Paraplatin


Paraplatin

 [par″ah-pla´tin] trademark for a preparation of carboplatin, an antineoplastic agent.

CARBOplatin

(kar-boe-pla-tin) carboplatin,

Paraplatin

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: alkylating agents
Pregnancy Category: D

Indications

Advanced ovarian carcinoma (with other agents).Palliative treatment of ovarian carcinoma unresponsive to other modalities.

Action

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

Therapeutic effects

Death of rapidly replicating cells, particularly malignant ones.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.Distribution: Unknown.Protein Binding: Platinum is irreversibly bound to plasma proteins.Metabolism and Excretion: Excreted mostly by the kidneys.Half-life: Carboplatin—2.6–5.9 hr (increased in renal impairment); platinum—5 days.

Time/action profile (effects on blood counts)

ROUTEONSETPEAKDURATION
IVunknown21 days28 days

Contraindications/Precautions

Contraindicated in: Hypersensitivity to carboplatin, cisplatin, or mannitol; Obstetric / Lactation: Pregnancy or lactation.Use Cautiously in: Hearing loss;Electrolyte abnormalities;Renal impairment (dose ↓ recommended if CCr <60 mL/min);Active infections;Diminished bone marrow reserve (dose ↓ recommended);Other chronic debilitating illnesses; Geriatric: ↑ risk of thrombocytopenia, consider renal function in dose determination;Patients with childbearing potential; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • weakness

Ear, Eye, Nose, Throat

  • ototoxicity

Gastrointestinal

  • abdominal pain (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • constipation
  • diarrhea
  • hepatitis
  • stomatitis

Genitourinary

  • gonadal suppression
  • nephrotoxicity

Dermatologic

  • alopecia
  • rash

Fluid and Electrolyte

  • hypocalcemia (most frequent)
  • hypokalemia (most frequent)
  • hypomagnesemia (most frequent)
  • hyponatremia (most frequent)

Hematologic

  • anemia (life-threatening)
  • leukopenia (life-threatening)
  • thrombocytopenia (life-threatening)

Metabolic

  • hyperuricemia

Neurologic

  • peripheral neuropathy

Miscellaneous

  • hypersensitivity reactions including anaphylactic-like reactions (life-threatening)

Interactions

Drug-Drug interaction

↑ nephrotoxicity and ototoxicity with other nephrotoxic and ototoxic drugs (aminoglycosides, loop diuretics).↑ bone marrow depression with other bone marrow–depressing drugs or radiation therapy.May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.

Route/Dosage

Other dosing formulas are usedIntravenous (Adults) Initial treatment—300 mg/m2 with cyclophosphamide at 4-wk intervals. Treatment of refractory tumors—360 mg/m2 as a single dose; may be repeated at 4-wk intervals, depending on response.

Renal Impairment

Intravenous (Adults) CCr 41–59 mL/min—initial dose 250 mg/m2; CCr 16–40 mL/min—initial dose 200 mg/m2.

Availability (generic available)

