Cisplatin-Ebeve

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Instructions for use:

1. Release form and composition
2. Indications for use
3. Contraindications
4. Method of application and dosage
5. Side effects
6. Special instructions
7. Drug interactions
8. Analogs
9. Terms and conditions of storage
10. Terms of dispensing from pharmacies

Cisplatin-Ebeve is a drug that disrupts the development of true tumors (sarcoma, cancer, etc.) and hemoblastoses; an alkylating compound of radiosensitizing and immunosuppressive action, containing platinum.

Release form and composition

The drug is available in the form of a concentrate for the preparation of a solution for infusion: a clear, colorless or slightly yellowish liquid (10 mg / 20 ml, 25 mg / 50 ml or 50 mg / 100 ml in brown glass vials, in a cardboard box 1 bottle).

Composition of 1 ml of concentrate:

active substance: cisplatin - 0.5 mg;
auxiliary components: diluted hydrochloric acid, sodium chloride, water for injection.

Indications for use

Cisplatin-Ebeve in combination chemotherapy is commonly used to treat the following solid tumors:

squamous cell carcinoma of the head and neck (SCC);
germ cell tumors (male and female);
small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC);
bladder cancer;
testicular and ovarian cancer.

Also, cisplatin has antitumor activity in cervical cancer, osteosarcoma, neuroblastoma, melanoma, esophageal cancer.

Contraindications

Absolute:

renal impairment (serum creatinine level ≥ 115 μmol / liter);
hearing impairment;
oppression of bone marrow hematopoiesis (aplastic anemia);
yellow fever vaccination;
pregnancy and lactation (lactation period);
hypersensitivity to cisplatin / other compounds containing platinum, and to any of the components of the drug.

Relative (use with caution): in acute infectious diseases of the viral (herpes zoster or chickenpox, including a recent illness / recent contact with a carrier of infection), bacterial or fungal genesis, hyperuricemia (including manifested by urate nephrourolithiasis and / or gout), polyneuritis, nephrourolithiasis, radiation or chemotherapy in history.

Method of administration and dosage

Cisplatin-Ebeve is administered as an intravenous (IV) infusion or injection into the abdominal cavity (as indicated for intraperitoneal tumors).

Cisplatin is used both in combination with other cytostatic drugs, and as a monotherapy drug, in various doses, depending on the chosen treatment regimen. Individual selection of the dose is carried out taking into account the recommendations set out in the special literature.

The standard dosage of the drug Cisplatin-Ebeve:

Scheme I: intravenous infusion from 50 to 120 mg / m ² 1 time every 3-4 weeks;
II scheme: in / in from 15 to 20 mg / m ² daily for 5 days every 3-4 weeks.

When bone marrow function is inhibited or when renal failure develops, the dose of the drug should be adjusted downward.

Recommendations for the preparation and administration of Cisplatin-Ebeve solution for intravenous infusion:

2–12 hours before the injection of the solution (optimally 2–3 hours) to stimulate diuresis and minimize the nephrotoxic effect, hydration is carried out by intravenous drip injection of saline in a volume of 0.5 to 1.5–2 l / m ² …
After the introduction of cisplatin for 6-24 hours, you need to provide sufficient fluid support in a volume of 2-3 l / m ² of sodium chloride solution and 5% glucose solution in a ratio of 1: 1.5 to achieve a diuresis rate of 100-200 ml per hour. If necessary, D-mannitol is prescribed; the use of loop diuretics is not recommended.
The use of cisplatin in a dose of <60 mg / m ² at a delay in the body of liquid in a volume greater than 1 liter and normal renal function can be combined with D-mannitol subject weight control and fluid balance.
The use of cisplatin at a dose of> 60 mg / m ² requires the mandatory intake of D-mannitol at a dose of 8 g / m ² immediately before the administration of cisplatin, which begins to be administered with a minimum urine output of 250 ml / 30 minutes.

The rate of intravenous drip infusion should be ≤ 1 mg / minute, excrete:

short-term infusion in low doses (up to 20 mg / m ²): administration time - from 30 to 60 minutes; dilute cisplatin with 20% D-mannitol solution in a volume of 62.5 ml;
long-term infusion in high doses: administration time - from 6-8 to 24 hours (provided there is sufficient urine output before and during infusion); dilute cisplatin in 1–2 liters of sodium chloride solution, in addition, 1 liter of solution may contain 18.75 g of D-mannitol and 50 g of glucose.

