Valdikardin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT VALDICARDIN (VALDICARDIN)

Composition:

Active substances: phenobarbital, ethyl ether of α-bromoisovaleric acid;

1 ml of solution (24 drops) contains phenobarbital – 18.4 mg, ethyl ether of α-bromoisovaleric acid – 18.4 mg;

Excipients: peppermint oil; hop oil; sodium citrate; citric acid monohydrate; ethanol 96%; purified water.

Pharmaceutical form. Oral drops.

Main physico-chemical properties: colorless liquid with a characteristic aromatic odor and bitter taste. Opalescence may be present.

Pharmacotherapeutic group. Hypnotics and sedatives. Barbiturates in combination with drugs from other groups. ATC code N05CB02.

Pharmacological properties.

Pharmacodynamics.

Valdikardin is a combination drug containing phenobarbital and ethyl bromisovalerate (ethyl ether of α-bromoisovaleric acid). Depending on the dose, both substances exhibit sedative and hypnotic effects, and at high doses exert narcotic action. Like other derivatives of barbituric acid, phenobarbital inhibits the inhibitory system of the reticular formation. Ethyl bromisovalerate demonstrates both spasmolytic and sedative properties. At the concentration present in Valdikardin, ethyl bromisovalerate acts as a synergist of phenobarbital (rapid onset of efficacy).

Pharmacokinetics.

Phenobarbital is rapidly absorbed (directly in the stomach). Approximately 35% of it binds to plasma proteins; the unbound portion is filtered by the kidneys. Reabsorption occurs at low pH levels. Reverse diffusion does not occur due to the alkalinity of urine. Approximately 30% of phenobarbital is excreted unchanged in urine, and only a small portion is oxidized in the liver. With prolonged use, accumulation of the active substance in plasma occurs, as well as induction of liver enzymes. As a result of this induction, the oxidation process of phenobarbital and other drugs is accelerated.

Bromine in ethyl bromisovalerate is excreted very slowly from the body. With prolonged administration, accumulation of the substance in the CNS occurs, leading to chronic bromine intoxication.

Clinical characteristics.

Indications.

• Functional disorders of the cardiovascular system;
• Neuroses accompanied by increased irritability and feelings of fear;
• Psychosomatically induced anxiety;
• Excitement states with pronounced vegetative manifestations;
• Sleep onset disorders.

Contraindications.

Hypersensitivity to the components of the drug, bromine. Acute hepatic porphyria, severe impairment of liver and kidney function, diabetes mellitus, depression, myasthenia gravis. Medicinal products containing phenobarbital are contraindicated in alcoholism, drug and narcotic dependence (including in medical history); in respiratory diseases with dyspnea, obstructive syndrome, pronounced arterial hypotension, acute myocardial infarction; in depressive disorders with patient's tendency towards suicidal behavior.

Pregnancy and lactation period. Pediatric age.

Interaction with other medicinal products and other forms of interaction.

When used concomitantly with other medicinal products that depress the central nervous system, mutual enhancement of effect (sedative-hypnotic effect) is possible, which may be accompanied by respiratory depression. Phenobarbital enhances the effect of analgesics, anesthetics, anesthetic agents, neuroleptics, and tranquilizers. Alcohol enhances the effect of the drug and may increase its toxicity.

The drug's effect is enhanced when used concomitantly with valproic acid preparations.

Phenobarbital, which is part of Valdikardin, may induce liver enzymes and thus may accelerate the metabolism of certain drugs metabolized by liver enzymes (including paracetamol, salicylates, indirect anticoagulants, cardiac glycosides (digoxin), antimicrobials (chloramphenicol, doxycycline, metronidazole, rifampicin), antivirals, antifungals (griseofulvin, itraconazole), antiepileptics (anticonvulsants), psychotropic agents (tricyclic antidepressants, clonazepam), hormones (estrogens, progestogens, corticosteroids, thyroid hormones), immunosuppressants (glucocorticoids, cyclosporine, cytostatics), antiarrhythmics, antihypertensives (β-blockers, calcium channel blockers), oral hypoglycemic agents, etc.), thereby reducing the efficacy of these drugs. Phenobarbital may accelerate the metabolism of oral contraceptives, leading to loss of their contraceptive effect.

MAO inhibitors prolong the effect of phenobarbital. Rifampicin may reduce the effect of phenobarbital.

When used concomitantly with gold-containing preparations, the risk of kidney damage increases.

With prolonged concurrent use with nonsteroidal anti-inflammatory drugs, there is a risk of gastric ulceration and bleeding.

Concomitant use of medicinal products containing phenobarbital with zidovudine increases the toxicity of both drugs.

The medicinal product increases the toxicity of methotrexate.

Special precautions for use.

