Leykladin (Leicladin)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Dosage form: & nbspconcentrate for solution for infusion
Composition:

1 ml of concentrate contains:

active substanceso: Cladribine - 1 mg;

Excipients: potassium dihydrogen phosphate - 6.8 mg, sodium chloride - 5.18 mg, sodium hydroxide - up to pH 7.3, water for injection - up to 1 ml.

Description:

Transparent colorless liquid.

Pharmacotherapeutic group:Antitumour agent, antimetabolite
Pharmacodynamics:

Cladribine (2-chloro-2'-deoxyadenosine) is an analog of 2'-deoxyadenosine, which is part of the DNA molecule. Lymphoid cells are more sensitive to cladribine than non-lymphoid cells, since the former are characterized by a higher level of deoxycytidine kinase and a low level of 5'-nucleotidase activity. Cladribine has cytotoxic effects on fissionable and non-dividing cells, inhibiting DNA synthesis and repair.

The cytotoxic effect is due to the action of the active metabolite - 5'-triphosphate of 2-chloro-2'-deoxyadenosine.

The effect of the drug is associated with inhibition of ribonucleotide reductase, catalyzing the reaction of the formation of deoxynucleoside triphosphates, necessary for DNA synthesis. The termination of DNA synthesis also occurs as a result of inhibition of the DNA polymerase. In addition, the 5'-triphosphate of 2-chloro-2'-deoxyadenosine activates a specificendonuclease, which leads to single-strand breaks in DNA. These phenomena are the cause of subsequent cell death.

Pharmacokinetics:

When administered intravenously, the elimination half-life (T1/2) - from 5.7 to 19.7 hours. The concentration of the drug in the cerebrospinal fluid is 25% of its concentration in the plasma. The drug is excreted predominantly in the urine, a minor amount (less than 1%) is excreted in the faeces.

The drug is subjected to intracellular metabolism. At the initial stage of phosphorylation to the 5'-monophosphate carries deoxycytidine. Since the level of deoxycytidine kinase activity in lymphocytes higher than that for 5'-nucleotidase, and also because of the stability of cladribine to action of adenosine deaminase, the cell rapidly accumulate all three phosphorylated form 2-chloro-2'-deoxyadenosine, including 5-triphosphate 2-chloro-2'-deoxyadenosine.

Indications:

Hairy cell leukemia.

Contraindications:

Hypersensitivity to cladribine or any other component of the dosage form.

Moderate or severe renal failure (CK <50 mL / min).

Moderate or severe hepatic impairment (≥ 4 on the Child-Pug scale).

Pregnancy and lactation.

Children's age (safety and efficacy of cladribine when used in children have not been studied.
Carefully:

With oppression of bone marrow function, mild renal and / or hepatic insufficiency, infectious complications of the underlying disease (the doctor should evaluate the risk-benefit relationship with the introduction of cladribine in patients with infectious complications), elderly.

Dosing and Administration:

Intravenously drip in the form of 2 hour or 24 hour infusion.

Dosages and duration of treatment are determined by the attending physician depending on the characteristics of the course of the disease and the severity of the condition.

The recommended dose is 0.09-0.1 mg / kg / day for 7 days. Usually only one course of therapy is given. Data on the increase in the antitumor effect in the course of additional courses are not available.

Before the introduction, the necessary amount of concentrate is diluted in 0.5-1 L of a 0.9% solution of sodium chloride, while the infusion solution for long (24 hour) infusions uses a bacteriostatic 0.9% solution of sodium chloride (containing benzyl alcohol as a preservative).In the form of saline solutions, the drug is stable during the day.

To prepare the infusion solution, it is not recommended to use a 5% dextrose solution due to the increased degradation of cladribine.

Side effects:

From the side of bone marrow hematopoiesis: leukopenia, neutropenia, thrombocytopenia, anemia, pancytopenia, aplastic anemia, hemolytic anemia; very rarely - myelodysplastic syndrome.

From the side of the digestive system: nausea, vomiting, anorexia, diarrhea, constipation, flatulence, abdominal pain, increased bilirubin and / or transaminase activity.

From the nervous system: headache, dizziness, insomnia, increased excitability, peripheral sensory neuropathies, polyneuropathy, loss of consciousness, ataxia, depression; very rarely - epileptic seizures.

