CISplatin

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation
sis-PLA-tin [Pronunciation]

Trade Name(s)

• Platinol

Indications

• Metastatic testicular and ovarian carcinoma.

• Advanced bladder cancer.

• Head and neck cancer.

• Cervical cancer.

• Lung cancer.

• Other tumors.

Action

Inhibits DNA synthesis by producing cross-linking of parent DNA strands (cell-cycle phase–nonspecific).

Therapeutic Effect(s):
Death of rapidly replicating cells, particularly malignant ones.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed; accumulates for months; enters breast milk.

Metabolism and Excretion: Excreted mainly by the kidneys.

Half-life: 30–100 hr.

TIME/ACTION PROFILE (effects on blood counts)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;

• OB: Lactation: Pregnancy or lactation.

• Hearing loss;

• Renal impairment (dosage ↓ recommended);

• HF;

• Electrolyte abnormalities;

• Active infections;

• Bone marrow depression;

• Geri: ↑ risk of nephrotoxicity and peripheral neuropathy;

• Chronic debilitating illnesses;

• Patients with childbearing potential.

Adverse Reactions/Side Effects

CNS: REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME, SEIZURES, malaise, weakness.

EENT: ototoxicity, tinnitus.

GI: severe nausea, vomiting, diarrhea, hepatotoxicity.

GU: nephrotoxicity, sterility.

Derm: alopecia.

F and E: hypocalcemia, hypokalemia, hypomagnesemia.

Hemat: LEUKOPENIA, THROMBOCYTOPENIA, anemia.

Local: phlebitis at IV site.

Metabolic: hyperuricemia.

Neuro: peripheral neuropathy.

Misc: anaphylactoid reactions.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Interactions

Drug-Drug

• ↑ risk of nephrotoxicity and ototoxicity with other nephrotoxic and ototoxic drugs (aminoglycosides, loop diuretics) .

• ↑ risk of hypokalemia and hypomagnesemia with loop diuretics and amphotericin B .

• May ↓ phenytoin levels.

• ↑ bone marrow depression with other antineoplastics or radiation therapy .

• May ↓ antibody response to live-virus vaccines and ↑ adverse reactions.

Route/Dosage

• Other regimens are used

• IV (Adults): Metastatic testicular tumors—20 mg/m² daily for 5 days repeated q 3–4 wk. Metastatic ovarian cancer—75–100 mg/m², repeat q 4 wk in combination with cyclophosphamide or 100 mg/m² q 3 wk if used as a single agent. Advanced bladder cancer—50–70 mg/m² q 3–4 wk as a single agent..

Availability

• Powder for injection: 50 mg/vial

• Injection: 1 mg/mL

Assessment

• Monitor vital signs frequently during administration. Report significant changes.

• Monitor intake and output and specific gravity frequently during therapy. Report discrepancies immediately. To reduce the risk of nephrotoxicity, maintain a urinary output of at least 100 mL/hr for 4 hr before initiating and for at least 24 hr after administration.

• Encourage patient to drink 2000–3000 mL/day to promote excretion of uric acid. Allopurinol and alkalinization of the urine may be used to help prevent uric acid nephropathy.

• Assess patency of IV site frequently during therapy. Cisplatin may cause severe irritation and necrosis of tissue if extravasation occurs. If a large amount of highly concentrated cisplatin solution extravasates, mix 4 mL of 10% sodium thiosulfate with 6 mL of sterile water or 1.6 mL of 25% sodium thiosulfate with 8.4 mL of sterile water and inject 1–4 mL (1 mL for each mL extravasated) through existing line or cannula. Inject subcut if needle has been removed. Sodium thiosulfate inactivates cisplatin.

• Severe and protracted nausea and vomiting usually occur 1–4 hr after a dose; vomiting may last for 24 hr. Administer parenteral antiemetic agents 30–45 min before therapy and routinely around the clock for the next 24 hr. Monitor amount of emesis and notify health care professional if emesis exceeds guidelines to prevent dehydration. Nausea and anorexia may persist for up to 1 wk.

• Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.

• Monitor for signs of anaphylaxis (facial edema, wheezing, dizziness, fainting, tachycardia, hypotension). Discontinue medication immediately and report symptoms. Epinephrine and resuscitation equipment should be readily available.

