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Cisplatin: Drug information

Copyright 1978-2020 Lexicomp, Inc. All rights reserved.

(For additional information see "Cisplatin: Patient drug information" and see "Cisplatin: Pediatric drug
information")

For abbreviations and symbols that may be used in Lexicomp (show table)

ALERT: US Boxed Warning

Myelosuppression:

Cisplatin can cause severe myelosuppression with fatalities due to infections.

Monitor blood counts accordingly. Interruption of therapy may be required.

Nausea and vomiting:

Cisplatin can cause severe nausea and vomiting. Use highly effective antiemetic
premedication.

Nephrotoxicity:

Cisplatin can cause severe renal toxicity, including acute renal failure. Severe renal
toxicities are dose-related and cumulative. Ensure adequate hydration and monitor
renal function and electrolytes. Consider dose reductions or alternative treatments in
patients with renal impairment.

Peripheral neuropathy:

Cisplatin can cause dose-related peripheral neuropathy that becomes more severe
with repeated courses of the drug.

Pharmacologic Category
Antineoplastic Agent, Alkylating Agent; Antineoplastic Agent, Platinum Analog
Dosing: Adult
Note: Administer appropriate pretreatment hydration and maintain adequate hydration
and urinary output for 24 hours following cisplatin administration. Cisplatin is associated
with a high emetic potential; antiemetics are recommended to prevent nausea and
vomiting (Hesketh 2017; Roila 2016). Cisplatin doses exceeding 100 mg/m2 per
treatment course are rarely used and should be verified with the prescriber.

Adrenocortical carcinoma (advanced) (off-label use): IV: 40 mg/m2 on days 3

and 4 every 4 weeks (in combination with doxorubicin, etoposide, and mitotane)
(Fassnacht 2012) or 40 mg/m2 on days 2 and 9 every 4 weeks (in combination with
doxorubicin, etoposide, and mitotane) until disease progression or unacceptable
toxicity up to a maximum of 6 cycles (Berruti 2005).

Anal carcinoma, squamous cell, metastatic (off-label use; based on limited

data): IV: 75 mg/m2 on day 1 every 4 weeks (in combination with continuous
infusion fluorouracil) (Eng 2014).

Biliary tract cancer, advanced (off-label use): IV: 25 mg/m2 over 2 hours on days
1 and 8; repeat cycle every 3 weeks (in combination with gemcitabine) for 4 to 8
cycles (Valle 2010).

Bladder cancer, advanced: IV: 50 to 70 mg/m2 every 3 to 4 weeks; heavily

pretreated patients: 50 mg/m2 every 4 weeks.

Bladder cancer, advanced (off-label dosing/combinations): IV:

Locally advanced or metastatic disease:

Dose-dense MVAC regimen: 70 mg/m2 on day 2 every 14 days (in

combination with methotrexate, vinblastine, doxorubicin, and growth
factor support) until disease progression or unacceptable toxicity
(Sternberg 2001; Sternberg 2006).

GC regimen: 70 mg/m2 on day 2 every 28 days (in combination with

gemcitabine) for up to 6 cycles (von der Maase 2000). Split-dose
cisplatin may be an option in select patients (Kim 2015).

MVAC regimen: 70 mg/m2 on day 2 every 28 days (in combination with

methotrexate, vinblastine, and doxorubicin) for up to 6 cycles (von der
Maase 2000) or 70 mg/m2 on day 2 every 28 days (in combination
 with methotrexate, vinblastine, and doxorubicin) until disease
progression or unacceptable toxicity (Sternberg 2001; Sternberg 2006)
or 70 mg/m2 on day 1 every 28 days (in combination with
methotrexate, vinblastine, doxorubicin, and filgrastim) for up to 6
cycles or until loss of clinical benefit (Bamias 2004).

Neoadjuvant treatment:

Note: Patients with non-organ confined disease at cystectomy who did

not receive cisplatin-based neoadjuvant chemotherapy should be
offered an adjuvant cisplatin-based chemotherapy regimen. Some
patients with borderline renal function may be treated with split-dose
cisplatin and aggressive hydration (AUA/ASCO/ASTRO/SUO [Chang
2017]).

Dose-dense MVAC regimen: 70 mg/m2 on day 1 or on day 2 every 14

days (in combination with methotrexate, doxorubicin, vinblastine, and
pegfilgrastim) for 3 or 4 cycles (Choueiri 2014; Plimack 2014).

GC regimen: 70 mg/m2 on day 1 every 21 days or (split-dose cisplatin)

35 mg/m2 on days 1 and 8 every 21 days (in combination with
gemcitabine) for 4 cycles (Dash 2008).

MVAC regimen: 70 mg/m2 on day 2 every 28 days (in combination with

methotrexate, vinblastine, and doxorubicin) for 3 cycles (Grossman
2003).

CMV regimen: 100 mg/m2 on day 1 every 21 days (in combination with
methotrexate, vinblastine, and leucovorin) for 3 cycles (Griffiths 2011).

Brain metastases (due to breast or non-small cell lung cancers) (off-label

use): IV: 100 mg/m2 on day 1 every 3 weeks (in combination with etoposide) for up
to 6 cycles in the absence of disease progression or unacceptable toxicity (Franciosi
1999).

Breast cancer, triple-negative (off-label use): IV: Neoadjuvant therapy (single

agent): 75 mg/m2 on day 1 every 3 weeks for 4 cycles (Silver 2010).

Cervical cancer (off-label use): IV: 40 mg/m2 over 4 hours prior to radiation
therapy on days 1, 8, 15, 22, 29, and 36 (Rose 2007) or 75 mg/m2 on day 1 every 3
weeks (in combination with fluorouracil and radiation) for 3 cycles (Morris 1999) or
70 mg/m2 on day 1 every 3 weeks for 4 cycles (in combination with fluorouracil;
cycles 1 and 2 given concurrently with radiation) (Peters 2000) or 50 mg/m2 on day
1 every 4 weeks (in combination with radiation and fluorouracil) for 2 cycles
(Whitney 1999) or 50 mg/m2 on day 1 every 3 weeks (in combination with paclitaxel
and bevacizumab) until disease progression or unacceptable toxicity (Tewari 2014)
or 50 mg/m2 once every 3 weeks (in combination with paclitaxel) for up to 6 cycles
in nonresponders, patients with a clinical response could continue beyond 6 cycles
(Monk 2009; Moore 2004) or 50 mg/m2 on day 1 every 3 weeks (in combination with
topotecan) for a maximum of 6 cycles (in nonresponders) or until disease
progression or unacceptable toxicity (Long 2005).

Endometrial carcinoma, recurrent, metastatic, or high-risk (off-label use): IV:

50 mg/m2 on day 1 every 3 weeks (in combination with doxorubicin ± paclitaxel) for
7 cycles or until disease progression or unacceptable toxicity (Fleming 2004).