From the side of the cardiovascular system: edema, tachycardia, noise in the heart, lowering blood pressure, ischemia of the myocardium.

From the respiratory system: cough, violation of percussion sound and auscultatory characteristics of breathing, rapid breathing, interstitial pneumonitis.

From the skin and subcutaneous tissue: rash, localized exanthema, skin peeling, itching, hives, soreness of the skin.

From the musculoskeletal system: myalgia, arthralgia, pain in the bones.

From the side of the organ of vision: conjunctivitis, blepharitis

Local Reactions: erythema, pain, swelling, thrombosis, phlebitis.

Other: fever, chills, weakness, asthenia, fatigue, excessive sweating, pain of different localization, purpura, petechiae, nosebleeds, decreased immunity, tumor lysis syndrome, development of secondary malignant tumors; a predisposition to infections, opportunistic infections caused by Herpes simplex, Herpes zoster, Cytomegalovirus.

Overdose:

It is manifested by irreversible disorders from the central nervous system (para- and tetraparesis, paralysis), nephrotoxic effects, and severe myelosuppression.

Treatment: cessation of leukladin therapy. Symptomatic means (there is no effective antidote).

Interaction:

When administered simultaneously or immediately after other myelotoxic drugs, additive inhibition of bone marrow function is possible.

When leukladin is prescribed in high (exceeding standard) doses, in combination with cyclophosphamide and radiotherapy, neurotoxicity (irreversible para- and tetraparesis) and nephrotoxicity (acute renal failure) increase.

Combination with allopurinol and antibiotics enhances skin rash.

When mixed with a 5% solution of dextrose - increased degradation of cladribine.

Special instructions:

Treatment with cladribine should be carried out under the supervision of a doctor who has experience in the use of antitumor therapy.

Observed with cladribine therapy, myelosuppression is dose-dependent and usually reversible. The effects of myelosuppression of cladribine mainly appear within a month from the moment of treatment. During treatment and at least 4-8 weeks after, careful monitoring of blood hematologic parameters is necessary. Particular care should be taken in patients with initial oppression of bone marrow function of any origin because of the risk of prolonged hypoplasia.

Treatment with cladribine can lead in some cases to severe forms of immunosuppression with a decrease in the level Cd4 white blood cells.

If a febrile condition occurs against a background of neutropenia, careful monitoring of the general condition of patients during the first month of treatment and, if necessary, the appointment of antibiotic therapy, are necessary. In the case of neurotoxicity, treatment with the drug should be suspended until the resolution of neurological symptoms. Treatment of patients with renal and / or liver failure should be carried out under the direct control of kidney and liver function. Treatment should be discontinued in case of nephro- or hepatotoxicity.

In the absence of data on pharmacokinetics in the elderly, careful monitoring of such patients is necessary.

In cases where the lysis of a significant cell mass is expected, preventive measures should be taken to avoid hyperuricemia and hyperuricosuria (the risk of acute renal failure). To prevent hyperuricemia, a generous drink is recommended, if necessary - allopurinol and alkaline drink.

Patients during treatment and at least 6 months afterwards should use reliable contraceptive methods.

Form release / dosage:

Concentrate for the preparation of a solution for infusions 5 mg / ml and 10 mg / ml (1 mg / ml).

Packaging:

10 ml in glass bottles.

1 bottle with instructions for use in a pack of cardboard.

5 ml in ampoules.

For 5 or 10 ampoules together with the instruction for use and scarifier ampullum in a pack of cardboard with partitions or special nests.

5 ampoules in the outline of the cell.

For 1 or 2 contour packs with instructions for use and a scapegrator ampoule in a pack of cardboard.

When using ampoules with a break ring, it is allowed to pack the ampoules without an ampoule scarifier.

Storage conditions:

The drug should be stored in a dry, dark place at a temperature of 2 to 10 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription
Registration number:LSR-001440/09
Date of registration:02.03.2009
Expiration Date:Unlimited
The owner of the registration certificate:BELMEDPREPARATY, RUP BELMEDPREPARATY, RUP Republic of Belarus
Manufacturer: & nbsp
BELMEDPREPARATY, JSC Republic of Belarus
Information update date: & nbsp06.03.2018
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