Tiodaron® [Amiodarone, Thiotriazoline]

TIODARON^® (TIODARON)

Arterium Corporation C01E X

Halichfarm

COMPOSITION AND FORM OF ISSUE:

tab. blister, number 30, number 60

No. UA / 6326/01/01 from 04/13/2012 to 04/13/2017

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamics Thiodarone is a combined drug whose properties are determined by its components - amiodarone hydrochloride and Thiotriazoline.
Amiodarone hydrochloride mainly affects the heart and blood vessels. It has an antiarrhythmic and antianginal effect due to the ability to block the ionic (mainly potassium, to a lesser extent calcium and sodium) channels of the membranes of cardiomyocytes, as well as inhibit mediator processes of excitation of α- and β-adrenergic receptors. Amiodarone hydrochloride has a negative chronotropic effect. Sympatolytic activity and blockade of potassium and calcium channels reduce myocardial oxygen demand, lead to a negative dromotropic effect: slower conductivity and lengthening of the refractory period in the sinus and AV nodes. In addition, it has the properties of a vasodilator, due to which it can reduce the resistance of the coronary vessels.
The second component is Thiotriazolinewhose effects are due to the predominant effect on biochemical processes in the heart and blood vessels. It has anti-ischemic, membrane-stabilizing, antioxidant and immunomodulating properties. It enhances the compensatory activation of anaerobic glycolysis, activates the oxidation processes in the Krebs cycle, while maintaining the intracellular ATP content. The drug also activates the antioxidant system and inhibits the processes of lipid oxidation in ischemic areas of the myocardium, reduces the sensitivity of the heart muscle to the action of catecholamines, prevents progressive inhibition of the contractile function of myocardiocytes, stabilizes and reduces the area and volume of the necrosis zone and activates the fibrinolytic system.
Pharmacokinetics due to the pharmacological properties of both components.
Amiodarone hydrochloride is slowly absorbed in the digestive tract. Bioavailability is 30–80%. After a single dose of C_max in plasma is reached after 3–7 hours. In the first days of use, it accumulates in almost all tissues, especially in fatty inclusions, liver, spleen, and lungs. Amiodarone hydrochloride with bile and feces is excreted. Renal excretion is negligible. T_½ long, has a fairly high level of interindividual variability and is 20-100 days.
Thiotriazoline after oral administration is rapidly absorbed, its absolute bioavailability is 53%. WITH_max in blood plasma is achieved 1.6 hours after a single dose of 200 mg. T_½ is about 8 hours

INDICATIONS:

relapse prevention:

• ventricular tachycardia, which threatens the patient’s life: treatment should be started in a hospital with constant monitoring of the patient’s condition;
• symptomatic ventricular tachycardia (documented), which leads to disability;
• supraventricular tachycardia (documented), which needs treatment, and in cases where other drugs do not have a therapeutic effect or are contraindicated;
• ventricular fibrillation.

Treatment of supraventricular tachycardia: slowing or decreasing atrial fibrillation or flutter.
IHD and / or dysfunction of the left ventricle.

APPLICATION:

Thiodarone is taken orally in doses calculated on amiodarone hydrochloride.
Usual Recommended Adult Dose is 1 tablet 3 times a day for 8-10 days. In some cases, at the beginning of treatment, you can take 4-5 tablets per day for a short time and under ECG control.
Maintenance Daily Dose for Adults is ½ –2 tablets per day, depending on the patient’s reaction to the use of the drug Tiodaron.
The drug can be prescribed at a dose of 1 tablet per day every other day or ½ tablet per day every day. There may be a break in admission 2 days a week.

CONTRAINDICATIONS:

sinus bradycardia, AV block II and III degree (in the absence of a pacemaker); sinus node weakness syndrome, sinoatrial block; severe conduction disturbances; hypersensitivity to iodine and amiodarone hydrochloride, Thiotriazoline and other components of the drug; thyroid dysfunction (hyperthyroidism), severe arterial hypotension, renal failure, combination with drugs that can cause paroxysmal ventricular tachycardia of the pirouette type (see INTERACTIONS).

SIDE EFFECTS:

effective and maintenance doses of tiodarone are well tolerated by patients. Adverse reactions can mainly occur due to excess doses of the drug.
With sides of the cardiovascular system: bradycardia (the degree depends on the dose); in some cases - blockage of the sinus node (usually with sinus node dysfunction or in elderly patients); in some cases - sinoatrial blockade, AV block;
with side of the organ of vision: the presence of amiodarone in the preparation can cause deposition of lipofuscin in the corneal epithelium (in rare cases - significant), which in exceptional cases can cause visual impairment in the form of a colored halo in bright light or blurred vision. It is extremely rare - optic neuropathy / neuritis, which is accompanied by blurred vision, decreased visual acuity and papillary edema in the fundus. If there is another obvious reason, it is recommended to stop taking the drug;
dermatological reactions: lead blue or bluish skin pigmentation, alopecia; extremely rare - erythema during radiation therapy, exfoliative dermatitis, although the connection between its appearance and taking the drug is not clearly established.
Allergic reactions: in persons prone to allergies, itching, skin hyperemia, fever, skin rash can occasionally occur; when taking other drugs - in some cases, urticaria and angioedema, with the exception of anaphylactic shock.
From the endocrine system: with prolonged use in some cases, the development of hypothyroidism is possible, much less often - hyperthyroidism.
From the central and peripheral nervous system: rarely - neuropathy, myopathy (disappear after discontinuation of the drug), tremor or other extrapyramidal symptoms, cerebral ataxia, sleep disturbances, nightmares, brain pseudotumor; very rarely - general weakness, dizziness, tinnitus, benign intracranial hypertension, headache.
From the digestive tract: rarely - nausea, vomiting, taste disturbance, dry mouth, bloating; hepatitis, cirrhosis, acute liver damage (including liver failure), which requires discontinuation of treatment, with an increase in transaminases in the blood and / or jaundice, sometimes with a fatal outcome.
From the respiratory system: shortness of breath and suffocation (on one occasion); diffuse interstitial or alveolar pneumopathy, pneumonitis, bronchospasm, fibrosis, pleurisy, bronchiolitis, pneumonia; in some cases, the development of acute respiratory distress syndrome immediately after surgery is possible, possibly due to the use of high doses of oxygen during anesthesia. Hemorrhages in the lungs have been reported.
From the reproductive system: very rare cases of epididymitis, impotence, however, a connection with the use of the drug is currently not established.
Other: vasculitis, renal failure, which is accompanied by a moderate increase in creatinine levels, kidney damage, thrombocytopenia, hemolytic or aplastic anemia.

SPECIAL INSTRUCTIONS:

ECG control is mandatory during treatment with Tiodarone, since it is possible: moderate lengthening of the interval Q – T (at constant width QRS), tooth extension T, a decrease in its amplitude, flattening of the apex or biphasicity, the appearance or increase in the amplitude of the tooth U. Caution is necessary for violations of AV conduction and AD, as well as for violations of the electrolyte balance (especially hypokalemia). Therefore, situations that may be accompanied by the occurrence of hypokalemia, possibly contributing to the appearance of a proarrhythmogenic effect, should be considered. Hypokalemia must be corrected before starting the use of the drug. It should be borne in mind that in elderly patients, a more pronounced decrease in heart rate is noted. When the appearance of AV blockade of II or III degree, sinoatrial or bifascicular blockade, the use of the drug must be stopped.
From the endocrine system: Amiodarone can cause dysfunction of the thyroid gland (hypo / hyperthyroidism), especially in patients with a history of dysfunction (including family), in elderly patients. Therefore, before starting, during treatment (every 6 months) and for several months after its completion, it is necessary to conduct thorough clinical and laboratory monitoring of thyroid function. Hyperthyroidism can appear during treatment with amiodarone preparations or several months after the cessation of their use. Cases of a fatal course of hyperthyroidism have been reported, therefore, if it occurs, the drug must be discontinued. Clinical recovery usually occurs after a few months. In cases of severe thyroid hyperactivity, it is necessary to consider the rationality of using antithyroid drugs, possibly in combination with corticosteroids.
In life-threatening situations, when hypothyroidism occurs, treatment with the drug can be continued in combination with sodium levothyroxine, the doses of which are corrected according to the level of thyroid hormones. The euthyroid state, as a rule, is restored 3 months after discontinuation of drug treatment.
Pulmonary manifestations: the appearance of shortness of breath or dry cough, either separately or against a background of worsening general condition, indicates the possibility of pulmonary toxicity, for example interstitial pneumopathy, and requires an X-ray examination.
From the liver: regular monitoring of liver function is recommended before and at regular intervals during the period of treatment with amiodarone preparations (see ADVERSE EFFECTS).
From the side of the organ of vision: in case of deterioration of clarity or decrease in visual acuity, a full ophthalmological examination should be immediately carried out, including examination of the fundus. It is necessary to stop taking the drug in case of neuropathy or optic neuritis caused by amiodarone, since there is a risk of their progression to complete blindness (see ADVERSE EFFECTS).
Neuromuscular manifestations: amiodarone may cause peripheral sensory, motor, or mixed peripheral neuropathy and / or myopathy with prolonged use (see ADVERSE EFFECTS).
When conducting combination therapy, it should be borne in mind that combinations (see INTERACTIONS) with β-adrenergic blockers, with the exception of sotalol (a combination is contraindicated) and esmolol (a combination that should be prescribed with caution), or verapamil and diltiazem should be used only for the prevention of ventricular life threatening arrhythmias.
Patients should be warned that during the treatment period they avoid exposure to sunlight or use protective measures.
Before surgery, the anesthetist should be informed that the patient is taking Tiodaron.
The use of the drug during pregnancy and lactation not studied.
Children. Experience with the drug in children is not enough.
The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Currently, there are no reports, however, the possibility of developing adverse reactions from the nervous system and organ of vision should be considered.

