Instructions for Espa-Carb tablets 10 mg blister No. 50
Composition
active ingredient: carbimazole;
1 tablet contains carbimazole 10 mg;
excipients:
10 mg tablets: mannitol (E 421), microcrystalline cellulose, corn starch, anhydrous citric acid, sodium starch glycolate (type A), magnesium stearate, yellow iron oxide (E 172).
Dosage form
Pills.
Main physicochemical properties:
10 mg tablets: round, convex tablets of yellowish color with a score line on one side.
Pharmacotherapeutic group
Antithyroid drugs. Sulfur-containing imidazole derivatives. ATX code H03B B01.
Pharmacological properties
Pharmacodynamics
Carbimazole, depending on its dosage, inhibits the incorporation of iodine into tyrosine, and therefore, the additional synthesis of thyroid hormones. This property makes it possible to carry out symptomatic therapy of hyperthyroidism, regardless of its etiology. Whether carbimazole also affects the natural course of the disease in immunologically determined form of hyperthyroidism (Graves' disease), i.e. whether it inhibits the immunopathogenetic process underlying the disease, cannot be determined with complete certainty at this time. It does not affect the secretion of already synthesized thyroid hormones. This explains in some cases the different duration of the latent period of the drug's action before the normalization of the concentration of thyroxine and triiodothyronine in the blood serum, i.e. until the clinical improvement of the condition. The drug also does not affect hyperthyroidism due to the secretion of hormones after the destruction of thyroid cells, for example, after radiotherapy or in thyroiditis.
Pharmacokinetics
Carbimazole is rapidly and completely absorbed and immediately after absorption is converted to its active form - thiamazole. After taking 15 mg of carbimazole, the maximum serum level of -150 ng/nl is reached within 24-72 minutes.
Protein binding of thiamazole can be neglected. Thiamazole accumulates in the thyroid gland, where it is only slowly metabolized, and since its duration of action is more directly related to the concentration of the substance in the thyroid gland than to its plasma half-life, this leads to a prolongation of antithyroid activity. This results in an almost 24-hour duration of action of a single dose and allows the drug to be used once a day. The kinetics of thiamazole, according to the information available at the moment, does not depend on the state of thyroid function.
The half-life from the body is about 3 hours, with insufficient liver function it is longer. Thiamazole is excreted both with urine and bile. But fecal excretion is insignificant, which allows us to conclude about enterohepatic circulation. 70% of thiamazole is excreted by the kidneys within 24 hours, of which only a small amount is in unchanged form. There is currently no information on the pharmacological activity of metabolites.
Indication
Thyroid dysfunction associated with hyperproduction of its hormones (hyperthyroidism). Preparation for thyroidectomy in hyperthyroidism. Therapy before and after radioactive iodine treatment.
Contraindication
Increased individual sensitivity to carbimazole, thiamazole or other components of the drug. Severe disorders of the blood system, severe liver failure, cholestasis. Simultaneous use of radioactive iodine preparations. Additional therapy with thyroid hormones during pregnancy. History of acute pancreatitis after taking carbimazole or thiamazole.
Interaction with other medicinal products and other types of interactions
There is insufficient data on the interaction of carbimazole with other drugs.
Carbimazole should be used with caution with agents that may cause agranulocytosis.
Since carbimazole is a vitamin K antagonist, the effect of anticoagulants may be enhanced.
Serum theophylline levels may increase and toxicity may develop if patients are treated with antithyroid drugs without reducing theophylline dose.
There is a risk of cross-allergy between carbimazole, thiamazole and propylthiouracil.
Application features
At the first signs of liver disorder (upper abdominal pain, loss of appetite, general itching), the drug should be discontinued and liver function should be monitored immediately.
Carbimazole should be used with caution in patients with mild to moderate hepatic impairment.
In case of severe liver dysfunction, treatment should be discontinued. The half-life may be increased due to liver dysfunction.
Acute pancreatitis may occur following the use of carbimazole or its active metabolite thiamazole. In this case, carbimazole should be discontinued immediately. To avoid recurrence, carbimazole should not be administered to patients with a history of acute pancreatitis due to previous use of carbimazole or thiamazole. In such patients, repeated administration may lead to a recurrence of acute pancreatitis with a shortened time to onset of symptoms.
