Tetracosactide (Tetracosactidum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Hormones of the hypothalamus, pituitary gland, gonadotropins and their antagonists

Included in the formulation
  • Sinakten Depot®
    suspension w / m 
    QuestCor Limited     Ireland
    • АТХ:

    H.01.A.A   ACTH

    H.01.A.A.02   Tetracosactide

    Pharmacodynamics:Synthetic polypeptide analogue of ACTH, contains 24 amino acid residues. The amino acid sequence repeats the N-terminal portion of the endogenous ACTH molecule and completely retains all of it pharmacological properties, stimulates the production of adrenal gland glucose and mineralocorticoids, to a lesser extent - androgens. This explains the therapeutic effect of tetracosactide in diseases usually treated with SCS.

    Has anti-inflammatory, antiallergic and immunosuppressive effect, inhibits the development of connective tissue, affects carbohydrate, fat, protein, mineral metabolism. The pharmacological activity of tetracosactide (even with an increase in its dose) can not be compared with the activity of SCS, because under the influence of ACTH (in contrast to treatment by GCS alone), tissues are exposed to the physiological spectrum of corticosteroids.

    ACTH is bound by a specific receptor of the membrane of the cells of the adrenal cortex. The resulting hormone-receptor complex activates adenylate cyclase, thereby increasing the formation of cAMP.Cyclic AMP activates protein kinase, which in turn promotes the synthesis of pregnenolone from cholesterol. Through various enzyme reactions, various corticosteroids are synthesized from pregnenolone.

    After intramuscular injection, 1 mg of tetracosactide the concentration of cortisol in the plasma increases, its maximum values ​​are recorded within 8-12 hours. The elevated concentration of cortisol persists for 24 hours and returns to the baseline level after 32-48 hours.

    Pharmacokinetics:After intramuscular administration, 1 mg of plasma tetracosactide concentration varies from 200 to 300 pg / ml and is maintained for 12 hours. The delayed release of the active substance from the site of intramuscular injection and its long-term effect ensures the absorption of tetracosactide on zinc phosphate. The apparent volume of distribution is 0.4 l / kg.

    In the blood plasma tetracosactide rapidly decays under the action of enzymatic hydrolysis first into inactive oligopeptides, then into free amino acids. The period of the terminal phase of the half-life of tetracosactide is 3 hours. It is excreted mainly by the kidneys.

    Indications:Neurological diseases: Multiple sclerosis (exacerbation), Vest syndrome (infantile myoclonic encephalopathy with gypsarhythmia).

    Rheumatic diseases: short-term therapy of diseases and conditions in which SCS is usually shown; therapy of patients with gastrointestinal diseases who do not tolerate SCS inside; cases when the use of conventional doses of GCS does not lead to an adequate effect.

    Skin diseases: long-term treatment of skin diseases, usually responding to SCS therapy (including pemphigus, chronic eczema of the severe course, erythrodermic or pustular forms of psoriasis).

    Diseases of the digestive tract: ulcerative colitis; regional enteritis.

    Oncological diseases: as an additional method of treatment to improve the tolerability of chemotherapy.

    Diagnostic use for the determination of adrenal cortex function deficiency (5-hour test with depot form is performed in those cases when a 30-minute test with the usual form of tetracosactide gave a doubtful result, as well as for determining the functional reserve of the adrenal cortex).

    ICD-10

    VI.G35-G37.G35   Multiple sclerosis

    XI.K50-K52.K50   Crohn's disease [regional enteritis]

    XI.K50-K52.K51   Ulcerative colitis

    XI.K50-K52.K52   Other non-infectious gastroenteritis and colitis

    XII.L10-L14.L10   Pemphigus [pemphigus]

    XII.L20-L30.L20.8   Other atopic dermatitis

    XII.L40-L45.L40   Psoriasis

    XIII.M05-M14.M06   Other rheumatoid arthritis

    XIII.M30-M36.M35.9   Systemic involvement of connective tissue, unspecified

    XIX.T66-T78.T78.3   Angioedema

    XXI.Z00-Z13.Z03   Medical surveillance and evaluation in case of suspected disease or pathological condition

    Contraindications:Hypersensitivity to tetrakozaktidu or ACTH, acute psychosis, infectious diseases, peptic ulcer and duodenal ulcer (in the phase of exacerbation), refractory heart failure, Isenko-Cushing syndrome, treatment of primary adrenal insufficiency, adrenogenital syndrome, pregnancy and the period of breastfeeding, systemic mycoses, simultaneous use of live or debilitated vaccines with immunosuppressive doses tetrakosaktida.

