cisplatin

CISPLATIN

Complete information including dosage, side effects, interactions and pregnancy & breast feeding warnings for patient and professional use

Overview

Cisplatin injection is a white to light yellow lyophilized powder. Each vial of Cisplatin contains 50 mg Cisplatin, 450 mg Sodium Chloride, USP, and 500 mg Mannitol, USP. The active ingredient, Cisplatin, is a yellow to orange crystalline powder.

Indication (uses)

  • Metastatic Testicular Tumors
    • In established combination therapy with other approved chemotherapeutic agents in patients with metastatic testicular tumors who have already received appropriate surgical and/or radiotherapeutic procedures.
  • Metastatic Ovarian Tumors
    • In established combination therapy with other approved chemotherapeutic agents in patients with metastatic ovarian tumors who have already received appropriate surgical and/or radiotherapeutic procedures.
    • An established combination consists of Cisplatin and cyclophosphamide.
    • Cisplatin, as a single agent, is indicated as secondary therapy in patients with metastatic ovarian tumors refractory to standard chemotherapy who have not previously received Cisplatin therapy.
  • Advanced Bladder Cancer
    • Cisplatin is indicated as a single agent for patients with transitional cell bladder cancer which is no longer amenable to local treatments, such as surgery and/or radiotherapy.
  • Other solid tumors like lung, esophageal, gastric, hepatic, head and neck carcinomas.

Pharmacological classification

Anti-cancer drug (Platinum coordination complex) used for the treatment of testicular, ovarian and bladder tumors.

Brand names

Platinol

Dosage form

  • Available as injection where each vial consists of 50 mg of Cisplatin.

Mechanism of action

It is hydrolysed intracellularly to produce a highly reactive moiety which causes cross linking of DNA. The favoured site is N7 of guanine residue. It can also react with –SH groups of cytoplasmic and nuclear proteins. Effects resemble those of alkylating agents and radiation.

Dosage

Adult dose for testicular cancer

  • 20 mg/m2 IV once a day for 5 days per cycle (in combination with other anti cancer drugs).

Adult dose for ovarian cancer

  • 75 to 100 mg/m2 iv once every 4 weeks (in combination with cyclophosphamide for the treatment of metastatic ovarian cancer).
  • Alternatively, 100 mg/m2 intravenously once every 4 weeks may be administered (as a single agent for the treatment of metastatic ovarian cancer).

Adult dose for bladder cancer

  • 50 to 70 mg/m2v. once every 3 to 4 weeks (as a single agent for the treatment of advanced bladder cancer in patients without history of extensive X-radiation or chemotherapy).
  • Alternatively, 50 mg/m2v. over 6 to 8 hours every 4 weeks may be administered (as a single agent for the treatment of advanced bladder cancer in patients with history of extensive X-radiation or chemotherapy)

Adult dose for neuroblastoma

  • 60 to 100 mg/m2 once every 3 to 4 weeks.

Adult Dose for Osteogenic Sarcoma

  • 60 to 100 mg/m2 once every 3 to 4 weeks.

Adult Dose for Brain/Intracranial Tumor

  • 60 mg/m2 once a day for two consecutive days every 3 to 4 weeks.

Adult Dose for Bone Marrow Transplantation

  • Continuous infusion: High Dose: 55 mg/m2/day for 72 hours (Total Dose = 165 mg/m2).

Adult Dose for Blood Cell Transplantation

  • Continuous infusion: High Dose: 55 mg/m2/day for 72 hours (Total Dose = 165 mg/m2).

Adult Dose for Non-Small Cell Lung Cancer

  • 60 to 100 mg/m2 intravenously on day one every 21 days (in combination with other antineoplastic drugs).

Adult Dose for Cervical Cancer

  • (In combination with radiation therapy) 40 mg/m2 IV weekly Maximum dose: 70 mg/week Cisplatin is given 4 hours before radiation therapy on weeks 1 through 6.
  • (In combination with paclitaxel) 75 mg/m2 IV on day 2. The cycle is repeated every 21 days.
  • (In combination with other chemotherapeutic agents as a part of the BIP regimen) 50 mg/m2 IV on day 2. The cycle is repeated every 21 days.
  • (In combination with other chemotherapeutic agents as a part of various regimens) 50 to 200 mg/m2 IV on day 1.

Renal dose adjustments

  • According to the manufacturer and the FDA, Cisplatin is contraindicated in patients with preexisting renal impairment.
  • Because hemodialysis is effective in removing Cisplatin within the first 90 minutes after drug administration, it is recommended that doses be given after dialysis (if doses are scheduled on the days this patient is dialyzed).

