Kanakinumab - instructions for use, doses, side effects, contraindications

Clinical and pharmacological group: & nbsp

Included in the formulation

lyophilizate PC

АТХ:

L.04.A.C.08 Kanakinumab

Pharmacodynamics:Kanakinumab - human monoclonal antibody IgG1 / kappa isotype to interleukin-1β. Kanakinumab with a high degree of affinity binds to human IL-1β, competitively inhibiting gene activation by interleukin-1β and production of inflammatory mediators-interleukin-6 and COX-2.

In patients with gouty arthritis and different phenotypes kriopirin-associated periodic syndrome, including family autovospalitelpy cold syndrome / family cold urticaria, Muckle Wells syndrome and infantile multisystem inflammatory disease / chronic infantile neurological cutaneous articular syndrome kanakinumab reduces the severity of local and systemic inflammatory reactions caused by excessive production of interleukin-1β. In applying the drug in patients with acute attack of gouty arthritis reduced concentration laboratory markers of inflammation (CRP, serum amyloid A), in a short time leaving the affected joint inflammation symptoms (pain, swelling, redness). Against the backdrop of using kanakinumab 150 mg subcutaneously in patients with frequent exacerbations of gouty attacks, the intensity of pain decreases (on a visual analog scale).When using kanakinumab, the risk of a new attack of gout is reduced by 62% during the 12 weeks of therapy and by 56% during 24 weeks of therapy.

Pharmacokinetics:Suction

In adult patients with different phenotypes of cryopyrin-associated periodic syndrome, after a single subcutaneous injection of the drug at a dose of 150 mg of Tmax, kanakinumab is about 7 days. With subcutaneous administration of kanakinumab, absolute bioavailability is 63% (population pharmacokinetic analysis). The maximum concentration of Kanakinumab in blood plasma and AUC increases proportionally to the dose in the dose range from 0.3 to 10.0 mg / kg with intravenous infusion or subcutaneous administration at a dose of 150 mg to 300 mg.

Distribution

The volume of kanakinumab distribution varies with body weight. For typical patients suffering from gouty arthritis, with a body weight of 93 kg, Vss is 7.92 l. For patients with different phenotypes of cryopirin-associated periodic syndrome, Vss is 6.01 L in a typical patient with a body weight of 70 kg.

Excretion

The average half-life is 26 days. Kanakinumab's clearance varies with body weight. For typical patients suffering from gouty arthritis, with a body weight of 93 kg, the clearance is 0.23 liters per day.For patients with different phenotypes of cryopirin-associated periodic syndrome, the clearance is 0.17 liters per day in a typical patient with a body weight of 70 kg. With repeated use of the drug, there is no increase in clearance or changes in any other time-dependent pharmacokinetic parameters of kanakinumab.

Pharmacokinetics in special clinical cases

With the appointment of the drug taking into account the body weight, the sex and age of the patients do not affect the pharmacokinetics of the drug. In patients aged 4 to 17 years after a single subcutaneous injection of the drug at a dose of 150 mg or 2 mg / kg 1 time to reach the maximum plasma concentration of kanakinumab is 2-7 days. The terminal half-life of kanakinumab in this category of patients is similar to that in adults and ranges from 22.9 to 25.7 days. There was no difference in pharmacokinetic parameters based on clearance values and Vss in patients aged ≥65 years and in adult patients less than 65 years of age.

Indications:Acute gouty arthritis:

- treatment of acute attacks of gouty arthritis and prevention of the development of new seizures withthe impossibility of using non-steroidal anti-inflammatory drugs and / or colchicine and if it is not possible to carry out therapy with repeated courses of glucocorticosteroids.

Cryopyrin-associated periodic syndrome in adults and children aged 4 years and older with a body weight of more than 15 kg, including:

- family cold auto-inflammatory syndrome / family cold urticaria;

- Mackle-Wales syndrome;

- Infant multisystem inflammatory disease / chronic infant neurologic skin-articular syndrome.

ICD-10

III.D80-D89.D84.9 Immunodeficiency, unspecified

IV.E70-E90.E85.0 Hereditary family amyloidosis without neuropathy

XII.L50-L54.L50.2 Hives caused by exposure to low or high temperature

XII.L50-L54.L50.8 Other urticaria

XIII.M05-M14.M08 Juvenile [juvenile] arthritis

XIII.M05-M14.M10 Gout

Contraindications:- acute infectious diseases;

- Pregnancy;

- the period of lactation (breastfeeding);

- Children under 4 years of age and body weight less than 15 kg (safety and efficacy for this category of patients have not been studied sufficiently);

- Hypersensitivity to the components of the drug.

Carefully:Caution should be used in elderly patients; with a history of recurring infections or any condition predisposing to the development of infection.

Pregnancy and lactation:Application during pregnancy and lactation is possible only if the potential benefit to the pregnant woman exceeds the risk to the fetus. There are limited data on the use of the drug in pregnancy. The action category for the fetus is FDA-C. In experimental animal studies, the drug did not show any reproductive toxicity. It is not known whether kanakinumab with breast milk. If it is necessary to use the drug in the mother during lactation, breastfeeding should be discontinued.

Dosing and Administration:The drug (lyophilizate) is dissolved in 1 ml of water for injection.