• Medication may cause ototoxicity and neurotoxicity. Assess patient frequently for dizziness, tinnitus, hearing loss, loss of coordination, loss of taste, or numbness and tingling of extremities; may be irreversible. Notify health care professional promptly if these occur. Audiometry should be performed before initiation of therapy and before subsequent doses. Hearing loss is more frequent with children and usually occurs first with high frequencies and may be unilateral or bilateral.

• Monitor for inadvertent cisplatin overdose. Doses >100 mg/m²/cycle once every 3–4 wk are rarely used. Differentiate daily doses from total dose/cycle. Symptoms of high cumulative doses include muscle cramps (localized, painful involuntary skeletal muscle contractions of sudden onset and short duration) and are usually associated with advanced stages of peripheral neuropathy.

• Monitor for signs of RPLS (headache, seizure, lethargy, confusion, blindness). Hypertension may or may not be present. May occur with in 16 hr to 1 yr of initiation of therapy. Treat hypertension if present and discontinue cisplatin therapy. Symptoms usually resolve within days.

• Monitor CBC with differential and platelet count before and routinely throughout therapy. The nadir of leukopenia, thrombocytopenia, and anemia occurs within 18–23 days and recovery 39 days after a dose. Withhold further doses until WBC is >4000/mm³ and platelet count is >100,000/mm³.

» Monitor BUN, serum creatinine, and CCr before initiation of therapy and before each course of cisplatin to detect nephrotoxicity. May cause ↑ BUN and creatinine and ↓ calcium, magnesium, phosphate, sodium, and potassium levels that usually occur the 2nd wk after a dose. Do not administer additional doses until BUN is <25 mg/100 mL and serum creatinine is <1.5 mg/100 mL. May cause ↑ uric acid level, which usually peaks 3–5 days after a dose.

» May cause transiently ↑ serum bilirubin and AST concentrations.

» May cause positive Coombs' test result.

Potential Nursing Diagnoses

• Risk for infection (Adverse Reaction)

• Risk for injury (Side Effects)

Implementation

• High Alert: Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations, and infusion pump settings.

» Do not confuse cisplatin with carboplatin. To prevent confusion, orders should include generic and brand names. Administer under the supervision of a physician experienced in the use of cancer chemotherapeutic agents.

• Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. If powder or solution comes in contact with skin or mucosa, wash thoroughly with soap and water. Discard equipment in specially designated containers (see Recommendations for the Safe Handling of Hazardous Drugs).

» Hydrate patient with at least 1–2 L of IV fluid 8–12 hr before initiating therapy with cisplatin. Amifostine may be administered to minimize nephrotoxicity.

» Do not use aluminum needles or equipment during preparation or administration. Aluminum reacts with this drug, forms a black or brown precipitate, and renders the drug ineffective.

» Unopened vials of powder and constituted solution must not be refrigerated.

• pH:
3.5–4.5.

• Intermittent Infusion:
Reconstitute 50-mg vial with 50 mL. Stable for 20 hr if reconstituted with sterile water, for 72 hr with bacteriostatic water. Do not refrigerate, because crystals will form. Solution should be clear and colorless; discard if turbid or if it contains precipitates.
Diluent: Dilution in 2 L of 5% dextrose in 0.3% or 0.45% NaCl containing 37.5 g of mannitol is recommended.
Concentration: Keep under 0.5 mg/mL to prevent tissue necrosis.

• Rate:
Variable. Maximum rate 1 mg/min.

• Continuous Infusion:
Has been administered as continuous infusion over 24 hr to 5 days with resultant decrease in nausea and vomiting. High Alert: Clarify dose to ensure cumulative dosage is not confused with daily dose; errors may be fatal.

