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Cisplatin

Class: Antineoplastic Agents
- Platinum-containing Agents
VA Class: AN900
Chemical Name: (SP-4-2)-Diamminedichloroplatinum
Molecular Formula: Cl2H6N2Pt
CAS Number: 15663-27-1
Brands: Platinol-AQ

Medically reviewed by Drugs.com on July 17, 2020. Written by ASHP.

Warning

    Experience of Supervising Clinician
  • Use under supervision of a qualified clinician experienced in therapy with antineoplastic agents. Use only when adequate treatment facilities for appropriate management of therapy and complications are available.

    Dose-Related Toxicities
  • Risk of dose-related toxicities, including myelosuppression, nausea, vomiting, and cumulative, severe renal toxicity. Dosages >100 mg/m2/cycle once every 3–4 weeks rarely used.

    Ototoxicity
  • Risk of ototoxicity; more pronounced in children. Manifestations include tinnitus, loss of high frequency hearing, decreased hearing acuity, and, occasionally, deafness.

    Anaphylaxis
  • Risk of anaphylactoid reactions (e.g., facial edema, bronchoconstriction, wheezing, tachycardia, hypotension); may occur within minutes following administration. (See Anaphylactoid Reactions under Cautions.) IV epinephrine, corticosteroids, and antihistamines have been effectively employed to alleviate symptoms.

    Potential Medication Errors
  • Avoid accidental, potentially fatal, overdosage due to confusion with carboplatin (Paraplatin) or due to failure to differentiate daily dosages from total dosage per cycle. Cisplatin dosages >100 mg/m2/cycle once every 3–4 weeks rarely used.

Introduction

Antineoplastic agent; platinum-containing compound.

Uses for Cisplatin

Testicular Cancer

Adjunct to other antineoplastic agents for the treatment of metastatic testicular tumors (including nonseminomatous testicular carcinoma, seminoma testis, and extragonadal germ-cell tumors) in patients who have already received appropriate surgery and/or radiation therapy.

For induction of remissions, a regimen of cisplatin, bleomycin, and vinblastine (with or without other antineoplastic agents) has been used.

For treatment of disseminated disease, a regimen of cisplatin, bleomycin, and etoposide has been used.

Regimen consisting of cisplatin, ifosfamide with mesna, and either vinblastine or etoposide considered standard initial salvage (i.e., second-line) regimen in patients with recurrent disease.

Ovarian Cancer

Used alone or in combination therapy for the treatment of ovarian cancer.

Platinum-based therapy has been used for adjuvant treatment following surgery in early-stage ovarian epithelial cancer.

For initial (first-line) treatment of advanced ovarian epithelial cancer, combination chemotherapy with a platinum-containing agent (e.g., cisplatin, carboplatin) and paclitaxel currently is preferred regimen. Carboplatin is as effective as but less toxic than cisplatin when used in combination with either paclitaxel or cyclophosphamide; therefore, carboplatin in combination with paclitaxel currently is a preferred regimen for initial treatment of advanced ovarian epithelial cancer. Regimen consisting of cisplatin and paclitaxel is superior to regimen consisting of cisplatin and cyclophosphamide.

Combined therapy with IV paclitaxel, intraperitoneal cisplatin, and intraperitoneal paclitaxel is recommended (accepted) for the initial adjuvant treatment of optimally debulked stage III epithelial ovarian cancer in patients with good performance status (Gynecologic Oncology Group [GOG] performance status of 0–2).

Second-line therapy for the treatment of advanced epithelial ovarian cancer when retreatment is indicated in patients with platinum-sensitive disease who relapse. However, carboplatin monotherapy preferred to cisplatin monotherapy by some clinicians due to its more favorable toxicity profile. Nonplatinum-based monotherapy regimens (e.g., paclitaxel) generally preferred for retreatment of platinum-resistant disease.

For the adjuvant therapy of ovarian germ-cell tumors, combination chemotherapy with cisplatin, bleomycin, and etoposide currently is regimen of choice.

