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CISplatin
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  Dosing & Indications
  Adult Dosing
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Important Note
  • To prevent inadvertent CISplatin overdosage use caution and confirm dosing if greater than 100 mg/m(2)/cycle [3].
  • This drug has one or more orphan drug designations, which may include approval or withdrawal of status: Access citation for FDA Orphan Drug Information [4].
Adrenal carcinoma, Locally advanced/metastatic
  • DOXOrubicin 20 mg/m(2) IV on days 1 and 8, CISplatin 40 mg/m(2) IV on days 2 and 9, and etoposide 100 mg/m(2) IV on days 5 through 7; mitotane 1 to 4 g orally was given concomitantly with chemotherapy, during the rest period between successive cycles, and afterwards [5][6]; repeat cycles every 4 weeks for up to 6 courses (off-label dosage) [5]
Biliary tract cancer
  • CISplatin 25 mg/m(2) IV infusion over 1 hour followed by gemcitabine 1000 mg/m(2) IV infusion over 30 minutes on days 1 and 8; repeat cycle every 21 days for a maximum of 8 cycles (off-label dosage) [7]
Bladder cancer, Advanced, transitional cell, monotherapy, no longer amenable to local treatments such as surgery or radiotherapy
  • Premedication, adequately hydrate before treatment and maintain hydration and urinary output for 24 hours after injection; give pretreatment and posttreatment antiemetics [3]
  • 50 to 70 mg/m(2) IV once every 3 to 4 weeks per cycle; for heavily pretreated patients, an initial dose of 50 mg/m(2) per cycle repeated every 4 weeks is suggested; other doses and combination in regimens have been used [3]
Bladder cancer, Muscle invasive, as neoadjuvant combination chemotherapy
  • (Dose-dense MVAC) methotrexate 30 mg/m(2) IV on day 1, vinBLAStine 3 mg/m(2) IV on day 2, DOXOrubicin 30 mg/m(2) IV on day 2, CISplatin 70 mg/m(2) IV on day 2, and pegfilgrastim 6 mg given 24 to 48 hours following completion of chemotherapy; repeat every 14 days for 2 to 4 cycles (off-label dosage) [8]
  • (MVAC) methotrexate 30 mg/m(2) IV on days 1, 15, and 22, vinBLAStine 3 mg/m(2) IV on days 2, 15, and 22, DOXOrubicin 30 mg/m(2) IV on day 2, and CISplatin 70 mg/m(2) IV on day 2; repeat every 28 days for 3 cycles (off-label dosage) [9]
  • (CMV) methotrexate 30 mg/m(2) IV on days 1 and 8, vinBLAStine 4 mg/m(2) IV on days 1 and 8, CISplatin 100 mg/m(2) IV on day 2 before hydration, folinic acid 15 mg orally or IV every 6 hours for 4 doses on day 2 after hydration (starting 24 hours after methotrexate dose) and 15 mg orally every 6 hours for 4 doses on day 9 (starting 24 hours after methotrexate dose); repeat every 21 days for 3 cycles (off-label dosage) [10]
  • (GC) gemcitabine 1000 mg/m(2) IV on days 1 and 8 and CISplatin 70 mg/m(2) IV on day 1; repeat every 21 days for 2 to 4 cycles (off-label dosage) [8]
Breast cancer
  • optimal dose and timing not defined in this setting
Carcinoma of esophagus
  • optimal dose and timing not defined in this setting
Cervical cancer
  • Induction therapy, CARBOplatin AUC 2 and paclitaxel 80 mg/m(2) once weekly for 6 weeks followed by chemoradiotherapy with CISplatin 40 mg/m(2) once weekly for 5 weeks with 40 to 50.4 Gy external beam radiotherapy delivered in 20 to 28 fractions plus brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78 to 86 Gy (off-label dosage) [11]
  • Metastatic or recurrent disease, paclitaxel 135 mg/m(2) IV over 24 hours on day 1, then CISplatin 50 mg/m(2) IV on day 2; repeat regimen every 3 weeks [12][13] for up to 6 cycles (off-label dosage) [12]
Endometrial cancer
  • (TAP regimen) DOXOrubicin 45 mg/m(2) followed immediately by CISplatin 50 mg/m(2) on day 1; on day 2, paclitaxel 160 mg/m(2) was given as a 3-hr infusion; filgrastim was administered at a dose of 5 mcg/kg subcutaneously on days 3 to 12; treatments were repeated every 21 days and continued for 7 cycles, if tolerated or until disease progression [14]
Gastric cancer
  • 30 mg/m(2) over 90 minutes plus irinotecan 60 mg/m(2) over 60 minutes on day 1 every 2 weeks; give with adequate hydration (study dose)[15]
Germ cell tumor of ovary
  • optimal dose and timing not defined in this setting
Gestational trophoblastic neoplasia
  • optimal dose and timing not defined in this setting
Head and neck cancer
  • optimal dose and timing not defined in this setting
Hodgkin's disease, Relapsed or refractory
  • Premedication, corticosteroid eye drops starting 12 hours (hr) before cytarabine and continuing for 2 days after cytarabine, and ondansetron 8 mg IV on days 1 and 2 (off-label dosage) [16]
  • (DHAP regimen) CISplatin 100 mg/m(2) IV as a 24 hr continuous IV infusion on day 1, and cytarabine 2 g/m(2) IV over 3 hr every 12 hr for 2 doses on day 2 with dexamethasone 40 mg IV daily on days 1 through 4; administered for 2 cycles (off-label dosage) [16]
  • Concomitant medications, granulocyte colony-stimulating factor (G-CSF) 5 mcg/kg/day subQ started 24 hr after the last dose of cytarabine and continued until leukocyte counts are at least 2500/mcL for 3 days (off-label dosage) [16]
Liver carcinoma
  • optimal dose and timing not defined in this setting
Malignant mesothelioma of pleura
  • Premedication, dexamethasone the day before, day of, and day after pemetrexed; folic acid 350 to 1000 mcg orally once daily and vitamin B12 1000 mcg IM repeated every 9 weeks initiated 1 to 3 weeks prior to and continued during therapy (off-label dosage) [17].
  • Pemetrexed 500 mg/m(2) IV over 10 minutes, followed 30 minutes later by CISplatin 75 mg/m(2) infused IV over 2 hours every 21 days(off-label dosage) [17].
