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

Active substanceIkatibantIkatibant

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Firazir

solution PC

Shayer Orfan Terapis, GmbH Germany

Dosage form: & nbsp

hypodermic solution

Composition:

1 ml of the solution contains:

Active substance: ikatibant (free base) 10.0 mg (corresponds to the content of ikatibant acetate about 12.5 mg);

Excipients: sodium hydroxide 0.64 mg, acetic acid ice 1.32 mg, sodium chloride 7.45 mg, water for injection up to 1.0 ml.

Description:

Transparent from a colorless to slightly yellowish solution.

Pharmacotherapeutic group:bradykinin B2 receptors selective antagonist

ATX: & nbsp

C.01.E.B Other drugs for the treatment of heart disease

Pharmacodynamics:Hereditary angioedema (NAD) is an autosomal dominant disease that occurs due to the absence or dysfunction of the CI-esterase inhibitor. Attacks of hereditary angioedema may be accompanied by increased release of bradykinin, which is the main mediator of inflammation, which underlies the development of clinical manifestations of the syndrome.
NAO is manifested in the form of recurrent edema of the skin and mucous membranes of the respiratory system and gastrointestinal tract. The duration of the attack is usually from 2 to 5 days. Ikatibant is a synthetic selective antagonist of bradykinin type 2 (B2) receptors. It is a synthetic decapeptide, a chemical structure close to bradykinin, which has 5 amino acids. Increasing the level of bradykinin is a key mediator in the development of clinical symptoms of an acute attack of NAO.
Ikatibant was administered to young healthy volunteers at doses of 0.8 mg / kg for more than 4 hours; 1.5 mg / kg / day or 0.15 mg / kg / day for 3 days, which was accompanied by the prevention of bradykinin-induced hypotension, vasodilation and reflex bradycardia. Determined that ikatibant exhibits the properties of a competitive antagonist even in the case of an increase in the concentration of bradykinin in a fold.
As shown in the conducted controlled studies, in most cases, single administration of ikatibant is necessary. The time of onset of stopping the attack of HLA is between 0.6 and 1.0 hours.

Pharmacokinetics:

The pharmacokinetics of ictibanth has been studied in studies with intravenous and subcutaneous administration of the drug to healthy individuals and patients with acute episodes of NAO. The pharmacokinetic parameters of ikatibant in the group of patients with NAO did not differ from the corresponding indices of the group of healthy individuals.

Absorption

With subcutaneous administration, the absolute bioavailability of ikatibant is 97%. The time to reach the maximum concentration in the blood plasma is approximately 30 minutes.

Distribution

The volume of distribution (Vss) of the drug in the human body is about 20-25 liters. Communication with blood plasma proteins - 44%.

Excretion

The drug is mainly subjected to the process of metabolism, and about 10% of it was excreted through the kidneys in an unchanged form. The clearance is 15-20 l / h, regardless of the dose of the drug. The half-life period (T1 / 2) is 1 -2 hours.

Metabolism

In the process of metabolism of ikatibant under the action of proteolytic enzymes, inactive metabolites are formed, which are completely excreted through the kidneys. In vitro studies confirmed that ikatibant is not metabolized by oxidation, it is not an inhibitor of the main enzymes (CYP 1A2, 2A6, 2B6, 2C8, 2C9, 2G19, 2D6, 2E1 and 4A4) cytochrome P450 (CYP) and does not induce CYP 1A2 and 3A4.

Special groups of patients

There is evidence that ikatibant excretion decreases with age by 50-60% in elderly patients (75-80 years) compared with patients aged 40 years. Sex and body weight do not affect the parameters of pharmacokinetics.

Limited data suggest that these indicators also do not change with a decrease in liver and kidney function. The influence of race on the pharmacokinetics of ikatibant has not been studied. There are no data on the pharmacokinetics of the drug in children.

Indications:

Symptomatic treatment of acute attacks of hereditary angioedema (caused by a deficiency of C1-esterase inhibitor) in adults.

Contraindications:

Hypersensitivity to the drug components (active substance and excipients), simultaneous administration of angiotensin-converting enzyme inhibitors, children under 18 years of age (efficacy and safety of use not established).

Carefully:

Should use the drug on your own in an outpatient setting

The administration of the drug Firazir to patients with whom the drug is prescribed for the first time should be performed in a hospital or outpatient setting under the guidance of a physician.

In case of insufficient effect of the drug, if it is administered alone, or when the edema develops or continues, the patient should consult a doctor, further administration of the drug is carried out in the hospital (see "Method of administration and dose").

Obligatory hospitalization of patients with symptoms of laryngeal edema, including in cases where the attack is arrested after self-administration of the drug on an outpatient basis.