Bladder Cancer

Used alone or in combination therapy for the treatment of muscle-invasive and advanced bladder cancer that is no longer amenable to surgery and/or radiation therapy.

For adjuvant treatment of muscle-invasive bladder cancer, regimens consisting of cisplatin, methotrexate, and vinblastine with or without doxorubicin (abbreviated as M-VAC or CMV, respectively) currently is used.

For palliative treatment of advanced or metastatic bladder cancer, M-VAC, CMV, or, alternatively, a regimen consisting of cisplatin and gemcitabine currently is used.

Head and Neck Cancer

Used in combination with docetaxel and fluorouracil as induction therapy prior to radiotherapy or chemoradiotherapy in the treatment of locally advanced squamous cell carcinoma of the head and neck.

Adjunct to fluorouracil or paclitaxel for the palliative treatment of recurrent or metastatic head and neck cancer. Regimen consisting of cisplatin, methotrexate, bleomycin, and vincristine also has been used.

Cervical Cancer

Used alone or in combination therapy as an adjunct to radiation therapy for the treatment of invasive cervical cancer (FIGO stages IB2 through IVA or FIGO stage IA2, IB, or IIA with poor prognostic factors).

Component of various combination chemotherapeutic regimens (e.g., bleomycin, cisplatin, and ifosfamide [BIP]; bleomycin, cisplatin, mitomycin, and vincristine [BOMP]) for the treatment of metastatic or recurrent cervical cancer.

Non-small Cell Lung Cancer

Component of various chemotherapeutic regimens for advanced non-small cell lung cancer.

Currently preferred regimens include the combination of cisplatin with another agent, such as paclitaxel, vinorelbine, gemcitabine, or docetaxel.

Small Cell Lung Cancer

Adjunct to other antineoplastic agents for the treatment of small cell lung cancer.

Regimens consisting of cisplatin and etoposide or irinotecan currently considered preferred regimens.

Malignant Pleural Mesothelioma

Used in combination with pemetrexed for the treatment of malignant pleural mesothelioma in patients not eligible for surgery.

Monotherapy or as adjunct to other antineoplastic agents (e.g., doxorubicin, gemcitabine, mitomycin) for the palliative treatment of advanced malignant pleural mesothelioma.

Esophageal Cancer

Monotherapy or as adjunct to other antineoplastic agents for the treatment of localized or advanced esophageal cancer.

For treatment of localized, resectable esophageal cancer, some experts recommend combined modality treatment with combination chemotherapy (e.g., cisplatin and fluorouracil) and concurrent radiation therapy with or without surgery.

For palliative treatment of metastatic (local or distant) disease or recurrent or locally advanced disease not amenable to surgery or radiation therapy, combination therapy with cisplatin and fluorouracil is considered regimen of choice.

Biliary Tract Cancer

Use in combination with gemcitabine is recommended (accepted) for the treatment of unresectable locally advanced or metastatic biliary tract cancer (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, or ampullary cancer), including unresectable recurrent disease following surgical resection, in patients with good performance status (ECOG performance status of 0 or 1).

Brain Tumors

Adjunct for the treatment of astrocytic tumors, such as anaplastic astrocytoma and glioblastoma multiforme.

Used in combination with lomustine and vincristine as adjuvant therapy following surgical resection and radiation therapy for the treatment of medulloblastoma.

Monotherapy or in combination chemotherapy regimens (e.g., cisplatin and etoposide) as salvage therapy for recurrent oligodendroglioma.

Adjunct to etoposide for the treatment of intracranial germ cell tumors.

Neuroblastoma

Component of combination therapy for high-risk neuroblastoma.

In patients with intermediate-risk tumors or some patients with low-risk tumors, combination chemotherapy with moderate doses of carboplatin, cyclophosphamide, doxorubicin, and etoposide is used in conjunction with surgery (with or without radiation therapy). In patients with high-risk tumors, aggressive chemotherapy using higher doses of these drugs and additional drugs (e.g., ifosfamide, high-dose cisplatin, vincristine) is used.

