CISPLATIN
Chemistry - An inorganic platinum-containing antineoplastic, cisplatin occurs as white powder.
One mg is soluble in 1 ml of water or normal saline. The drug is available commercially as powderfor injection and as a solution for injection. The powder for injection occurs as a white, lyophilizedpowder that also contains mannitol, sodium chloride and HCl (to adjust pH). After reconstitutingwith sterile water for injection a clear solution results having a pH from 3.5-5. Cisplatin injection(premixed solution) has a pH of 3.7-6. Cisplatin may also be known as cis-Platinum II, cis-DDP,
CDDP, cis-diamminedichloroplatinum, or DDP.
During use, the injection should be protected from direct bright sunlight, but does not need to beprotected from normal room incandescent or fluorescent lights.
After reconstituting, the powder for injection is stable for at least 20 hours at room temperature. Ifusing bacteriostatic water for injection to reconstitute the drug to a concentration of 1 mg/ml, solutions are reportedly stable for at least 72 hours at room temperature. Cisplatin is reportedlystable for at least 3 weeks when frozen.
Do not use aluminum hub needles or aluminum containing IV sets as aluminum may displaceplatinum from the cisplatin molecule with the resulting formation of a black precipitate. Should aprecipitate form from either cold temperatures or aluminum contact, discard the solution.
Cisplatin is reportedly compatible with the following intravenous solutions and drugs: dextrose/saline combinations, sodium chloride 0.225%-0.9%, magnesium sulfate, and mannitol. It isalso compatible in syringes or at Y-sites with: bleomycin sulfate, cyclophosphamide, doxorubicin
HCl, droperidol, fluorouracil, furosemide, heparin sodium, leucovorin calcium, methotrexate, mitomycin, vinblastine sulfate, and vincristine sulfate.
Cisplatin compatibility information conflicts or is dependent on diluent or concentration factors with the following drugs or solutions: dextrose/saline combinations, dextrose 5% in water, andmetoclopramide. Compatibility is dependent upon factors such as pH, concentration, temperatureand diluents used. It is suggested to consult specialized references for more specific information(e.g., Handbook on Injectable Drugs by Trissel; see bibliography).
Cisplatin is reportedly incompatible with the following solutions or drugs: sodium chloride0.1% and sodium bicarbonate 5%.
Uses, Indications - In veterinary medicine, the use of cisplatin is presently limited to use in dogs.
The drug has been or may be useful in a variety of neoplastic diseases including squamous cellcarcinomas, transitional cel carcinomas, ovarian carcinomas, mediastinal carcinomas, osteosarcomas, pleural adenocarcinomas, nasal carcinomas and thyroid adenocarcinomas.
Platinum will accumulate in the body and may be detected 6 months after a course of therapy hasbeen completed. Cisplatin is highly bound to serum proteins.
In dogs, cisplatin exhibits a biphasic elimination profile. The initial plasma half-life is short(approximately 20 minutes), but the terminal phase is very long (about 120 hours). Approximately80% of a dose can be recovered as free platinum in the urine within 48 hours of dosing in dogs.
Cisplatin is also contraindicated in patients with preexisting significant renal impairment, myelosuppression, or a history of hypersensitivity to platinum-containing compounds.
When preparing the product for injection, wear gloves and protective clothing as local reactionsmay occur with skin or mucous membrane contact. Should accidental exposure occur, wash the areathoroughly with soap and water.
Cisplatin's safe use in pregnancy has not been established. It is teratogenic and embryotoxic inmice. In human men, the drug may cause azoospermia and impaired spermatogenesis.
Nephrotoxicity may commonly occur unless the animal is adequately diuresed with sodiumchloride prior to, and after therapy; diuresis will generally reduce significantly the incidence andseverity of nephrotoxicity in the majority of dogs. Other adverse effects that have been reportedinclude hematologic abnormalities (thrombocytopenia and/or granulocytopenia), ototoxicity (high-frequency hearing loss and tinnitus), anorexia, diarrhea (including hemorrhagic diarrhea), seizures, peripheral neuropathies, electrolyte abnormalities, hyperuricemia, increased hepatic enzymes, anaphylactoid reactions and death.
Direct IV infusion over 1-5 minutes should be avoided as it may cause increased nephrotoxicity orototoxicity.
Overdosage, Acute Toxicity - The minimum lethal dose of cisplatin in dogs is reportedly 2.5mg/kg (ยป80 mg/m2). Because of the potential for serious toxicity associated with this agent, dosagecalculations should be checked thoroughly to avoid overdosing. See Adverse effects above for moreinformation.
Because cisplatin can cause significant nephrotoxicity, use of other nephrotoxic drugs (e.g., aminoglycosides, amphotericin B) within 2 weeks after cisplatin therapy should be avoided.
One mg is soluble in 1 ml of water or normal saline. The drug is available commercially as powderfor injection and as a solution for injection. The powder for injection occurs as a white, lyophilizedpowder that also contains mannitol, sodium chloride and HCl (to adjust pH). After reconstitutingwith sterile water for injection a clear solution results having a pH from 3.5-5. Cisplatin injection(premixed solution) has a pH of 3.7-6. Cisplatin may also be known as cis-Platinum II, cis-DDP,
CDDP, cis-diamminedichloroplatinum, or DDP.