Esophageal and gastric cancers (off-label uses): IV:

CF regimen: 100 mg/m2 over 30 minutes on days 1 and 29 (preoperative

chemoradiation; in combination with fluorouracil) (Tepper 2008).

ECF, ECX regimens (advanced disease): 60 mg/m2 on day 1 every 21 days for
up to 8 cycles in combination with epirubicin and either fluorouracil or
capecitabine (Cunningham 2008).

ECF regimen: 60 mg/m2 on day 1 every 21 days for 3 preoperative and 3

postoperative cycles in combination with epirubicin and fluorouracil
(Cunningham 2006).

TCF or DCF regimen: 75 mg/m2 on day 1 every 3 weeks (in combination with
docetaxel and fluorouracil) until disease progression or unacceptable toxicity
(Ajani 2007; Van Cutsem 2006).

Gestational trophoblastic neoplasia, high-risk metastatic disease (off-label

use): IV:

EMA-EP regimen: 60 to 80 mg/m2 on day 8 every 2 weeks (in combination with

etoposide, methotrexate, leucovorin, and dactinomycin); continue for 2 to 4
treatment cycles after a normal hCG level (Ghaemmaghami 2004).
 EP-EMA regimen: EP: 25 mg/m2/dose over 4 hours each for 3 consecutive
doses on day 1 (in combination with etoposide), alternating weekly with EMA
(etoposide, methotrexate, leucovorin, and dactinomycin) (Newlands 2000).

Head and neck cancer (off-label use): IV:

Locally-advanced disease: 100 mg/m2 on day 1 every 3 weeks for 3 doses

(with concurrent radiation) (Bernier 2004; Cooper 2004) or 75 mg/m2 on day 1
every 3 weeks (in combination with docetaxel and fluorouracil) for 4 cycles or
until disease progression or unacceptable toxicity (if no disease progression
after 4 cycles, chemotherapy was followed by radiation) (Vermorken 2007) or
100 mg/m2 on day 1 every 3 weeks (in combination with docetaxel and
fluorouracil) for 3 cycles or until disease progression or unacceptable toxicity
(chemotherapy was followed by chemoradiation) (Posner 2007).

Metastatic disease: 100 mg/m2 on day 1 every 3 weeks (in combination with
fluorouracil and cetuximab) until disease progression or unacceptable toxicity or
a maximum of 6 cycles (Vermorken 2008).

Hodgkin lymphoma, relapsed/refractory (off-label use): IV:

DHAP regimen: 100 mg/m2 continuous infusion over 24 hours on day 1 for 2
cycles; median duration between cycle 1 and 2 was 16 days (in combination
with dexamethasone and cytarabine) (Josting 2002).

ESHAP regimen: 25 mg/m2 on days 1 to 4 (in combination with etoposide,

methylprednisolone, and cytarabine) every 3 to 4 weeks for 3 or 6 cycles
(Aparicio 1999).

Malignant pleural mesothelioma (off-label use): IV: 75 mg/m2 on day 1 every 3

weeks (in combination with pemetrexed) (Vogelzang 2003) or 100 mg/m2 on day 1
every 4 weeks (in combination with gemcitabine) (Nowak 2002) or 80 mg/m2 on day
1 every 3 weeks (in combination with gemcitabine) (van Haarst 2002).

Multiple myeloma (off-label use): IV:

DT-PACE regimen: 10 mg/m2/day administered as a continuous infusion on

days 1 to 4 of each cycle; repeat every 4 to 6 weeks (in combination with
dexamethasone, thalidomide, doxorubicin, cyclophosphamide, and etoposide)
(Lee 2003).
 VDT-PACE regimen: 10 mg/m2/day administered as a continuous infusion on
days 1 to 4 of each cycle; repeat every 4 to 6 weeks (in combination with
bortezomib, dexamethasone, thalidomide, doxorubicin, cyclophosphamide, and
etoposide) (Lee 2003; Pineda-Roman 2008).

DCEP regimen: 10 mg/m2/day administered as a continuous infusion on days 1

to 4 every 21 days (in combination with cyclophosphamide, etoposide, and
dexamethasone) until disease progression or unacceptable toxicity (Lazzarino
2001; Park 2014).

Neuroendocrine tumors (metastatic carcinoma) (off-label use): IV: 45

mg/m2/day as a continuous infusion on days 2 and 3 every 4 weeks (in combination
with etoposide) until disease progression or unacceptable toxicity (Fjällskog 2001;
Moertel 1991) or 80 mg/m2 over 30 minutes on day 1 every 3 weeks (in combination
with etoposide) for up to 6 cycles (Le Treut 2013).

Non-Hodgkin lymphoma, relapsed/refractory (off-label use): IV:

DHAP regimen (for DLBCL): 100 mg/m2 continuous infusion over 24 hours on
day 1 every 3 to 4 weeks for 6 to 10 cycles (in combination with
dexamethasone and cytarabine) (Velasquez 1988).

ESHAP regimen: 25 mg/m2/day continuous infusion over 24 hours on days 1 to

4 every 3 to 4 weeks for 6 to 8 cycles (in combination with etoposide,
methylprednisolone, and cytarabine) (Velasquez 1994).

R-GDP or GDP regimen: 75 mg/m2 on day 1 (in combination with gemcitabine

and dexamethasone ± rituximab) every 3 weeks for 2 to 6 cycles (Crump 2004;
Crump 2014).

Non-small cell lung cancer (NSCLC; off-label use): IV: Note: There are multiple
cisplatin-containing regimens for the treatment of NSCLC. Listed below are several
commonly used regimens:

Adjuvant therapy: 100 mg/m2 on day 1 every 4 weeks (in combination with
etoposide) for 3 to 4 cycles (Arriagada 2004) or 100 mg/m2 on day 1 every 4
weeks (in combination with vinorelbine) for 4 cycles (Douillard 2006).

Advanced or metastatic disease: 100 mg/m2 on day 1 every 4 weeks (in

combination with vinorelbine) for 6 to 10 cycles (Kelly 2001) or 100 mg/m2 on
day 1 every 4 weeks (in combination with vinorelbine) until disease progression
 or unacceptable toxicity (Wozniak 1998) or 100 mg/m2 on day 1 every 4 weeks
(in combination with gemcitabine) (Comella 2000) or 80 mg/m2 on day 1 every
3 weeks (in combination with gemcitabine) until disease progression or
unacceptable toxicity (Ohe 2007) or 75 mg/m2 on day 1 every 3 weeks (in
combination with pemetrexed) for up to 6 cycles or until disease progression or
unacceptable toxicity (Scagliotti 2008).

Osteosarcoma (off-label use): IV: Adults ≤40 years of age: 60 mg/m2/day (over 4
hours) for 2 days (total of 120 mg/m2/cycle) of weeks 1 and 6 (neoadjuvant therapy)
and then 60 mg/m2/day (over 4 hours) for 2 days (total of 120 mg/m2/cycle) of
weeks 12 and 17 (adjuvant therapy) in combination with methotrexate, leucovorin,
and doxorubicin (Marina 2016; Whelan 2015).