With ischemic heart disease

With concomitant ischemic heart disease, taking into account the properties of the bradykinin type 2 receptor antagonist, the possibility of worsening of myocardial function and a decrease in coronary circulation can not be ruled out. Therefore, with caution should appoint Firazir to patients with acute coronary syndrome.

With stroke

Ikatibant may reduce the positive neuroprotective effect of bradykinin of the late phase, although it is obvious that the blockade of B2 receptors has a positive effect in the acute period of cerebrovascular accident. Therefore, it is necessary to appoint with caution ikatibant patients in the first weeks of a stroke.

Pregnancy and lactation:

Pregnancy

Due to the lack of clinical data, the use of Firazira during pregnancy and in women planning pregnancy is not recommended. Pre-clinical data indicate an adverse effect of the drug on the process of implantation of the fetal egg and on delivery.

However, Firazir can be used in pregnancy with a careful comparison of the benefit / risk ratio for the mother and fetus, for example, for the treatment of life-threatening acute attack of NAO accompanied by laryngeal edema.

Breast-feeding

Phyrazir penetrates into breast milk, so after the use of the drug should exclude breast-feeding for 12 hours.

Dosing and Administration:

The drug Firazir is intended for subcutaneous administration, most often the drug is injected into the anterior abdominal wall area.

The drug is administered under the supervision of a qualified medical officer.

After training in the technique of performing subcutaneous injections under the supervision of a medical officer, the patient (or the person caring for him) can administer the drug on his own.

The decision on the possibility of self-administration of the drug Firazir by the patient is taken by a doctor who has experience in the diagnosis and treatment of NAO.

Patients with clinical manifestations of the laryngeal edema should be urgently hospitalized, they should be under the supervision of a doctor until the NAP assault is completely stopped.

The syringe containing the preparation of Firazir is intended only for single use.

Dose selection

The recommended dose of a single dose of Firazir is 30 mg.

Phyrazir should be administered slowly, in full (3 ml).

In most cases, a single injection of the drug is sufficient to stop the symptoms of NAO. In case of insufficient effectiveness or recurrent attack of NAO, the drug Firazir in a dose of 30 mg can be re-introduced after 6 hours. If, after repeated administration of the drug, NAO symptoms persist or the attack of NAO recurs, a third dose of the drug can be injected after another 6 hours. Do not exceed the maximum daily dose of the drug - 90 mg (3 injections of the drug). There are data on the conduct of no more than 8 injections of the drug Firazir within a month.

Special Groups

Elderly patients

Data on the use of the drug Firazir in the group of patients over 65 years of age are limited. It has been established that the concentration of ikatibant in blood plasma can increase in elderly patients, however, the clinical significance of this observation regarding the safety of the drug Firazir is not determined.

Dysfunction of the liver

When liver disease is not required to reduce the dose of the drug Firazir.

Renal impairment

In cases of kidney disease, there is no need to reduce the dose of Firazir.

Children and teens

The effectiveness and safety of the use of the drug Firazir in children under 18 years of age is not established.

There are no data on the use of Firazir in children.

Information necessary for self-administration of the drug

Instructions for the introduction of the drug includes the following main steps:

1) General relevant information

2) Preparation of syringe and needle for injection

3) Preparation of injection site

4) Administration of the drug

5) Destruction of injecting materials

Step-by-step instruction on the technique of injection

1) General relevant information

-Wash your hands with water and soap before handling.

-Expand the blister by pulling the seal

-Pre-fill the pre-filled syringe from the blister pack

-Remove the tip of the cap from the syringe by turning the cap

-Apply the pre-filled syringe after unscrewing the cap

2) Preparation of the syringe and needle for injection

-Pull the cap with the blister needle

- Open the container containing the needle (the needle must remain in it)

- Hold the syringe tightly. Carefully put the needle on a pre-filled syringe containing a colorless solution

- Secure the syringe and needle with the screw movement of the syringe, do not remove the needle from the container

-Pull the needle out of the container by pulling the syringe. Do not press the plunger

-Syringe prepared for injection

3) Preparation of injection site

-Select a place for injection. Mark a skin fold in the anterior abdominal wall at a distance of 5-10 cm below the navel, to the left or right of the midline of the abdomen. It is necessary to retreat 2 cm from the patch of altered skin. The drug should not be injected into skin areas with scar changes, tissue swelling, or local soreness

-Treat the skin with a swab with alcohol solution, wait a little to dry the skin

4) Administration of the drug

-Take a syringe into your hand between two fingers, placing your thumb on the piston

-Check that air bubbles are not in the syringe, pressing the plunger until the first drop of solution appears on the tip of the needle

4) Administration of the drug (continued)

- Hold the syringe at an angle of 45-90 to the surface of the skin with a needle facing toward the injection site

-Holding the syringe in one hand, with the other hand, between the thumb and forefinger, take a careful skin fold at the place where the skin was previously treated

- Continue to hold the skin fold, bring the syringe to the injection site, quickly insert the needle into the skin fold

- Slowly push the plunger of the syringe with a constant force until the drug is completely inserted into the skin

-Introduce the drug slowly for 30 seconds

- Release the skin fold and gently remove the needle

5) Destruction of injecting materials

- Place the used syringe and needle in a container for disposal of potentially hazardous materials.