Cisplatin Dosage and Administration

General

  • Consult specialized references for procedures for proper handling and disposal of antineoplastics.

  • Consider pretreatment with antiemetics (e.g., selective inhibitors of type 3 [5-HT3] serotonergic receptors) or combination antiemetic therapy (e.g., 5-HT3 receptor antagonist and corticosteroid) to prevent nausea and vomiting,.

Hydration

  • Hydrate with 1–2 L IV fluid 8–12 hours prior to administration. Maintain adequate hydration and urinary output during and for 24 hours after administration to minimize nephrotoxicity.

  • In adults, IV fluids usually administered alone or with mannitol and/or furosemide to achieve a diuresis of 150–400 mL/hour (during and for at least 4–6 hours after administration of cisplatin) or ≥100–200 mL/hour (for the next 18–24 hours or until vomiting stops and oral fluids are tolerated).

  • Potassium chloride (e.g., 10–20 mEq/L) often added to IV fluids to replace losses and prevent deficiencies.

Administration

Administer by IV infusion. Also has been administered intraperitoneally.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion.

Aluminum displaces platinum from cisplatin molecule, causing formation of a black precipitate and loss of potency; do not use needles or IV administration sets that contain aluminum parts for preparation or administration.

Handle cautiously (e.g., use gloves); avoid exposure during handling and preparation of IV solution. If skin or mucosal contact occurs, immediately and thoroughly wash skin with soap and water and flush mucosa with water.

Dilution

Dilute preservative-free solution with 2 L of 5% dextrose and 0.33 or 0.45% sodium chloride injection containing 18.75 g of mannitol/L (i.e., 37.5 g in 2 L). Do not dilute with 5% dextrose injection.

If not used within 6 hours, protect from light.

Rate of Administration

Manufacturer recommends administering dose by IV infusion over 6–8 hours.

Has been administered over 15 minutes to 2 hours with minimal adverse renal effects. Continuous 24-hour or 5-day IV infusions also have been used.

Rapid IV injection (e.g., over 1–5 minutes) associated with increased risk of nephrotoxicity or ototoxicity.

Intraperitoneal Instillation

In patients with advanced epithelial ovarian cancer (GOG-172 study), dose was diluted in 2 L of 0.9% sodium chloride solution that was warmed to 37°C and administered as rapidly as possible through a surgically implanted peritoneal catheter. Following peritoneal infusion, patient was asked to roll into a different position every 15 minutes for the next 2 hours to disperse the drug throughout the peritoneal cavity.

Some clinicians have recommended mixing intraperitoneal chemotherapeutic agents in 1 L of warmed saline solution and then, in the absence of pain, administering an additional 1 L of saline solution to ensure adequate distribution within the peritoneal cavity.

Consult specialized sources for guidance on how to administer intraperitoneal therapy. Further study needed to optimize techniques for intraperitoneal therapy to minimize risk of complications (e.g., infection, catheter obstruction, catheter retraction, bowel perforation, pain, leakage, port access problems).

Dosage

Contact prescriber if prescribed dose >100 mg/m2/cycle. (Cisplatin dosages exceeding 100 mg/m2/cycle once every 3–4 weeks are rarely used.) Inadvertent substitution of cisplatin for carboplatin can result in potentially fatal overdosage. (See Boxed Warning.)

Do not administer repeat course until Scr <1.5 mg/dL and/or BUN <25 mg/dL, platelet count ≥100,000/mm3, and leukocyte count ≥4000/mm3, and unless auditory acuity is within normal limits.

Consult published protocols for dosages of other chemotherapeutic agents and alternative cisplatin dosages, the method and sequence of administration, and duration of therapy.

Adults

Testicular Cancer
IV

20 mg/m2 daily for 5 consecutive days every 3 weeks for 3 or 4 courses of therapy. 3 cycles of therapy are sufficient for favorable-prognosis germ cell tumors.

