Cilatin 50

Cilatin 50

cisplatin

Manufacturer:

Amarox
Full Prescribing Info
Contents
Cisplatin.
Description
CILATIN Injection 50 mg/50 mL, each vial contains Cisplatin 50 mg.
Action
Pharmacology: Cisplatin is a heavy metal complex containing a central atom of platinum surrounded by two chloride atoms and two ammonia molecules in the cis positions. Cisplatin is an anticancer drug with biochemical properties similar to that of bi-functional alkylating agents producing inter-strand and intra-strand cross links in DNA; it is cell-cycle nonspecific. After a single I.V. dose, Cisplatin concentrates in liver, kidneys and large and small intestines.
It has poor penetration into the CNS. More than 90% of the drug is bound to plasma protein. The distribution half-life ranges from 58 - 73 hours.
Cisplatin excreted primarily in the urine, although urinary excretion is incomplete with only 27 - 43% of the dose being excreted within the first 5 days post-dose.
Indications/Uses
CILATIN is indicated as palliative therapy either alone or in combination with other approved chemotherapeutic against and in patients who have already received appropriate surgical and/or radio therapeutic procedures in the management of metastatic testicular tumors or metastatic ovarian tumors and advanced bladder cancer.
Dosage/Direction for Use
Do not use needles or I.V. sets containing Aluminium parts because Al reacts with Cisplatin, causing precipitate formation and a loss of potency.
Prehydration therapy: A prehydration therapy is required 8 - 12 hours before Cisplatin administration. This consists of 1 - 2 litre physiological saline solution per m2 body surface area (BSA) per infusion over at least 2 - 3 hours.
Cisplatin administration: Short-term infusion: I.V. infusion over 15 minutes. The Cisplatin dose to be administered is given immediately following I.V. administration of 62.5 mL 20% Mannitol solution.
Long-term infusion: I.V. infusion over 1 - 8 hours. The Cisplatin dose to be administered is diluted with 1 - 2 L physiological saline solution.
The solution can contain 50 g Glucose and 18.75 g Mannitol/L.
Dosages for monochemotherapy: 50 - 120 mg Cisplatin/m2 BSA at 3 - 4 weeks intervals; or 50 mg Cisplatin/m2 BSA on day 1 and 8 at 3 - 4 weeks intervals or 15 - 20 mg Cisplatin/m2 BSA on day 1 - 5 at 3 - 4 weeks intervals. Cisplatin is generally administered in chemotherapeutic combinations in which the dose is accordingly reduced.
Posthydration therapy: Adequate fluids must be given during the period after the Cisplatin administration, i.e. in the (6 - 12) 24 hours following the drug administration (this consists of 2 - 3 litres physiological saline solution/m2 BSA together with a 5% glucose solution at a ratio of 1 : 1.5). The urine volume during the posthydration should be at least 100 - 200 mL/hour. A forced diuresis must be induced in the case of inadequate excretion.
Forced diuresis: For patients who have received proper prehydration and posthydration therapy and Cisplatin doses below 60 mg/m2 BSA and who have normal renal function, the administration of Mannitol to induce a diuresis can be replaced by careful balancing and weight control. Mannitol must be administered when the retention ≥ 1000 mL. For Cisplatin doses above 60 mg/m2 BSA, Mannitol administration (8 g/m2) BSA is obligatory immediately prior to the first Cisplatin administration. Only after the onset of a minimal diuresis of 250 mL within 30 minutes may the Cisplatin administration be started.
During the therapy with Cisplatin, attention must be paid to electrolyte losses, namely losses of potassium, magnesium and calcium and an appropriate replacement therapy must be carried out as required. An adequate antiemetic therapy best with serotonin-receptor antagonists with or without Dexamethasone, is to be carried out as required. Larger fluid losses, resulting from vomiting or diarrhea are to be replaced.
Various therapy regimens recommended the following dose reductions for patients with impaired renal failure: Serum creatinine ≤ 2 mg/dL: No reduction in the Cisplatin dose. Some therapy regimens recommend a dose reduction of 50% of the standard dose already in the serum creatinine range 1.5 - 2 mg/dL. The clinical benefits and risks must be assessed here individually. It is particularly important to also differentiate between the benefit-risk relationship of a Cisplatin administration in patients with healthy kidneys by whom renal function impairment are observed after Cisplatin administration and the benefits and risks involved with such a treatment in patients with pre-existing renal impairment.