Life-threatening skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with phenobarbital use. Therefore, if characteristic symptoms occur (e.g., progressive skin rash, often with blistering, and mucous membrane involvement), Valdikardin should be discontinued immediately, and phenobarbital-containing medicinal products must not be used again under any circumstances. The risk of developing Stevens-Johnson syndrome or Lyell's syndrome (toxic epidermal necrolysis) is highest during the first weeks of treatment. Early diagnosis and immediate discontinuation of the suspected causative drug are crucial for achieving the best treatment outcomes.

If chest pain persists after taking the medicinal product, medical advice must be sought to exclude acute coronary syndrome. Use with caution in patients with hyperkinesias, hyperthyroidism, adrenal insufficiency, uncompensated heart failure, severe arterial hypotension, and persistent pain, as well as in cases of acute intoxication with medicinal products.

Prolonged use of Valdikardin is not recommended due to the risk of bromide accumulation in the body and subsequent bromide poisoning.

Long-term continuous use of the drug may lead to habituation, drug dependence, and withdrawal syndrome; abrupt discontinuation may result in rebound symptoms. Prolonged use may occasionally lead to increased psychomotor activity rather than the expected sedative effect.

Valdikardin contains 55% v/v ethanol (alcohol).

The minimum dose (18 drops) contains 325.57 mg of ethanol, equivalent to 8.25 ml of beer or 3.44 ml of wine. This is harmful for patients suffering from alcoholism. Use with caution in patients with liver disease and in patients with epilepsy.

This medicinal product contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially "sodium-free".

Use during pregnancy or breastfeeding.

Do not use during pregnancy or breastfeeding.

Ability to influence reaction speed when driving or operating machinery.

Valdikardin impairs reaction speed. Patients taking this medicinal product should refrain from potentially hazardous activities requiring heightened attention and rapid mental and motor responses.

Method of Administration and Dosage.

For adults only.

Administer orally during meals, diluting the single dose in a small amount of liquid.

The usual dosage is 18–24 drops three times daily. If the patient suffers from insomnia, the dose may be increased to 36 drops.

The duration of treatment is determined by a physician.

Children.

There is no experience with the use of this medicinal product in pediatric patients; therefore, the drug should not be used in pediatric practice.

Overdose.

Symptoms.

Acute (mild to moderate) barbiturate poisoning:

dizziness, fatigue, and even deep sleep from which the patient cannot be awakened.

Hypersensitivity reactions may occur: angioneurotic edema, urticaria, pruritus, skin eruptions.

Acute severe poisoning:

deep coma accompanied by tissue hypoxia, shallow respiration (initially rapid, later slowed), tachycardia, cardiac arrhythmia, low blood pressure, bradycardia, vascular collapse, diminished or absent reflexes, nystagmus, headache, nausea, weakness, cardiac dysfunction, decreased body temperature, pulse slowing, and reduced diuresis.

If left untreated, poisoning may result in death due to circulatory failure, respiratory paralysis, or pulmonary edema.

Prolonged use of preparations containing bromide may lead to bromism, characterized by the following symptoms: confusion, ataxia, apathy, depressive mood, conjunctivitis, cold-like symptoms, acne, or purpura.

Treatment.

Cases of acute poisoning with Valdikardin should be treated similarly to poisoning with other hypnotics and barbiturates, depending on the severity of symptoms. The patient should be transferred to an intensive care unit. Respiratory and circulatory functions must be stabilized and normalized. Respiratory failure should be managed by artificial ventilation; shock should be treated with plasma and plasma substitutes. If a significant amount of time has passed since ingestion, gastric lavage should be performed (introduce 10 g of activated charcoal powder and sodium sulfate into the stomach). To accelerate the elimination of barbiturates from the body, forced alkaline diuresis, hemodialysis, and/or hemoperfusion may be performed.

Treatment of bromide poisoning: elimination of bromide ions from the body can be accelerated by administering a large volume of sodium chloride solution along with saluretic agents.

In case of hypersensitivity reactions, administer desensitizing agents.

Adverse reactions.

The frequency of adverse reactions is presented according to the following classification: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), frequency not known (cannot be estimated based on available data).

Long-term use of drugs containing bromine may lead to bromine poisoning, characterized by the following symptoms: central nervous system depression, depressive mood, confusion, ataxia, apathy, conjunctivitis, rhinitis, lacrimation, acne, or purpura.

Shelf life.

3 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

20 mL or 50 mL in a bottle; 1 bottle per carton.

Prescription status. Over-the-counter – 20 mL; prescription only – 50 mL.

Manufacturer.

LLC "DKP "Pharmaceutical Factory".

Manufacturer's address and place of business.

4, Korolova St., Stanishivka village, Zhytomyr district, Zhytomyr region, 12430, Ukraine.