• Y-Site Compatibility:

» acyclovir

» alfentanil

» allopurinol

» amikacin

» aminophylline

» amiodarone

» ampicillin

» ampicillin/sulbactam

» anidulafungin

» argatroban

» atracurium

» azithromycin

» aztreonam

» bivalirudin

» bleomycin

» bumetanide

» buprenorphine

» butorphanol

» calcium chloride

» calcium gluconate

» carmustine

» caspofungin

» cefazolin

» cefoperazone

» cefotaxime

» cefotetan

» cefoxitin

» ceftazidime

» ceftriaxone

» cefuroxime

» chlorpromazine

» ciprofloxacin

» cisatracurium

» cladribine

» clindamycin

» cyclophosphamide

» cyclosporine

» cytarabine

» dactinomycin

» daptomycin

» daunorubicin hydrochloride

» dexamethasone

» dexmedetomidine

» dexrazoxane

» digoxin

» diltiazem

» diphenhydramine

» dobutamine

» docetaxel

» dopamine

» doripenem

» doxacurium

» doxorubicin

» doxorubicin liposome

» doxycycline

» droperidol

» enalaprilat

» ephedrine

» epinephrine

» epirubicin

» ertapenem

» erythromycin

» esmolol

» etoposide

» etoposide phosphate

» famotidine

» fenoldopam

» fentanyl

» filgrastim

» fluconazole

» fludarabine

» fluorouracil

» foscarnet

» fosphenytoin

» furosemide

» ganciclovir

» gemcitabine

» gentamicin

» glycopyrrolate

» granisetron

» haloperidol

» heparin

» hetastarch

» hydrocortisone

» hydromorphone

» idarubicin

» ifosfamide

» imipenem/cilastatin

» indomethacin

» irinotecan

» isoproterenol

» ketorolac

» labetalol

» leucovorin calcium

» levofloxacin

» levorphanol

» lidocaine

» linezolid

» lorazepam

» magnesium sulfate

» mannitol

» melphalan

» meperidine

» meropenem

» methohexital

» methotrexate

» methylprednisolone

» metoclopramide

» metoprolol

» metronidazole

» midazolam

» milrinone

» mitomycin

» mitoxantrone

» mivacurium

» nafcillin

» naloxone

» nesiritide

» nicardipine

» nitroglycerin

» nitroprusside

» norepinephrine

» octreotide

» ondansetron

» oxaliplatin

» paclitaxel

» palonosetron

» pamidronate

» pancuronium

» pemetrexed

» pentamidine

» pentazocine

» pentobarbital

» phenobarbital

» phenylephrine

» phenytoin

» potassium acetate

» potassium chloride

» potassium phosphates

» procainamide

» prochlorperazine

» promethazine

» propofol

» propranolol

» quinupristin/dalfopristin

» ranitidine

» remifentanil

» rituximab

» sargramostim

» sodium acetate

» sodium bicarbonate

» sodium phosphates

» succinylcholine

» sufentanil

» tacrolimus

» teniposide

» theophylline

» thiopental

» ticarcillin/clavulanate

» tigecycline

» tirofiban

» tobramycin

» topotecan

» trastuzumab

» vancomycin

» vasopressin

» vecuronium

» verapamil

» vinblastine

» vincristine

» vinorelbine

» voriconazole

» zidovudine

» zolendronic acid

• Y-Site Incompatibility:

» amifostine

» amphotericin B cholesteryl sulfate

» amphotericin B colloidal

» amphotericin B lipid complex

» amphotericin B liposome

» cefepime

» dantrolene

» diazepam

» insulin

» pantoprazole

» piperacillin/tazobactam

» thiotepa

Patient/Family Teaching

• Instruct patient to report pain at injection site immediately.

• Instruct patient to notify health care professional promptly if fever; chills; cough; hoarseness; sore throat; signs of infection; lower back or side pain; painful or difficult urination; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; increased fatigue; dyspnea; or orthostatic hypotension occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs; may precipitate gastric bleeding.

• Instruct patient to report promptly any numbness or tingling in extremities or face, difficulty with hearing or tinnitus, unusual swelling, or joint pain.

• Instruct patient not to receive any vaccinations without advice of health care professional.

• Advise patient of the need for contraception, although cisplatin may cause infertility.

• Emphasize the need for periodic lab tests to monitor for side effects.

Evaluation/Desired Outcomes

Decrease in size or spread of malignancies. Therapy should not be administered more frequently than every 3–4 wk, and only if lab values are within acceptable parameters and patient is not exhibiting signs of ototoxicity or other serious adverse effects.