    Carefully:In connection with the increased risk of anaphylactic reactions should not be used tetracosactide for the treatment of bronchial asthma and other allergic diseases. It is necessary to compare the potential risk from the use of tetracosactide and the expected benefit of therapy when it is administered to patients with the following diseases: arterial hypertension, predisposition to thromboembolism, ulcerative colitis, diverticulitis, newly created intestinal anastomosis, renal failure, osteoporosis, myasthenia gravis. Care should be taken when prescribing to patients suffering from eye damage due to herpes simplex (the risk of corneal perforation). Tetrakosaktid can activate latent amoebiasis (before the start of therapy to exclude latent or active amoebiasis). It is necessary to closely monitor the appointment of tetracosactide to patients with latent tuberculosis or a positive reaction to tuberculin (possibly the development of clinical manifestations of the disease). During prolonged therapy, such patients should receive preventive chemotherapy. During treatment with tetracosactide, vaccination against smallpox should not be carried out. Care should be taken when conducting any immunization procedure, because against the background of tetrakozaktidom therapy reduces the formation of antibodies.

    Pregnancy and lactation:Contraindicated in pregnancy and lactation. It does not penetrate the placental barrier, the possibility of penetration into breast milk has not been studied.

    Action category for the fetus by FDA - FROM. Studies in humans and animals have not been conducted.

    Dosing and Administration:Introduce intramuscularly. The dose is set individually, depending on the indications.

    Adults and children over 15 years of age: at an initial dose of 1 mg per day, in acute cases and with cancer - 1 mg 2 times a day. After the disappearance of acute symptoms - 1 mg every 2-3 days. With a good effect of therapy, the dose can be reduced to 0.5 mg every 2-3 days or up to 1 mg per week.

    To children of younger age (from 3 till 6 years): initial dose - 0,25-0.5 mg per day, maintenance dose - 0,25-0.5 mg through 2-8 days.

    Children of school age (from 6 to 15 years): initial dose - 0,25-1 mg per day, maintenance dose - 0,25-1 mg every 2-8 days.

    Diagnostic application (5-hour test): the concentration of cortisol is measured immediately before administration and after 0.5, 1, 2, 3, 4 and 5 hours after intramuscular injection of the depot form tetrakosaktida. Then, according to a special table, the rate of increase in the concentration of cortisol is evaluated. If it increases more slowly than indicated in the table, this may indicate the following diseases: Addison's disease, secondary adrenocortical insufficiency due to hypothalamic-pituitary system disorders or SCS overdosage.For a differential diagnosis of primary and secondary adrenal hypofunction, a 3-day test should be performed.

    Studies of the use of tetracosactide in patients with impaired renal function and patients with impaired liver function have not been performed. Data on the need for dose adjustment in patients older than 65 years is not obtained.

    Side effects:Hypersensitivity reactions: anaphylactic shock (in patients with bronchial asthma), angioedema (Quincke's edema), skin rash, hives, itching, skin reactions at the injection site, dizziness, nausea, vomiting, weakness, dyspnea.

    From the side of the adrenal glands: there are separate reports of cases of hemorrhage in the adrenal glands.

    Side effects associated with increased secretion of SCS and mineralocorticoids during the treatment with tetracosactide.

    Infections and invasions: increased adherence to infections, abscess.

    From the peripheral blood: leukocytosis.

    From the endocrine system: violations of the menstrual cycle, the syndrome of Itenko-Cushing (violation of protein, carbohydrate, fat and water-electrolyte metabolism), secondary adrenal insufficiency and pituitary gland (especially during stress), reduced tolerance to carbohydrates, hyperglycemia,clinical manifestations of latent diabetes mellitus, hirsutism.

    Metabolic and nutritional disorders: increased appetite, weight gain, hypokalemia, steroid osteoporosis, sodium and water retention.

    From the side of the psyche: mental disorders (euphoria, insomnia, mood swings, severe depression and others).

    From the side of the central nervous system: headache, dizziness, seizures, a slight increase in intracranial pressure with edema of the nipple of the optic nerve.

    From the side of the organ of vision: posterior subcapsular cataract, increased intraocular pressure, glaucoma, exophthalmos, decreased vision.

    From the side of the cardiovascular system: congestive heart failure, increased blood pressure, thromboembolism, necrotizing angiitis. In some cases, in infants and young children with prolonged treatment with the drug in large doses, reversible hypertrophy of the myocardium can develop.

    From the gastrointestinal tract: peptic ulcer with possible perforation and bleeding, pancreatitis, bloating, ulcerative esophagitis.

    From the skin and its appendages: skin atrophy, petechiae and ecchymosis, erythema, hyperhidrosis, acne, hyperpigmentation of the skin.

    From the musculoskeletal system and connective tissue: osteoporosis, muscle weakness, steroid myopathy, decreased muscle mass, compression fractures of the vertebrae, aseptic necrosis of femoral and humerus head, pathological fractures of long (tubular) bones, rupture of tendons.