Ovarian cancer, advanced: IV: 75 to 100 mg/m2 once every 3 to 4 weeks or (off-
label combination) 75 mg/m2 every 3 weeks (in combination with paclitaxel) (Ozols
2003).

Intraperitoneal (off-label route): 100 mg/m2 on day 2 of a 21-day treatment

cycle (in combination with IV and intraperitoneal paclitaxel) for 6 cycles
(Armstrong 2006).

Ovarian germ cell tumors (off-label dosing): IV:

BEP regimen (adjuvant treatment): 20 mg/m2 on days 1 to 5 every 21 days (in

combination with bleomycin and etoposide) for 3 cycles (Williams 1994).

EP regimen: 20 mg/m2 on days 1 to 5 every 21 days (in combination with

etoposide) for 4 cycles (Culine 2007); while the BEP regimen is preferred in the
treatment of ovarian germ cell tumors, EP may be considered if pulmonary
toxicity is a concern. Note: Use of this regimen in ovarian germ cell tumors is
extrapolated from data in the management of testicular germ cell tumors.

TIP regimen: 25 mg/m2 on days 2 to 5 every 3 weeks (in combination with

paclitaxel, ifosfamide, and mesna) for 4 cycles (Kondagunta 2005b). Note: Use
of this regimen in ovarian germ cell tumors is extrapolated from data in the
management of testicular germ cell tumors.

Pancreatic cancer, locally advanced or metastatic (off-label use; alternative

regimen): IV: 50 mg/m2 over 1 hour on days 1 and 15 every 4 weeks (in
combination with gemcitabine) (Heinemann 2006).
Penile cancer, metastatic (off-label use): IV: 25 mg/m2 over 2 hours on days 1, 2,
and 3 every 3 to 4 weeks (in combination with paclitaxel and ifosfamide) for 4 cycles
(Pagliaro 2010).

Primary CNS lymphoma, relapsed or refractory (off-label use; based on limited

data): IV: 100 mg/m2 continuous infusion over 24 hours on day 1 every 3 to 4 weeks
(in combination with dexamethasone and high-dose cytarabine) for ~6 to 10 cycles
in responding patients (Velasquez 1988; McLaughlin 1988).

Prostate cancer, castration-resistant, metastatic (small cell variant or with

anaplastic feature) (off-label use): IV: 25 mg/m2 on days 1, 2, and 3 every 3
weeks (in combination with etoposide, as second-line treatment following first-line
treatment with carboplatin and docetaxel) for at least 4 cycles (Aparicio 2013).

Small cell lung cancer (off-label use): IV:

Limited-stage disease: 60 mg/m2 on day 1 every 3 weeks for 4 cycles (in

combination with etoposide and concurrent radiation) (Turrisi 1999) or 80
mg/m2 on day 1 every 3 weeks (in combination with etoposide and sequential
radiation therapy) for 4 cycles (Takada 2002) or 80 mg/m2 on day 1 every 4
weeks (in combination with etoposide and concurrent radiation therapy) for 4
cycles (Takada 2002) or 25 mg/m2 on days 1, 2, and 3 every 3 to 4 weeks (in
combination with etoposide) for 6 cycles (Evans 1985).

Extensive-stage disease: 80 mg/m2 on day 1 every 3 weeks (in combination

with etoposide) for 4 cycles (Lara 2009) or a maximum of 8 cycles (Ihde 1994)
or 60 mg/m2 on day 1 every 4 weeks for 4 cycles (in combination with
irinotecan) (Lara 2009) or 25 mg/m2 on days 1, 2, and 3 every 3 to 4 weeks (in
combination with etoposide) for 6 cycles (Evans 1985).

Testicular cancer, advanced: IV: 20 mg/m2 once daily for 5 days repeated every 3
weeks (in combination with bleomycin and etoposide) (Cushing 2004; Saxman
1998).

Testicular germ cell tumor, metastatic, good-risk (off-label combination): IV: 20

mg/m2 on days 1 to 5 every 3 weeks (in combination with etoposide) for 4
cycles (Culine 2007; Kondagunta 2005a).

Testicular germ cell tumor, metastatic, intermediate or poor-risk (off-label

dosing): IV: 25 mg/m2 on days 2 to 5 every 3 weeks (in combination with
paclitaxel, ifosfamide, and mesna) for 4 cycles (Kondagunta 2005b) or 20
 mg/m2 on days 1 to 5 every 3 weeks (in combination with bleomycin and
etoposide) for 4 cycles (Nichols 1998) or 20 mg/m2 on days 1 to 5 every 3
weeks (in combination with etoposide and ifosfamide) for 4 cycles (Nichols
1998) or 20 mg/m2 on days 1 to 5 every 3 weeks (in combination with
vinblastine, ifosfamide, and mesna) for 4 cycles (Loehrer 1998).

Thymic carcinoma, locally advanced or metastatic (off-label use; based on

limited data): IV:

CODE regimen: 25 mg/m2 on day 1 (in combination with vincristine,

doxorubicin, and etoposide) during weeks 1, 2, 4, 6, and 8 (Yoh 2003).

VIP regimen: 20 mg/m2 on days 1 to 4 (in combination with etoposide,

ifosfamide, mesna and colony-stimulating growth factor support) every 3 weeks
for up to 4 cycles or until disease progression or unacceptable toxicity (Loehrer
2001).

Thymomas, advanced or metastatic (off-label use): IV:

CAP regimen: 50 mg/m2 over at least 1 hour on day 1 every 3 weeks for up to 8
cycles (in combination with cyclophosphamide and doxorubicin) (Loehrer 1994).

ADOC regimen: 50 mg/m2 on day 1 every 3 weeks (in combination with

doxorubicin, vincristine, and cyclophosphamide) (Fornasiero 1991).

PE regimen: 60 mg/m2 over 1 hour on day 1 every 3 weeks (in combination

with etoposide) for up to 8 cycles (Giaccone 1996).

VIP regimen: 20 mg/m2 on days 1 to 4 (in combination with etoposide,

ifosfamide, mesna, and colony-stimulating growth factor support) every 3 weeks
for up to 4 cycles or until disease progression or unacceptable toxicity (Loehrer
2001).

Unknown primary, adenocarcinoma (off-label use): IV: 100 mg/m2 on day 1

every 3 weeks (in combination with gemcitabine) (Culine 2003; Gross-Goupil 2012)
or 80 mg/m2 on day 1 every 3 weeks (in combination with docetaxel) for 2 to 6
cycles (Mukai 2010).