Side effects:

The most frequent adverse reactions in clinical trials in patients were local signs of inflammation (characterized by skin irritation, sensation of itching, burning, pain, edema, erythematous rashes). In general, the reactions were mild, short-term, did not require additional therapy.

The incidence of adverse events (PE) presented in Table 1 was evaluated

as follows: very often: ≥1 / 0, often: ≥1 / 100, <1/10; infrequently: ≥1 / 1000.

In connection with the limited number of observations, each of the infrequently occurring phenomena was noted in one patient.

Table 1:

Side effects recorded in the clinical studies of ikatibanth

Side effects
Classification of diseases, organs and systems	highly often	often	infrequently
Hereditary, family and genetic diseases		hereditary angioedema *
From the gastrointestinal tract			nausea, vomiting
Local and systemic reactions	Local signs of inflammation (characterized by skin irritation, sensation of itching, burning, pain, the appearance of edema, erythematous rashes)		asthenia, fatigue, hyperthermia *
infectious diseases			Shingles, pharyngitis
Injuries, intoxications and complications associated with the administration of the drug			Closed injury
Disorders from the metabolism and nutrition			Hyperuricemia, hyperglycemia
From instrumental and laboratory indicators		increased activity of creatine phosphokinase, increased prothrombin time	weight gain, blood glucose, changes in functional liver tests
Disturbances from musculoskeletal and connective tissue			Muscle spasms
From the nervous system		dizziness, headache
Disorders from the kidneys and urinary tract			proteinuria
On the part of the respiratory organs, the mediastinum			an attack of asthma, coughing, stuffy plaque
From the skin and subcutaneous fat		rash, itching, redness	generalized urticaria
From the side of the cardiovascular system			tides (sudden redness of the face, neck, chest, nape, accompanied by a feeling of heat, resulting in profuse sweating)

* Attacks of NAO were registered as side reactions, however, taking into account the peculiarities of the occurrence of episodes, in most cases, attacks of NAO had a recurrent nature, they had no connection with the use of the drug Firazir.

Self-administration of the drug

The profile of the safety of the drug Firazir, when applied by health care professionals and self-administered by patients, is no different.

Overdose:

There were no cases of overdose of the drug Firazir.

In a clinical study, the drug was used in healthy volunteers at a dose of 3.2 mg / kg intravenously (approximately 8 times the therapeutic dose),The administration of the drug Firazir was accompanied by short-term arterial hypotension and / or local reaction (reddening, itching at the injection site).

Special treatment is not available.

Interaction:

The pharmacokinetic interaction of the drug Firazir with isoenzymes (CYP) of cytochrome P450 is not established.

Simultaneous use of the drug Firazir and angiotensin-converting enzyme (ACE) inhibitors has not been studied.

Special instructions:

In connection with the increase in bradykinin in blood plasma in patients with NAO, the combined use of the drug Firazir with angiotensin converting enzyme (ACE) inhibitors is contraindicated.

One dose of the drug is administered once. In clinical studies for one month, the preparation of Firazir was applied no more than 8 times.

Effect on the ability to drive transp. cf. and fur:

Phyrazir has little or moderate influence on the ability to drive vehicles and mechanisms. Patients during the treatment period should refrain from driving vehicles and practicing potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:A solution for subcutaneous administration of 10 mg / ml.

Packaging:3.0 ml of the preparation in a prefilled syringe of transparent glass type I, equipped with a stopper for the gray piston stroke of bromobutyl coated with fluoropolymer, an adapter with Luer lasers made of polycarbonate, closed with a screw cap, and an abutment for white fingers made of polypropylene. 1 syringe with 1 needle (25G, 16 mm) in a blister pack.
1 blister pack together with instructions for use in a pack of cardboard with the control of the first opening.

Storage conditions:

At a temperature of no higher than 25 ° C. Do not freeze.

KEEP OUT OF THE REACH OF CHILDREN.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LSR-008206/09

Date of registration:16.10.2009 / 11.09.2012

The owner of the registration certificate:Shayer Orfan Terapis, GmbHShayer Orfan Terapis, GmbH Germany

Manufacturer: & nbsp

RENTSCHLER BIOTECHNOLOGIE, GmbH Germany