Melanoma
  • optimal dose and timing not defined in this setting
Metastatic malignant tumor of testis, In combination with other chemotherapy agents
  • Premedication, adequately hydrate before treatment and maintain hydration and urinary output for 24 hours after injection; give pretreatment and posttreatment antiemetics [3]
  • 20 mg/m(2) IV every day for 5 days per cycle; other doses and combination regimens have been used [3]
Metastatic ovarian tumor
  • Premedication, adequately hydrate before treatment and maintain hydration and urinary output for 24 hours after injection; give pretreatment and posttreatment antiemetics [3]
  • 75 to 100 mg/m(2) IV once every 3 to 4 weeks on day 1 of each cycle; other doses and combination regimens have been used [3]
Multiple myeloma, Relapsed/refractory
  • (DTPACE Regimen) Dexamethasone 40 mg orally for 4 days, thalidomide 400 mg orally at night, and a 4-day continuous IV infusion of CISplatin 10 mg/m(2)/day, DOXOrubicin 10 mg/m(2)/day, cyclophosphamide 400 mg/m(2)/day, and etoposide 40 mg/m(2)/day repeated every 4 to 6 weeks (off-label dosage) [18]
Nasopharyngeal cancer
  • (GP regimen) Gemcitabine 1 g/m(2) IV on days 1 and 8 and CISplatin 80 mg/m(2) IV on day 1 every 3 weeks for 3 cycles plus chemoradiotherapy (concurrent CISplatin at a dose of 100 mg/m(2) IV every 3 weeks for three cycles plus intensity-modulated radiotherapy) (off-label dosage) [19]
  • (TPF regimen, Induction) Docetaxel 75 mg/m(2) day 1, CISplatin 75 mg/m(2) day 1, and fluorouracil 750 mg/m(2)/day on days 1 to 5 every 3 weeks for 3 cycles plus concomitant CISplatin radiotherapy (off-label dosage) [20]
Non-Hodgkin's lymphoma, Relapsed or refractory, as part of the DHAP or ESHAP regimen
  • (DHAP regimen) CISplatin 100 mg/m(2) as a continuous IV infusion over 24 hours on day 1, cytarabine 2 g/m(2)/dose (1 g/m(2)/dose in patients older than 70 years) IV over 3 hours every 12 hours on day 2 (after the completion of the CISplatin infusion), and dexamethasone 40 mg/day orally or IV over 15 minutes days 1 to 4 was given in a clinical trial; treatment cycles were repeated every 3 to 4 weeks for a total of 6 to 10 cycles (4 cycles after maximum response); patients received hydration with normal saline plus mannitol 50 g/L at 250 cm(3)/hr over 36 hours (CISplatin was initiated after 6 hours of hydration) and antiemetics with metoclopramide 1 mg/kg and diphenhydrAMINE 25 mg IV regularly during chemotherapy [21]
  • (ESHAP regimen) CISplatin 25 mg/m(2)/day as a continuous IV infusion on days 1 to 4 (for a total CISplatin dose per cycle of 100 mg/m(2)) , etoposide 40 mg/m(2)/day IV over 1 hour on days 1 to 4, methylPREDNISolone 250 to 500 mg/day IV over 15 minutes on days 1 to 5, and cytarabine 2 g/m(2) IV over 2 hours on day 5 was administered in a clinical trial; treatment cycles were repeated every 3 to 4 weeks for a total of 6 to 8 cycles; patients received a minimum of 1 L/day of saline with mannitol 25 to 50 g and antiemetics (eg, metoclopramide 0.5 to 1 mg/kg) regularly during chemotherapy [22]
Non-small cell lung cancer
  • Docetaxel 75 mg/m(2) IV over 1 hour immediately followed by CISplatin 75 mg/m(2) IV over 1 hour on day 1, repeated every 3 weeks [23][24]; repeat 3-week cycles for 6 cycles until progressive disease or unacceptable toxicity (off-label dosage) [23]; premedication, hydrate with at least 1 to 2 L over 4 to 24 hours [25] and consider an appropriate polyantiemetic regimen [25][26].
  • CISplatin 75 mg/m(2) IV over 1 hour on day 1 plus etoposide 100 mg/m(2) over 45 minutes on days 1, 2, and 3 [26][27]; repeat 21-day cycles for a MAX of 10 cycles (off-label dosage) [26]; premedication, hydrate with at least 1 to 2 L over 4 to 24 hours and consider an appropriate polyantiemetic regimen [25].
  • CISplatin 80 mg/m(2) IV on day 1 and irinotecan 60 mg/(2) IV on days 1, 8, and 15; repeat cycle every 4 weeks for 3 or more cycles until progressive disease or unacceptable toxicity (off-label dosage) [28]; premedication, hydrate with at least 1 to 2 L over 4 to 24 hours and consider an appropriate polyantiemetic regimen [25].
  • CISplatin 80 mg/m(2) IV on day 1 and gemcitabine 1000 mg/m(2) IV on days 1 and 8; repeat cycle every 3 weeks for 3 or more cycles until progressive disease or unacceptable toxicity (off-label dosage) [28] OR gemcitabine 1000 mg/m(2) IV on days 1, 8, and 15 and CISplatin 100 mg/m(2) IV on day 1 [29][24] after gemcitabine, followed by 1 week of rest [29]; repeat 28-day cycles [24][29] until progressive disease or unacceptable toxicity for a MAX of 6 cycles (off-label dosage) [29] OR CISplatin 100 mg/m(2) IV over 60 minutes on day 1 and gemcitabine 1250 mg/m(2) IV over 30 minutes on days 1 and 8 of a 21-day cycle; repeat cycle every 3 weeks until progressive disease or unacceptable toxicity for a MAX of 6 cycles (off-label dosage) [30]; premedication, hydrate with at least 1 to 2 L over 4 to 24 hours and consider an appropriate polyantiemetic regimen [25].
  • Paclitaxel 135 mg/m(2) over 24 hours on day 1 plus CISplatin 75 mg/m(2) on day 2; repeat in 3-week cycles (off-label dosage) [24][27]; premedication, hydrate with at least 1 to 2 L over 4 to 24 hours and consider an appropriate polyantiemetic regimen [25].
  • CISplatin 100 mg/m(2) over 30 to 60 minutes on days 1 and 29 in combination with vinBLAStine 5 mg/m(2) bolus on days 1, 8, 15, 22, and 29 and radiation (total dose of 60 Gy in 30 fractions over 6 weeks) (off-label dosage) [31].
