Imfinzi concentrate solution for infusion 50mg/ml 2.4ml,1pcs

Composition

1 ml of the concentrate contains: Active ingredient:  

• durvalumab 50 mg

Auxiliary substances:  

• L-histidine 2 mg,
• L-histidine hydrochloride monohydrate 2.7 mg,
• α, α-trehalose dihydrate 104 mg,
• polysorbate 80 0.2 mg,
• water for injection approximately 900 mg

Pharmacological action

Pharmacodynamics

Mechanism of action

Expression of the programmed cell death receptor ligand 1 (PD-L1) protein is a response to the adaptive immune system that allows tumors to avoid detection and elimination by the immune system.

PD-L1 expression can be induced by inflammatory signals (for example, IFN-gamma) and occurs both in tumor cells and in tumor-associated immune cells of the tumor microenvironment. PD-L1 blocks T cell function and activation by interacting with PD-1 and CD80 (B7.1).

By binding to the corresponding receptors, PD-L1 reduces the cytotoxic activity of T cells, proliferation and cytokine production.

Durvalumab is a fully human, high-affinity monoclonal antibody, kappa immunoglobulin G1 (IgGlK), which selectively blocks the interaction of PD-L1 with PD-1 or CD80 (B 7.1), while not affecting the interaction between PD-1 and PD-L2.

Durvalumab does not induce antibody-dependent cellular cytotoxicity. Selective blocking of interactions between PD-L1 and PD-1 and PD-L1 and CD80 leads to an enhanced antitumor immune response, which can lead to tumor elimination.

In preclinical studies, PD-L1 blockade resulted in increased T-cell activation and reduced tumor size.

Pharmacokinetics

The pharmacokinetics of durvalumab were studied in 1902 patients, with doses ranging from 0.1 mg/kg to 20 mg/kg, and the drug was administered once every two, three or four weeks.

Pharmacokinetic effects increased more than proportionally to the dose (non-linear pharmacokinetics) at doses of The equilibrium state was reached after about 16 weeks.

Based on a population pharmacokinetic analysis that included data from 1,878 patients treated with the drug at doses ≥10 mg / kg every 2 weeks, the geometric mean volume of distribution at steady state (Vss) was 5.64 liters.

Durvalumab clearance decreased over time, resulting in a geometric mean steady-state clearance (CLss) of 8.16 ml/hr on day 365 of therapy; the decrease in CLss is not considered clinically significant. Based on baseline clearance, the elimination half-life was approximately 18 days.

Pharmacokinetics in special patient groups

Age (19-96 years), body weight (34-149 kg), gender, presence of durvalumab antibodies, albumin concentration, lactate dehydrogenase activity, creatinine concentration, soluble PD-L1 concentration, tumor type, race, mild renal impairment (creatinine clearance 60-89 ml/min), moderate renal impairment (creatinine clearance 30-59 ml/min), mild hepatic impairment (bilirubin < the upper limit of normal (ULN) and aspartate aminotransferase (ACT) activity > ULN or bilirubin concentration > ULN up to 1.5 x ULN at any ACT activity) and general health on the WHO/ECOG scale did not have a clinically significant effect on the pharmacokinetics of durvalumab.

The effect of severe renal impairment (creatinine clearance 15-29 ml/min) or moderate hepatic impairment (bilirubin concentration >1.5 x ULN to 3 x ULN and any ACT activity) and severe hepatic impairment (bilirubin concentration >3 x ULN and any ACT activity) on the pharmacokinetics of durvalumab is unknown.

Elderly patients

Dose adjustment in elderly patients (≥65 years) not required. Of the 476 patients with locally advanced unresectable non-small cell lung cancer (NSCLC) in the PACIFIC study (primary efficacy population) treated with Imfinzi®,215 patients were aged 65 years or older. Overall, there were no differences in safety profiles between patients aged 65 years and older and younger patients.

Indications

Unresectable locally advanced non-small cell lung cancer in adult patients who did not show disease progression after platinum-based chemoradiotherapy.

Use during pregnancy and lactation

Women with preserved childbearing functionwomen with preserved childbearing function should use reliable methods of contraception during durvalumab therapy and for at least 3 months after the last dose of the drug. Pregnancy Data on the use of durvalumab in pregnant women are not available. Taking into account the mechanism of action, durvalumab may have an effect on the course of pregnancy and harmful effects on the fetus when used during pregnancy. In a mouse model of allogeneic pregnancy, it was shown that impaired signal transmission via PD-L1 leads to an increase in the frequency of fetal loss. No reproductive toxicity was detected in animal studies. Human immunoglobulin IgGl penetrates the placental barrier. In animal studies, durvalumab has also been shown to cross the placental barrier. The use of durvalumab during pregnancy can cause harm to the fetus. Therefore, durvalumab should not be used during pregnancy and in the absence of reliable contraception during therapy, and for at least 3 months after the last dose of the drug. Breast-feeding There is no information regarding the excretion of durvalumab in breast milk. According to the results of toxicological studies, low concentrations of durvalumab were detected in the milk of Javanese macaques on the 28th day after delivery. In humans, monoclonal antibodies can be released into breast milk, but there are no data on their possible absorption and harm to the newborn. However, the risk to breastfed children cannot be excluded. Therefore, you should either stop breastfeeding or refrain from durvalumab therapy, taking into account the benefits of breastfeeding for the children and the benefits of durvalumab therapy for the woman. Fertility Data on the possible effect of durvalumab on fertility in animals and humans are not available.

Contraindications

• Hypersensitivity to durvalumab or excipients included in the drug.
• Children under 18 years of age.
• Pregnancy and breast-feeding period.
• Moderate to severe hepatic impairment.

With caution:  severe autoimmune diseases in the active stage, in which further activation of the immune system can pose a potential threat to life.

Interaction

The use of systemic corticosteroids or immunosuppressants prior to durvalumab therapy, with the exception of systemic corticosteroids at a physiological dose (up to 10 mg prednisone per day or equivalent), is not recommended due to the possible effect on the pharmacodynamic activity and effectiveness of durvalumab. However, systemic corticosteroids and immunosuppressants may be used after initiation of durvalumab therapy to treat immune-mediated adverse reactions (see section “Special Instructions”). Formal drug interaction studies of durvalumab have not been conducted. Since the main pathways of durvalumab metabolism are protein catabolism involving the reticuloendothelial system and target-mediated clearance, interactions with other drugs at the metabolic level are not expected.

How to take, course of use and dosage

Recommended dose of Imfinzi® It is 10 mg / kg as an intravenous infusion lasting at least 60 minutes. The drug should be administered once every 2 weeks before the disease progresses or unacceptable toxicity develops. Increasing or decreasing the dose of the drug is not recommended. Taking into account the tolerability and safety of the drug, it may be necessary to suspend therapy or cancel it.

Overdose

In case of overdose of Imfinzi®, there is no specific treatment, and no symptoms of overdose have been established. In case of overdose, symptomatic treatment and general supportive measures should be taken.

Storage conditions

At a temperature of 2 to 8 °C. Keep out of reach of children.

Shelf

life is 3 years.

Active ingredient

Durvalumab

Conditions of release from pharmacies

By prescription

Dosage form

infusion solution