Solution for injection: 10 mg/mL

Nursing implications

Nursing assessment

  • Assess for nausea and vomiting; often occur 6–12 hr after therapy (1–4 hr for aqueous solution) and may persist for 24 hr. Prophylactic antiemetics may be used. Adjust diet as tolerated to maintain fluid and electrolyte balance and ensure adequate nutritional intake. May require discontinuation of therapy.
  • Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and 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 and may be cumulative; transfusions are frequently required. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
  • Monitor for signs of anaphylaxis (rash, urticaria, pruritus, facial swelling, wheezing, tachycardia, hypotension). Discontinue medication immediately and notify physician if these occur. Epinephrine and resuscitation equipment should be readily available.
  • Audiometry is recommended before initiation of therapy and subsequent doses. Ototoxicity manifests as tinnitus and unilateral or bilateral hearing loss in high frequencies and becomes more frequent and severe with repeated doses. Ototoxicity is more pronounced in children.
  • Lab Test Considerations: Monitor CBC, differential, and clotting studies before and weekly during therapy. The nadirs of thrombocytopenia and leukopenia occur after 21 days and recover by 30 days after a dose. Nadir of granulocyte counts usually occurs after 21–28 days and recovers by day 35. Withhold subsequent doses until neutrophil count is >2000/mm3 and platelet count is >100,000/mm3.
    • Monitor renal function and serum electrolytes before initiation of therapy and before each course of carboplatin.
    • Monitor hepatic function before and periodically during therapy. May cause ↑ serum bilirubin, alkaline phosphatase, and AST concentrations.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)
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.
    • high alert: Do not confuse carboplatin with cisplatin. Do not confuse Paraplatin (carboplatin) with Platinol (cisplatin).
    • high alert: Carboplatin should be administered in a monitored setting under the supervision of a physician experienced in cancer chemotherapy.
  • Intravenous Administration
  • pH: 5.0–7.0.
  • Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in specially designated containers.
    • Do not use aluminum needles or equipment during preparation or administration; aluminum reacts with the drug.
  • Intermittent Infusion: Concentration: 0.5 mg/mL. Stable for 8 hr at room temperature.
  • Rate: Infuse over 15–60 min.
  • Y-Site Compatibility: acyclovir, alfentanil, amifostine, amikacin, aminocaproic acid, aminophylline, amiodarone, amphotericin B colloidal, amphotericin B lipid complex, amphotericin B liposome, ampicillin, ampicillin/sulbactam, anidulafungin, argatroban, atracurium, azithromycin, aztreonam, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium acetate, calcium chloride, calcium gluconate, caspofungin, cefazolin, cefepime, cefoperazone, defotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, chloramphenicol, chlorpromazine, ciprofloxacin, cisatracurium, cisplatin, clindamycin, cyclophosphamide, cyclosporine, cytarabine, daptomycin, dexamethasone, dexmedetomidine, dextrazoxane, digoxin, diltiazem, diphenhydramine, decetaxel, dopamine, doxacurium, doxorubicin hydrochloride, doxycycline, droperidol, enelaprilat, ephedrine, ertapenem, erythromycin, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, filgrastim, fluconazole, fludarabine, fluorouracil, foscarnet, fosphenytoin, furosemide, gemcitabine, gentamicin, glycopyrrolate, granisetron, haloperidol, heparin, hetastarch, hydralazine, hydrocortisone, hydromorphone, imipenem/cilastatin, insulin, isoproterenol, ketorolac, labetalol, leucovorin, levofloxacin, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, melphalan, meperidine, meropenem, mesna, metaraminol, methotrexate, methyldopate, methylprednisolone, metoprolol, metronidazole, midazolam, milrinone, mintxantrone, morphine, nafcillin, nalbuphone, naloxone, nesiritide, nicardipine, nitroglycerine, nitroprusside, norepinephrine, octreotide, ondansetron, paclitaxel, palonosetron, pamidronate, pancuronium, pantoprazole, pemetrexed, pentamidine, pentazocine, pentobarbital, phenylephrine, piperacillin/tazobactam, potassium acetate, potassium chloride, potassium phosphates, prochlorperazine, propranolol, quinupristin/dalfopristin, ranitidine, remifentanil, rituximab, rocuronium, sargramostim, sodium acetate, sodium bicarbonate, sodium phosphates, succinylcholine, sufentanil, tacrolimus, teniposide, theophylline, thiotepa, ticarcillin/clavulanate, tigecycline, tirofiban, tobramycin, trastuzumab, trimethoprim/sulfamethoxazole, vancomycin, vecuronium, verapamil, vincristine, vinorelbine, voriconizole, zidovudine, zoledronic acid
  • Y-Site Incompatibility: allopurinol, dantrolene, diazepam, dobutamine, epinephrine, metoclopramide, phenobarbital, phentolamine, phenytoin, procainamide, promethazine, thiopental

Patient/Family Teaching

  • Instruct patient to notify health care professional promptly if fever; chills; sore throat; signs of infection; lower back or side pain; difficult or painful urination; bleeding gums; bruising; pinpoint red spots on skin; 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 patients not to drink alcoholic beverages or take medication containing aspirin or NSAIDs because they may precipitate gastric bleeding.
  • Instruct patient to promptly report any numbness or tingling in extremities or face, decreased coordination, difficulty with hearing or ringing in the ears, unusual swelling, or weight gain to health care professional.
  • Instruct patient not to receive any vaccinations without advice of health care professional and to avoid contact with persons who have received oral polio vaccine within the past several months.
  • Advise patient of the need for contraception (if patient is not infertile as a result of surgical or radiation therapy).
  • Instruct patient to inspect oral mucosa for erythema and ulceration. If ulceration occurs, advise patient to notify health care professional, rinse mouth with water after eating, and use sponge brush. Mouth pain may require treatment with opioids.
  • Discuss with patient the possibility of hair loss. Explore methods of coping.
  • Emphasize the need for periodic lab tests to monitor for side effects.

Evaluation/Desired Outcomes

  • Decrease in size or spread of ovarian carcinoma.

carboplatin

A chemotherapeutic agent used to manage advanced ovarian, lung, head and neck and other cancers; it interacts with DNA in a manner similar to that of alkylating agents.
Adverse effects
Myelosuppression, nausea, vomiting diarrhoea, hair loss, pain, neurologic complaints.