  • CISplatin 80 mg/m(2) IV on day 1 and vinorelbine 25 mg/m(2) IV on days 1 and 8; repeat cycle every 3 weeks for 3 or more cycles until progressive disease or unacceptable toxicity (off-label dosage) [28] OR CISplatin 100 mg/m(2) IV on day 1 plus vinorelbine 25 mg/m(2) IV over 6 to 10 minutes on days 1, 8, 15, and 22; repeat cycle every 4 weeks for 6 cycles until progressive disease or unacceptable toxicity (study dose) [23] OR CISplatin 100 mg/m(2) IV every 4 weeks and vinorelbine 25 mg/m(2) IV once every week (off-label dosage) [25]; premedication, hydrate with at least 1 to 2 L over 4 to 24 hours and consider an appropriate polyantiemetic regimen [25].
Ovarian cancer
  • non-FDA approved dosing, intraperitoneal regimen: paclitaxel 135 mg/m(2) INTRAVENOUSLY over 24 hours on day 1, CISplatin 100 mg/m(2) INTRAPERITONEALLY on day 2, and paclitaxel 60 mg/m(2) INTRAPERITONEALLY on day 8 [32]
Retinoblastoma
  • optimal dose and timing not defined in this setting
Sarcoma
  • optimal dose and timing not defined in this setting
Small cell lung cancer
  • (First-line treatment) etoposide 100 mg/m(2) IV followed by CISplatin 75 mg/m(2) IV on day 1, then etoposide 200 mg/m(2) orally daily on days 2 to 4 on an empty stomach; given every 3 weeks for a MAX of 5 cycles; standard pre- and post-hydration was also administered (off-label dosage) [33]
  • (Second-line treatment) CISplatin 25 mg/m(2) IV over 60 minutes on days 1 and 8; etoposide 60 mg/m(2) IV over 60 minutes on days 1 through 3; irinotecan 90 mg/m(2) IV over 90 minutes on day 8 of each cycle; given for five 2-week cycles; granulocyte colony-stimulating factors were also administered (off-label dosage) [34]
  • (Limited stage) CISplatin 75 to 100 mg/m(2) IV on day 1 and etoposide 80 to 100 mg/m(2) IV days 1 through 3; repeat cycle every 3 weeks for a MAX of 4 to 6 cycles; if bolus etoposide-CISplatin is selected for treatment, the sequence of administration of the regimen is CISplatin followed by etoposide (guideline dosage) [35]
  • (Limited stage) CISplatin 25 mg/m(2) IV days 1 through 3 and etoposide 100 mg/m(2) IV days 1 through 3; repeat cycle every 3 weeks for a MAX of 4 to 6 cycles; if bolus etoposide-CISplatin is selected for treatment, the sequence of administration of the regimen is CISplatin followed by etoposide (guideline dosage) [35]
  • (Extensive stage) CISplatin 75 mg/m(2) on day 1 and etoposide 100 mg/m(2) days 1 through 3; repeat every 3 weeks; if bolus etoposide-CISplatin is selected for treatment, the sequence of administration of the regimen is CISplatin followed by etoposide (guideline dosage) [35]
  • (Extensive stage) CISplatin 80 mg/m(2) on day 1 and etoposide 80 mg/m(2) days 1 through 3; repeat every 3 weeks; if bolus etoposide-CISplatin is selected for treatment, the sequence of administration of the regimen is CISplatin followed by etoposide (guideline dosage) [35]
  • (Extensive stage) CISplatin 25 mg/m(2) days 1 through 3 and etoposide 100 mg/m(2) days 1 through 3; repeat every 3 weeks; if bolus etoposide-CISplatin is selected for treatment, the sequence of administration of the regimen is CISplatin followed by etoposide (guideline dosage) [35]
  • (Extensive stage) CISplatin 60 mg/m(2) on day 1 and irinotecan 60 mg/m(2) days 1, 8, and 15; repeat every 4 weeks (guideline dosage) [35]
  • (Extensive stage) CISplatin 30 mg/m(2) and irinotecan 65 mg/m(2) days 1 and 8; repeat every 4 weeks (guideline dosage) [35]
Thymoma
  • CISplatin 60 mg/m(2) IV over 1 hour on day 1 and etoposide 120 mg/m(2) IV over at least 30 minutes on days 1 through 3; repeat cycles every 3 weeks for MAX, 8 cycles (off-label dosage) [36]
  • (ADOC regimen) CISplatin 50 mg/m(2) IV and DOXOrubicin 40 mg/m(2) IV on day 1, vinCRIStine 0.6 mg/m(2) IV on day 3, and cyclophosphamide 700 mg/m(2) IV on day 4; repeat every 3 weeks (off-label dosage) [37]
  • (PAC regimen) CISplatin 50 mg/m(2) in 250 mL IV over 1 hour (with at least 1 L of NS over at least 2 hours before and after CISplatin), DOXOrubicin 50 mg/m(2) IV, and cyclophosphamide 500 mg/m(2) IV; repeat every 21 days for up to 8 cycles (off-label dosage) [38]
Triple-negative breast cancer
  • (Metastatic) CISplatin 75 mg/m(2) IV and docetaxel 75 mg/m(2) IV on Day 1 every 3 weeks for 6 cycles or disease progression, unacceptable toxicity, or death (off-label dosage) [39]
Vulvar cancer
  • (Locally advanced) CISplatin 40 mg/m(2) IV (MAX dose, 70 mg) weekly with radiation administered daily for 5 days repeated weekly; CISplatin treatment cycles were repeated weekly to a MAX of 7 cycles (off-label dosage) [40]
  • (Neoadjuvant chemotherapy) CISplatin 50 mg/m(2) IV on day 1 and a continuous infusion of 5-fluorouracil 1000 mg/m(2)/day IV on days 1 through 4 with radiation on days 1 through 4, day 5, and days 8 through 12; repeat the 2-week cycle of chemoradiation after 1.5 to 2.5 weeks (off-label dosage) [41]
  Pediatric Dosing
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Important Note
  • To prevent inadvertent CISplatin overdosage use caution and confirm dosing if greater than 100 mg/m(2)/cycle [3].
  • This drug has one or more orphan drug designations, which may include approval or withdrawal of status: Access citation for FDA Orphan Drug Information [4].
Germ cell tumor
  • optimal dose and timing not defined in this setting
Hepatoblastoma
  • (monotherapy) standard risk, 80 mg/m(2) as a continuous 24-hour IV infusion every 14 days for 4 cycles prior to surgery was used in a clinical trial [42]
Neuroblastoma
  • optimal dose and timing not defined in this setting
Osteosarcoma
  • optimal dose and timing not defined in this setting
 