Ovarian Cancer
IV

Combination chemotherapy with paclitaxel: 75 mg/m2 once every 3 weeks.

Combination chemotherapy with cyclophosphamide: 50–100 mg/m2 once every 3–4 weeks. Administer cisplatin and cyclophosphamide sequentially.

Monotherapy: Manufacturer recommends 100 mg/m2 once every 4 weeks. Some experts recommend 50–100 mg/m2 once every 3 weeks; dosages of 30–120 mg/m2 once every 3–4 weeks have been used.

Intraperitoneal

Combination chemotherapy with IV and intraperitoneal paclitaxel: IV paclitaxel 135 mg/m2 by 24-hour infusion on day 1, followed by intraperitoneal cisplatin 100 mg/m2 on day 2 and intraperitoneal paclitaxel 60 mg/m2 on day 8, has been administered every 21 days for up to 6 cycles. Modified regimens (e.g., with shorter IV infusion times that may permit outpatient administration) are being investigated.

Bladder Cancer
IV

50–70 mg/m2 once every 3–4 weeks, depending on extent of prior radiation therapy and/or chemotherapy.

In extensively pretreated patients, 50 mg/m2 once every 4 weeks.

Head and Neck Cancer†
IV

Monotherapy: 80–120 mg/m2 once every 3 weeks or 50 mg/m2 on the first and eighth days of every 4 weeks.

Combination chemotherapy: 50–120 mg/m2; frequency of administration depends on the specific regimen employed (consult specialized references).

Induction therapy (in combination with docetaxel and fluorouracil): 75–100 mg/m2 once every 3 weeks.

Cervical Cancer†
Invasive Cervical Cancer†
IV

Monotherapy: 40 mg/m2 once weekly has been administered concurrently with radiation therapy up to a maximum of 6 doses.

Combination chemotherapy (e.g., with fluorouracil): 50–75 mg/m2 has been administered concurrently with radiation therapy according to various dosage schedules.

Metastatic or Recurrent Cervical Cancer†
IV

50 mg/m2 once every 3 weeks up to a maximum of 6 courses. Higher dosages (e.g., 100 mg/m2 once every 3 weeks) produce higher response rates but also increased toxicity.

Non-small Cell Lung Cancer†
IV

75–100 mg/m2 once every 3–4 weeks.

Esophageal Cancer†
IV

Monotherapy: 50–120 mg/m2 once every 3–4 weeks.

Combination chemotherapy: 75–100 mg/m2 once every 3–4 weeks.

Biliary Tract Cancer†
IV

Combination chemotherapy with gemcitabine: Cisplatin 25 mg/m2 (as 1-hour infusion) has been given on days 1 and 8 of each 21-day cycle; administered in combination with gemcitabine (1 g/m2 as 30-minute infusion on days 1 and 8 after cisplatin). Treatment continued for 24 weeks (8 cycles) in the absence of disease progression or unacceptable toxicity.

Prescribing Limits

Adults

Do not administer cycle more frequently than once every 3–4 weeks.

Contact prescriber if prescribed dose >100 mg/m2/cycle. (Cisplatin dosages exceeding 100 mg/m2/per cycle once every 3–4 weeks are rarely used.)

Consider that renal toxicity becomes more severe with repeated courses of cisplatin.

Cervical Cancer†

Invasive cervical cancer: Maximum 6 doses.

Metastatic or recurrent cervical cancer: Maximum 6 courses.

Special Populations

Geriatric Patients

Careful dosage selection and monitoring of renal function recommended due to possible age-related decrease in renal function.

Cautions for Cisplatin

Contraindications

  • Patients with preexisting renal impairment, myelosuppression, or hearing impairment.

  • Known hypersensitivity to cisplatin or other platinum-containing compounds or any ingredient in the formulation.

Warnings/Precautions

Warnings

Renal Effects

Risk of dose-related (cumulative), severe nephrotoxicity (manifested as increased Scr, BUN, serum uric acid concentrations, and/or decreased Clcr and GFR); nephrotoxicity more common and severe than with carboplatin.