Patients who are unable to follow the instructions for use of the drug or who cannot be examined regularly should not be treated with carbimazole.
Patients who may experience seizures or memory impairment should have regular blood tests.
Patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Caution is necessary in patients with intrathoracic goiter, which may worsen initial treatment with carbimazole. Tracheal obstruction may occur due to intrathoracic goiter.
During treatment, non-pregnant women of reproductive age should use a reliable method of contraception.
There is a risk of cross-allergy between carbimazole, thiamazole and propylthiouracil.
Ability to influence reaction speed when driving vehicles or other mechanisms
The effect on the ability to drive or operate machinery is unknown.
Use during pregnancy or breastfeeding
Carbimazole and its active metabolite thiamazole cross the placenta and enter the fetal blood at the same concentration as in the maternal serum. Carbimazole should be used in pregnant women only at the lowest effective dose without additional thyroid hormone and with a careful individual benefit-risk assessment. If the maternal dose is within the standard range and her thyroid status is monitored, there is no evidence of thyroid disorders in the newborn. Studies have shown that the incidence of congenital malformations is higher in children whose mothers had untreated hyperthyroidism than in those who were treated with carbimazole.
However, in very rare cases, congenital malformations have been observed after the use of carbimazole or its active metabolite methimazole during pregnancy. A possible association of malformations, in particular choanal atresia and aplasia cutis congenita, cannot be excluded due to transplacental exposure of carbimazole and methimazole. The use of carbimazole in pregnant women, especially during the first trimester and at high doses, may cause congenital malformations. The reported malformations include: congenital aplasia cutis, craniofacial malformations (choanal artesia, facial dysmorphism), omphalocele, esophageal artesia, bile duct anomaly, ventricular septal defect, hypoplastic breast shape and mental and motor developmental delay. Thus, the use of carbimazole in pregnant women and women of reproductive age is possible only when the expected benefit to the mother outweighs the potential risk to the fetus.
Cases of renal dysfunction, skull, congenital cardiovascular malformations, umbilical hernia, gastrointestinal malformations, umbilical malformations and duodenal atresia have also been reported. Therefore, carbimazole should only be used during pregnancy when propylthiouracil is not suitable. If carbimazole is necessary during pregnancy, the dose should be adjusted according to the clinical condition of the patient. Low doses may be used and treatment may be discontinued 3-4 weeks before the due date to reduce the risk of neonatal complications. Treatment should not be discontinued during pregnancy, as very small amounts of thyroxine cross the placenta in the last trimester.
Additional treatment with thyroid hormones is prohibited (the Blockade-Replacement Scheme is not used, since a small amount of thyroxine is able to pass through the placenta in the last trimester of pregnancy).
The use of carbimazole in women during pregnancy necessarily requires close monitoring of the condition of the woman, fetus or newborn.
Breastfeeding can be continued during carbimazole therapy, but only small doses (up to 10 mg per day) should be used without additional thyroid hormone supplementation. In this case, it is necessary to monitor the child's thyroid function.
Method of administration and doses
ESPA-CARB® is used only for hyperthyroidism, which has been confirmed by laboratory tests.
Adults
The initial dose should be 20-60 mg and should be titrated according to thyroid function until the patient is euthyroid to reduce the risk of overtreatment and subsequent hypothyroidism. Further treatment is carried out in one of two ways.
Maintenance therapy: The final dose is usually 5-15 mg per day, which can be taken as a single daily dose. Therapy is continued for at least 6-18 months. Regular monitoring of thyroid function is recommended, along with appropriate dose adjustment to maintain a euthyroid state.
Blockade-replacement regimen: initial doses of 20-60 mg per day are maintained, additionally L-thyroxine 50-150 mcg per day is prescribed to prevent hypothyroidism. Therapy continues for at least 6-18 months.
Elderly patients
If there are no contraindications or precautions, such patients do not require special dosage.
Children
There is not enough experience with the use of carbimazole in children, so the drug is not prescribed to this age group of patients.