Unknown primary, squamous cell carcinoma (off-label use; based on limited

data): IV: 75 mg/m2 on day 1 every 3 weeks (in combination with fluorouracil ±
docetaxel) for 3 cycles (Pointreau 2009) or 20 mg/m2 on days 1 to 5 every 4 weeks
 (in combination with fluorouracil) until disease progression or unacceptable toxicity
(Kusaba 2007).

Dosing: Renal Impairment: Adult

Note: The manufacturer recommends considering alternate treatments or cisplatin dose
reductions for patients with baseline renal impairment or who develop significantly
reduced CrCl during cisplatin treatment. The following adjustments have been
recommended.

Kintzel 1995:

CrCl 46 to 60 mL/minute: Administer 75% of dose.

CrCl 31 to 45 mL/minute: Administer 50% of dose.

CrCl <30 mL/minute: Consider use of alternative drug.

Hemodialysis: Partially cleared by hemodialysis.

Administer 50% of dose posthemodialysis or on nondialysis days (Aronoff 2007;

Janus 2010).

Continuous ambulatory peritoneal dialysis: Administer 50% of dose (Aronoff

2007).

Continuous renal replacement therapy: Administer 75% of dose (Aronoff 2007).

Bladder cancer (neoadjuvant treatment): CrCl >50 to <60 mL/minute: Split-dose

cisplatin (35 mg/m2 on days 1 and 2) has been reported as an option in one study
(Plimack 2014).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling. However,
cisplatin undergoes nonenzymatic metabolism and predominantly renal elimination;
therefore, dosage adjustment is likely not necessary.

Dosing: Pediatric

(For additional information see "Cisplatin: Pediatric drug information")

Note: Dosing and frequency may vary by protocol and/or treatment phase; refer to
specific protocol. Cisplatin is associated with a high emetic potential; antiemetics are
recommended to prevent nausea and vomiting (Basch 2011; Dupuis 2011; Roila 2010).
TO PREVENT POSSIBLE OVERDOSE, VERIFY ANY CISPLATIN DOSE
EXCEEDING 100 mg/m2 PER COURSE (eg, every 3 to 4 week cycle).
Pretreatment hydration is recommended.

Germ cell tumors: Limited data available:

Cushing 2004:

Infants: IV: 0.7 mg/kg on days 1 to 5 of a 21-day cycle (in combination

with bleomycin and etoposide)

Children and Adolescents: IV: 20 mg/m2 on days 1 to 5 of a 21-day

cycle (in combination with bleomycin and etoposide)

Pinkerton 1986: Children and Adolescents: IV: 100 mg/m2on day 1 of a 21-
day cycle (in combination with bleomycin and vinblastine or etoposide)

Lopes 2016: Children and Adolescents:

Intermediate risk: PE regimen: IV: 35 mg/m2 on days 1, 2, and 3 of a

21-day cycle for 3 cycles (weeks 1, 4, and 7) in combination with
etoposide; a fourth cycle may be considered depending on response

High risk: PEI regimen: IV: 35 mg/m2 on days 1, 2, and 3 of a 21-day

cycle for 4 cycles (weeks 1, 4, 7, and 11) in combination with
etoposide and ifosfamide; a fifth or sixth cycle may be considered
depending on response

Hepatoblastoma: Limited data available: IV:

Continuous IV infusion:

Infants and Children <10 kg: PLADO regimen: 2.7 mg/kg/day

continuous infusion over 24 hours on day 1 of a 21-day cycle in
combination with doxorubicin for 4 to 6 cycles (Pritchard 2000)

Children ≥10 kg and Adolescents:

Monotherapy: Standard risk: 80 mg/m2/day continuous infusion

over 24 hours every 2 weeks on day 1

Combination therapy: PLADO regimen: 80 mg/m2/day continuous

infusion over 24 hours on day 1 of a 21-day cycle in combination
 with doxorubicin (Perilongo 2004; Perilongo 2009; Pritchard 2000)
or doxorubicin and sorafenib (Schmid 2012)

Intermittent infusion (over 6 hours):

Infants and Children <10 kg: 3 mg/kg over 6 hours on day 1 of a 21-
day cycle for 4 to 8 cycles in combination with vincristine and
fluorouracil or continuous infusion doxorubicin (Douglass 1993;
Malogolowkin 2008; Ortega 2000)

Children ≥10 kg and Adolescents: 90 mg/m2 over 6 hours on day 1 of

a 21-day cycle for 4 to 8 cycles in combination with vincristine and
fluorouracil or continuous infusion doxorubicin (Douglass 1993;
Malogolowkin 2008; Ortega 2000)

Medulloblastoma: Limited data available: Children ≥3 years and Adolescents:

IV: 75 mg/m2 every 6 weeks on either day 0 in combination with vincristine and
cyclophosphamide or day 1 in combination with lomustine and vincristine of
each chemotherapy cycle for 8 cycles (Packer 2006; Packer 2013)

Medulloblastoma/PNET, relapsed or refractory: Very limited data available:

Children and Adolescents: IV: 60 mg/m2 on day 0 every 4 weeks (in
combination with irinotecan, vincristine, cyclophosphamide, and etoposide)
(Kim 2013)

Neuroblastoma, high-risk: Limited data available: Infants, Children, and

Adolescents: IV: 50 mg/m2 on days 0 to 3 of a 21-day cycle in combination with
etoposide (cycles 3 and 5) (Kreisman 2013; Naranjo 2011) or 50 mg/m2 on
days 1 to 4 in combination with etoposide (cycles 3, 5, and 7) (Kushner 1994)

Osteosarcoma: Limited data available: Children and Adolescents: IV: 60

mg/m2/day for 2 days at weeks 2, 7, 25, and 28 (neoadjuvant) or weeks 5, 10,
25, and 28 (adjuvant) in combination with doxorubicin (Goorin 2003) or 120
mg/m2/day at weeks 0, 5, 12, and 17 in combination with doxorubicin (Meyers
2005)

Dosing: Renal Impairment: Pediatric

Note: The manufacturer(s) recommend that repeat courses of cisplatin should not
be given until serum creatinine is <1.5 mg/dL and/or BUN is <25 mg/dL and use is
contraindicated in preexisting renal impairment. Consult protocols for specific renal
 impairment dosing adjustments. The following adjustments have been
recommended:

Aronoff 2007: All patients:

GFR >50 mL/minute/1.73 m2: No dosage adjustment necessary

GFR 10 to 50 mL/minute/1.73 m2: Administer 75% of dose

GFR <10 mL/minute/1.73 m2: Administer 50% of dose

Hemodialysis: Partially cleared by hemodialysis: Administer 50% of dose

posthemodialysis

Peritoneal dialysis: Administer 50% of dose

Continuous renal replacement therapy (CRRT): Administer 75% of dose

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; however,
cisplatin undergoes nonenzymatic metabolism and predominantly renal elimination;
therefore, dosage adjustment is likely not necessary.