  Dose Adjustments
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  • Renal impairment: Consider dosage reduction in patients with baseline renal impairment or consider alternative agent [3]
  • Renal impairment (GFR greater than 60 mL/min): 50 to 120 mg/m(2) IV every 3 to 6 weeks [43]; a guideline recommends 75% of the usual dose when CrCl is 60 mL/min [44]
  • Renal impairment (GFR 30 to 60 mL/min): 35 to 80 mg/m(2) IV every 3 to 6 weeks [43]; a guideline recommends 50% of usual dose when CrCl is 45 mL/min and consider use of an alternative drug, if feasible, when CrCl is 30 mL/min [44]
  • Renal impairment (GFR 15 to 29 mL/min): 25 to 60 mg/m(2) IV every 3 to 6 weeks [43]
  • Renal impairment (GFR less than 15 mL/min): Not recommended; if necessary or use is unavoidable, consider 25 mg/(2) IV [43]
  • Renal impairment (GFR 50 to 59 mL/min) in curative or palliative regimens: Give 75% of the original dose [45]
  • Renal impairment (GFR less than 50 mL/min) in palliative regimens: Use is not recommended [45]
  • Renal impairment (GFR 40 to 49 mL/min) in curative regimens: Give 50% of the original dose [45]
  • Renal impairment (GFR less than 40 mL/min) in curative regimens: Use is not recommended [45]
  • Hepatic impairment: No specific recommendations are available in hepatically-impaired patients [3]. No need for dosage adjustment is expected based upon findings from a review of adult patients starting therapy; recommendations are based on published literature, drug labels, and/or extrapolated from pharmacokinetic properties of the drug [45].
  • Geriatric: Carefully select dose due to increased risk of some adverse events [3]
  • Continuous ambulatory peritoneal dialysis (CAPD): Not recommended; if necessary or use is unavoidable, consider 25 mg/(2) IV every 3 to 6 weeks [43]
  • Continuous renal replacement therapy (CRRT): Not recommended [43]
  • Hemodialysis: Not recommended; if necessary or use is unavoidable, consider 25 to 30 mg/(2) IV every 1 to 6 weeks [43]
  • Hemodialysis in curative regimens: May consider giving 50% of the original dose [45]
  • Hemodialysis in palliative regimens: Use is not recommended; consider alternative agents [45]
  • Hemodialysis, ESRD: Reduce dose by 50% to 75% and give after hemodialysis [46]
  • Hemodialysis, ESRD in patients with lung cancer receiving CISplatin plus vinorelbine: CISplatin 25 to 50 mg/m(2) day 1 plus vinorelbine 20 mg/m(2)/week on days 1 and 8; dialysis 1 hour after chemotherapy, daily [46]
  • Hemodialysis, ESRD in patients with lung cancer receiving CISplatin plus gemcitabine: CISplatin 25 to 50 mg/m(2) day 1 plus gemcitabine 800 mg/m(2) on days 1 and 8; dialysis 1 hour after CISplatin [46]
  • Hemodialysis, ESRD in patients with lung cancer receiving CISplatin plus paclitaxel: CISplatin 25 to 50 mg/m(2) day 1 plus paclitaxel 175 mg/m(2) on day 1; dialysis 1 hour after CISplatin [46]
  • Hemodialysis, ESRD in patients with lung cancer receiving CISplatin plus etoposide: Dialysis 1 hour after CISplatin [46]
  • Hemodialysis, ESRD in patients with gastrointestinal cancer receiving CISplatin plus fluorouracil: CISplatin 25 to 50 mg/m(2) day 1 plus fluorouracil 500 mg/m(2) continuous infusion on days 1 to 5; dialysis 1 hour after CISplatin, every 2 days [46]
  • Hemodialysis, ESRD in patients with germ cell tumors receiving CISplatin plus etoposide: CISplatin 14 to 20 mg/m(2) plus etoposide 50 to 100 mg/m(2) on day 1 to 4; dialysis daily or on days 2 and 4 [46]
  • Hemodialysis, ESRD in patients with urothelial cancer receiving M-VAC (methotrexate, vinBLAStine, DOXOrubicin, CISplatin): Methotrexate 15 mg/m(2), CISplatin 40 mg/m(2), vinBLAStine 1.8 mg/m(2), DOXOrubicin 18 mg/ m(2) day 1; dialysis 1 hour after CISplatin [46]
  • Myelosuppression: Consider dosage reduction or alternative treatment [3]
  • Nephrotoxicity: Consider dosage reduction in patients who develop significant reductions in CrCl [3]; CrCl 60 mL/min, give 75% of the normal dose; CrCl 45 mL/min give 50% of normal dose; CrCl 30 mL/min consider use of alternative drug if feasible [44]
  • Neurotoxicity: Consider dosage reduction or alternative treatment [3]
  FDA-Labeled Indications
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  • Bladder cancer, Advanced, transitional cell, monotherapy, no longer amenable to local treatments such as surgery or radiotherapyView additional information.
  • Metastatic malignant tumor of testis, In combination with other chemotherapy agentsView additional information.
  • Metastatic ovarian tumorView additional information.
  Non-FDA Labeled Indications
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  • Adrenal carcinoma, Locally advanced/metastaticView additional information.
  • Biliary tract cancerView additional information.
  • Bladder cancer, Muscle invasive, as neoadjuvant combination chemotherapyView additional information.
  • Breast cancerView additional information.
  • Carcinoma of esophagusView additional information.
  • Cervical cancerView additional information.
  • Endometrial cancerView additional information.
  • Gastric cancerView additional information.
  • Germ cell tumorView additional information.
  • Germ cell tumor of ovaryView additional information.
  • Gestational trophoblastic neoplasiaView additional information.
  • Glial tumor of brainView additional information.
  • Head and neck cancerView additional information.
  • HepatoblastomaView additional information.
  • Hodgkin's disease, Relapsed or refractoryView additional information.
  • Liver carcinomaView additional information.
  • Malignant mesothelioma of pleuraView additional information.
  • MelanomaView additional information.
  • Multiple myeloma, Relapsed/refractoryView additional information.
  • Nasopharyngeal cancerView additional information.
  • NeuroblastomaView additional information.
  • Non-Hodgkin's lymphoma, Relapsed or refractory, as part of the DHAP or ESHAP regimenView additional information.
  • Non-small cell lung cancerView additional information.
  • OsteosarcomaView additional information.
  • Ovarian cancerView additional information.
  • RetinoblastomaView additional information.
  • SarcomaView additional information.
  • Small cell lung cancerView additional information.
  • ThymomaView additional information.
  • Triple-negative breast cancerView additional information.
  • Vulvar cancerView additional information.
  Boxed Warning
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Boxed Warning
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Intravenous (Powder for Solution)
  • Nephrotoxicity: cisplatin injection can cause severe renal toxicity, including acute renal failure. Severe renal toxicities are dose-related and cumulative. Consider dose reductions or alternative treatments in patients with renal impairment.
  • Peripheral Neuropathy: cisplatin injection can cause dose-related peripheral neuropathy.
  • Nausea and Vomiting: cisplatin injection can cause severe nausea and vomiting. Premedicate with antiemetics.
  • Myelosuppression: cisplatin injection can cause severe myelosuppression with fatalities due to infections. Monitor blood counts and interrupt therapy accordingly [3].
  Contraindications/Warnings
 