Hepatic dose adjustments

  • Data not available. Dose adjustments may be required.

Geriatric dose adjustments

  • Data not available. Dose adjustments may be required.

Pediatric use

  • Safety and effectiveness of Cisplatin in pediatric patients have not been established.

Overdosage

  • Acute Overdosage with Cisplatin may cause kidney failure, liver failure, deafness, ocular toxicity (including detachment of the retina), significant myelosuppression, intractable nausea and vomiting and/or neuritis. In addition, death can occur following overdosage.
  • No specific antidote is known.
  • Hemodialysis is effective in removing Cisplatin within the first 90 minutes after drug administration.
  • Hemodialysis when initiated four hours after the overdosage, appears to have little effect on removing platinum from the body because of Cisplatin’s rapid and high degree of protein binding.
  • Seek immediate medical attention.
  • Treatment of overdosage involves
  • General supportive measures.

Side effects or adverse effects

Side effects specific to Ciplatin for injection

  • Nephrotoxicity
    • Dose-related and cumulative renal insufficiency, including acute renal failure, is the major dose-limiting toxicity of Cisplatin
    • Renal toxicity becomes more prolonged and severe with repeated courses of the drug.
    • Renal function must return to normal before another dose of Cisplatin can be given.
    • Elderly patients may be more susceptible to nephrotoxicity.
    • Impairment of renal function has been associated with renal tubular damage.
    • The administration of Cisplatin using a 6 hour to 8 hour infusion with intravenous hydration, and mannitol has been used to reduce nephrotoxicity.
    • However, renal toxicity still can occur after utilization of these procedures.
  • Ototoxicity
    • Hearing loss can be unilateral or bilateral and tends to become more frequent and severe with repeated Cisplatin doses.
    • It is unclear whether Cisplatin-induced ototoxicity is reversible.
    • Vestibular toxicity has also been reported.
    • Audiometric monitoring should be performed prior to initiation of therapy, prior to each subsequent dose, and for several years post therapy.
    • The risk of ototoxicity may be increased by prior or simultaneous cranial irradiation, and may be more severe in patients less than 5 years of age, patients being treated with other ototoxic drugs (e.g., aminoglycosides and vancomycin), and in patients with renal impairment.
  • Hematologic
    • Anemia
    • Leukopenia and thrombocytopenia are more pronounced at higher doses.
    • Coombs’ positive hemolytic anemia.
    • The development of acute leukemia coincident with the use of Cisplatin has been reported.
  • Gastrointestinal
    • Nausea
    • Vomiting
    • Diarrhea
  • Serum Electrolyte Disturbances
    • Hypomagnesemia, hypocalcemia, hyponatremia, hypokalemia, and hypophosphatemia have been reported to occur in patients treated with Cisplatin and are probably related to renal tubular damage.
    • Tetany has been reported in those patients with hypocalcemia and hypomagnesemia.
    • Generally, normal serum electrolyte levels are restored by administering supplemental electrolytes and discontinuing Cisplatin.
    • Inappropriate antidiuretic hormone syndrome has also been reported.
  • Hyperuricemia
    • Hyperuricemia has been reported to occur at approximately the same frequency as the increases in BUN and serum creatinine.
    • It is more pronounced after doses greater than 50 mg/m2, and peak levels of uric acid generally occur between 3 to 5 days after the dose.
    • Allopurinol therapy for hyperuricemia effectively reduces uric acid levels.
  • Neurotoxicity
    • Neurotoxicity, usually characterized by peripheral neuropathies, has been reported. The neuropathies usually occur after prolonged therapy (4 to 7 months); however, neurologic symptoms have been reported to occur after a single dose.
    • Although symptoms and signs of Cisplatin neuropathy usually develop during treatment, symptoms of neuropathy may begin 3 to 8 weeks after the last dose of Cisplatin.
    • Cisplatin therapy should be discontinued when the symptoms are first observed.
    • The neuropathy, however, may progress further even after stopping treatment.
    • Preliminary evidence suggests peripheral neuropathy may be irreversible in some patients.
    • Elderly patients may be more susceptible to peripheral neuropathy.
    • Lhermitte’s sign, dorsal column myelopathy, and autonomic neuropathy have also been reported.
    • Loss of taste, seizures, leukoencephalopathy, and reversible posterior leukoencephalopathy syndrome (RPLS) have also been reported.
    • Muscle cramps, defined as localized, painful, involuntary skeletal muscle contractions of sudden onset and short duration, have been reported and were usually associated in patients receiving a relatively high cumulative dose of Cisplatin and with a relatively advanced symptomatic stage of peripheral neuropathy.
  • Ocular Toxicity
    • Optic neuritis, papilledema, and cerebral blindness have been reported in patients receiving standard recommended doses of Cisplatin.
    • Improvement and/or total recovery usually occurs after discontinuing Cisplatin.
    • Steroids with or without mannitol have been used; however, efficacy has not been established.
    • Blurred vision and altered color perception have been reported after the use of regimens with higher doses of Cisplatin or greater dose frequencies than recommended in the package insert.
    • The altered color perception manifests as a loss of color discrimination, particularly in the blue-yellow axis.
    • The only finding on funduscopic exam is irregular retinal pigmentation of the macular area.
  • Anaphylactic-Like Reactions
    • Anaphylactic-like reactions have been reported in patients previously exposed to Cisplatin.
    • The reactions consist of facial edema, wheezing, tachycardia, and hypotension within a few minutes of drug administration.
    • Reactions may be controlled by intravenous epinephrine with corticosteroids and/or antihistamines as indicated.
    • Patients receiving Cisplatin should be observed carefully for possible anaphylactic-like reactions and supportive equipment and medication should be available to treat such a complication.
  • Hepatotoxicity
    • Transient elevations of liver enzymes, especially SGOT, as well as bilirubin, have been reported to be associated with Cisplatin administration at the recommended doses.
  • Other events
    • Cardiac abnormalities, hiccups, elevated serum amylase, rash, alopecia, malaise, asthenia, and dehydration have been reported.
    • Local soft tissue toxicity has been reported following extravasation of Cisplatin.
    • Severity of the local tissue toxicity appears to be related to the concentration of the Cisplatin solution.
    • Infusion of solutions with a Cisplatin concentration greater than 0.5 mg/mL may result in tissue cellulitis, fibrosis, necrosis, pain, edema, and erythema.