Dosing: Geriatric
Refer to adult dosing. Select dose cautiously and monitor closely in the elderly; may be
more susceptible to nephrotoxicity and peripheral neuropathy.

Dosing: Obesity: Adult

ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer:
Utilize patient's actual body weight (full weight) for calculation of body surface area- or
weight-based dosing, particularly when the intent of therapy is curative; manage
regimen-related toxicities in the same manner as for nonobese patients; if a dose
reduction is utilized due to toxicity, consider resumption of full weight-based dosing with
subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is
resolved (Griggs 2012).

Dosing: Adjustment for Toxicity: Adult

Consider alternative treatments or dose reductions for toxicities.

Hematologic toxicity: May require treatment interruption and/or dosage reduction.

 Hypersensitivity: Discontinue cisplatin immediately (and manage appropriately) for
severe hypersensitivity reactions; do not rechallenge with cisplatin in patients with a
history of severe hypersensitivity reactions.

Neurotoxicity: Consider discontinuing cisplatin if symptomatic grade 3 or 4

peripheral neuropathy develops.

Dosage Forms: US
Excipient information presented when available (limited, particularly for generics);
consult specific product labeling.

Solution, Intravenous [preservative free]:

Generic: 50 mg/50 mL (50 mL); 100 mg/100 mL (100 mL); 200 mg/200 mL (200
mL)

Solution Reconstituted, Intravenous [preservative free]:

Generic: 50 mg (1 ea)

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics);
consult specific product labeling.

Solution, Intravenous:

Generic: 1 mg/mL (10 mL, 50 mL, 100 mL)

Administration: Adult
Cisplatin is associated with a high emetic potential; antiemetics are recommended to
prevent nausea and vomiting (Hesketh 2017; Roila 2016). Administer appropriate
pretreatment hydration and maintain adequate hydration and urinary output for 24 hours
following cisplatin administration.

IV: Cisplatin has been infused over 30 minutes to 4 hours, at a rate of 1 mg/minute,
or as a continuous infusion (off-label rates); infusion rate varies by protocol (refer to
specific protocol for infusion details). Do not administer as a rapid IV injection. Also
refer to specific protocol for information regarding recommended concomitant
hydration, diuretics, and (for combination regimens) the administration sequence.
 Intraperitoneal (off-label route): Solution was prepared in warmed saline and infused
as rapidly as possible through an implantable intraperitoneal catheter (Armstrong
2006).

Needles or IV administration sets that contain aluminum should not be used in the
preparation or administration; aluminum may react with cisplatin resulting in
precipitate formation and loss of potency.

Vesicant (at higher concentrations); ensure proper needle or catheter placement prior to
and during infusion; avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and

disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do
NOT flush the line); initiate sodium thiosulfate antidote; elevate extremity.

Sodium thiosulfate 1/6 M solution: Inject 2 mL into existing IV line for each 100
mg of cisplatin extravasated; then consider also injecting 1 mL as 0.1 mL
subcutaneous injections (clockwise) around the area of extravasation, may
repeat subcutaneous injections several times over the next 3 to 4 hours (Ener
2004).

Dimethyl sulfoxide (DMSO) may also be considered an option: Apply to a region

covering twice the affected area every 8 hours for 7 days; begin within 10
minutes of extravasation; do not cover with a dressing (Perez Fidalgo 2012).

Administration: Pediatric
Cisplatin is associated with a high emetic potential; antiemetics are recommended to
prevent nausea and vomiting (Basch 2011; Dupuis 2011; Roila 2010).

Pretreatment hydration is recommended prior to cisplatin administration; adequate

posthydration and urinary output (eg, >100 mL/hour in adults) should be maintained
for 24 hours after administration.

IV: Infuse over 6 to 8 hours; has also been infused over 30 minutes to 3 hours, at a
rate of 1 mg/minute, or as a continuous infusion; infusion rate varies by protocol
(refer to specific protocol for infusion details)

Needles or IV administration sets that contain aluminum should not be used for
administration; aluminum may react with cisplatin resulting in precipitate formation
and loss of potency.
 Vesicant (at higher concentrations); ensure proper needle or catheter placement
prior to and during infusion; avoid extravasation. If extravasation occurs, stop
infusion immediately and disconnect (leave cannula/needle in place); gently aspirate
extravasated solution (do NOT flush the line); initiate sodium thiosulfate antidote;
elevate extremity. Dimethyl sulfoxide (DMSO) may also be considered an option
(See Management of Drug Extravasations for more details).

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing,

administration, and disposal. Follow NIOSH and USP 800 recommendations and
institution-specific policies/procedures for appropriate containment strategy (NIOSH
2016; USP-NF 2020).

Use: Labeled Indications

Bladder cancer, advanced: Treatment of advanced bladder cancer

Ovarian cancer, advanced: Treatment of advanced ovarian cancer

Testicular cancer, advanced: Treatment of advanced testicular cancer

Use: Off-Label: Adult

Adrenocortical carcinoma (advanced); Anal carcinoma, squamous cell (metastatic);

Biliary tract cancer (advanced); Brain metastases (due to breast or non-small cell lung
cancers); Breast cancer (triple-negative); Cervical cancer; Endometrial carcinoma
(recurrent, metastatic, or high-risk); Esophageal cancer; Gastric cancer; Gestational
trophoblastic neoplasia (high-risk); Head and neck cancer (locally advanced disease);
Head and neck cancer (metastatic disease); Hodgkin lymphoma; Malignant pleural
mesothelioma; Multiple myeloma; Neuroendocrine tumors (metastatic carcinoma); Non-
Hodgkin lymphoma (relapsed/refractory); Non-small cell lung cancer; Osteosarcoma;
Pancreatic cancer (locally advanced or metastatic); Penile cancer (metastatic); Primary
CNS lymphoma (relapsed or refractory); Prostate cancer, castration-resistant
(metastatic); Small cell lung cancer (extensive-stage disease); Small cell lung cancer
(limited-stage disease); Thymic carcinoma (locally advanced or metastatic); Thymomas
(advanced or metastatic); Unknown primary, adenocarcinoma; Unknown primary,
squamous cell carcinoma
Medication Safety Issues
Sound-alike/look-alike issues:

CISplatin may be confused with CARBOplatin, oxaliplatin

Platinol may be confused with Patanol

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP)
includes among its list of drug classes which have a heightened risk of causing
significant patient harm when used in error.

Administration issues:

Cisplatin doses >100 mg/m2 once every 3 to 4 weeks are rarely used and
should be verified with the prescriber.

