Irinex, 70 mg/ml 1 ml

The drug is used to prevent migraine in adults who have at least 4 days of migraine in a month.

Active ingredient

Composition

1 ml of the drug contains:

the active ingredient:

erenumab 70 mg;

supplementary substances: sucrose, polysorbate-80, glacial acetic acid, sodium hydroxide, water for injection.

How to take, the dosage

Treatment should be initiated by physicians experienced in the diagnosis and treatment of migraine.

The recommended dose is 70 mg once every 4 weeks (per month). In some patients, clinical effect may be achieved with a dose of 140 mg once every 4 weeks (per month).

Clinical studies have shown that most patients who respond to therapy have an effect within 3 months. Consideration should be given to discontinuing treatment in patients who do not respond after 3 months of therapy.

We recommend regular assessment of the need for continuation of therapy.

If the next dose is missed, it is recommended that treatment be resumed as soon as possible. Thereafter, the drug is used once every 4 weeks (per month), starting with the last dose received.

The drug Irinex should be administered subcutaneously (i.p.).

The drug Irinex is intended to be self-administered by the patient.

Injection must be done by a person trained in insertion techniques. Two consecutive subcutaneous injections of Irinex of 70 mg each should be made to administer the 140 mg dose.

Detailed instructions on storage, handling and administration are given in the section “Injection instructions for Irinex”.

Special patient groups

Application in patients with impaired renal function

Do not use in patients with impaired renal function./p>

Dose adjustment is not required when using the drug in patients with mild to moderate renal impairment. No differences in pharmacokinetics of erenumab were found in patients with mild to moderate renal dysfunction and patients with normal renal function according to population pharmacokinetic analysis. No studies have been performed in patients with severe renal dysfunction (rSFR < 30 ml/min/1.73 m2).

Application in patients with impaired liver function

There have been no clinical studies in patients with impaired liver function. Erenumab, like other monoclonal antibodies, is not metabolized by cytochrome P450 isoenzymes. Excretion via the liver is not the main route of administration of erenumab.

Application in patients 65 years of age and older

In clinical trials of erenumab, insufficient numbers of patients 65 years of age and older have participated to detect differences in response to treatment between elderly patients and younger patients. No dose adjustments are required in patients 65 years of age or older.

Application in patients under 18 years of age

The safety and effectiveness of Irinex in this category of patients has not been established.

Interaction

In an open-label study of pharmacokinetic drug interactions between erenumab and combined oral contraceptives in healthy women, erenumab (a single p/c injection of 140 mg) did not affect the pharmacokinetics of combined oral contraceptives containing ethinylestradiol and norgestimat.

In a randomized, double-blind, placebo-controlled study in healthy volunteers, erenumab (single IV dose of 140 mg) administered concomitantly with sumatriptan had no effect on resting blood pressure compared with sumatriptan as monotherapy. Erenumab had no effect on the pharmacokinetics of sumatriptan.

Erenumab is not metabolized by cytochrome P450 isoenzymes; it is also unlikely that it can cause marked changes in the concentration of proinflammatory cytokines that can affect the expression or activity of cytochrome P450 isoenzymes. For this reason, drug interactions with concomitant use of drugs that are substrates, inducers or inhibitors of cytochrome P450 isoenzymes seem unlikely.

Influence on the results of laboratory and diagnostic studies

The effect of erenumab on the results of laboratory and/or diagnostic studies has not been studied.

Special Instructions

Patients with certain underlying cardiovascular diseases have been excluded from clinical trials and therefore no safety data are available in these patients.

Patients with latex hypersensitivity

The removable cap of the pre-filled syringe and autoinjector (syringe pen) contains dry natural rubber latex, which may cause allergic reactions in latex-sensitive individuals.

Influence on the ability to drive vehicles and/or mechanisms

The drug Irinex has no significant effect on the ability to drive vehicles and/or mechanisms.

Synopsis

Contraindications

Side effects

Data from 2 phase II clinical trials and 2 phase III clinical trials in patients with migraine were pooled to assess the safety of erenumab at 12 weeks after treatment initiation compared to placebo.

A total of 2,656 patients were included in these studies (1,613 received erenumab and 1,043 received placebo). Of these, 893 patients received enrenumab at a dose of 70 mg and 507 received enrenumab at a dose of 140 mg.

The total sample for the safety assessment, which takes into account ongoing open-label phases of additional studies, includes 2,537 patients (2,310.3 patient-years) who received at least 1 dose of erenumab: 2,066 patients received the drug for at least 6 months and 1,213 patients received it for at least 12 months.