Serum creatinine ≥ 2 mg/dL: Stop the Cisplatin therapy until the serum creatinine again ≤ 2 mg/dL. If the recovery phase until reaching this value takes longer than 6 weeks, then an alternative treatment with another cytostatic agent is to be started. Cisplatin administered as an intravenous infusion.
As with other potentially toxic compounds, handle the solution of Cisplatin with caution. Accidental exposure to Cisplatin may cause skin reaction. The use of gloves is recommended. If Cisplatin powder or solution contact skin or mucosae, immediately wash the skin or mucosae thoroughly with soap and water.
CILATIN Injection occurs as a clear solution, colorless to light yellow. It is odorless, pH 3.5 - 6.5 and contains 1 mg of Cisplatin per mL.
CILATIN Injection should only be used intravenously and should be administered by I.V. infusion over a period of 6 - 8 hours. If it is refrigerated, a precipitate will form.
Overdosage
In the event of an overdosage, the described side effects are more intense. As a rule, bone marrow toxicity predominates. An overdose is potentially lethal and leads to the following symptoms, among other: Liver failure, deafness, ocular toxicity (including retinal detachment), incontrollable vomiting or retching and/or neuritis. A direct influence on the respirator center with life-threatening impaired ventilation and acid-base imbalances is possible with an overdose (> 200 mg/m2 BSA) due to the crossing of the blood-brain barrier.
Therapeutic measures for overdose: There is no known specific antidote against Cisplatin. The immediate emergency measures to be taken in the event of severe intolerance reactions consist of withdrawing the therapy immediately, symptomatic treatment and shock therapy if required.
The following individual counter measures are recommended: Renal function impairment: The frequency and severity of renal function impairments can be substantially reduced through adequate hydration before and after the administration (see DOSAGE & ADMINISTRATION). Modulators, such as Sodium thiosulphate can be applied to reduce the nephrotoxic effect of Cisplatin.
Hyperuricemia: Elevated serum uric acid levels can be lowered by administering Allopurinol.
Plasma electrolytes losses: Clinically relevant electrolytes losses (mostly sodium, magnesium and calcium) can be compensated by appropriate electrolyte replacement therapy.
Anaphylactic reactions: Symptomatic treatment, e.g. with sympathomimetics, corticoids and antihistamines.
Dialysis: Over 90% of the Cisplatin administered is bound to plasma proteins 2 hours after the administration. Due to the rapid protein binding, Cisplatin is dialyzable only in the first 2 hours after the administration. Approximately 8% of the administered dose can be removed from the plasma via dialysis immediately after administration.
Contraindications
Preexisting renal impairment.
Myelosuppressed patients.
Hearing impairment.
Hypersensitivity to Cisplatin or other platinum containing compounds.
Special Precautions
Administer Cisplatin under the supervision of qualified physician experienced in the use of anticancer agents.
Cisplatin procedure cumulative renal toxicity which is severe and potentiated by Aminoglycoside antibiotics. Therefore, measure the serum creatinine, BUN, creatinine clearance and Mg, K and Ca levels prior to initiating therapy and prior to each subsequent course. At the recommended dosage, do not give this drug more frequently than once every 3 - 4 weeks.
Since the ototoxicity of Cisplatin is also cumulative, perform audiometric testing prior to initiating therapy and prior to each subsequent dose of drug.
Cisplatin aslo causes dose-related myelosuppression. Peripheral blood counts should be monitored weekly.
Anaphylactic-like reactions to Cisplatin have occurred in patients with prior exposure to this drug and have been alleviated by administration of Epinephrine, corticosteroid and antihistamines.
Cisplatin may cause severe neuropathies and these may be irreversible in some patients. Neurologic examination should be performed regularly.
Liver function should also be monitored periodically; elevated SGOT may occur.
Safe use in pregnant woman has not established. In mice, Cisplatin is teratogenic and embryotoxic.
Adverse Reactions
Nephrotoxicity: Dose-related and cumulative renal insufficiency associated with renal tubular damages the major dose-limiting toxicity of Cisplatin. A single dose of 50 mg/m2 BSA has caused renal toxicity in 28 - 36% patients. Elevations in BUN and creatinine, serum uric acid and/or a decrease in creatinine clearance are first sign during the second week after the dose. Renal function must return to normal before the next dose of Cisplatin can be given.