Storage, Stability, Compatibility
The injection and powder for injection should be stored atroom temperature and away from light; do not refrigerate the injection as a precipitate may form.During use, the injection should be protected from direct bright sunlight, but does not need to beprotected from normal room incandescent or fluorescent lights.
After reconstituting, the powder for injection is stable for at least 20 hours at room temperature. Ifusing bacteriostatic water for injection to reconstitute the drug to a concentration of 1 mg/ml, solutions are reportedly stable for at least 72 hours at room temperature. Cisplatin is reportedlystable for at least 3 weeks when frozen.
Do not use aluminum hub needles or aluminum containing IV sets as aluminum may displaceplatinum from the cisplatin molecule with the resulting formation of a black precipitate. Should aprecipitate form from either cold temperatures or aluminum contact, discard the solution.
Cisplatin is reportedly compatible with the following intravenous solutions and drugs: dextrose/saline combinations, sodium chloride 0.225%-0.9%, magnesium sulfate, and mannitol. It isalso compatible in syringes or at Y-sites with: bleomycin sulfate, cyclophosphamide, doxorubicin
HCl, droperidol, fluorouracil, furosemide, heparin sodium, leucovorin calcium, methotrexate, mitomycin, vinblastine sulfate, and vincristine sulfate.
Cisplatin compatibility information conflicts or is dependent on diluent or concentration factors with the following drugs or solutions: dextrose/saline combinations, dextrose 5% in water, andmetoclopramide. Compatibility is dependent upon factors such as pH, concentration, temperatureand diluents used. It is suggested to consult specialized references for more specific information(e.g., Handbook on Injectable Drugs by Trissel; see bibliography).
Cisplatin is reportedly incompatible with the following solutions or drugs: sodium chloride0.1% and sodium bicarbonate 5%.
Pharmacology - CISPLATIN
While the exact mechanism of action of cisplatin has not been determined, itsproperties are analogous to those of bifunctional alkylating agents producing inter- and intrastrandcrosslinks in DNA. Cisplatin is cell cycle nonspecific.Uses, Indications - In veterinary medicine, the use of cisplatin is presently limited to use in dogs.
The drug has been or may be useful in a variety of neoplastic diseases including squamous cellcarcinomas, transitional cel carcinomas, ovarian carcinomas, mediastinal carcinomas, osteosarcomas, pleural adenocarcinomas, nasal carcinomas and thyroid adenocarcinomas.
Pharmacokinetics - CISPLATIN
After administration, the drug concentrates in the liver, intestines and kidneys.Platinum will accumulate in the body and may be detected 6 months after a course of therapy hasbeen completed. Cisplatin is highly bound to serum proteins.
In dogs, cisplatin exhibits a biphasic elimination profile. The initial plasma half-life is short(approximately 20 minutes), but the terminal phase is very long (about 120 hours). Approximately80% of a dose can be recovered as free platinum in the urine within 48 hours of dosing in dogs.
Contraindications, Precautions, Reproductive Safety
Because of severe dose-related primarypulmonary toxicoses (dyspnea, hydrothorax, pulmonary edema, mediastinal edema, and death)associated with cisplatin in cats, the drug is considered contraindicated in this species at the presenttime. It is presently unknown whether non-toxic doses will have any therapeutic benefits in cats.Cisplatin is also contraindicated in patients with preexisting significant renal impairment, myelosuppression, or a history of hypersensitivity to platinum-containing compounds.
When preparing the product for injection, wear gloves and protective clothing as local reactionsmay occur with skin or mucous membrane contact. Should accidental exposure occur, wash the areathoroughly with soap and water.
Cisplatin's safe use in pregnancy has not been established. It is teratogenic and embryotoxic inmice. In human men, the drug may cause azoospermia and impaired spermatogenesis.
Adverse Effects, Warnings
In dogs, the most frequent adverse effect seen after cisplatin treatment is vomiting, which usually occurs within 6 hours after dosing and persists for 1-6 hours.Nephrotoxicity may commonly occur unless the animal is adequately diuresed with sodiumchloride prior to, and after therapy; diuresis will generally reduce significantly the incidence andseverity of nephrotoxicity in the majority of dogs. Other adverse effects that have been reportedinclude hematologic abnormalities (thrombocytopenia and/or granulocytopenia), ototoxicity (high-frequency hearing loss and tinnitus), anorexia, diarrhea (including hemorrhagic diarrhea), seizures, peripheral neuropathies, electrolyte abnormalities, hyperuricemia, increased hepatic enzymes, anaphylactoid reactions and death.
Direct IV infusion over 1-5 minutes should be avoided as it may cause increased nephrotoxicity orototoxicity.
Overdosage, Acute Toxicity - The minimum lethal dose of cisplatin in dogs is reportedly 2.5mg/kg (ยป80 mg/m2). Because of the potential for serious toxicity associated with this agent, dosagecalculations should be checked thoroughly to avoid overdosing. See Adverse effects above for moreinformation.
Drug Interactions
Cisplatin may reduce serum levels of phenytoin.Because cisplatin can cause significant nephrotoxicity, use of other nephrotoxic drugs (e.g., aminoglycosides, amphotericin B) within 2 weeks after cisplatin therapy should be avoided.