis, papilledema). Urogenital: Nephrotoxicity.

Interactions

Drug: aminoglycosides, amphotericin B, vancomycin, other nephrotoxic drugs increase nephrotoxicity and acute renal failure—try to separate by at least 1–2 wk; aminoglycosides, furosemide increase risk of ototoxicity.

Pharmacokinetics

Peak: Immediately after infusion. Distribution: Widely distributed in body fluids and tissues; concentrated in kidneys, liver, and prostate; accumulated in tissues. Metabolism: Not known. Elimination: 15–50% in urine within 24–48 h. Half-Life: 73–290 h.

Nursing Implications

Assessment & Drug Effects

  • Obtain baseline ECG and cardiac monitoring during induction therapy because of possible myocarditis or focal irritability.
  • Lab tests: The following tests should be done before initiating every course of therapy and repeated each week during treatment period: serum uric acid, serum creatinine, BUN, urinary creatinine clearance. CBC and platelet counts are done weekly for 2 wk after each course of treatment. Monitor periodically serum electrolytes and liver function tests.
  • A repeat course of therapy should not be given until (1) serum creatinine is below 1.5 mg/dL; (2) BUN is below 25 mg/dL; (3) platelets ≥100,000/mm3; (4) WBC ≥4000/mm3; (5) audiometric test is within normal limits.
  • Monitor urine output and specific gravity for 4 consecutive hours before treatment and for 24 h after therapy. Report if output is less than 100 mL/h or if specific gravity is more than 1.030. A urine output of less than 75 mL/h necessitates medical intervention to avert a renal emergency.
  • Audiometric testing should be performed before the first dose and before each subsequent dose. Ototoxicity (reported in 31% of patients) may occur after a single dose of 50 mg/m2. Children who receive repeated doses are especially susceptible.
  • Monitor for anaphylactoid reactions (particularly in patient previously exposed to cisplatin), which may occur within minutes of drug administration.
  • Monitor closely for dose-related adverse reactions. Drug action is cumulative; therefore severity of most adverse effects increases with repeated doses.
  • Nephrotoxicity (reported in 28–36% of patients receiving a single dose of 50 mg/m2) usually occurs within 2 wk after drug administration and becomes more severe and prolonged with repeated courses of cisplatin.
  • Suspect ototoxicity if patient manifests tinnitus or difficulty hearing in the high frequency range.
  • Intractable nausea and vomiting severe enough to warrant discontinuation of drug usually begin 1–4 h after treatment and may last 24 h or persist for up to 1 wk after treatment is ended.
  • Monitor and report abnormal electrolyte levels: sodium >145 or <135 mEq/L, and potassium >5 or <3.5 mEq/L.
  • Monitor results of blood studies. The nadirs in platelet and leukocyte counts occur between day 18 and 23 (range: 7.5–45) with most patients recovering in 13–62 d. A decrease in Hgb (more than 2 g/dL) occurs at approximately the same time and with the same frequency.
  • Check BP, mental status, pupils, and fundi every hour during therapy. Hydration and mannitol may increase the danger of elevated intracranial pressure (ICP).
  • Neurologic examinations at regular intervals should include tests of muscle strength, Romberg, vibratory and position sense, tests of sensation.
  • Monitor and report abnormal bowel elimination pattern. Constipation and the possibility of fecal impaction may be caused by neurotoxicity; diarrhea is a possible response to GI irritation.
  • Inspect oral membranes for xerostomia (white patches and ulcerations) and tongue for signs of fungal overgrowth (black, furry appearance).
  • Institute infection precautions promptly if a temperature increase of 0.6° F over the previous reading is noted.
  • Weigh the patient under standard conditions every day. A gradual ascending weight profile occurring over a period of several days should be reported.

Patient & Family Education

  • Continue maintenance of adequate hydration (at least 3000 mL/24 h oral fluid if physician agrees) and report promptly: reduced urinary output, flank pain, anorexia, nausea, vomiting, dry mucosae, itching skin, urine odor on breath, fluid retention, and weight gain.
  • Avoid rapid changes in position to minimize risk of dizziness or falling.
  • Tingling, numbness, and tremors of extremities, loss of position sense and taste, and constipation are early signs of neurotoxicity. Report their occurrence promptly to prevent irreversibility. Pain with heel walking and difficulty in getting out of bed or chair are late indicators of nerve damage.
  • Report tinnitus or any hearing impairment.
  • Report promptly evidence of unexplained bleeding and easy bruising.
  • Report unusual fatigue, fever, sore mouth and throat, abnormal body discharges.

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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