Other side effects associated with cancer therapy

  • Bone marrow depression
    • Bone marrow depression is the most serious side effect/toxicity. It is also a limiting factor for the dose. Infections and bleeding are the common complications.
    • Bone marrow depression results in granulocytopenia, agranulocytosis, thrombocytopenia and aplastic anemia.
    • Consult your doctor as soon as possible if you observe any of the below mentioned symptoms:
      • Sore throat
      • Chills
      • Sudden fever
      • Weakness in limbs
      • Mouth ulcers
      • Bleeding gums
      • Sore mouth
      • Fast heart rate
      • Low blood pressure
      • Sore gums
      • Skin abscesses
      • Rapid breathing
      • Rapid progression of infection of any organ
      • Rapid progression of Septicemia
    • Gastrointestinal side effects
      • Nausea and vomiting are commonly observed with anti-cancer medicines.
      • Mucositis – painful inflammation and ulceration of mucus membrane lining the digestive tract.
      • Diarrhea, shredding of mucosa and haemorrhage due to decreased rate of renewal of gastrointestinal mucosa lining.
    • Skin
      • Alopecia or hair loss.
      • Dermatitis
    • Oral side effects
      • Breaches during chewing.
      • Depression of immunity due to reduction in number of WBCs largely increases the risk of oral infections.
      • Bleeding gums
      • Rapid progression of dental caries.
    • Gonadal side effects
      • Infertility due to Oligozoospermia in males.
      • Impotence in males.
      • Loss or reduces sex drive.
      • Inhibition of ovulation in females
      • Amenorrhea in females.
      • Damage to germinal cells may lead to mutagenesis.
    • Lymphoreticular tissue
      • Lymphocytopenia (reduced number of lymphocytes)
      • Inhibition of lymphocyte function.
      • Suppression of immunity due to bone marrow depression and reduced lymphocyte function highly increases the risk of opportunistic infections like:
        • Candida and other infections causing deep mycosis.
        • Cytomegalo virus
        • Herpes zoster
        • Pneumocystis jiroveci
        • Toxoplasma
      • Fetal side effects
        • Use of anti-cancer medicines in pregnant women may cause fetal damage leading to:
          • Fetal death
          • Abortion
          • Teratogenesis
        • Renal side effects
          • Renal failure, Gout and Urate stones may develop in urinary tract.
        • Hyperuricemia
          • An elevated level of uric acid is common in leukemia and bulky lymphomas.