Nephrotoxicity generally occurs during second week following initiation of therapy; may occur within several days following administration of high-dose regimens. (See Clinical/Laboratory Monitoring under Cautions.)

High or repeated doses can increase severity and duration of renal impairment. Recovery generally occurs within 2–4 weeks after administration of cisplatin, but renal insufficiency may be irreversible (sometimes fatal).

Maintain adequate hydration and urinary output during and for 24 hours after administration of cisplatin to minimize nephrotoxicity. (See Hydration under Dosage and Administration.)

Nervous System Effects

Risk of neurotoxicity, usually characterized by severe neuropathy (e.g., paresthesia, areflexia, loss of proprioception and vibratory sensation) in patients receiving higher single or cumulative doses, prolonged therapy (4–7 months), or greater dose frequency than recommended. Neurotoxicity more severe and occurs more frequently than with carboplatin.

Perform neurologic examination regularly. If manifestations of neuropathy occur, discontinue cisplatin immediately; neuropathy may worsen even after discontinuance. Peripheral neuropathy may be irreversible in some patients.

Possible motor (especially gait) difficulties, reduced or absent deep-tendon reflexes, leg weakness, or loss of motor function. Muscle cramps reported, particularly in patients receiving high cumulative dose and at advanced symptomatic stage of peripheral neuropathy.

Loss of taste, seizures, Lhermitte’s sign, dorsal column myelopathy, and autonomic neuropathy reported.

Otic Effects

Risk of dose-related, cumulative ototoxicity. (See Boxed Warning.) Hearing loss can be unilateral or bilateral and becomes more frequent and severe with repeated doses; may occasionally require dosage reduction or discontinuance of therapy. (See Clinical/Laboratory Monitoring under Cautions.)

Risk of vestibular ototoxicity (manifested as vertigo ) or vestibular dysfunction.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity and embryolethality demonstrated in animals. Avoid pregnancy during therapy. If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.

Carcinogenic Effects

Malignancies (e.g., leukemia, renal fibrosarcoma) reported in rats. Bladder cancer reported in at least 1 patient, but causal relationship not established. Acute leukemia rarely reported in humans; in such cases, cisplatin generally was given in combination with other leukemogenic agents and/or radiation.

Sensitivity Reactions

Anaphylactoid Reactions

Anaphylactoid reactions reported. (See Boxed Warning.) Anaphylactoid reactions usually have occurred only after multiple cycles (e.g., at least 5 doses), but also can occur after the initial dose. Observe patients carefully; supportive equipment and medication should be available for immediate use.

Major Toxicities

Hematologic Effects

Risk of cumulative myelosuppression (manifested as leukopenia, thrombocytopenia, and anemia). Leukopenia and thrombocytopenia are dose-related. Anemia not clearly dose-related but may be severe, possibly requiring transfusions.

Myelosuppression may be more severe in patients previously treated with other antineoplastic agents or radiation therapy. Myelosuppression less pronounced than with carboplatin.

Nadir in circulating platelets, leukocytes, and hemoglobin occurs 18–23 days (range: 7.2–45 days) following single dose; levels return to pretreatment values in most patients within 39 days (range: 13–62 days). (See Clinical/Laboratory Monitoring under Cautions.)

Fever and infection reported in patients with neutropenia.

Hemolytic anemia reported. Repeat course may result in increased hemolysis; carefully weigh benefit of therapy versus risk.

GI Effects

Marked nausea and vomiting reported in virtually all patients; occasionally may require discontinuance of therapy.

Increased incidence and severity in females, in young patients, following administration of high doses or by rapid infusion, and/or following concomitant administration with other emetogenic drugs (e.g., doxorubicin); patients with history of chronic heavy alcohol use may experience less frequent and severe emetogenic effects.

Nausea and vomiting generally begin within 1–6 (usually 2–3) hours after administration of cisplatin; persist for up to 24 hours or longer. Average of 10–12 vomiting episodes reported within first 24 hours after initial dose. Various degrees of nausea, vomiting, and anorexia may persist for up to 5–10 days.