Adverse Reactions

>10%:

Central nervous system: Neurotoxicity (peripheral neuropathy is dose and

duration dependent)

Gastrointestinal: Nausea and vomiting (76% to 100%)

Genitourinary: Nephrotoxicity (28% to 36%; acute renal failure and chronic

renal insufficiency)

Hematologic & oncologic: Anemia (≤40%), leukopenia (25% to 30%; nadir: Day
18 to 23; recovery: By day 39; dose related), thrombocytopenia (25% to 30%;
nadir: Day 18 to 23; recovery: By day 39; dose related)

Hepatic: Increased liver enzymes

Otic: Ototoxicity (children 40% to 60%; adults 10% to 31%; as tinnitus, high
frequency hearing loss)

1% to 10%: Local: Local irritation

<1%, postmarketing, and/or case reports: Alopecia (mild), ageusia, anaphylaxis,

autonomic neuropathy, bradycardia (Schlumbrecht 2015), bronchoconstriction,
 cardiac arrhythmia, cardiac failure, cerebral arteritis, cerebrovascular accident,
dehydration, diarrhea, dysgeusia (Rehwaldt 2009), extravasation, heart block,
hemolytic anemia (acute), hemolytic-uremic syndrome, hiccups,
hypercholesterolemia, hyperuricemia, hypocalcemia, hypokalemia,
hypomagnesemia, hyponatremia, hypophosphatemia, hypotension, increased
serum amylase, ischemic heart disease, leukoencephalopathy, Lhermitte's sign,
mesenteric ischemia (acute; Morgan 2011), myocardial infarction, neutropenic
enterocolitis (Furonaka 2005), optic neuritis, pancreatitis (Trivedi 2005),
papilledema, peripheral ischemia (acute), phlebitis (Tokuda 2015), reversible
posterior leukoencephalopathy syndrome, seizure, SIADH, skin rash, tachycardia,
tetany, thrombosis (aortic; Fernandes 2011), thrombotic thrombocytopenic purpura,
vasospasm (acute arterial; Morgan 2011), vision color changes, vision loss

Contraindications
Severe hypersensitivity to cisplatin or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: [US Boxed Warning]: Cisplatin may cause

severe myelosuppression; fatalities due to infection (secondary to
myelosuppression) have been reported. Monitor blood counts (prior to
cisplatin initiation, prior to each subsequent treatment course, and as
clinically indicated). May require treatment interruption. Fever has been
reported in patients with neutropenia. Monitor closely for signs/symptoms of
infection (during and after cisplatin treatment). Geriatric patients may be at
higher risk for hematologic toxicity. Hematologic toxicity may require dosage
modification.

• Extravasation: Cisplatin is a vesicant at higher concentrations, and an irritant

at lower concentrations; ensure proper needle or catheter placement prior to
and during infusion; avoid extravasation. Monitor infusion site during
administration. Local soft tissue toxicity has been reported following cisplatin
extravasation; the severity of the local tissue toxicity appears to be related to
the cisplatin concentration. Cisplatin infusion solutions at a concentration >0.5
mg/mL may result in tissue cellulitis, fibrosis, necrosis, pain, edema, and
erythema.
• Gastrointestinal toxicity: [US Boxed Warning]: Cisplatin can cause severe
nausea and vomiting; use highly effective antiemetic premedication.
Cisplatin is associated with a high emetic potential; antiemetics are
recommended to prevent nausea and vomiting (Dupuis 2011; Hesketh 2017;
Paw Chow Sing 2019; Roila 2016). Nausea and vomiting are dose-related and
may be immediate and/or delayed, usually lasting up to 72 hours, although may
persist for up to 1 week. Diarrhea may also occur.

• Hypersensitivity: Cisplatin may cause severe hypersensitivity reactions,

including anaphylaxis (some fatal). Manifestations of hypersensitivity include
facial edema, wheezing, tachycardia, and hypotension. Hypersensitivity
reactions have occurred within minutes of administration (in patients with prior
cisplatin exposure). Monitor for hypersensitivity reactions. Ensure supportive
equipment and medications for management of severe hypersensitivity
reactions are available. Discontinue cisplatin immediately (and manage
appropriately) for severe hypersensitivity reactions. Do not rechallenge with
cisplatin in patients with a history of severe hypersensitivity reactions. Cross-
reactivity between platinum-based antineoplastic agents has been reported;
severe hypersensitivity reactions have recurred following rechallenge with a
different platinum agent (case reports).

• Nephrotoxicity: [US Boxed Warning]: Cisplatin can cause severe renal

toxicity, including acute renal failure. Severe renal toxicities are dose-
related and cumulative. Ensure adequate hydration (before, during, and
following cisplatin administration); monitor renal function and
electrolytes. Consider dose reductions or alternative treatments in
patients with renal impairment. Acute renal failure may be prolonged and
severe with repeat cisplatin courses. The onset of nephrotoxicity usually begins
during the second week following a cisplatin dose. Patients with renal
impairment at baseline, geriatric patients, those taking other nephrotoxic
medications, and/or patients who are not well hydrated may be at higher risk for
nephrotoxicity. Monitor serum creatinine, blood urea nitrogen, creatinine
clearance, and serum electrolytes (calcium, magnesium, potassium, and
sodium) prior to treatment initiation and as clinically indicated. Magnesium
supplementation may be indicated. According to clinical treatment guidelines,
consider alternate treatments or cisplatin dose reductions for patients with
baseline renal impairment or who develop significantly reduced creatinine
clearance during cisplatin treatment.
• Neurotoxicity: [US Boxed Warning]: Cisplatin may cause dose-related
peripheral neuropathy that becomes more severe with repeated cisplatin
courses. Neurotoxicity has been reported following a single cisplatin dose.
Neuropathy may be delayed, with an onset occurring 3 to 8 weeks after the last
cisplatin dose. Neuropathy manifestations include paresthesias with a stocking-
glove distribution, areflexia, and loss of proprioception and vibratory sensation.
Neuropathy may progress following cisplatin discontinuation. In some patients,
peripheral neuropathy may be irreversible. Perform a neurological examination
prior to cisplatin initiation, as appropriate during therapy, and following
completion of cisplatin therapy. Consider discontinuing cisplatin if symptomatic
peripheral neuropathy develops. Geriatric patients may be more susceptible to
peripheral neuropathy. Seizures, loss of motor function, loss of taste,
leukoencephalopathy, and posterior reversible leukoencephalopathy syndrome
have also been described.

• Ocular toxicity: Optic neuritis, papilledema, and cortical blindness have been
reported in patients receiving standard recommended cisplatin doses. Blurred
vision and altered color perception have been reported after the use of
regimens with higher or more frequent cisplatin doses. Altered color perception
manifests as a loss of color discrimination, particularly in the blue-yellow axis
and irregular retinal pigmentation of the macular area on fundoscopic exam.
Improvement and/or total recovery usually occurs following cisplatin
discontinuation, although may be delayed.