In case of moderately severe renal impairment (with creatinine clearance <115 μmol / l), it is recommended to reduce the standard dose by 50%.

To dilute cisplatin, use a 0.9% sodium chloride solution (up to a concentration of 1 mg / ml), dextrose solutions cannot be used.

The stability of the infusion solution prepared with 0.9% sodium chloride solution at a concentration of 1 mg / ml is maintained for 6–8 hours at storage temperatures up to 25 ° C in a place protected from light.

Since aluminum interacts with cisplatin, inactivating it and causing the formation of a precipitate, it is very important not to use needles and other equipment containing aluminum when preparing and injecting the Cisplatin-Ebeve solution.

Side effects

central nervous system (CNS): rarely - peripheral neuropathy, leukoencephalopathy, seizures; with an unknown frequency - hemorrhagic / ischemic stroke, ageusia / partial loss of taste, Lhermitte's symptom (acute pain when flexing the neck, similar to an electric shock, passing down the arms or torso), myelopathy, autonomic neuropathy, cerebral arteritis;
sense organs: infrequently - unilateral / bilateral tinnitus, ototoxicity; with an unknown frequency - a change in color perception, especially in the yellow-blue zone of the spectrum, optic neuritis, edema of the optic papilla, cortical blindness, irregular retinal pigmentation in the macular region, deafness (side effects of a dose-dependent, cumulative and reversible nature);
gastrointestinal tract: rarely - inflammation of the mucous membranes of the oral cavity; with an unknown frequency - hiccups, nausea / vomiting, diarrhea, anorexia, increased plasma concentrations of bilirubin and liver enzymes;
cardiovascular system: often - arrhythmia, tachycardia, bradycardia; rarely - myocardial infarction; very rarely - cardiac arrest; with an unknown frequency - thrombolytic microangiopathy, Raynaud's disease, cerebral arteritis;
genitourinary system: infrequently - impaired spermatogenesis; with an unknown frequency - renal failure in the acute stage, toxic renal damage (including tubular), expressed by an increase in the plasma concentration of uric acid, urea, creatinine and / or a decrease in creatinine clearance;
water-electrolyte metabolism: very often - hyponatremia (possibly as a consequence of the syndrome of inadequate secretion of antidiuretic hormone); infrequently - hypomagnesemia; with an unknown frequency - hypocalcemia, dehydration, hypokalemia, hyperuricemia, hypophosphatemia;
hematopoietic organs: very often - leukopenia, thrombocytopenia, anemia, myelosuppression; due to the administration of high doses of cisplatin, a deep inhibition of the hematopoietic function of the bone marrow (including agranulocytosis / aplastic anemia) is possible; with an unknown frequency - positive Coombs' test and hemolytic anemia;
allergic reactions: infrequently - anaphylactic reactions (edema and redness of the face, wheezing in the lungs, bronchospasm, tachycardia, arterial hypotension); very rarely - maculopapular skin rash, urticaria;
others: very often - a feverish state; often - sepsis; infrequently - acute leukemia; with an unknown frequency - alopecia, gingival platinum line, increased serum amylase concentration, asthenia, malaise, pulmonary embolism, infection (up to death), accidental ingestion of the solution into the subcutaneous tissue at the injection site, accompanied by local toxicity of soft tissues: pain, cellulite, redness, fibrosis, edema, necrosis.

Symptoms of an overdose with Cisplatin-Ebeve include an increase in the severity of side effects, mainly manifested by impaired renal / liver function, vision (including retinal detachment) and hearing (deafness), severe myelosuppression, indomitable nausea and vomiting and / or neuritis; there is a possibility of death. It is recommended to carry out symptomatic therapy and constant monitoring of the patient's condition and the work of vital organs and systems. The specific antidote is unknown. A partial effect can be achieved by carrying out hemodialysis within the first 3 hours after an overdose, since platinum binds to plasma proteins quickly.

special instructions

Therapy with Cisplatin-Ebeve should be carried out by appropriately qualified medical personnel under the supervision of a qualified specialist with experience in the use of anticancer chemotherapy drugs.

The dose of the drug and the therapeutic regimen are selected individually.