Delayed nausea and vomiting (beginning or persisting ≥24 hours following chemotherapy) has occurred in patients who had attained complete emetic control on the day of cisplatin therapy.

Cardiovascular and Cerebrovascular Effects

Bradycardia, left bundle-branch block, ST-T-wave changes with CHF, postural hypotension, MI, cerebrovascular accident, thrombotic microangiopathy, or cerebral arteritis reported rarely.

Electrolyte Disturbances

Hypomagnesemia, hypocalcemia, hypokalemia, hypophosphatemia, and hyponatremia reported. SIADH reported.

Manifestations of hypomagnesemia and/or hypocalcemia include muscle irritability or cramps, clonus, tremor, carpopedal spasm, and/or tetany.

Electrolyte disturbances may occur within several days after administration of initial dose; hypomagnesemia usually develops within 3–4 weeks and appears to increase in severity with progressive courses of treatment. (See Clinical/Laboratory Monitoring under Cautions.)

Normal serum electrolyte concentrations generally restored by administration (usually parenteral) of appropriate supplemental electrolytes and drug discontinuance.

Metabolic Effects

Hyperuricemia (resulting from drug-induced nephrotoxicity ) reported; more pronounced with doses >50 mg/m2. Peak uric acid concentrations generally occur 3–5 days after administration of drug.

Allopurinol effectively reduces uric acid concentrations.

Ocular Effects

Optic neuritis (principally retrobulbar), papilledema, and cerebral (cortical) blindness reported infrequently. Corticosteroids, with or without mannitol, have been used; however, efficacy of such treatment not established.

Blurred vision and altered color perception reported following administration of higher dosages or greater dosing frequencies.

Hepatic Effects

Mild and transient elevations of serum AST (SGOT), ALT (SGPT), and bilirubin reported. (See Clinical/Laboratory Monitoring under Cautions.)

Local Effects

Soft tissue toxicity (e.g., severe cellulitis with residual fibrosis, and full-thickness skin necrosis ) reported following extravasation of drug.

Infusion of solutions with concentration >0.5 mg/mL may result in tissue cellulitis, fibrosis, and necrosis.

General Precautions

Clinical/Laboratory Monitoring

Monitor Scr, BUN, Clcr, and serum magnesium, sodium, potassium, and calcium concentrations prior to initiating therapy and prior to each subsequent course. Do not administer repeat dose until Scr <1.5 mg/dL and/or BUN <25 mg/dL. (See Dosage under Dosage and Administration.)

Monitor peripheral blood counts weekly.

Perform neurologic examination regularly.

Monitor liver function periodically.

Perform audiometric testing prior to initiating therapy and prior to each subsequent dose. Do not administer repeat doses unless auditory acuity is within normal limits.

Specific Populations

Pregnancy

Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Distributed into milk. Discontinue nursing.

Pediatric Use

Safety and efficacy not established.

More severe ototoxic effects. Increased risk of hypomagnesemia.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

Possible increased risk for myelosuppression, infectious complications, peripheral neuropathy, and nephrotoxicity.

Careful dosage selection and monitoring of renal function recommended due to possible age-related decrease in renal function.

Common Adverse Effects

Nausea, vomiting, nephrotoxicity, ototoxicity, myelosuppression. (See Warnings under Cautions.)

Interactions for Cisplatin

No evidence to date that cisplatin undergoes enzymatic biotransformation.

Renally Excreted Drugs

Potentially altered elimination of renally excreted drugs, possibly as a result of cisplatin-induced nephrotoxicity.

Specific Drugs

Drug

Interaction

Comments

Aminoglycosides

Increased risk of nephrotoxicity.

Increased risk of ototoxicity.

Avoid concomitant use; if must be used concomitantly (during or shortly after cisplatin therapy), exercise extreme caution. Some clinicians recommend avoiding aminoglycoside for at least 2 weeks after cisplatin to minimize risk.