• Ototoxicity: Cisplatin may cause cumulative and severe ototoxicity. Ototoxicity

is manifested by tinnitus, high-frequency (4,000 to 8,000 Hz) hearing loss,
and/or decreased ability to hear normal conversational tones. Ototoxicity may
occur during or after treatment; may be unilateral or bilateral. Deafness
following the initial cisplatin dose has been reported. Vestibular toxicity has also
been reported. Ototoxic effects may be more severe and/or detrimental in
pediatric patients, particularly those <5 years of age. The prevalence of hearing
loss in pediatric patients is estimated to be 40% to 60%. Additional risk factors
for ototoxicity include simultaneous cranial irradiation, treatment with other
ototoxic medications, and/or renal impairment. Consider audiometric and
vestibular testing, particularly in all pediatric patients receiving cisplatin. Certain
genetic variations in the thiopurine S-methyltransferase (TPMT) gene may be
associated with an increased risk of ototoxicity in children administered
conventional cisplatin doses (Pussegoda 2013). Controversy may exist
 regarding the role of TPMT variants in cisplatin ototoxicity (Ratain 2013; Yang
2013); the association has not been consistent across populations and studies.
Children without the TPMT gene variants may still be at risk for ototoxicity.
Cumulative dose, prior or concurrent exposure to other ototoxic agents (eg,
aminoglycosides, carboplatin), prior cranial radiation, younger age, and type of
cancer may also increase the risk for ototoxicity in children (Knight 2005;
Landier 2014). Pediatric patients should receive audiometric testing at baseline,
prior to each dose, and for several years after discontinuing therapy. An
international grading scale (SIOP Boston scale) has been developed to assess
ototoxicity in children (Brock 2012). In a randomized phase 3 study in pediatric
patients with hepatoblastoma (standard risk) receiving cisplatin, a single dose
of sodium thiosulfate (STS [brand name Pedmark]) was administered following
each cisplatin dose; compared to a control group that did not receive STS,
patients in the group receiving STS had a lower incidence of hearing loss and
similar 3-year event-free survival and overall survival (Brock 2018).

• Secondary malignancies: Secondary malignancies, including acute leukemias,

have been reported with cisplatin, usually when used in combination with other
chemotherapy agents.

• Tumor lysis syndrome: Hyperuricemia has been reported with cisplatin;

consider antihyperuricemic therapy to reduce uric acid levels.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring

dose or frequency adjustment, additional monitoring, and/or selection of
alternative therapy. Consult drug interactions database for more detailed
information.

Special populations:

• Elderly: Select dose cautiously and monitor closely in elderly patients; they
may be more susceptible to hematologic toxicity, infections, nephrotoxicity,
and/or peripheral neuropathy.

Other warnings/precautions:

• Medication safety: Doses >100 mg/m2/cycle (once every 3 to 4 weeks) are

rare; verify with the prescriber. At the approved dose, cisplatin should not be
administered more frequently than once every 3 to 4 weeks. Exercise caution to
 avoid inadvertent overdose due to potential sound-alike/look-alike confusion
between CISplatin and CARBOplatin or prescribing practices that fail to
differentiate daily doses from the total dose per cycle.

Metabolism/Transport Effects
None known.

Drug Interactions
(For additional information: Launch drug interactions program)

Alpha-Lipoic Acid: May diminish the therapeutic effect of CISplatin. Risk C: Monitor
therapy

Aminoglycosides: CISplatin may enhance the nephrotoxic effect of

Aminoglycosides. Risk C: Monitor therapy

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of

Baricitinib. Management: Use of baricitinib in combination with potent
immunosuppressants such as azathioprine or cyclosporine is not recommended.
Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease
modifying antirheumatic drugs (DMARDs) is permitted. Risk D: Consider therapy
modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of

BCG (Intravesical). Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of

BCG (Intravesical). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of

Myelosuppressive Agents. Risk C: Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants.

Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents.

Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of

CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
therapy
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic
effect of Coccidioides immitis Skin Test. Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of

Deferiprone. Management: Avoid the concomitant use of deferiprone and
myelosuppressive agents whenever possible. If this combination cannot be avoided,
monitor the absolute neutrophil count more closely. Risk D: Consider therapy
modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants.

Specifically, the risk for serious infections may be increased. Risk C: Monitor
therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents.

Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X:
Avoid combination

Echinacea: May diminish the therapeutic effect of Immunosuppressants.

Management: Consider avoiding Echinacea in patients receiving therapeutic
immunosuppressants. If coadministered, monitor for reduced efficacy of the
immunosuppressant during concomitant use. Risk D: Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of

Fingolimod. Management: Avoid the concomitant use of fingolimod and other
immunosuppressants when possible. If combined, monitor patients closely for
additive immunosuppressant effects (eg, infections). Risk D: Consider therapy
modification

Fosphenytoin-Phenytoin: Platinum Derivatives may decrease the serum

concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy

Inebilizumab: May enhance the immunosuppressive effect of Immunosuppressants.

Risk C: Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of

Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia,
agranulocytosis, and/or thrombocytopenia may be increased. Management:
Consider not using a leflunomide loading dose in patients receiving other
immunosuppressants. Patients receiving both leflunomide and another
immunosuppressant should be monitored for bone marrow suppression at least
monthly. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of
Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24
hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D:
Consider therapy modification

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of

Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and
myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered
at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy.
Risk D: Consider therapy modification

Loop Diuretics: May enhance the nephrotoxic effect of CISplatin. Loop Diuretics
may enhance the ototoxic effect of CISplatin. Risk C: Monitor therapy

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive

Agents. Risk C: Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of

Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X:
Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab.

Management: Avoid use of immunosuppressants (including systemic
corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after
administration of nivolumab (eg, for immune-related toxicity) is unlikely to affect
nivolumab efficacy. Risk D: Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants.

Risk C: Monitor therapy

Ozanimod: Immunosuppressants may enhance the immunosuppressive effect of

Ozanimod. Risk C: Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents.

Specifically, the duration and severity of oral mucositis may be increased.
Management: Do not administer palifermin within 24 hours before, during infusion
of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D:
Consider therapy modification

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod.

Risk C: Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk
X: Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents.

Risk C: Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants.

Management: Consider avoiding concomitant use of roflumilast and
immunosuppressants as recommended by the Canadian product monograph.
Inhaled or short-term corticosteroids are unlikely to be problematic. Risk D:
Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of

Siponimod. Risk C: Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of

Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to
reduce or discontinue therapy with immunosuppressants prior to initiating
sipuleucel-T therapy. Risk D: Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the

therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Risk C: Monitor
therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants.

