Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 1mg/mL
Metastatic Testicular Tumors
Usual dose in combination with other approved chemotherapeutic agents is 20 mg/m²/day IV for 5 days repeated every 3 weeks (in combination with bleomycin and etoposide)
Advanced Bladder Cancer
50-70 mg/m² IV cycle q3-4Weeks, depending on prior radiation therapy or chemotherapy; for heavily pretreated patients, give 50 mg/m²/cycle initially; repeat q4Weeks
Metastatic Ovarian Carcinoma
75-100 mg/m² IV per cycle q4Weeks with cyclophosphamide (600 mg/m² IV q4Weeks); administer sequentially
Off-label: 90-270 mg/m² intraperitoneal; retain for 4 hr before draining; repeat q3Weeks (may coadminister systemic Na thiosulfate)
Cancers (Off-label)
Cancer of cervix, endometrium, prostate, esophagus, kidney; non-small cell lung cancer; head & neck squamous cell cancer; osteogenic sarcomas; bone marrow transplants
75-100 mg/m² IV q4Weeks when used with cyclophosphamide
100 mg/m² IV q4Weeks as single agent
Dosing Considerations
Pretreatment hydration: 1-2 L fluid infused for 8-12 hr before dose
May use concomitant amifostine to decrease nephrotoxicity
Do not repeat course until SCr <1.5 mg/dL [<133 micromoles/L] or BUN <25 mg/dL [<8.93 mmol/L] or WBC >4000/mm³ AND platelets >100 k/mm³
Renal Impairment
CrCl 10-50 mL/min: Decrease dose by 25%
CrCl <10 mL/min: Administer 50% of dose
Hemodialysis
- Partially cleared by hemodialysis
- Posthemodialysis: Administer 50% of dose
- Continuous ambulatory peritoneal dialysis: Administer 50% of dose
- Continuous renal replacement therapy (CRRT): Administer 75% of dose
Metastatic Osteogenic Sarcoma (Orphan)
Liposomal cisplatin for inhalation: Treatment of osteogenic sarcoma metastatic to the lung
Orphan indication sponsor
- Transave, Inc; 11 Deer Park Drive, Suite 117; Monmouth Junction, NJ 08852-1923
Ovarian Cancer (Orphan)
Liposomal ciplatin: Treatment of ovarian cancer
Orphan indication sponsor
- Transave, Inc; 11 Deer Park Drive, Suite 117; Monmouth Junction, NJ 08852-1923
Squamous Cell Carcinoma (Orphan)
Cisplatin with epinephrine: Treatment of squamous cell carcinoma of the head and neck
Orphan indication sponsor
- Matrix Pharmaceutical, Inc; 34700 Campus Drive; Fremont, CA 94555-3612
Malignant Melanoma (Orphan)
Cisplatin with epinephrine: Treatment of metastatic malignant melanoma
Orphan indication sponsor
- Matrix Pharmaceutical, Inc; 34700 Campus Drive; Fremont, CA 94555-3612
Oral Cancers (Orphan)
ChemoThin wafer: Orphan designation for treatment of anatomically accessible oral cancers (lip, tongue, gum, floor of mouth, salivary gland, and other oral cavity)
Sponsor
- Privo Technologies; 13 Bristol Street, Unit #1; Cambridge, Massachusetts 02141
Anal Cancer (Orphan)
Orphan designation for treatment of anal cancer
Sponsor
- Privo Technologies; 13 Bristol Street Unit #1; Cambridge, Massachusetts 02141
Monitor
CBC; audiometric testing before each dose
Dosage Forms & Strengths
injectable solution
- 1mg/mL
Dosing Considerations
Verify any cisplatin dose exceeding 100 mg/m² per regimen
Pretreatment hydration: 1-2 L fluid infused for 8-12 hr before dose
May use concomitant amifostine to decrease nephrotoxicity
Do not repeat course until SCr <1.5 mg/dL [<133 micromoles/L] or BUN <25 mg/dL [<8.93 mmol/L] or WBC >4000/mm³ AND platelets >100 k/mm³
Monitor therapy closely; elderly maybe more susceptible to nephrotoxicity and peripheral neuropathy
Metastatic Testicular Tumors
Usual dose in combination with other approved chemotherapeutic agents is 20 mg/m²/day IV for 5 days/cycle
Advanced Bladder Cancer
50 -70 mg/m² IV cycle q3-4Weeks, depending on prior radiation therapy or chemotherapy; for heavily pretreated patients, give 50 mg/m²/cycle initially; repeat q4Weeks
Metastatic Ovarian Carcinoma
75-100 mg/m² IV per cycle q3-4Weeks on Day 1 with cyclophosphamide (600 mg/m² IV q4Weeks); administer sequentially
Unlabeled: 90-270 mg/m² intraperitoneal; retain for 4 hr before draining; repeat q3Weeks (may coadminister systemic Na thiosulfate)
Dosing considerations
Pretreatment hydration: 1-2 L fluid infused for 8-12 hr before dose
May use concomitant amifostine to decrease nephrotoxicity
Do not repeat course until SCr <1.5 mg/dL [<133 micromoles/L] or BUN <25 mg/dL [<8.93 mmol/L] or WBC >4000/mm³ AND platelets >100 k/mm³
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Nausea (76-100%)
Vomiting (76-100%)
Nephrotoxicity (28-36%)
Ototoxicity, especially in children (31%)
Myelosuppression (25-30%)
Anaphylaxis (1-20%)
Alopecia
Frequency Not Defined
