Instruction for use: Daclizumab

Trade name of the drug – Zenapax

The Latin name of the substance Daclizumab

Daclizumabum (genus. Daclizumabi)

Pharmacological group:

Immunosuppressive drugs

The nosological classification (ICD-10)

T86.1 Kidney transplant death and rejection: Reaction of acute rejection of a transplanted kidney; Refractory tissue rejection in patients after allogeneic kidney transplantation

Characteristics of the substance Daclizumab

Recombinant humanized antibodies IgG1 (anti-Tas).

Pharmacology

Mode action - Immunosuppressive.

It is an antagonist of interleukin-2 (IL-2) receptors: it binds highly highly to the alpha-subunit (Tas) of the high-affinity IL-2 receptor complex, which is expressed on activated T-cells. Oppresses IL-2-mediated activation of lymphocytes, inhibits the immune reaction of graft rejection.

Reliably reduces the frequency of confirmed histologically acute rejection of the renal allograft for 6 months after transplantation (rejection frequency does not increase after daclizumab abolition) and lengthens the time until the first episode of rejection. Increases the 6- and 12-month survival of patients after transplantation.

Antibodies to daclizumab are found in 9% of patients, but they do not change its serum concentrations, efficacy and safety.

Mutagenic and carcinogenic activity was not detected. Multiple intravenous administration of Cynomolgus monkeys with doses of 1.5; 5,0 and 15 mg / kg / day for 28 days and single administration of 125 mg / kg to mice was not accompanied by toxicity.

Cmax in patients who underwent allogeneic kidney transplantation after a single dose of 1 mg / kg is 21 ± 14 mkg / ml, after 5 infusions (1 mg / kg dose) every 14 days - 32 ± 22 mkg / ml. Complete saturation of the receptors for IL-2 occurs at serum concentrations of 0.5-0.9 mkg / ml, inhibition of IL-2 mediated biological activity - at a plasma level of 5-10 mkg / ml. Compliance with the dosing regimen allows maintaining sufficient serum concentrations for more than 90 days after transplantation. The volume of distribution is 0.074 l / kg body weight. T1 / 2 in patients with renal allograft is 270-919 hours (average 480 hours) and corresponds to T1 / 2 IgG in humans. Passes through the placenta. Systemic clearance depends on the body weight, age, sex, race, the presence of proteinuria.

Application of the substance Daclizumab

Prevention of acute rejection of the kidney allograft (as part of combined immunosuppressive therapy along with cyclosporine and corticosteroids).

Contraindications

Hypersensitivity.

Restrictions

Elderly age (safety and efficacy in people over 65 years of age are not defined due to the limited number of transplants performed by patients in this age group).

Pregnancy and breast-feeding

Perhaps, if the expected effect of therapy exceeds the potential risk to the fetus. At the time of treatment should stop breastfeeding.

Side effects of Belatacept

From the nervous system and sensory organs: ≥5% - headache, dizziness, insomnia, tremor; 2-5% - tingling and cramps in the legs, depression, anxiety, impaired vision.

From the cardiovascular system and blood (hematopoiesis, hemostasis): ≥5% - arterial hypertension or hypotension, tachycardia, bleeding or thrombosis.

On the part of the respiratory system: ≥5% - cough, shortness of breath, pulmonary edema; 2-5% - atelectasis, congestion and pleural effusions, wheezing, pharyngitis, rhinitis, hypoxia.

On the part of the intestine: ≥5% - nausea, vomiting, constipation or diarrhea, indigestion, abdominal pain, epigastric pain; 2-5% - flatulence, gastritis, hemorrhoids.

On the part of the genitourinary system: ≥5% - dysuria, oliguria, edema, necrosis of renal tubules, lymphocele; 2-5% - kidney damage, hydronephrosis, renal failure, fluid retention, dehydration, hematuria, urinary retention.

On the part of the musculoskeletal system: ≥5% - pain in the bones and muscles, pain in the lower back; 2-5% - pain in the joints.

From the skin: ≥5% - deterioration of skin regeneration, acne; 2-5% - itching, hirsutism, rash, sweating, reactions at the injection site.

Other: ≥5% - chest pain, fever, weakness; 2-5%: hyperglycemia, chills, anaphylactoid reactions.

Interaction

Pharmaceutically incompatible with other solutions. There was no reported interaction with immunoglobulin antilymphocytic, cyclosporine, corticosteroids, mycophenolate mofetil, azathioprine, ganciclovir, acyclovir, and others.

Overdose

Overdose were not found.

Routes of administration

IV, slowly.

Precautionary measures

Women of childbearing age should use adequate contraceptive measures during the treatment period and within 4 months after the end.

Special instructions

It is used only under the supervision of qualified medical personnel.