Expiration date: 07/2026

Composition: 

active ingredients: Adonis extract dense – 69, 07 mg, potassium bromide – 250 mg 

excipients: magnesium carbonate basic, potato starch, talc, calcium stearate, Advance Prepaid (includes: hypromellose, copolyvidone, polyethylene glycol, Caprylic capric triglyceride, Polydextrose (E 1200), titanium dioxide (E 171), iron oxide yellow (E 172)). 

Pharmacotherapeutic group: other combined drug for the treatment of diseases of the heart.

Pharmacological action

Pharmacodynamics

The drug of plant origin, has sedative and cardiotonic effect. 

Action due to members of the extract of Adonis (spring Adonis) polar glycosides zimarina (1-10 % of total glycosides) and odontocera (3-20 % of total glycosides) and bromide ions. Bromide ions stabilize the GABA receptors in the open state, after the interaction with ?-aminobutyric acid, providing the supply of bromide and chloride ions into the cell and decrease the activity of the neuron. Zimarin vzaimodeistvuet with neurosteroids recognizing plot Gabaa receptor and increases its sensitivity to the action of ?-aminobutyric acid. In the membrane of the neuron and of the myocardium, zimarin blocks the Na+/K+-ATPase, which prevents the removal of sodium ions from the cell. The increase in intracellular sodium disrupts the process of removal of calcium from the cells and increases the contractile activity of the myocardium.

Adonis-bromine is a weak cardiotonic effect, mainly due to the systolic component increases the strength of heart contractions (positive inotropic effect), the excitability of the myocardium (positive batmotropony effect). Diastolic effect is much less pronounced and is characterized by a decrease in heart rate (negative chronotropic effect) and conduction of impulses in the myocardium (negative Chrono dromotroponoe effect). Application of the Adonis-bromine slightly increases the strength of cardiac contractions, shortens the period of systole and lengthens the time of diastole, heart rate decreases.

Adonis-bromine concentrates and enhances the processes of inhibition in the cerebral cortex. Restores the balance between the processes of excitation and inhibition in the Central nervous system.

Pharmacokinetics

After intake of the active ingredients are absorbed quickly and adequately. The maximum concentration zimarina (glycoside of Adonis) and bromide ions is achieved through 1-2 hours after administration. Bioavailability of 47% for zimarina and about 96 % for bromide ions. In blood, about 51-59 % zimarina circulates bound to plasma proteins condition. The bromide ions with plasma proteins are practically not linked.

In the body, cymarin and bromide ions are distributed mainly in extracellular fluid. In the cerebrospinal fluid concentrations of bromide-ion and zimarina make up 37 % of their concentration in plasma. The bromide ions do not undergo metabolism, zimarin partially biotransformiroetsa in the liver and the intestinal wall. Elimination of the bromide ions and zimarina is carried out mainly by the kidneys.

Bromide ions are excreted by means of glomerular filtration, but subsequently undergo tubular reabsorption in competition with chloride ions. The period of preliminaly bromide ions is an average of 11, 9±1, 4 days and depends on the level of salt intake (shortened with increasing consumption of sodium chloride). Additional ways of elimination of the bromide ions are the intestines, sweat and mammary glands.

Zimarin is eliminated as metabolites and unchanged substance (about 21 % of the administered dose). The ratio of daily elimination is 50%. The period of preliminaly about 13-23 h

Indications for use

Used in the initial stages of chronic heart failure, irritability.

Contraindications

• hypersensitivity to Adonis, bromides, 
  
• depression, 
  
• respiratory insufficiency, 
  
• chronic congestive heart failure high grades (III-IV????? NYHA), 
  
• severe hepatic and renal failure, 
  
• erosions, gastric ulcer and duodenal ulcer, 
  
• receiving cardiac glycosides, 
  
• digitalisnaya intoxication, 
  
• hypercalcemia, hypokalemia, 
  
• bradycardia, atrioventricular block or ventricular form of arrhythmia.
  

Method of application and doses

Assign inside of 1 tablet 3 times a day. 