INTERACTIONS:

contraindicated combinations. Medicines that can cause paroxysmal ventricular tachycardia like pirouette and increase the risk of its development while using amiodarone: antiarrhythmic drugs of class Ia (quinidine, hydroquinidine, disopyramide); class III antiarrhythmic drugs (dofetilide, ibutilide, sotalol); other drugs, such as bepridil, cisapride, difemanil, moxifloxacin, misolastine, sultopride; IV preparations - erythromycin, vincamine and spiramycin.
Combinations that are not recommended. Cyclosporin - with simultaneous use with amiodarone, an increase in the level of cyclosporin circulating in the blood plasma is noted due to a decrease in its metabolism in the liver, there is a risk of a nephrotoxic effect. It is necessary to control the concentration of cyclosporin in the blood and careful monitoring of renal function due to the risk of nephrotoxic effect.
When using a combination with an injectable form of diltiazem and verapamil, there is a risk of developing bradycardia and AV block. If such a combination is necessary, you should carefully monitor the patients condition and conduct constant ECG monitoring.
It is also not recommended to combine Thiodarone with such drugs: methadone, antiparasitic drugs (halofantrine, lumefantrine, pentamidine), antipsychotics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, amisulpride, sulpiride, tiapride, droperideral) cause paroxysmal ventricular tachycardia like pirouette.
Combinations requiring extreme caution when used simultaneously. Oral anticoagulants - increased anticoagulant effect and increased risk of bleeding due to increased concentration of anticoagulants in blood plasma. It is necessary to more often control the level of prothrombin in the blood and the international normalized ratio (INR), to adjust the dose of oral anticoagulants during treatment with the drug and after its cancellation.
Β-adrenoreceptor blockers, except sotalol (a combination is contraindicated) and esmolol (a combination that requires special care when used) - the risk of impaired contractility of the heart, automatism and conduction (inhibition of the compensatory mechanisms of the sympathetic nervous system).
Β-adrenoreceptor blockers in case of heart failure (bisoprolol, carvedilol, metoprolol, nebivolol) - a violation of automatism and cardiac conduction (synergism of effects) with a risk of severe bradycardia. There is an increased risk of ventricular arrhythmias.
Digitalis drugs - oppression of automatism (severe bradycardia) and violation of AV conduction. Perhaps an increase in the concentration of digoxin in blood plasma due to a decrease in its clearance.
Oral forms of diltiazem and verapamil - there is a risk of developing bradycardia and AV blockade of the heart, especially in elderly patients.
Drugs that cause hypokalemia: diuretics that remove potassium (alone or in combination), laxatives, amphotericin B (iv), glucocorticoids (systemic), tetracosactide - an increased risk of ventricular arrhythmias, especially paroxysmal ventricular tachycardia of the pirouette type (hypokalemia is a provoking factor )
Lidocaine is the risk of increasing the concentration of lidocaine in blood plasma with the possibility of developing side neurological and cardiac effects through a decrease in its hepatic metabolism under the influence of amiodarone.
Orlistat - the risk of a decrease in the concentration of amiodarone in blood plasma and its active metabolism.
Phenytoin (phosphenytoin) - an increase in the concentration of phenytoin in blood plasma with signs of an overdose, especially neurological (decreased metabolism of phenytoin in the liver).
When taking all of the above drugs, clinical and ECG monitoring of the patients condition is necessary.
With the simultaneous use of Tiodarone with lipid-lowering drugs, the concentration of the latter in the blood can increase 10–20 times (lovastatin, simvastatin) or 2–4 times (atorvastatin), while this effect was not detected with rosuvastatin.
Tacrolimus is an increase in blood levels due to inhibition of its metabolism by amiodarone.
Flecainide - amiodarone increases its concentration in blood plasma as a result of inhibition of cytochrome CYP 2D6. With simultaneous use with amiodarone, it is necessary to correct the dose of drugs that are metabolized by CYP 2D6 and CYP 3A4 (sildenafil, midazolam, triazolam, dihydroergotamine).
General anesthesia (means for inhalation anesthesia), oxygen therapy - the risk of bradycardia (resistant to atropine), arterial hypotension, impaired conduction, decreased minute blood volume.
Long-term use of grapefruit juice with Tiodarone may increase the concentration of amiodarone in blood plasma.
Incompatibility is unknown.

OVERDOSE:

Symptoms sinus bradycardia, conduction block, paroxysmal ventricular tachycardia of the pirouette type, circulatory disturbance, impaired liver function. With prolonged overdose of the drug, an increase in the concentration of sodium and potassium in the urine is possible.
Treatment: conduct symptomatic therapy. Dialysis is ineffective.

STORAGE CONDITIONS:

in the original packaging at a temperature not exceeding 25 ° C.