Overdose
Cases of overdose are not described.
Adverse reactions
The following categories were identified in the frequency analysis of side effects:
very common (≥ 10%);
common (≥1% - < 10%);
uncommon (≥ 0.1% -< 1%);
rare (≥ 0.01%-< 0.1%);
very rare (< 0.01%);
not known (frequency not estimated due to lack of data).
Blood and lymphatic system disorders:
Uncommon: Agranulocytosis occurs in about 0.3–0.6% of cases. It may also occur weeks or months after the start of therapy and necessitate discontinuation of the drug. In most cases, it resolves spontaneously. Recent data support the use of granulocyte colony-stimulating factors (granulocyte colony-stimulating factor Filgrastim) for the treatment of drug-induced agranulocytosis. However, the use of such factors should be in consultation with a hematologist.
Very rare: thrombopenia, pancytopenia, aplastic anemia, hemolytic anemia.
From the endocrine system:
Due to increased dosage, subclinical or clinical hypothyroidism may occur, as well as goiter growth associated with increased thyroid-stimulating hormone (TSH). In this regard, after achieving a euthyroid state, the dose of ESPA-CARB® should be reduced and/or levothyroxine sodium should be additionally used. It is not advisable to completely stop taking ESPA-CARB® and continue therapy with thyroid hormones.
Growth of goiter during ESPA-CARB® therapy with suppressed TSH should be perceived as a consequence of the underlying disease and not treated with additional thyroid hormone supplementation.
After a single thyreostatic therapy, there is a small percentage of posthypothyroidism. In such cases, it is not a side effect of the drug, but rather inflammatory and destructive processes in the thyroid parenchyma within the framework of the underlying disease.
On the part of the organs of vision:
The occurrence or worsening of endocrine orbitopathy is possible regardless of the course of the thyroid disease: such a complication, in itself, is not a reason to change the therapeutic program (thyroid drugs, surgery, radioactive iodine), and it should not be perceived as a side effect of qualified therapy.
From the nervous system: headache.
On the part of the digestive tract: nausea, minor gastrointestinal disorders, acute pancreatitis.
General disorders: fever, malaise, bruising.
Uncommon: drug fever, taste disturbances (dysgeusia, ageusia) or smell disturbances, which resolve after discontinuation of treatment, and normalization may take several weeks.
Very rare: Arthralgia and myalgia, which usually develop slowly and persist after many months of long-term therapy. Clinical signs of joint inflammation are absent.
Generalized lymphadenopathy, arthritis, nephritis, acute salivary gland swelling, vasculitis, neuritis and polyneuropathies, insulin-autoimmune syndrome (with a sharp drop in blood sugar).
When taking ESPA-CARB®, due to the reduction of the pathologically increased energy requirement in hyperthyroidism, a (generally desirable) increase in body weight may occur. Patients should be informed that as the disease improves, the body's energy requirement normalizes.
From the hepatobiliary system:
Very rare: Cholestatic jaundice or toxic hepatitis. In general, the symptoms disappear after discontinuation of the drug. Clinically hidden signs of cholestasis during treatment should be distinguished from serum gamma-glutamyltransferase activity already increased before the start of therapy as a sign of enzyme induction due to hyperthyroidism, as well as an increase in alkaline phosphatase or its bone isoenzymes.
On the part of the skin and its derivatives:
Very common: Allergic skin reactions (itching, exanthema, urticaria) of a periodic nature. In most cases they are mild and often disappear with continued therapy.
Very rare: Severe manifestations up to generalized dermatitis.
Hair loss, drug-induced lupus erythematosus.
Musculoskeletal system: in isolated cases - myopathy. Patients who develop muscle pain after treatment with carbimazole should constantly monitor the level of creatine phosphokinase.
Hypersensitivity reactions: Quincke's edema, multisystem hypersensitivity reactions (cutaneous vasculitis, reactions from the liver, lungs and kidneys).
Vascular: bleeding.
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25°C.
Keep out of reach of children.
Packaging
25 tablets in a blister, 2 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Lindopharm GmbH.
Location of the manufacturer and its business address
Neustrasse 82, 40721 Gilden, Germany.