Risk X: Avoid combination

Taxane Derivatives: Platinum Derivatives may enhance the myelosuppressive effect

of Taxane Derivatives. Administer Taxane derivative before Platinum derivative
when given as sequential infusions to limit toxicity. Management: Administer
paclitaxel before cisplatin, when given as sequential infusions, to limit toxicity.
Problems associated with other taxane/platinum combinations are possible,
although unsubstantiated. Administering the taxane before platinum is likely
warranted Risk D: Consider therapy modification

Tertomotide: Immunosuppressants may diminish the therapeutic effect of

Tertomotide. Risk C: Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of

Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate
or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and
 this warning seems particularly focused on more potent immunosuppressants. Risk
D: Consider therapy modification

Topotecan: Platinum Derivatives may enhance the adverse/toxic effect of

Topotecan. Management: Consider administering platinum derivatives after
topotecan when possible to minimize toxicity or using lower doses if administering
platinum derivatives prior to topotecan. Monitor for hematologic toxicity (eg,
neutropenia, thrombocytopenia). Risk D: Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C:

Monitor therapy

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of

Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of

Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete
all age-appropriate vaccinations at least 2 weeks prior to starting an
immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate
at least 3 months after immunosuppressant discontinuation. Risk D: Consider
therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of

Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of
Vaccines (Live). Management: Avoid use of live organism vaccines with
immunosuppressants; live-attenuated vaccines should not be given for at least 3
months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine
(Live). Risk X: Avoid combination

Vinorelbine: CISplatin may enhance the adverse/toxic effect of Vinorelbine.

Specifically, the combination may be associated with a higher risk of
granulocytopenia. Risk C: Monitor therapy

Reproductive Considerations

Verify pregnancy status prior to treatment initiation in females of reproductive potential.

Females of reproductive potential should use effective contraception during treatment
and for 14 months after the last cisplatin dose. Male patients with female partners of
reproductive potential should use effective contraception during treatment and for 11
months after the last cisplatin dose.
Cisplatin has been associated with cumulative dose-dependent ovarian failure,
premature menopause, impairment of spermatogenesis (oligospermia, azoospermia;
possibly irreversible), and reduced female and male fertility.

Pregnancy Considerations

Cisplatin has been reported to cross the human placenta.

Cisplatin may cause fetal harm if administered to a pregnant female. Adverse events
associated with cisplatin containing regimens include oligohydramnios, intrauterine
growth restriction and preterm birth; acute respiratory distress syndrome, cytopenias,
and hearing loss have been reported in the neonate.

Breast-Feeding Considerations

Cisplatin is present in breast milk. Due to the potential for serious adverse reactions
in the breastfed infant, breastfeeding is not recommended by the manufacturer.

Dietary Considerations
Some products may contain sodium.

Monitoring Parameters
Monitor blood counts (prior to cisplatin initiation, prior to each subsequent treatment
course, and as clinically indicated). Monitor serum creatinine, blood urea nitrogen,
creatinine clearance, and serum electrolytes (calcium, magnesium, potassium, and
sodium) prior to treatment initiation and as clinically indicated. Consider audiometric and
vestibular testing, particularly in all pediatric patients receiving cisplatin (pediatric
patients should receive audiometric testing at baseline, prior to each dose, and for
several years after discontinuing therapy). Monitor for hypersensitivity reactions. Monitor
for signs/symptoms of infection (during and after cisplatin treatment), neuropathy, ocular
toxicity, and secondary malignancies. Monitor infusion site during administration.

Mechanism of Action
Cisplatin inhibits DNA synthesis by the formation of DNA cross-links; denatures the
double helix; covalently binds to DNA bases and disrupts DNA function; may also bind to
proteins; the cis-isomer is 14 times more cytotoxic than the trans-isomer; both forms
cross-link DNA but cis-platinum is less easily recognized by cell enzymes and, therefore,
not repaired. Cisplatin can also bind two adjacent guanines on the same strand of DNA
producing intrastrand cross-linking and breakage.
Pharmacodynamics and Pharmacokinetics

Distribution: IV: 11 to 12 L/m2

Protein binding: Plasma platinum: >90%

Metabolism: Nonenzymatic; inactivated (in both cell and bloodstream) by sulfhydryl

groups; covalently binds to glutathione and thiosulfate

Half-life elimination:

Children: Free drug: 1.3 hours; Total platinum: 44 hours

Adults: Cisplatin: 20 to 30 minutes; Platinum: ≥5 days

Excretion: Cisplatin: Urine (13% to 17% within 1 hour); Platinum: Urine (35% to
51%)

Pricing: US

Solution (CISplatin Intravenous)

50 mg/50 mL (per mL): $0.35 - $0.48

100 mg/100 mL (per mL): $0.36 - $0.48

200 mg/200 mL (per mL): $0.43 - $0.60

Solution (reconstituted) (CISplatin Intravenous)

50 mg (per each): $600.00

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is

provided as reference price only. A range is provided when more than one
manufacturer's AWP price is available and uses the low and high price reported by the
manufacturers to determine the range. The pricing data should be used for
benchmarking purposes only, and as such should not be used alone to set or adjudicate
any prices for reimbursement or purchasing functions or considered to be an exact price
for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of
any kind or nature, whether express or implied, and assumes no liability with respect to
accuracy of price or price range data published in its solutions. In no event shall Medi-
Span be liable for special, indirect, incidental, or consequential damages arising from
use of price or price range data. Pricing data is updated monthly.
Brand Names: International
Abiplatin (IL, NZ, TW); Accocit (CR, DO, GT, HN, NI, PA, SV); Bioplatino (PE); Blastolem
(CL, CO, CR, DO, GT, HN, NI, PA, SV); Blastolem RU (MX); Cesalin (BD, LK); Cidiamine
(PH); Ciscan (ID); Cisly (LU); Cispatin (KR); Cisplan (KR); Cisplat (IN); Cisplatin (AU, ID,
IN, NZ); Cisplatin Ebewe (HU); Cisplatin medac (LU); Cisplatin Teva (HU); Cisplatine-
Lilly (LU); Cisplatino (CO, EC, PE); Cisplatinum Cytosafe-Delta West (LU); Cisplatyl (FR,
SA); Cisteen (PH, ZW); Citoplatino (IT); Citoplax (BR); Cytoplatin (EG, LB); Elvecis (AR);
Fangtan (CN); Incel (BR, PY); Kemocarb (VN); Kemoplat (IN, PH, SG, TW, ZW);
Lederplatin (DK); Noveldexis (CR, DO, GT, HN, MX, NI, PA, SV); Oncotin (PH); P&U
Cisplatin (ZA); Placis (ES, JO, TH, TR); Platamine (AE, BH, CY, HR, IQ, IR, IT, JO, LB,
LY, OM, SA, SY, YE); Platiblastin (CH, DE); Platicin (LK); Platidiam (BG, CZ, HN, HU,
PL, RU); Platimit (HR); Platin (PH); Platinex (BD, HR, IT); Platinol (AR, AT, BE, CH, EE,
FI, GR, LU, SE, UY); Platistil (PT); Platistin (FI, SE); Platistine (LU); Platol (ET, MY, ZW);
Platosin (GB, KR, MY, PK, RO, TH); Randa (JP); Sicatem (PY); Sinplatin (BG, RO);
Tecnoplatin (MX); Unistin (EG)

For country abbreviations used in Lexicomp (show table)

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