  Do Not Confuse
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  • CISplatin - CARBOplatin[1][2]
  • Platinol - Patanol[2]
 
  Contraindications
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  • Severe hypersensitivity to cisplatin [3]
 
  Precautions
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  • Dermatologic: Injection site reactions has been reported; monitoring recommended [3]
  • Dermatologic: Local soft tissue toxicity has been reported following extravasation; monitoring recommended [3]
  • Dermatologic: Cellulitis, fibrosis, necrosis, pain, edema, and erythema have been reported with solution concentrations greater than 0.5 mg/mL; monitoring recommended [3]
  • Gastrointestinal: Severe nausea and vomiting commonly occurs. Premedication required and discontinuation or additional post-infusion antiemetics may be necessary [3]
  • Hematologic: Myelosuppression has been reported with increased risk in geriatric patients; monitoring recommended and dose adjustments may be necessary [3]
  • Immunologic: Fatal cases of neutropenic fever and infection have been reported [3]
  • Immunologic: Severe hypersensitivity reactions, including anaphylaxis, have been reported; monitoring recommended and discontinuation may be necessary [3]
  • Immunologic: Cross-reactivity between platinum-based antineoplastic agents have been reported. Severe hypersensitivity reactions have recurred after rechallenging patients with different platinum agent [3].
  • Neurologic: Dose-related peripheral neuropathy has been reported and may become more severe with repeated courses; increased risk in geriatric patients. May be irreversible and progress further after discontinuation; monitoring recommended and discontinuation may be necessary [3]
  • Ophthalmic: Optic neuritis, papilledema, and cortical blindness have been reported [3]
  • Ophthalmic: Blurred vision and altered color perception have been reported with higher doses and dose frequencies [3]
  • Otic: Ototoxicity has been reported and may occur during or after treatment and can be unilateral or bilateral with increased risk in pediatric patients, simultaneous cranial irradiation, treatment with other ototoxic drugs, and renal impairment [3]
  • Otic: Deafness after the initial dose has been reported [3]
  • Otic: Vestibular toxicity has been reported [3]
  • Renal: Dose-related nephrotoxicity may occur, including acute renal failure that becomes more prolonged and severe with repeated courses; increased risk in patients with baseline renal impairment, geriatric patients, patients who are taking other nephrotoxic drugs, or patients who are not well hydrated. Monitoring recommended and alternative treatments or dose adjustment may be necessary [3]
  • Reproductive: May cause fetal harm; advise use of effective contraception during treatment and for 14 months after last dose in females of reproductive potential and 11 months after last dose in male patients with female partners of reproductive potential [3]
 
  Pregnancy Category
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  Breast Feeding
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  Drug Interactions (single)
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Contraindicated
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  • Bacillus of Calmette and Guerin Vaccine, Live (established)
  • Dengue Tetravalent Vaccine, Live (established)
  • Measles Virus Vaccine, Live (established)
  • Mumps Virus Vaccine, Live (established)
  • Rubella Virus Vaccine, Live (established)
  • Smallpox Monkeypox Vaccine (established)
  • Typhoid Vaccine (established)
  • Varicella Virus Vaccine (established)
  • Yellow Fever Vaccine (established)
 
Major
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  • Adenovirus Vaccine Type 4, Live (established)
  • Adenovirus Vaccine Type 7, Live (established)
  • Aspirin (theoretical)
  • Cholera Vaccine (established)
  • Doxorubicin (probable)
  • Doxorubicin Hydrochloride Liposome (probable)
  • Ebola Zaire Vaccine, Live (established)
  • Fosphenytoin (probable)
  • Furosemide (theoretical)
  • Influenza Virus Vaccine, Live (established)
  • Melphalan (theoretical)
  • Paclitaxel (probable)
  • Paclitaxel Protein-Bound (probable)
  • Phenytoin (probable)
  • Rituximab (probable)
  • Rotavirus Vaccine, Live (established)
  • Tacrolimus (theoretical)
  • Teicoplanin (theoretical)
  • Thioctic Acid (theoretical)
  • Trilaciclib (theoretical)
  • Valproic Acid (probable)
  • Vinorelbine (established)
 
Moderate
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  • Aldesleukin (probable)
  • Docetaxel (established)
  • Lithium (probable)
  • Tobramycin (probable)
  • Warfarin (probable)
  Adverse Effects
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Common
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  • Hematologic: Anemia (11% ), Leukopenia (27% ), Thrombocytopenia (16% )
  • Neurologic: Peripheral neuropathy (Common )
   
Serious
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  • Dermatologic: Injection site disorder, Injection site extravasation
  • Gastrointestinal: Nausea and vomiting (Up to 100% )
  • Hematologic: Myelosuppression (25% to 30% )
  • Hepatic: Liver failure
  • Immunologic: Hypersensitivity reaction, Hypersensitivity reaction
  • Neurologic: Cerebral herniation, Encephalopathy, Neuropathy (61% ), Neurotoxicity (47% ), Posterior reversible encephalopathy syndrome, Seizure
  • Ophthalmic: Cortical blindness, Optic disc edema, Optic neuritis
  • Otic: Ototoxicity (Up to 60% )
  • Renal: Hemolytic uremic syndrome, Nephrotoxicity (Common )
  Name Info
 
Drug Images
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No images available.