Gouty Arthritis

Subcutaneously to adults 150 mg, the drug is administered during an attack of gouty arthritis one-time. The earlier the administration after the onset of an attack of gouty arthritis, the greater the effectiveness of the drug. Patients who did not respond to the first injection of kanakinumab should not be re-injected.Repeated administration is possible at least 12 weeks after the previous injection. The drug therapy can be initiated and performed only by a doctor who has experience in diagnosing and treating patients with gouty arthritis.

Cryopyrin-associated Periodic Syndrome

For patients with a body weight of more than 40 kg, the drug is administered (subcutaneously) at a dose of 50 mg - 1 injection at an interval of 8 weeks. For patients with a body weight of ≥ 15 kg and ≤ 40 kg, the drug is administered subcutaneously at a dose of 2 mg / kg - 1 injection at an interval of 8 weeks. The drug is administered subcutaneously to those parts of the body where the subcutaneous fat is expressed: in the abdomen, the anterior surface of the thighs, the posterolateral surface of the shoulders.

Systemic Juvenile Idiopathic Arthritis

The recommended dose for patients weighing ≥ 7.5 kg is 4 mg / kg (with increase to 300 mg) every 4 weeks as a subcutaneous injection.

Application in elderly patients

There was no difference in pharmacokinetic parameters in patients older than or younger than 65 years.

Use in children

In patients older than 4 years after subcutaneous single administration of the drug at a dose of 150 mg or 2 mg / kg, the time to reach the maximum concentration of the drug in the blood is 2-7 days.The half-life of kanakinumab in this category of patients is similar to that of adults and is 23 days.

Gouty arthritis - there is no data on the use of kanakinumab for the treatment of gouty arthritis in children and adolescents ≤ 18 years old. The experience of using kanakinumab in children younger than 2 years is limited.

Side effects:Infectious and parasitic diseases: very often - infections, in particular, nasopharyngitis, sinusitis (viral), upper respiratory tract infection, bronchitis, influenza, urinary tract infections, gastroenteritis, panniculitis, pneumonia, pharyngitis, ear infections.

From the nervous system: often - dizziness / vertigo.

From the musculoskeletal system: often - pain in the back.

On the part of the hematopoiesis system: often - thrombocytopenia, leukopenia; infrequently - neutropenia.

From the side of metabolism: often - dyslipidemia; possibly a transient increase in the concentration of uric acid.

From the side of the hearing organ and labyrinthine disorders: often - dizziness.

From the digestive tract: often - vomiting; infrequently - gastroesophageal reflux disease; sometimes on the background of drug therapy in patients with cryopyrin-associatedPeriodic syndrome there was an asymptomatic insignificant increase in serum bilirubin without increasing the activity of hepatic transaminases.

From the liver and bile ducts: often - increasing the level of bilirubin, increasing the activity of ACT.

Allergic reactions: were not observed, however, the risk of developing severe hypersensitivity reactions that can be noted with the injection of drugs of protein origin can not be ruled out.

Immunological reactions: 1% - in patients who received kanakinumab about gouty arthritis, antibodies to kanakinumab were detected; in patients with cryopyrin-associated periodic syndrome, these antibodies were not detected.

Common reactions: infrequently, general weakness.

Local reactions: often a reaction at the injection site.

Overdose:There were no cases of overdose. The goals of therapy with a possible overdose are maintenance of vital functions, rapid administration of symptomatic therapy. It is unknown whether the drug can be excreted from the body by hemodialysis.

Interaction:Special studies on the interaction of kanakinumab with other drugs have not been conducted.

In clinical studies, the safe use of kanakinumab with antidotal agents has been noted.

The drug is not recommended to be administered simultaneously with inhibitors tumor necrosis factor and other interleukin-1β blockers, since their use against the background of kanakinumab increases the risk of developing severe infections.

Special instructions:On the background of therapy with cannacinumab, neutropenia is possible (the absolute number of neutrophils is below 1.5 × 10%). Before the beginning of treatment with the drug, 1-2 months after the beginning and periodically during the therapy the drug needs monitoring (a standard clinical blood test) in order to detect neutropenia. In patients with initial neutropenia, the treatment with cannabis should be postponed until the number of neutrophils is normalized. If there is a decrease in the absolute number of neutrophils on the background of drug therapy, it is canceled.

Patients with impaired renal function do not need dose adjustment. It should be borne in mind that the experience of clinical use in this category of patients is limited.

In patients with impaired hepatic function, the efficacy and safety of the drug have not been studied. As kanakinumab - human IgG, it is assumed that liver failure does not affect the pharmacokinetics of this drug.

Before the appointment of Kanakinumab, screening for active or latent TB infection (anamnesis, tuberculin test or chest X-ray) is necessary. During treatment with the drug, careful monitoring of tuberculosis infection is necessary. In the case of a tuberculin test from negative to positive, especially in high-risk patients, alternative screening tests should be performed. When a tuberculosis infection is detected, the treatment with kanakinumab is stopped.

Patients who, when using kanakinumab, get vertigo, do not drive vehicles or work with mechanisms until this side reaction disappears completely.

Instructions

Kanakinumab (Canakinumabum)