Cerebral herniation
Encephalopathy
Leukoencephalopathy and reversible posterior leukoencephalopathy syndrome
Seizure
Peripheral neuropathy (dose and duration dependent)
Diarrhea
Electrolyte changes
Hyperuricemia
Hepatotoxicity
Local tissue irritation
Blood and lymphatic system disorders: Coombs-positive hemolytic anemia. hemolytic uremic syndrome, thrombotic thrombocytopenic purpura
Cardiovascular disorders: Venous thromboembolism, arterial thromboembolism, myocardial infarction, cerebrovascular accident, thrombotic microangiopathy, cerebral arteritis, pericardial effusion, cardiac failure, ventricular dysfunction, Raynaud’s phenomenon
Eye disorders: Optic neuritis, papilledema, cortical blindness, blurred vision, color blindness, retinal pigmentation
Gastrointestinal disorders: Nausea, vomiting, anorexia, diarrhea, stomatitis, gastrointestinal perforation, pancreatitis, hiccups
General disorders: Asthenia, malaise
Hepatobiliary disorders: Elevations of aminotransferases, lactate dehydrogenase, and bilirubin; hepatic failure
Hypersensitivity: Anaphylaxis, facial edema, wheezing, tachycardia, and hypotension
Local Site Reactions: Tissue cellulitis, fibrosis, necrosis, pain, edema, and erythema
Metabolism and nutrition disorders: Hypomagnesemia, often requiring magnesium supplementation; hyperuricemia, other electrolyte abnormalities (hypocalcemia, hyponatremia, hypokalemia, and hypophosphatemia), Syndrome of Inappropriate Antidiuretic Hormone Excretion (SIADH), dehydration, tumor lysis syndrome, increased serum amylase
Musculoskeletal disorders: Muscle cramps (localized, painful, involuntary skeletal muscle contractions of sudden onset and short duration)
Nervous system disorders: Peripheral neuropathy, encephalopathy, loss of motor function, loss of taste, leukoencephalopathy, reversible posterior leukoencephalopathy syndrome, progressive multifocal leukoencephalopathy, seizures, Lhermitte’s sign, dorsal column myelopathy, autonomic neuropathy, seizures, involuntary skeletal muscle contractions, tetany (with hypocalcemia and hypomagnesemia)
Ototoxicity: Tinnitus, hearing loss, deafness, vestibular toxicity
Renal and urinary disorders: Nephrotoxicity including renal failure, renal electrolyte wasting, azotemia, decreased creatinine clearance
Respiratory disorders: Pneumonitis/interstitial lung disease, pulmonary embolism
Warnings
Black Box Warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician
Severe nephrotoxicity, myelosuppression, and nausea and vomiting are dose related
Significant ototoxicity, manifested by tinnitus and occasionally deafness, reported in children
Anaphylactic-like reactions have occurred. Facial edema, bronchoconstriction, tachycardia, and hypotension may occur within minutes of cisplatin administration
Failure to differentiate daily doses from total dose per treatment cycle may result in cisplatin overdose
Contraindications
Hypersensitivity to cisplatin, other platinum compounds
Severe myelosuppression, renal impairment, hearing impairment
Pregnancy, lactation
Cautions
Irritant; injection site reactions may occur during administration; local soft tissue toxicity reported following extravasation of cisplatin for injection; severity of local tissue toxicity appears to be related to concentration of drug; closely monitor infusion site during drug administration
Avoid aluminum needles/equipment
Pediatric patients, hearing impairment, neuropathy, neuromuscular disease, with neurotoxic agents, with ototoxic agents, elderly
Risk of cumulative nephrotoxicity (exacerbated by aminoglycoside antibiotics); renal toxicity becomes more prolonged and severe with repeated courses; renal function must return to normal before administering another dose
Myelosuppression occurs in 25-30%; nadirs in circulating platelets and leukocytes occur between days 18-23 (range 7.5-45) with most patients recovering by day 39; elderly may be more susceptible to myelosuppression
Development of acute leukemia secondary to therapy reported; in these reports, cisplatin for injection was generally given in combination with other leukemogenic agents
Optic neuritis, papilledema, and cortical blindness reported in patients receiving standard recommended doses; blurred vision and altered color perception reported after use of regimens with higher doses and dose frequencies; the altered color perception manifests as a loss of color discrimination, particularly in the blue-yellow axis and irregular retinal pigmentation of macular area on fundoscopic exam; improvement and/or total recovery usually occurs after discontinuing cisplatin for injection but can be delayed