If impaired renal function with a decrease in creatinine clearance by more than 50% from normal values it is recommended to reduce the dose in 2 times, or increase the interval between doses of the drug up to 12 hours.

Side effects 

From the side of cardiovascular system: bradycardia, arrhythmia (premature beats on the type bigeminy).

From the Central nervous system: headache, anxiety, insomnia, depression effects, visual disturbances, lethargy, confusion, weakness, drowsiness, slowing of speech, in severe cases, the symptoms of bromism (if overdose), 

The gastro-intestinal tract: nausea, vomiting (emetic effect is partly due to the reflexes arising from the excitation of receptors in the heart), gastralgia (due to a direct effect of cardiac glycosides on the vomiting center and homocysteine receptor zones and reflexes due to the irritating effect on the mucous membrane of the stomach), in high doses, possible loss of appetite, diarrhea.

Allergic reactions.

Special instructions

Should follow hyposalemia diet (restrict the intake of sodium chloride) during treatment Adonis-bromine. During treatment to prevent undesirable effects of bromide ions on the skin and mucous membranes we recommend regular emptying of the bowel, mouthwash and hygiene of the skin (bathing, showering).

Pregnancy and lactation. Bromide ions easily penetrate through the placenta and are excreted into the milk of lactating women. The use of Adonis-bromine during pregnancy only if the expected benefit outweighs the potential risk to the fetus. If necessary, the appointment of Adonis-bromine lactation it is necessary to separate the child from the breast for the entire period of treatment and for 1 month after.

Use in Pediatrics. The safety and efficacy of medicines in children is not established. The experience of its application in patients of this age group is limited.

Effects on ability to drive vehicles and management mechanisms. Reception Adonis-bromine disrupts the patient's ability to control a motor vehicle or that the operator's activities, so during treatment you must be careful when driving and occupation of other potentially hazardous activities, require high concentration and psychomotor speed reactions.

Interaction with other drugs 

With simultaneous use may increase the toxic effect of other cardiac glycosides (digitalis preparations, strophanthus and Convallaria).

While the application increases the effect and toxicity of antiarrhythmic agents in class IA (quinidine, procainamide, disopyramide), calcium supplements, laxatives and corticosteroids.

Enhances depressing effect on the Central nervous system benzodiazepines, anticonvulsant and sedative-hypnotic means, antipsychotics and alcohol.

Galotanovogo anesthesia increases the level of bromide ions in organism in patients taking Adonis-Brom, and enhances its effect and toxic effect.

The intake of salty foods increases the excretion of bromide in the urine and reduces the effect of the drug.

Overdose

Symptoms: expressed aetiology, arrythmia polytopes, bigeminy or trigeminy, slowing of atrioventricular conduction, in severe cases, ventricular flutter, cardiac arrest.

Treatment: treatment of intoxication associated with an overdose of cardiac glycosides, make a break in use of the drug, if necessary, prescribe potassium supplements and antiarrhythmic drugs.

The use of diuretics to create a forced diuresis and accelerate the excretion of bromide ions is contraindicated as it increases the risk of toxic effects of glycosides of Adonis.

Symptoms of overdose bromides: cough, runny nose, lethargy, headache, weakness, impaired perception, memory loss, skin rash, conjunctivitis.

Treatment: in these cases the cessation of the drug, the administration of large quantities (in the absence of contraindications) sodium chloride 10-20 g a day (speeds up the excretion of bromine) in combination with fluids (3-5 liters per day).

Symptoms of overdose cardiac glycosides: severe bradycardia, extrasystoles polytopes, bigeminy or trigeminy, slowing of atrioventricular conduction, in severe cases, ventricular flutter cardiac arrest. 

Treatment: treatment of intoxication associated with the drug overdose of cardiac glycosides, making a break in their application, if necessary, prescribe potassium preparations and antiarrhythmic agents.

Packaging

There are 10 tablets in a contour acheikova packing or 25 tablets in a jar. Each Bank or 3 contour packing with a leaflet in the pack.

Storage conditions

In safe dry place at a temperature not exceeding 25º C.

Keep out of reach of children.

Shelf life 

2 years. Medicine do not use after the expiry date.