Monitor carefully for ototoxicity.

Amphotericin B

Increased risk of nephrotoxicity.

Avoid concomitant use.

Anticonvulsants (e.g., phenytoin)

Possible decreased phenytoin concentrations (due to decreased absorption and/or increased metabolism).

Monitor serum phenytoin concentrations; adjust dosage accordingly.

Bleomycin

Possible altered renal elimination of bleomycin.

Possible synergistic antineoplastic effects.

Diuretics, loop (e.g., ethacrynic acid, furosemide)

Increased risk of ototoxicity.

Monitor carefully for ototoxicity.

Etoposide

Possible decreased etoposide elimination.

Possible synergistic antineoplastic effects.

Methotrexate

Possible altered renal elimination of methotrexate.

Possible synergistic antineoplastic effects.

Pyridoxine

Response duration adversely affected when used concomitantly with cisplatin and altretamine (hexamethylmelamine).

Cisplatin Pharmacokinetics

Absorption

Following rapid IV injection over 1–5 minutes or rapid IV infusion over 15 minutes or 1 hour, peak plasma drug and platinum concentrations occur immediately.

Distribution

Extent

After cisplatin administration, platinum is widely distributed into body fluids and tissues, with highest platinum concentrations in the kidneys, liver, and prostate; somewhat lower concentrations in the bladder, muscle, testes, pancreas, and spleen; and lowest concentrations in the small and large intestines, adrenals, heart, lungs, lymph nodes, thyroid, gallbladder, thymus, cerebrum, cerebellum, ovaries, and uterus. Distributed minimally into leukocytes and erythrocytes.

Platinum present in tissues for as long as 180 days after administration of last dose.

Possible accumulation of platinum compound when administered on a daily basis.

Crosses the placenta and is distributed into milk.

Plasma Protein Binding

Platinum from cisplatin is 90% irreversibly bound (mainly to albumin, transferrin, and γ-globulin). Only nonprotein-bound platinum is cytotoxic.

Special Populations

Increased plasma concentrations of nonprotein-bound platinum in patients with renal impairment.

Elimination

Metabolism

No evidence to date that cisplatin undergoes enzymatic biotransformation. Chloride ligands of the cisplatin complex believed to be displaced by water, forming positively charged platinum complexes that react with nucleophilic sites.

Elimination Route

Excreted principally in urine (predominantly via glomerular filtration ) as intact cisplatin and platinum-containing product(s); approximately 10–50% of dose excreted within 24–48 hours.

Fecal elimination appears to be insignificant.

May undergo enterohepatic circulation.

Minimally removed by hemodialysis.

Half-life

Intact cisplatin: 20–30 minutes (initial phase) following rapid IV injection or infusion.

Total platinum: 8.1–49 minutes (initial phase) and 30.5–107 hours or possibly longer (terminal phase) following rapid IV injection or infusion. Following 6-hour IV infusion, terminal elimination half-life is 73–290 hours.

Nonprotein-bound platinum: 2.7–30 minutes (initial phase) and 32–53.5 minutes (terminal phase) following rapid IV injection or infusion.

Special Populations

Impaired elimination and prolonged terminal half-life in renal impairment.

Stability

Storage

Parenteral

Injection

15–25°C; do not refrigerate (since precipitation may occur). Protect from light.

Following initial entry of vial, cisplatin is stable for 28 days (protected from light) or 7 days (under fluorescent room light).

Protect diluted solution from light if not used within 6 hours.