   
US Trade Names
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  • Platinol-AQ
All Trade Names
 
  Class
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View Detailed information in DRUGDEX
  • Antineoplastic Agent
  • Platinum Coordination Complex
   
Regulatory Status
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  • RX
   
Generic Availability
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  • Yes
  Mechanism of Action/Pharmacokinetics
 
  Mechanism of Action
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View Detailed information in DRUGDEX
  • Cisplatin is an alkylating-like chemotherapeutic agent [57].
  Pharmacokinetics
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View Detailed information in DRUGDEX
  Absorption
  • Tmax, IV: 90 to 150 minutes (red blood cells) [58]
  Distribution
  • Vd: 11 to 12 L/m(2) [58]
  • Protein binding, albumin, transferrin, and gamma globulin: Platinum 90% bound [58][59]
  Excretion
  • Renal clearance: 50 to 62 mL/min/m(2) [58]
  • Renal excretion: 13% to 17% [58]
  • Fecal excretion: Insignificant amounts [58]
  • Biliary excretion: Small amounts [58]
  • Total body clearance: 15 to 21 L/hr/m(2) [58][60]
  • Hemodialysis: No [58]
  • Peritoneal dialysis: Nominal [61][57][62]
  Elimination Half Life
  • Terminal t(1/2): 36 to 47 days[58]; initial t(1/2), 25 to 49 minutes [59]
  Administration/Monitoring
  Administration
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View Detailed information in DRUGDEX
General Information
  • NIOSH: Table 1 Hazardous drug [47]
  • NIOSH: When preparing a hazardous injectable drug from a vial or ampule, wear double chemotherapy gloves, protective gown, and hair and shoe covers. Prepare in a ventilated engineering control, use a closed system drug-transfer device when dosage form allows, and use eye/face and respiratory (N95) protection if not prepared in a ventilated engineering control [48].
  • NIOSH: When administering a hazardous injectable drug, wear double chemotherapy gloves and a protective gown and add eye/face protection if there is a potential that the substance could splash. Use a closed system drug-transfer device when dosage form allows. Single chemotherapy gloves are appropriate if administering from prefilled syringe or injector [48].
  • For IV use only [3].
Intravenous
  • Inspect visually for particulate matter and discoloration prior to administration [3]
  • Infuse via slow IV infusion over 6 to 8 hours [3]
  • Materials used to prepare and administer CISplatin should not contain aluminum as aluminum interacts with CISplatin causing precipitate formation and loss of potency [3].
 
  Monitoring
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View Detailed information in DRUGDEX
  • Evidence of tumor response is indicative of efficacy.
  • Renal function, including serum creatinine, blood urea nitrogen, and CrCl: Prior to initiating therapy and as clinically indicated [3][49]
  • Serum electrolytes, including magnesium: Prior to initiating therapy and as clinically indicated [3][49]
  • Hematologic tests: Prior to therapy, before each subsequent course, and as clinically indicated [3][49]
  • Audiometric and vestibular functioning: Especially in pediatric patients [3][49]
  • Extravasation and injection site reactions [3][49]
  • Hypersensitivity reactions: Which have occurred within minutes of administration [3][49]
  • Neurologic examination: For signs of peripheral neuropathy, prior to, during, and after therapy, especially in geriatric patients [3][49]
  • Pregnancy status: Of females of reproductive potential prior to initiation [49]
  • Signs and symptoms of infection: During and after therapy [3][49]
  How Supplied
 
How Supplied
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Generic
  • Intravenous Powder for Solution: 50 MG
  • Intravenous Solution: 1 MG/1 ML
Kemoplat
  • Intravenous Solution: 1 MG/1 ML
  Toxicology
 
Clinical Effects
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CISPLATIN
  • USES: CISplatin is a widely used anticancer agent. Most commonly, CISplatin is used to treat cancers of the testes, ovary, bladder, head and neck, esophagus, stomach, and lung. PHARMACOLOGY: CISplatin binds to DNA bases, forming inter- and intra-strand crosslinks, which causes conformational changes, leading to DNA strand breaks and inhibiting DNA synthesis. TOXICOLOGY: An extension of therapeutic effects with inhibition of DNA synthesis affecting rapidly dividing cells first (eg, bone marrow, GI tract). EPIDEMIOLOGY: Inadvertent iatrogenic overdose has occurred, but is rare. OVERDOSE: Immediate effects (hours to days) include: severe nausea and vomiting and, less often, diarrhea. Early signs (within days) of toxicity are most commonly renal insufficiency and electrolyte abnormalities (hyponatremia, hypokalemia, hypomagnesemia, hypocalcemia). Ototoxicity (tinnitus, high-frequency deafness), peripheral neuropathy (mostly sensorineural), and bone marrow suppression are common, whereas retinopathy, seizures, hepatotoxicity, pancreatitis, respiratory failure, and overt encephalopathy are less often observed. ADVERSE EFFECTS: Adverse effects are expected with therapeutic doses. Nausea, vomiting, renal insufficiency (28% to 36%), electrolyte abnormalities, and neurotoxicity (peripheral neuropathy, mostly sensorineural) are the most often reported events. Nephrotoxicity is generally the dose-limiting effect. Hypersensitivity reactions may be observed in patients treated with more than 5 cycles of CISplatin therapy.
 