Cardiac abnormalities, hiccups, elevated serum amylase, rash, alopecia, malaise, asthenia, and dehydration have been reported
Avoid pregnancy
Renal toxicity
- Ensure adequate hydration before, during, and after administration; measure serum creatinine, blood urea nitrogen, creatinine clearance, and serum electrolytes including magnesium prior to initiating therapy, and as clinically indicated; consider magnesium supplementation as clinically needed
- Consider alternative treatments or reduce dose for patients with baseline renal impairment or who develop significant reductions in creatinine clearance during treatment
Peripheral neuropathy
- Drug can cause dose-related peripheral neuropathy that becomes more severe with repeated courses of drug; neurologic symptoms have been reported to occur after a single dose
- Neuropathy can also have a delayed onset from 3-8 weeks after last dose of cisplatin for injection; manifestations include paresthesias in a stocking-glove distribution, areflexia, and loss of proprioception and vibratory sensation
- Neuropathy may progress further even after stopping treatment; peripheral neuropathy may be irreversible in some patients
- Perform a neurological examination before initiating therapy, at appropriate intervals during therapy, and after completion of therapy; consider discontinuation of cisplatin for injection for patients who develop symptomatic peripheral neuropathy; geriatric patients may be more susceptible to peripheral neuropathy
Nausea and vomiting
- Cisplatin for injection is a highly emetogenic antineoplastic agent; premedicate with anti-emetic agents; without antiemetic therapy, marked nausea and vomiting occur in almost all patients treated with cisplatin for injection and may be so severe that drug must be discontinued; nausea and vomiting may begin within 1 to 4 hr after treatment and last up to 72 hr; maximal intensity occurs 48 to 72 hours after administration
- Various degrees of vomiting, nausea, and/or anorexia may persist for up to 1 week after treatment; delayed nausea and vomiting (begins or persists 24 hours or more after chemotherapy) has occurred in patients attaining complete emetic control on day of injection therapy; consider use of additional anti-emetics following infusion
Myelosuppression
- Potential fatalities due to infection (secondary to myelosuppression) reported
- Perform standard hematologic tests before initiating therapy, before each subsequent course, and as clinically indicated; closely monitor patients for development of signs and symptoms of infection during and after treatment with cisplatin for injection; for patients who develop severe myelosuppression, consider dose modifications and manage according to clinical treatment guidelines
Hypersensitivity
- Therapy can cause severe hypersensitivity reactions, including anaphylaxis and death; manifestations have included facial edema, wheezing, tachycardia, hypotension; hypersensitivity reactions have occurred within minutes of administration to patients with prior exposure to cisplatin
- Severe hypersensitivity reactions require immediate discontinuation of cisplatin for injection and aggressive therapy; patients with a history of severe hypersensitivity reactions should not be rechallenged with cisplatin for injection
- Cross-reactivity between platinum-based antineoplastic agents reported; cases of severe hypersensitivity reactions have recurred after rechallenging patients with a different platinum agent
Ototoxicity
- Cisplatin for injection can cause ototoxicity, which is cumulative and may be severe; consider audiometric and vestibular function monitoring
- Ototoxic effects may be more severe and detrimental in pediatric patients receiving cisplatin for injection, particularly in patients less than 5 years of age; consider audiometric and vestibular function monitoring in all patients receiving cisplatin for injection; the prevalence of hearing loss in pediatric patients is particularly high and is estimated to be 40% to 60%
- Earlier detection of hearing loss can limit potential impact of hearing impairment on a pediatric patient’s cognitive and social development
Pregnancy & Lactation
Pregnancy
Based on human data from published literature, cisplatin can cause fetal harm when administered to pregnant women; data demonstrates transplacental transfer of cisplatin