    Other: hypersensitivity reactions, slower growth rates in children, negative nitrogen balance due to protein catabolism, wound healing failure, suppression of skin reactions during tests, fever, nausea, vomiting,

    Overdose:Symptoms: fluid retention, development of Isenko-Cushing syndrome.
    Treatment    : antidote does not exist, treatment should be discontinued or dose reduced tetracosactide. Symptomatic therapy is indicated.

    Interaction:With simultaneous application tetracosactide and valproate in children with severe jaundice (joint use should be avoided). Co-administration with other anticonvulsants (phenytoin, clonazepam, nitrazepam, phenobarbital, primidon) may increase the risk of liver damage. Concerning tetracosactide in combination therapy should be used in the lowest possible dose and for a minimum time.

    Because the tetracosactide causes an increase in the production of the adrenal cortex of SCS and mineralocorticoids, typical interactions can be noted.

    When co-appointed tetrakozaktida with hypoglycemic or antihypertensive agents may reduce their effectiveness (doses of these drugs should be reviewed).

    Special instructions:Apply only under medical supervision. The depot form can not be administered intravenously.

    Special instructions related to tetracosactide

    Hypersensitivity reactions

    Patients prone to allergic reactions (including those suffering from bronchial asthma) should not be treated tetrakozaktidom, except for cases when other therapeutic measures were ineffective and the reason for his appointment is the seriousness of the patient's condition.

    Before the appointment of therapy tetracosactide the doctor should find out whether the patient is inclined to allergic reactions, does not suffer from bronchial asthma. It is also important to establish whether the patient was previously treated with ACTH drugs, and if it was treated, then it should be clarified whether the treatment of hypersensitivity reactions caused the reaction.

    If local or systemic hypersensitivity reactions develop during or after the injection (eg, severe erythema and tenderness at the injection site, hives, itching, heat, weakness or shortness of breath), treatment tetracosactide should cease, and in the future, avoid the use of any drugs ACTH.

    Hypersensitivity reactions (if they occur at all) tend to develop within 30 minutes after injection. Therefore, during this time the patient must remain under medical supervision. In the event of a serious anaphylactic reaction, a 0.1% solution of epinephrine (0.4-1 ml intramuscularly or 0.1-0.2 ml in 10 ml of 0.9% solution of sodium chloride intravenously slowly), as well as GCS intravenously in large doses, if necessary, repeat them.

    Insufficient diagnostic accuracy

    In some clinical situations, in connection with a change in the concentration of cortisol-binding globulins, monitoring the plasma cortisol concentration in a test with a depot form tetrakozaktida can give erroneous results. These are cases of the use of the test in patients receiving oral contraceptives,in patients after surgical interventions, in a critical condition, in patients with severe liver damage, nephrotic syndrome. In these conditions, alternative parameters (cortisol saliva, free cortisol index, free plasma cortisol) can be used to evaluate the functioning of the hypothalamic-pituitary-adrenal system.

    Special instructions related to with enhanced secretion of SCS and mineralocorticoids during the treatment with tetracosactide

    Delayed sodium and water arising in response to the introduction tetracosactide, can in many cases be avoided when prescribing a low-salt diet. With prolonged treatment, it may sometimes be necessary to administer additional potassium.

    If fluid retention (weight gain) or Isenko-Cushing syndrome develops, tetrakozaktid should be temporarily canceled or prescribed in a smaller dose (either reduce the daily dose, or increase the interval between injections).

    Act tetracosactide can be amplified in patients with hypothyroidism or cirrhosis of the liver.

    Long-term therapy tetracosactide may be accompanied by the development of posterior subcapsular cataract and glaucoma.Observation of the ophthalmologist is necessary.

    Patients who undergone trauma or surgery during treatment tetracosactide or within one year after its termination, it is necessary to increase a dose tetracosactide or resume treatment. In some cases, additional use of a fast acting GCS may be required. When administering therapy, the minimum effective dose should be applied tetracosactide. Dose reduction should be carried out gradually. Prolonged use of it leads to a relative insufficiency of the pituitary-adrenal system, which can persist for several months after discontinuation of treatment. In these cases, the question of the appropriate steroid therapy should be decided.

    Use in children

    It is unlikely that tetracosactide, appointed in individually selected doses, will lead to growth disruption in children. Nevertheless, children who undergo long-term therapy need regular monitoring of body growth.

    Infants and young children should regularly carry out echocardiography, since during prolonged therapy with high doses tetracosactide can develop reversible hypertrophy of the myocardium.

    Influence on ability to drive a car and work with mechanisms

    As tetracosactide can affect the central nervous system, patients should be careful when driving vehicles or working with mechanisms.

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