Care is required when working with Cisplatin-Ebeve:

The procedures should be carried out by trained personnel.
The concentrate should be diluted under aseptic conditions in a specially equipped room.
It is important to avoid getting cisplatin on the skin and mucous membranes, for which you should use protective clothing (mask, robe, cap, glasses, disposable gloves).
If the solution comes into contact with the skin or mucous membranes, they are thoroughly washed with water and soap, and if it gets into the eyes, with a large amount of water.
Residues of the drug, all instruments and materials used to prepare the solution for Cisplatin-Ebeve infusion must be disposed of in accordance with the standard hospital procedure for the disposal of cytotoxic waste, in accordance with the requirements of the current regulations on the disposal of hazardous waste.

Men and women of reproductive age should use reliable contraceptives during treatment and 6 months after it ends. Men should consider storing sperm in a cryobank prior to starting the course, as irreversible infertility may develop during therapy.

You should periodically be examined by a neurologist and, if there are obvious symptoms of the toxic effect of the drug on the central nervous system, interrupt the course of cisplatin therapy.

Patients undergo audiometry before starting treatment, in case of symptoms of damage to the organ of hearing, detection of dysfunctions of the hearing system during therapy - again. A clinically significant hearing loss may require dose adjustment or discontinuation of therapy.

During the course, it is necessary to regularly monitor the indicators of the clinical blood test, hepatic and renal function tests, as well as the serum electrolyte level.

During the first hour of therapy with Cisplatin-Ebeve, patients usually develop nausea / vomiting that lasts for 24 hours or more. These side effects can only be partially reversed with standard antiemetics. Their severity can be reduced by using the II dosage regimen of the drug, designed for a cycle of 5 smaller doses administered once a day.

The drug is not reapplied until the following indicators are achieved: serum creatinine level - ≥ 15–20 mg / l, platelets in the blood -> 100,000 / mm ³, leukocytes - ≥ 4000 / mm ³. The lowest content of platelets and leukocytes in the blood is observed, as a rule, from the 18th to the 23rd day after the infusion of cisplatin, by the 39th day in most patients these indicators are restored.

If allergic reactions develop in the form of bronchospasm, facial edema, tachycardia, hypotension, antihistamines, corticosteroids and adrenaline are used.

Care should be taken when engaging in potentially hazardous types of work that require quick psychomotor reactions and increased concentration of attention, since with Cisplatin-Ebeve therapy, there is a high likelihood of side effects such as seizures, impaired vision and hearing.

Drug interactions

amphotericin B, aminoglycosides, cephalosporins, contrast agents and other nephrotoxic drugs: with simultaneous or sequential use with cisplatin, it is possible to potentiate its ototoxic and nephrotoxic effects;
ifosfamide: an increase in its nephrotoxicity with an increase in protein excretion is possible;
furosemide, clopamide, ethacrynic acid (loop diuretics), ifosfamide, aminoglycosides: may increase the ototoxicity of cisplatin;
bleomycin and methotrexate: due to the nephrotoxic effect of cisplatin, their excretion through the kidneys may be impaired, with increased toxicity;
hexamethylmelamine and pyridoxine: when treating ovarian cancer in combination with cisplatin, the period of remission can be shortened;
anticonvulsants: cisplatin reduces their serum concentration to subtherapeutic values;
allopurinol, colchicine, probenecid, sulfinpyrazone (anti-gout agents): due to the likelihood of an increase in the concentration of uric acid due to taking cisplatin, it may be necessary to adjust the doses of these drugs to control hyperuricemia and gout attacks;
aluminum: a precipitate forms;
paclitaxel: when administered after cisplatin, the clearance of paclitaxel may decrease by 70–75%;
bleomycin and etoposide: in several episodes, a decrease in the concentration of lithium in the blood was recorded (such a combination of drugs requires monitoring the level of lithium);
phenytoin: a decrease in its absorption is possible and, as a result, a decrease in the effectiveness of antiepileptic therapy;
chelates (in particular penicillamine): may reduce the effectiveness of cisplatin therapy;
antihistamines, phenothiazides, thioxanthenes: may mask symptoms of ototoxicity such as dizziness, ringing / tinnitus.

Analogs

Analogs of Cisplatin-Ebeve are: Platidiam, Gemzar, Gemzitover, Alimta, Kemoplat, etc.

Terms and conditions of storage

Store in a dark place at temperatures up to 25 ° C, do not freeze. Keep out of the reach of children.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!