Summary of adverse reactions (ARs)

All ARs reported in patients who received erenumab during the 12-week placebo-controlled clinical trial period are shown in Table 1. Most HPs were mild to moderate in severity.

The following HPs are grouped according to the MedDRA classification of organs and organ systems, and are listed in decreasing order of frequency of occurrence.

The frequency of occurrence was rated as follows: “very common” – ≥10%, “frequent” – ≥1 to < 10%, “infrequent” – ³0.1% to < 1%, “rare” – ≥0.01 to < 0.1%, “very rare” – < 0.01%, including individual reports, “frequency unknown” – could not be determined from available data. Within each frequency category, HPs are distributed in decreasing order of frequency of occurrence.

Table 1. NRs that occurred during the use of erenumab

System-organ class NR frequency category

Immune system disorders – Hypersensitivity reactions, including rash, edema, and urticaria – Frequent
General disorders and disorders at the injection site – Reactions at the injection site – Often
Disorders of the gastrointestinal tract – Constipation – Often
Disorders of the musculoskeletal system and connective tissue – Muscle spasm – Oftenbr> Skin and subcutaneous tissue disorders – Itching – Often

.Description of individual adverse reactions

Injection site reactions

In a pooled analysis of a 12-week placebo-controlled clinical trial period, the most common injection site reactions in patients receiving erenumab were injection site pain, erythema at the injection site, and itching at the injection site. Most injection site reactions were grade 1 (mild) and transient. In general, pain at the injection site resolved within 1 hour of injection. In one patient who received erenumab at a dose of 70 mg p/k, the drug was withdrawn due to the development of a rash at the injection site. None of the patients who received erenumab at a dose of 140 mg p/q had the drug withdrawn due to injection site reactions in a 12-week placebo-controlled study period.

Immunogenicity

Like all proteins with therapeutic effects, erenumab can induce an immune response. Immunogenicity was evaluated using an immunoassay to detect binding antibodies against erenumab. For patients whose sera were found to have antibodies to erenumab by screening immunoassay, a in vitro biological assay was performed to detect neutralizing antibodies.

In 4 studies of prophylactic migraine treatment throughout the double-blind phase of the study, the incidence of antibodies to erenumab in patients receiving erenumab at 70 mg and 140 mg was 6.3% (56/884, with 3 patients having neutralizing activity detected in vitro) and 2.6% (13/504, with in vitro neutralizing activity not determined in any patient). The formation of antibodies to erenumab did not affect its efficacy or safety.

The detectable rate of antibody formation to the drug is highly dependent on the sensitivity and specificity of the assay. In addition, the detection rate of antibodies (including neutralizing antibodies) in serum can be affected by a number of factors, including the method of analysis, method and timing of sample acquisition, concomitant therapy and disease. For these reasons, comparing the rate of antibody formation for erenumab to the rate of antibody formation for other drugs may lead to incorrect conclusions.

If any of the side effects listed in the instructions worsen, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose

Pregnancy use

Pregnancy

There have been no adequate and strictly controlled studies on the use of erenumab in pregnant women. In a study of reproductive toxicity in Javanese macaques in which animals received erenumab during pregnancy and its exposure (assessed by AUC) was 40 or 17 times that of patients receiving erenumab at a dose of 70 mg or 140 mg once a month, respectively, no effects on pregnancy, embryophetal or postnatal development (until 6 months of age) were detected. Significant serum concentrations of erenumab were detected in newly born monkeys, confirming that erenumab, like other IgG class antibodies, penetrates the placental barrier.

The damaging effect of erenumab on the fetus when used in women during pregnancy is unknown, since animal studies are not always able to predict the effect of the drug in humans. As a precautionary measure, it is advisable to avoid using the drug during pregnancy. The use of erenumab during pregnancy is possible only if the expected benefit to the mother exceeds the possible risk to the fetus.

Breastfeeding period

It is not known whether erenumab penetrates into human breast milk. There are no data on the effects of erenumab on the breastfed baby or on breast milk production in the mother. Because many drugs penetrate into breast milk, and because of possible adverse reactions to the drug in breastfed infants, the decision to stop breastfeeding or to discontinue the drug should be made taking into account the potential benefit of erenumab to the mother and the potential benefit of breastfeeding to the baby.

Fertility

There are no data on the effects of erenumab on human fertility. No adverse effects on surrogate markers of fertility (pathologic or histopathologic changes in reproductive organs) were observed with systemic exposures of erenumab in sexually mature monkeys up to 283 or 123 times the exposure (estimated by AUC for serum) in humans achieved when the drug was used at a clinical dose of 70 mg or 140 mg once per month.