Treatment
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CISPLATIN
  • Supportive care: MANAGEMENT OF MILD TO MODERATE TOXICITY: Aggressive IV fluid resuscitation with normal saline 3 to 6 L per day. Target urine output 1 to 3 mL/kg/hr. Avoid nephrotoxic drugs. Administer amifostine as soon as possible to prevent/limit nephrotoxicity (dose 910 mg/m(2) once daily as an intravenous infusion over 15 minutes). Treat persistent nausea and vomiting with several antiemetics of different classes. Diphenhydramine may be required to prevent dystonic reactions from dopamine antagonists, phenothiazines, and antipsychotics. Patients with severe neutropenia should be placed in protective isolation; administer granulocyte colony stimulating factor (filgrastim or sargramostim). Platelet and red cell transfusions may be necessary. MANAGEMENT OF SEVERE TOXICITY: Aggressive IV fluid resuscitation with normal saline 3 to 6 L per day. Target urine output 1 to 3 mL/kg/hr. Avoid nephrotoxic drugs. Administer amifostine as soon as possible to prevent/limit nephrotoxicity (dose 910 mg/m(2) once daily as an intravenous infusion over 15 minutes). Consider administration of sodium thiosulfate, ideally within 1 to 2 hours of overdose. In case of large overdoses, consider early plasmapheresis. Patients with severe neutropenia should be placed in protective isolation; administer granulocyte colony stimulating factor (filgrastim or sargramostim). Platelet and red cell transfusions may be necessary. Severe nausea and vomiting may respond to a combination of agents from different drug classes. Administer high-dose dopamine (D2) receptor antagonists (eg, metoclopramide), phenothiazines (eg, promethazine or prochlorperazine), corticosteroids (eg, dexamethasone), benzodiazepines (eg, lorazepam), 5-HT3 serotonin antagonists (eg, ondansetron, dolasetron, or granisetron), and/or antipsychotics (eg, haloperidol); diphenhydramine may be required to prevent dystonic reactions from dopamine antagonists, phenothiazines, and antipsychotics.
  • Patient disposition: HOME CRITERIA: There is no data to support home management. Patients with CISplatin overdose need to be admitted. OBSERVATION CRITERIA: Patients should be closely monitored in an inpatient setting, with frequent monitoring of vital signs (every 4 hours for the first 24 hours), daily monitoring of CBC with differential until bone marrow suppression is resolved, and monitoring of serum electrolytes, renal function, and hepatic enzymes. CONSULT CRITERIA: Consult an oncologist, medical toxicologist, and/or a poison center for assistance in managing patients with CISplatin overdose. TRANSFER CRITERIA: Patients with large overdoses may benefit from early transfer to a cancer treatment or bone marrow transplant center.
  • Decontamination: PREHOSPITAL: Not helpful since overdose most often occurs by the intravenous route. HOSPITAL: Activated charcoal and/or gastric lavage are not helpful since overdose most often occurs by the intravenous route.
  • Airway management: Consider orotracheal intubation in patients with significant encephalopathy (ie, agitation, delirium), seizures, or respiratory failure.
  • Antidote: Amifostine reduces CISplatin-induced nephrotoxicity and neutropenia when administered prior to CISplatin therapy; there are no studies on its use after CISplatin overdose. However, if amifostine is being utilized as a remedy for CISplatin overdose, it should be administered as soon as possible after an overdose (dose 910 mg/m(2) once daily as an intravenous infusion over 15 minutes, optimal duration of therapy after overdose is not known). Sodium thiosulfate has been prophylactically administered in patients treated with CISplatin to prevent neurotoxicity and nephrotoxicity, and has been used in several cases of overdose. While there are no controlled studies of its use in overdose, sodium thiosulfate has limited toxic effects and it should be considered after significant overdose. It should ideally be administered within 1 to 2 hours of overdose, with a loading dose of 4 g sodium thiosulfate/m(2) intravenously over 15 minutes. This can be followed by an infusion of 12 g/m(2) over 6 hours or 2.7 g/m(2) per day in 3 divided doses. The optimal duration of therapy is not known. It is not known if administration of thiosulfate and amifostine is more beneficial than administration of amifostine alone.
  • Myelosuppression: Administer colony stimulating factors following a significant overdose as these patients are at risk for severe neutropenia. Filgrastim: 5 mcg/kg/day IV or subQ. Sargramostim: 250 mcg/m(2)/day IV over 4 hours. Monitor CBC with differential and platelet count daily for evidence of bone marrow suppression until recovery has occurred. Transfusion of platelets and/or packed red cells may be needed in patients with severe thrombocytopenia, anemia or hemorrhage. Patients with severe neutropenia should be in protective isolation. Transfer to a bone marrow transplant center should be considered.
  • Neutropenia: Prophylactic therapy with a fluoroquinolone should be considered in high risk patients with expected prolonged (more than 7 days), and profound neutropenia (ANC 100 cells/mm(3) or less).
  • Febrile neutropenia: If fever (38.3 C) develops during neutropenic phase (ANC 500 cells/mm(3) or less), cultures should be obtained and empiric antibiotics started. HIGH RISK PATIENT (anticipated neutropenia of 7 days or more; unstable; significant comorbidities): IV monotherapy with either piperacillin-tazobactam; a carbapenem (meropenem or imipenem-cilastatin); or an antipseudomonal beta-lactam agent (eg, ceftazidime or cefepime). LOW RISK PATIENT (anticipated neutropenia of less than 7 days; clinically stable; no comorbidities): oral ciprofloxacin and amoxicillin/clavulanate.
  • Nausea and vomiting: Treat patients with dopamine (D2) receptor antagonists (eg, metoclopramide), phenothiazines (eg, prochlorperazine), 5-HT3 antagonists (eg, dolasetron, granisetron, ondansetron, palonosetron), NK1 receptor antagonist (eg, aprepitant, fosaprepitant, rolapitant), benzodiazepines (eg, lorazepam), corticosteroids (eg, dexamethasone), and antipsychotics (eg, haloperidol, olanzapine) in addition to continuing the standard antiemetic regimen; diphenhydramine may be required to prevent dystonic reactions from dopamine antagonists, phenothiazines, and antipsychotics. In general, rectal medications should be avoided in patients with neutropenia.
  • Nephrotoxicity: Aggressive IV fluid resuscitation with normal saline 3 to 6 L per day. Target urine output 1 to 3 mL/kg/hr. Avoid nephrotoxic drugs. For prevention of CISplatin-induced nephrotoxicity, administer amifostine. The recommended dose is 910 mg/m(2) administered once daily as an intravenous infusion, over a 15-minute period.
  • Extravasation injury: If extravasation occurs, stop the infusion. Disconnect the IV tubing, but leave the cannula or needle in place. Attempt to aspirate the extravasated drug from the needle or cannula. If possible, withdraw 3 to 5 mL of blood and/or fluids through the needle/cannula. Elevate the affected area. Apply ice packs for 15 to 20 minutes at least 4 times daily. Do not apply excessive cold to avoid tissue injury. Cold can cause local vasoconstriction and reduces fluid absorption. Administer analgesia for severe pain. If pain persists, there is concern for compartment syndrome, or injury is apparent, an early surgical consult should be considered. Close observation of the extravasated area is suggested. If tissue sloughing, necrosis or blistering occurs, treat as a chemical burn (ie, antiseptic dressings, silver sulfadiazine, antibiotics when applicable). Surgical or enzymatic debridement may be required. Risk of infection is increased in chemotherapy patients with reduced neutrophil count following extravasation. Consider culturing any open wounds. Monitor the site for the development of cellulitis, which may require antibiotic therapy. DIMETHYL SULFOXIDE (DMSO): Treat site with topical DMSO (for a minimum of 7 days and maximum of 14 days); however, if blistering develops, discontinue DMSO and review site. SODIUM THIOSULFATE (SODIUM HYPOSULFITE): There are no clinical reports of the use of sodium thiosulfate following CISplatin extravasation. Its use for CISplatin extravasation is based on the ability of sodium thiosulfate to inactivate CISplatin. For extravasation of large amounts (greater than 20 mL) of highly concentrated (greater than 0.5 mg/mL solution) prepare a 0.17 moles/L solution by mixing 4 mL sodium thiosulfate 10% weight/volume with 6 mL sterile water for injection. Inject into extravasation site. Another source recommended the following dosing: inject 3 to 10 mL subQ into extravasation site.
  • Monitoring of patient: Monitor vital signs and mental status. CISplatin plasma levels are not clinically useful or readily available. Closely monitor renal function, hepatic enzymes, and electrolytes. Monitor daily CBC with differential to detect bone marrow depression. Nadirs in circulating platelets and leukocytes typically occur between days 18 to 23 (range 7.5 to 45), with the majority of patients recovering by day 39 (range 13 to 62). Monitor for clinical evidence of infection, with particular attention to: odontogenic infection, oropharynx, esophagus, soft tissues particularly in the perirectal region, exit and tunnel sites of central venous access devices, upper and lower respiratory tracts, and urinary tract. Nerve conduction studies may be useful to evaluate neuropathy and audiometry to evaluate hearing loss.
  • Intrathecal injection: No clinical reports are available. The following information is derived from experience with other antineoplastic drugs. Keep patient upright if possible. Immediately drain at least 20 mL CSF; drainage of up to 70 mL has been tolerated in adults. Follow with CSF exchange (remove serial 20 mL aliquots CSF and replace with equivalent volumes of warmed, preservative free 0.9% saline). Consult a neurosurgeon for placement of a ventricular catheter and begin ventriculolumbar perfusion (infuse warmed preservative free normal saline through ventricular catheter, drain fluid from lumbar catheter; typical volumes 80 to 150 mL/hr for 18 to 24 hr). FFP (25 mL FFP/liter NS) or albumin 5% have also been used for perfusion; may be useful because of high protein binding of CISplatin. Dexamethasone 4 mg IV every 6 hours to prevent arachnoiditis.
  • Enhanced elimination procedure: CISplatin is highly protein bound and can be removed by plasmapheresis. There is limited experience in the use of plasmapheresis after overdose, but it should be performed as soon as possible after significant overdose. The optimal volume, timing and duration of plasmapheresis is not known; monitor CISplatin concentrations, if possible, to guide therapy.
 