Cisplatin Stability in Various IV Solutions and Admixtures

IV Solution

Cisplatin Concentration (mg/ml)

Duration of Stability (time and temperature)

5% Dextrose and 0.45 or 0.9% Sodium Chloride

0.05, 0.5

at least 24 h at room temperature

5% Dextrose and 0.33% Sodium Chloride with 1.875% Mannitol (with or without 0.15% Potassium Chloride)

0.05, 0.1, 0.2

at least 72 h at 4 or 25°C

5% Dextrose and 0.45% Sodium Chloride with 1.875% Mannitol

0.05, 0.1, 0.2

at least 72 h at 4 or 25°C

0.2% Sodium Chloride

0.2

at least 24 h at room temperature

0.225% Sodium Chloride

0.05, 0.1, 0.2

at least 72 h at 4 or 25°C

0.3% Sodium Chloride

0.05, 0.1, 0.2

at least 72 h at 4 or 25°C

0.45% Sodium Chloride

0.2

at least 24 h at room temperature

0.05, 0.5

at least 24 h at 25°C

0.9% Sodium Chloride

0.2

at least 24 h at room temperature

0.05, 0.5

at least 24 h at 25°C

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Aluminum displaces platinum from cisplatin molecule, causing formation of a black precipitate and loss of potency; do not use needles or IV administration sets that contain aluminum parts for preparation or administration.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in sodium chloride 0.225, 0.45, or 0.9%

Dextrose 5% in sodium chloride 0.33 or 0.45% with mannitol 1.875%

Dextrose 5% in sodium chloride 0.33% with potassium chloride 20 mEq/L and mannitol 1.875%

Sodium chloride 0.225, 0.3, 0.45, or 0.9%

Incompatible

Sodium bicarbonate 5%

Variable

Dextrose 5% in water

Drug Compatibility
Admixture CompatibilityHID

Compatible

Carboplatin

Cyclophosphamide with etoposide

Etoposide

Etoposide with floxuridine

Floxuridine

Floxuridine with leucovorin calcium

Hydroxyzine HCl

Ifosfamide

Ifosfamide with etoposide

Leucovorin calcium

Magnesium sulfate

Mannitol

Ondansetron HCl

Incompatible

Etoposide with mannitol and potassium chloride

Fluorouracil

Mesna

Thiotepa

Variable

Paclitaxel

Y-Site CompatibilityHID

Compatible

Allopurinol sodium

Anidulafungin

Aztreonam

Bleomycin sulfate

Caspofungin acetate

Cladribine

Cyclophosphamide

Doripenem

Doxorubicin HCl

Doxorubicin HCl liposome injection

Droperidol

Etoposide phosphate

Filgrastim

Fludarabine phosphate

Fluorouracil

Furosemide

Gemcitabine HCl

Granisetron HCl

Heparin sodium

Leucovorin calcium

Linezolid

Melphalan HCl

Methotrexate sodium

Metoclopramide HCl

Mitomycin

Ondansetron HCl

Paclitaxel

Palonosetron HCI

Pemetrexed disodium

Propofol

Sargramostim

Teniposide

Topotecan HCl

Vinblastine sulfate

Vincristine sulfate

Vinorelbine tartrate

Incompatible

Amifostine

Amphotericin B cholesteryl sulfate complex

Gallium nitrate

Piperacillin sodium–tazobactam sodium

Thiotepa

Actions

  • Heavy metal complex containing a platinum atom surrounded by 2 chloride atoms and 2 ammonia molecules.

  • Chloride ligands of the cisplatin complex are displaced by water (aquation), forming positively charged platinum complexes. These toxic platinum complexes bind to specific DNA base sequences, producing intrastrand and interstrand DNA cross-links, which are thought to inhibit DNA replication, transcription, and ultimately cell division.

  • Cycle-phase nonspecific.

  • Exhibits immunosuppressive, radiosensitizing, and antimicrobial properties.

  • Possible cross-resistance with carboplatin.

Advice to Patients

  • Risk of nausea, vomiting, nephrotoxicity, myelosuppression, and ototoxicity.

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed. Necessity for clinicians to advise women to avoid pregnancy during therapy; advise pregnant women of risk to the fetus.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

CISplatin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion

1 mg/mL (50 or 100 mg)*

CISplatin Injection

Platinol-AQ

Bristol-Myers Squibb

AHFS DI Essentials™. © Copyright 2021, Selected Revisions July 27, 2015. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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