Cisplatin-LNS concentrate 0.5 mg/ml, 20 ml

Pharmacodynamics

Antitumor agent containing platinum. Mechanism of action is similar to that of alkylating drugs and consists in disruption of DNA strands function and formation of cross-links between them.

Pharmacokinetics

Cisplatin poorly penetrates through the BBB. It is rapidly metabolized by non-enzymatic conversion to inactive metabolites. Binding to proteins (as metabolites) is 90%.

T_1/2 in the initial phase is 25-49 min; in the final phase with normal renal excretory function – 58-73 h, with anuria – up to 240 h. Excreted by the kidneys, 27-43% after 5 days; platinum can be detected in tissues for 4 months after administration.

Indications

Active ingredient

Composition

1 ml of the concentrate contains:

Active ingredients:

Cisplatin 500 µg.

In a light-shielded glass bottle 10, 50 or 100 ml of concentrate.

In a carton pack of 1, 4, 6, 10, 25 or 40 vials.

How to take, the dosage

Intravenously. By infusion, for 6-8-24 h (pre-diluted in 1-2 liters of sodium chloride isotonic solution or 5% glucose solution) – 50-120 mg/m2 every 3-4 weeks. By drip, for 40-60 minutes (pre-diluted in 500 ml of isotonic solution) – 15-20 mg/m2 daily for 5 days, every 3-4 weeks.

Before cisplatin is administered, hydration is necessary: 1.6-2 liters of 0.9% sodium chloride solution or 5% glucose solution are administered by IV drip for 2-4 h. After the end of cisplatin injection – another 400 ml of one of these solutions. To increase diuresis – during the last 30 minutes of pre-hydration, 375 ml of 20% mannitol solution for injection can be administered by IV drops. Plenty of fluids should be provided for another 24 h.

Intravesical and intravesical administration of the drug is possible, as well as in the pleural and abdominal cavities.

Interaction

The concomitant use of cisplatin with uricosuric antipodagric agents may increase the risk of nephropathy.

Combined use with antihistamines, phenothiazines, thioxanthenes may mask the symptoms of ototoxic effects of cisplatin.

Concomitant use with drugs with ototoxic, nephrotoxic, neurotoxic effects may increase the toxic effects.

Special Instructions

Cisplatin is not recommended in patients with varicella (including recent or after exposure), herpes zoster and other acute infectious diseases.

With caution, use in patients with gout or nephrolithiasis (including a history) and in patients who have previously received cytotoxic chemotherapy or radiation therapy.

Peripheral blood count, laboratory data of renal and hepatic function, parameters of water-electrolyte exchange and uric acid level, audiometry and neurological examinations should be performed before and during the treatment with cisplatin. The first manifestations of nephrotoxic effects of cisplatin occur on the 2nd week after injection and are manifested by increased levels of creatinine, uric acid, residual nitrogen and/or decreased CK. To reduce nephrotoxicity, an intravenous infusion of 0.9% sodium chloride solution or 5% glucose solution and an additional administration of mannitol are recommended before starting treatment.

Patients and family members should not be vaccinated during cisplatin therapy.

Carcinogenic and mutagenic effects of cisplatin have been established in experimental studies.

Contraindications

Side effects

Digestive system: nausea, vomiting, stomatitis, anorexia.

Hematopoietic system disorders: leukopenia, anemia, thrombocytopenia.

CNS disorders: seizures, peripheral neuropathy, optic neuritis, color perception disorders, ototoxicity.

Metabolism disorders: hyperuricemia, hypocalcemia, hypomagnesemia, ADH inadequate secretion syndrome.

Reproductive system disorders: amenorrhea, azoospermia.

Cardiovascular system disorders: tachycardia, arterial hypotension.

Allergic reactions: skin rash, angioneurotic edema, hoarseness of the voice.

Others: nephrotoxic effect.

Overdose

The main expected complications of overdose are renal, hepatic, visual (including retinal detachment) and hearing (deafness) disorders, severe myelosuppression, uncontrollable nausea and vomiting and/or neuritis. In case of overdose, lethal outcome is possible.

An antidote in case of overdose of Cisplatin is unknown. The effect, at least partial, is achieved only with hemodialysis, if it is used within the first three hours after overdose, because platinum quickly binds to plasma proteins. Symptomatic therapy is used to eliminate the symptoms of overdose.

Pregnancy use

Cisplatin is contraindicated in pregnancy. If use during lactation is necessary, discontinuation of breastfeeding should be considered.

Women of childbearing age should use reliable methods of contraception during therapy with cisplatin.

The teratogenic and embryotoxic effects of cisplatin have been established in experimental studies.