Please note: The side effects mentioned above are from the reported cases. However, side effects are not limited to above-mentioned conditions and symptoms. Consult your doctor as soon as possible if you feel or observe any symptoms that you relate to your treatment.

Warnings & Precautions

Cisplatin should only be administered under the strict supervision of a specialist doctor experienced in administrating chemotherapy.

Please read adverse effects to know more on warnings and precautions.

Contraindications

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

Pregnancy & breast feeding warnings

  • Pregnancy

Category D, which means there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

  • Nursing
  • Cisplatin has been reported to be found in human milk; patients receiving Cisplatin should not breast-feed.

Interactions

Drug – drug interactions

  • Because of the potential for increased risk of PML and other infections, avoid the concomitant use of Cisplatin with natalizumab.
  • Concomitant use of Cisplatin with following drugs/medicines should be strictly avoided.
    • Adefovir, Deferasirox, diatrizoate, Tenofovir, ioxilan, ioxagalate, ioversol, iothalamate, iopromide, iopalmidol, iohexol, iodixanol, iodipamide, iodamide, sirolimus, tacrolimus and Cidofovir may increase the risk of renal problems.
    • Clozapine and topotecan as it may lower the WBC count.
    • Deferiprone as it increases the risk of infections.
    • Aldesleukin may cause tumor lysis syndrome.
    • Amiodarone, dronedarone, droperidol, pimozide, ziprasidone and Dofetilide may increase the risk of irregular heart rate.
    • Leflunomide as it increases the risk of infections.
    • Thalidomaide as it increases the risk of dangerous blood clots.
    • Adalimumab as it increases the risk of infections.
    • Talimogene laherparepvec may increase the risk of potentially life threatening herpes infection.
    • Teriflunomide as it increases the risk of infections.
    • Certolizumab as it increases the risk of infections.
    • Influenza virus vaccine (live, trivalent) as it increases the risk of infections.
    • Small pox vaccine as it increases the risk of infections.
    • Measles virus vaccine as it increases the risk of infections.
    • Mumps virus vaccine as it increases the risk of infections.
    • Polio virus vaccine (live, trivalent) as it increases the risk of infections.
    • Varicella virus vaccine as it increases the risk of infections.
    • Typhoid vaccine (live) as it increases the risk of infections.
    • BCG vaccine as it increases the risk of infections.
    • Yellow fever vaccine as it increases the risk of infections.
    • Zoster vaccine (live) as it increases the risk of infections.
    • Tofacitinib as it increases the risk of infections.
    • Etelcalcetide as it increases the risk of hypocalcemia.
    • Etanercept as it increases the risk of infections.
    • Fingolimod as it increases the risk of infections.
    • Golimumab as it increases the risk of infections.
    • Infliximab as it increases the risk of infections.
    • Alefacept as it increases the risk of infections.
    • Alemtuzumab as it increases the risk of infections.
    • Azathioprine as it increases the risk of infections.
    • Canakinumab as it increases the risk of infections.
    • Cladribine as it increases the risk of infections.
    • Denosumab as it increases the risk of infections.
    • Efalizumab as it increases the risk of infections.
    • Ocrelizumab as it increases the risk of infections.
    • Omacetaxine as it increases the risk of infections.
    • Ustekinumab as it increases the risk of infections.

Click here to go to Cisplatin forums.

By |2017-12-20T12:58:19+00:00September 2nd, 2017|medicines|1 Comment

About the Author:

B. Pharm (K.L.E. society's S.V.V. Patil College of Pharmacy, Bengaluru) M. Pharm (Maharishi Arvind Institute of Pharmacy, Jaipur)

One Comment

  1. Rashmi Sharma February 8, 2018 at 11:02 am - Reply

    Your work is great .

Leave A Comment

WE NEED YOUR HELP IN CREATING AWARENESS ABOUT DISEASES AND MEDICINES

In today's fast paced life, we often come across minor health issues that we often neglect due to lack of time for paying a visit to a doctor, which usually takes away 2-3 hours of a person's time and are expensive too. Further more, such minor conditions may grow big at any time if neglected. Our aim in setting up this platform is that any person can search for any health condition or medicines and can get all the needed information within hardly 10-15 minutes, which saves a lot of time and money. After going through every information, if the person has any questions, he/she can go to our forums section and raise a topic. This will help him/her decide better whether he/she needs to pay an immediate visit to a doctor or can it wait for a day or two? Help us in bringing awareness about diseases and medicines by spreading the word to at least 5 of your friends and relatives.