Exposure associated with oligohydramnios, intrauterine growth restriction, and preterm birth; cases of neonatal acute respiratory distress syndrome, cytopenias, and hearing loss reported
Verify the pregnancy status of females of reproductive potential before initiating prior to initiation of cisplatin for injection
Contraception
- Females: Advise females of reproductive potential to use effective contraception during treatment and for 14 months following the last dose
- Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 11 months after the last dose
Infertility
- Females: Use associated with cumulative dose-dependent ovarian failure, premature menopause, and reduced fertility
- Males: Use associated with a cumulative dose-dependent impairment of spermatogenesis (oligospermia, azoospermia; possibly irreversible) and reduced fertility
Animal data
- Cisplatin for injection administration to animals during and after organogenesis resulted in teratogenicity; a published study in mice showed placental transfer of cisplatin increased with placenta maturation
Lactation
Limited data from published literature report lthe presence of drug in human milk; because of potential for serious adverse reactions in a breastfed child and because of potential for tumorigenicity, advise lactating women not to breastfeed during treatment
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
Mechanism of Action
Platinum coordination compound that inhibits DNA synthesis; cross-links and denatures strands of DNA; disrupts DNA function by covalently binding to DNA bases; can also produce DNA intrastrand cross-linking and breakage
Not a true alkylating agent
Pharmacokinetics
Half-life elimination (terminal): 24hr to 47 days
Protein bound: >90%
Excretion: Urine (90%); feces (10%)
Clearance: 15 L/hr/m²
Vd: 11 L/m²
Administration
IV Incompatibilities
Solution: Na-bicarb 5%, D5W(?)
Additive: fluorouracil, mesna, paclitaxel(?), thiotepa
Y-site: amifostine, amphotericin B cholesteryl-SO4, cefepime, piperacillin/tazobactam, thiotepa
IV Compatibilities
Solution: dextrose-saline, NS, 1/2NS, other saline concentrations
Additive: carboplatin, cyclophosphamide w/ etoposide, etoposide, floxuridine, floxuridine w/ leucovorin, hydroxyzine, ifosfamide, leucovorin, MgSO4, mannitol, ondansetron
Syringe: bleomycin, cyclophosphamide, doxapram, doxorubicin, droperidol, fluorouracil, furosemide, heparin, leucovorin, methotrexate, metoclopramide, mitomycin, vinblastine, vincristine
Y-site (partial list): allopurinol, aztreonam, bleomycin, chlorpromazine, cladribine, cyclophophamide, dexamethasone Na-succinate, diphenhydramine, doxorubicin, doxorubicin liposomal, etoposide phosphate, filgrastim, fludarabine, fluorouracil, furosemide, gemcitabine, granisetron, heparin, leucovorin, linezolid, lorazepam, melphalan, methotrexate, methylprednisolone Na-succinate, metoclopramide, mitomycin, morphine, ondansetron, paclitaxel, prochlorperazine edisylate, propofol, sargramostim, vinblastine, vincristine, vinorelbine
IV Preparation
Further dilution stability is dependent on chloride ion concentration & should be mixed in solutions of NS (at least 0.3% NaCl)
Further dilution in NS, D5/½NS or D5/NS to a concentration of 0.05-2 mg/mL are stable for 72 hr at 4-25°C in combination with mannitol
May administer 12.5-50 g mannitol/L
Standard dilution: dose/250-1000 mL NS, D5W/NS or D5/½NS
IV Administration
Perform pretreatment hydration
Do not use aluminum-containing needles or IV administration sets that may come in contact with carboplatin (aluminum can react causing precipitate formation & loss of potency)
Administration rate has varied from a 15-120 min infusion, 1 mg/min infusion, 6-8 hr infusion, 24 hr infusion, or per protocol
Maximum rate of infusion: 1 mg/min in patients with CHF
When administered as sequential infusions, taxane derivatives (docetaxel, paclitaxel) should be administered before platinum derivatives to limit myelosuppression & to enhance efficacy
Extravasation Management
Large extravasations (>20 mL) of concentrated solutions (>0.5 mg/mL) produce tissue necrosis
Tx is not recommended unless a large amount of highly concentrated solution is extravasated
Mix 4 mL of 10% sodium thiosulfate with 6 mL SWI; inject 1-4 mL through existing IV line cannula; administer 1 mL for each mL extravasated; inject SC if needle is removed
Storage
Store intact vials at 15-25°C (59-77°F)
Protect from light
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Formulary
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