Ototoxicity: Manifested by tinnitus and/or loss of hearing in the high frequency range. Decreased ability to hear normal conversational tones may occur occasionally. Hearing loss can be unilateral or bilateral. A single dose of 50 mg/m2 BSA has caused ototoxicity in up to 31% of patients. Cisplatin induced ototoxicity in up to 31% of patients. Cisplatin induced ototoxicity is cumulative, may be more severe in children and it is unclear whether reversible or not.
Hematologic: Dose-related myelosuppression occurs in 25 - 30% of patients. The lowest platelet and leukocyte counts occur between days 18 - 23 (ranges 7.5 - 45). Most patients recover by day 39 (range 13 - 62). Anemia (decrease of > 2 g Hb/100 mL) occurs at approximately the same frequency and with the same timing as leucopenia and thrombocytopenia.
Gastrointestinal: Marked nausea and vomiting occur in almost all patients and are occasionally so severe that the drug must be discontinued. Nausea and vomiting usually begin within 1 - 4 hours after treatment and last up to 24 hours. Various degrees of nausea and anorexia may persist up to one week after treatment.
Neurotoxicity: Has occurred in some patients. It is usually manifested by peripheral neuropathies and rarely by optic neuritis, papilledema, cerebral blindness, loss of appetite and seizures. Cisplatin induced neuropathies may occur after prolonged therapy (4 - 7 months), but may also occur after a single dose. The drug should be discontinued when the symptoms are first observed. Improvement and/or total recovery usually occurs. In some patients, however, peripheral neuropathy may be irreversible.
Anaphylactic-like reactions: Have been occasionally reported in patients previously exposed to Cisplatin. The reactions consist of facial edema, wheezing, tachycardia and hypotension within a few minutes or drug administration.
Serum electrolyte disturbances: Hypocalcemia, hypokalemia and hypophosphatemia have occurred and are probably related to renal tubular damage. Tetany has occasionally accompanied hypocalcemia and hypomagnesemia. Discontinuation usually restores the serum electrolyte levels to normal.
Hyperuricemia: Occurs at approximately the same frequency as the increased in BUN and serum creatinine. It peaks between 3 - 5 days after the dose. Allopurinol therapy effectively reduces uric acid levels.
Other toxicities which rarely occurred are cardiac abnormalities, anorexia and elevated SGOT.
Drug Interactions
An increased bone marrow toxicity must be expected when combined with other myelosuppressants or therapeutic measures such as radiotherapy. Nephrotoxic and ototoxic substances (e.g. Aminoglycosides, Amphotericin-B) must not be administered concomitantly with Cisplatin since an increased nephrotoxicity and ototoxicity is to be expected also this case.
Chelating agents such as Penicillamine should not be administered concomitantly with Cisplatin since this combination lowers the efficacy of Cisplatin.
Due to a possibly reduced renal excretion, substances which are eliminated primarily via the kidneys among other cytostatic agents such as Bleomycin and Methotrexate should only be administered with special care during or after the treatment with Cisplatin.
A randomized study of advanced ovarian cancer showed that simultaneous administration of Pyridoxin and Hexamethylamine negatively influenced the therapeutic response.
A Raynaud's phenomenon can occur when Cisplatin is combined with Bleomycin or Vinblastine. Concomitant treatment with anticonvulsants can result in their plasma concentrations dropping to the subtherapeutic range (adjust dose as required).
The combination of Cisplatin and Docetaxel caused neuropathy, which was more pronounced than that of the single agents at similar dosage.
Cisplatin exerts an immunosuppressive effect: Vaccination with live vaccines should be avoided in patients on Cisplatin therapy.
Please keep in mind that this information can also apply to drugs taken a short-time ago.
Storage
Store below 30°C and protect from light. Do not refrigerate.
Shelf life after reconstitution: To reconstitute: CILATIN must be diluted prior to infusion in 0.9% Sodium Chloride + 5% Dextrose or 0.9% Sodium Chloride to a final concentration range of 0.01 - 0.1 mg/mL.
In 0.9% Sodium Chloride + 5% Dextrose: After reconstitution, the solution is stable within 8 hours at 15 - 25°C in ambient light or within 24 hours at 15 - 25°C protected from light.
In 0.9% Sodium Chloride: After reconstitution, the solution is stable within 8 hours at 15 - 25°C in ambient light or within 24 hours at 15 - 25°C protected from light.
ATC Classification
L01XA01 - cisplatin ; Belongs to the class of platinum-containing antineoplastic agents. Used in the treatment of cancer.
Presentation/Packing
Inj (vial) 50 mg/50 mL x 1's.
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