Range of Toxicity
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CISPLATIN
  • TOXICITY: Expect toxicity with therapeutic doses. Mild toxicity occurs with doses of 180 mg/m(2) or less, moderate toxicity may occur with doses of 180 to 300 mg/m(2), and severe toxicity has been reported with doses greater than 300 mg/m(2). Doses of 400 mg/m(2) are usually fatal. ADULT: Deaths have been reported with a total CISplatin dose of 640 mg over 4 days and 750 mg over 1 day. PEDIATRIC: A 3-year-old child died after receiving 400 mg/m(2). THERAPEUTIC DOSE: ADULT: BLADDER CANCER, ADVANCED: As a single agent, 50 to 70 mg/m(2) IV per cycle once every 3 to 4 weeks. For heavily pretreated patients, an initial dose of 50 mg/m(2) per cycle repeated every 4 weeks is recommended. OVARIAN CANCER, ADVANCED: 75 to 100 mg/m(2) IV per cycle once every 3 to 4 weeks. TESTICULAR CANCER, METASTATIC: 20 mg/m(2) IV daily for 5 days per cycle. Other doses and combination regimens have been used for all indications. PEDIATRIC: Although the manufacturer of cisplatin states that safety and efficacy have not been established in children, CISplatin monotherapy, 80 mg/m(2), has been administered as a continuous 24-hr IV infusion every 14 days for 4 cycles in clinical trials.
  Clinical Teaching
   
Clinical Teaching
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  • Advise patient to report new paresthesias [3][49].
  • Warn patient to report new onset fever, symptoms of infection, or bleeding [3][3].
  • Recommend female patient of reproductive potential avoid pregnancy and use effective contraception during therapy and for 14 months after last dose [3][49].
  • Tell male patient with female partner of reproductive potential to avoid pregnancy and use effective contraception during therapy and for 11 months after last dose [3][49].
  • Side effects may include nephrotoxicity, blurred vision, diarrhea, asthenia, muscle cramps, and alopecia [3][49].
  • Advise patient to report symptoms of hearing loss or vestibular dysfunction [3][49].
  • Tell patient to report persistent or severe symptoms of nausea and vomiting [3][49].
  • Encourage patient to maintain adequate fluid intake before, during, and after therapy [3][49].
  • Cisplatin (Intravenous route, Solution)
  References
 
References
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 3. Product Information: CISPLATIN intravenous injection, cisplatin intravenous injection. BluePoint Laboratories (per DailyMed), Columbus, OH, 2019.

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