Cisplatinum

Cisplatinum Uses, Dosage, Side Effects, Food Interaction and all others data.

Cisplatinum modifies cell cycle by interfering with DNA structure and function. Effects are most prominent during the S phase but cells are killed at all stages. Cisplatinum synergises with other anticancer drugs e.g. fluorouracil. It has a narrow therapeutic margin and is highly toxic.

Cisplatinum is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.

Trade Name Cisplatinum
Availability Prescription only
Generic Cisplatin
Cisplatin Other Names CDDP, Cis-DDP, Cisplatin, cisplatino
Related Drugs Opdivo, methotrexate, fluconazole, Diflucan, Keytruda, carboplatin, capecitabine, pembrolizumab, fluorouracil, doxorubicin
Weight 50mg/ml, 10mg/ml, 25mg/ml
Type Injection
Formula Cl2H6N2Pt
Weight Average: 300.05
Monoisotopic: 298.955596
Protein binding

Cisplatin does not undergo instantaneous and reversible binding to plasma protein that is characteristic of normal drug-protein binding. However, the platinum itself is capable of binding to plasma proteins, including albumin, transferrin, and gamma globulin. Three hours after a bolus injection and two hours after the end of a three-hour infusion, 90% of the plasma platinum is protein bound.

Groups Approved
Therapeutic Class Cytotoxic Chemotherapy
Manufacturer S, Ejazuddin & Company
Available Country Pakistan
Last Updated: September 19, 2023 at 7:00 am
Cisplatinum
Cisplatinum

How Cisplatinum works

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.

Dosage

Cisplatinum dosage

Metastatic ovarian cancer: As monotherapy: 100 mg/m2 per cycle, given as a single dose infused in 0.9% sodium chloride or glucose once every 4 wk. For combination therapy with cyclophosphamide: 75-100 mg/m2 on day 1 of every 4-wk cycle.

Metastatic testicular tumours: 20 mg/m2 BSA daily for 5 days per cycle.

Advanced bladder cancer: 50-70 mg/m2 per cycle once every 3-4 wk, depending on the extent of prior exposure to radiation and/or chemotherapy treatment. An initial dose of 50 mg/m2 every 4 wk may be used in heavily pre-treated patients.

Usual dosage and schedule: 40 to 120 mg/m2 I.V. on day 1 as infusion every 3 weeks. 15 to 20 mg/m2 I.V. on days 1 to 5 as infusion every 3 to 4 weeks. The usual dose in adults and children when used as single agent therapy is 50-100 mg/m2.

Cisplatinum lyophilized powder for injection 10 mg and 50 mg should be reconstituted with 10 ml and 50 ml of water for inj. respectively.

Cisplatinum solution after reconstitution should be added to 2 liters of 5% glucose or 0.9% saline and intravenously administered in 6-8 hours; after administration an adequate hydration and diuresis should be maintained during 24 hours.

Side Effects

Severe nausea and vomiting. Serious toxic effects on the kidneys, bone marrows and ears. Hypomagnesaemia, hypocalcaemia, hyperuricaemia. Peripheral neuropathies, papilloedema, optic neuritis, seizures. Ototoxicity (children) manifested as tinnitus, loss of hearing, deafness or vestibular toxicity.

Precaution

Patients with renal or hepatic disorder, myelosuppression. Monitor renal, neurological and auditory function. Perform blood counts regularly. Maintain adequate hydration before and 24 hr after admin to minimise nephrotoxicity.

Interaction

Synergistic with 5-fluorouracil and etoposide. Efficacy increased and toxicity reduced when combined with radioprotecting agent WR 2721. At doses ≤100 mg, cisplatin is an ideal drug to combine with other cytotoxic drugs; unlike other antineoplastic drugs, it causes little myelosuppression.

Food Interaction

  • Avoid echinacea. Echinacea should be used with caution, if at all, in patients receiving therapeutic immunosuppressants. Monitor for reduced efficacy of the immunosuppressant during concomitant use.

Volume of Distribution

Volume of distribution at steady state = 11-12 L/m^2

Elimination Route

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.

Half Life

Cisplatinum decays monoexponentially with a half life of 20 to 30 minutes following administrations of 50 or 100 mg/m^2. Cisplatinum has a plasma half-life of 30 minutes. The complexes between albumin and the platinum from cisplatin do not dissociate to a significant extent and are slowly eliminated with a minimum half-life of five days or more.

Clearance

  • 15-16 L/h/m^2 [total body clearance, 7-hour infusion of 100 mg/m^2]
  • 62 mL/min/m^2 [renal clearance, 2-hour infusion of 100 mg/m^2]
  • 50 mL/min/m^2 [renal clearance, 6- to 7-hour infusion of 100 mg/m^2] The renal clearance of free (ultrafilterable) platinum also exceeds the glomerular filtration rate indicating that cisplatin or other platinum-containing molecules are actively secreted by the kidneys. The renal clearance of free platinum is nonlinear and variable and is dependent on dose, urine flow rate, and individual variability in the extent of active secretion and possible tubular reabsorption.

Elimination Route

The parent compound, cisplatin, is excreted in the urine. Although small amounts of platinum are present in the bile and large intestine after administration of cisplatin, the fecal excretion of platinum appears to be insignificant.

Pregnancy & Breastfeeding use

Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Contraindication

Cisplatinum is contraindicated in patients with pre-existing renal impairment. Cisplatinum should not be employed in myelosuppressed patients, or patients with hearing impairment. It is also contraindicated in patients with a history of allergic reactions to cisplatin or other platinum-containing compounds.

Acute Overdose

Acute overdosage may result in kidney failure, liver failure, deafness, ocular toxicity, significant myelosuppression, intractable nausea and vomiting and/or neuritis. Death may also occur following overdosage. Treatment should include general supportive measures.

Storage Condition

Stability: The cisplatin remaining in vial following initial entry is stable for 28 days protected from light or for 7 days under fluorescent room light.

Storage: Product should be stored at controlled room temperature 25° C and protected from light.

Innovators Monograph

You find simplified version here Cisplatinum

Cisplatinum contains Cisplatin see full prescribing information from innovator Cisplatinum Monograph, Cisplatinum MSDS, Cisplatinum FDA label

*** Taking medicines without doctor's advice can cause long-term problems.
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