Diammindichloroplatin

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration.

The platinum compounds generally are not considered to be hepatotoxic, but cisplatin has been associated with a low rate of serum enzyme elevations during therapy. These elevations are usually mild, self-limited and asymptomatic, rarely requiring dose modification. There have been only rare case reports of clinically apparent liver injury attributed to cisplatin. In one instance, steatosis and necrosis (steatohepatitis) was found by liver biopsy in a patient who developed liver enzyme elevations 4 weeks after starting a regimen of cisplatin. In another instance, hepatocellular liver injury was described. The number of cases of liver injury attributed to cisplatin have been too few to characterize the liver injury clinically. Autoimmune and immunoallergic features have not been described and cases have all been self-limited. Cisplatin is usually given in combination with other antineoplastic agents and adverse events that occur with these combinations cannot always be attributed to cisplatin. In this regard, individual case reports of reactivation of hepatitis B, sinusoidal obstruction syndrome and severe hyperammonemic coma (without liver injury) have been described after chemotherapeutic regimens that include cisplatin and other platinum coordination complexes such as carboplatin and oxaliplatin.

IARC Carcinogen - Class 2: International Agency for Research on Cancer classifies chemicals as probable (2a), or possible (2b) human carcinogens.

Extravasation - If extravasation is suspected, the infusion should stop immediately. Any obvious fluid collection should be aspirated, and the extremity elevated. The antidote, sodium thiosulfate, should be administered.

Following cisplatin doses of 20 to 120 mg/m^2, the concentrations of platinum are highest in liver, prostate, and kidney; somewhat lower in bladder, muscle, testicle, pancreas, and spleen; and lowest in bowel, adrenal, heart, lung, cerebrum, and cerebellum. Platinum is present in tissues for as long as 180 days after the last administration.

CIsplatin has several black box warnings, including nephrotoxicity, peripheral neuropathy, severe nausea and vomiting, and myelosupression.

Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.

Cisplatin

Group 2A: Probably carcinogenic to humans

Volume 26: (1981) Some Antineoplastic and Immunosuppressive Agents

1987

1987

NB Overall evaluation upgraded to Group 2A with supporting evidence from other relevant data

Drug Induced Liver Injury Rank (DILIrank 2.0)

Cisplatin

vLess-DILI-concern

3

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

Human(iv): TD Lo: 2500 ug/kg

Rat(po): LD50: 25800 ,ug/kg

Rat(ip): LD50: 8300 ,ug/kg

Rat(sc): LD50: 8100 ,ug/kg

Rat(iv): LD50: 8 mg/kg

Rat(im): LD50: 9200 ,ug/kg

An antineoplastic drug; [HSDB]

Use (kg; approx.) in Germany (2009): >10

For the treatment of metastatic testicular tumors, metastatic ovarian tumors and advanced bladder cancer.