Valocordin

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT VAKOCORDIN® (VALOCORDIN®)

Composition:

Active substances: phenobarbital, ethylbromovalerianate;

1 ml (30 drops) of solution contains phenobarbital 18.4 mg, ethylbromovalerianate 18.4 mg;

Excipients: peppermint oil, hop oil, ethanol 96%*, purified water.

*The finished product contains 55% v/v ethanol.

Pharmaceutical form. Oral drops, solution.

Main physico-chemical characteristics: colorless solution with a fragrant odor, bitter taste.

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

Pharmacological properties.

Pharmacodynamics.

Valocordin® is a combined preparation containing phenobarbital and ethylbromovalerianate (ethyl ether of α-bromoisovalerianic acid). Depending on the dose, both substances exhibit sedative and hypnotic effects, while at high doses they produce narcotic action. Like other barbituric acid derivatives, phenobarbital inhibits the inhibitory system of the reticular formation. Ethylbromovalerianate exhibits both spasmolytic and sedative properties. At the concentration contained in Valocordin®, ethylbromovalerianate acts as a synergist of phenobarbital (rapid onset of efficacy).

Pharmacokinetics.

Phenobarbital is rapidly absorbed (directly in the stomach). Approximately 35% of it is bound 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 ethylbromovalerianate is very slowly excreted from the body. With prolonged administration of the drug, bromine accumulates in the CNS, 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;
• Agitated states with pronounced vegetative manifestations;
• Sleep onset disorders.

Contraindications.

Hypersensitivity to the active substances or to any other component of the medicinal product; acute hepatic porphyria; severe impairment of liver or kidney function; diabetes mellitus; depression; myasthenia gravis. Medicinal products containing phenobarbital are contraindicated in alcoholism, drug or narcotic dependence (including in medical history); in respiratory diseases associated with dyspnea, obstructive syndrome, severe arterial hypotension, acute myocardial infarction; in depressive disorders with patient's tendency to suicidal behavior.

Interaction with other medicinal products and other forms of interaction.

When used concomitantly with other medicinal products that depress the CNS (central nervous system), mutual enhancement of action (sedative-hypnotic effect) is possible, which may be accompanied by respiratory depression. Alcohol enhances the effect of the medicinal product and may increase its toxicity.

Medicinal products containing valproic acid enhance the effect of barbiturates.

Phenobarbital induces liver enzymes and, consequently, may accelerate the metabolism of certain drugs metabolized by liver enzymes (e.g., coumarin derivatives, antibiotics, and sulfonamides). Phenobarbital enhances the effect of analgesics, anesthetics, general anesthetics, neuroleptics, and tranquilizers; it reduces the effect of paracetamol, indirect anticoagulants, metronidazole, tricyclic antidepressants, salicylates, and digoxin.

Possible influence on blood concentrations of phenytoin, as well as carbamazepine and clonazepam. MAO inhibitors prolong the effect of phenobarbital. Rifampicin may reduce the effect of phenobarbital. When used concomitantly with gold compounds, the risk of kidney damage increases. With prolonged concurrent use with nonsteroidal anti-inflammatory drugs, there is a risk of gastric ulceration and bleeding. Concurrent administration of medicinal products containing phenobarbital and zidovudine enhances the toxicity of both agents. Undesirable interaction of Valocordin® (containing phenobarbital) with lamotrigine, thyroid hormones, doxycycline, chloramphenicol, antifungals (azole group), griseofulvin, glucocorticoids, and oral contraceptives due to the possibility of reduced efficacy of the aforementioned agents.

The medicinal product increases the toxicity of methotrexate.

Special precautions for use.

Life-threatening skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported with the use of phenobarbital.

Patients should be informed about the signs and symptoms and closely monitored for skin reactions. The highest risk of Stevens-Johnson syndrome or toxic epidermal necrolysis occurs during the first weeks of treatment.

If symptoms of Stevens-Johnson syndrome or toxic epidermal necrolysis occur (e.g., progressive skin rashes, often with blisters, and mucosal lesions), treatment should be discontinued immediately.

The best outcomes in treating Stevens-Johnson syndrome or toxic epidermal necrolysis are observed with early diagnosis and immediate discontinuation of any suspected causative drug. Prognosis is significantly improved by prompt withdrawal of the suspected drug.

If a patient has developed Stevens-Johnson syndrome or toxic epidermal necrolysis while taking Valocordin®, the drug must never be administered to this patient again.

If chest pain does not resolve after taking the medication, medical advice must be sought to rule out acute coronary syndrome. Use with caution in patients with hyperkinesia, hyperthyroidism, adrenal insufficiency, uncompensated heart failure, severe arterial hypotension, persistent pain, or acute intoxication with medicinal products.

Valocordin® contains 55% v/v ethanol.

Prolonged use of Valocordin® is not recommended due to the risk of developing drug dependence, possible accumulation of bromide in the body, and bromide poisoning.

Use during pregnancy or breastfeeding.

Contraindicated during pregnancy and breastfeeding.

Ability to affect reaction rate when driving or operating machinery.

Valocordin® impairs reaction speed. Patients taking this medication should refrain from potentially hazardous activities requiring heightened attention and increased speed of mental and motor reactions.

Dosage and Administration

For adult use only.

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

The usual dosage is 22–30 drops three times daily. If the patient suffers from insomnia, the dose may be increased to 45 drops.

The duration of treatment should be determined by a physician.

Children

There is no experience with the use of this medication in children.

Overdose

Symptoms

Acute (mild to moderate) barbiturate poisoning:

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

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

Acute severe poisoning:

Deep coma associated with tissue hypoxia, shallow respiration—initially rapid, later becoming slow, tachycardia, cardiac arrhythmia, low blood pressure, bradycardia, vascular collapse, diminished or absent reflexes, nystagmus, headache, nausea, weakness, cardiac dysfunction, hypothermia, 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, upper respiratory tract infections, acne, or purpura.

Treatment

Cases of acute poisoning with Valocordin® should be treated in the same manner as poisoning with other sedatives 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 is necessary (10 g of activated charcoal and sodium sulfate powder should be introduced 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.

Central nervous system: asthenia, weakness, impaired motor coordination, nystagmus, ataxia, hallucinations, paradoxical excitation, insomnia (in elderly patients), decreased concentration, fatigue, slowed reaction time, headache, cognitive disturbances. In individual cases, somnolence and mild dizziness, confusion may occur.

Musculoskeletal system: with prolonged use of products containing phenobarbital, there is a risk of impaired osteogenesis and development of rickets. Cases of decreased bone mineral density, osteopenia, osteoporosis, and fractures have been reported in patients receiving long-term phenobarbital therapy. The mechanism by which phenobarbital affects bone tissue metabolism has not been established.

Gastrointestinal tract: nausea, vomiting, constipation, epigastric fullness; with prolonged use – impaired liver function.

Hematopoietic system: agranulocytosis, megaloblastic anemia, thrombocytopenia, anemia.

Cardiovascular system: decreased arterial pressure, bradycardia.

Very rare: allergic reactions, including angioneurotic edema, dyspnea, facial swelling, rash, pruritus.

Serious skin adverse reactions reported with phenobarbital use: Stevens-Johnson syndrome and toxic epidermal necrolysis, urticaria, Lyell's syndrome, rhinitis, conjunctivitis, acne, purpura, lacrimation.

Shelf life.

3 years.

Storage conditions.

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

Keep out of reach of children.

Incompatibility.

Not known.

Packaging.

Dropper bottle of 20 ml or 50 ml, 1 dropper bottle per cardboard box.

Supply category. Over-the-counter – 20 ml, prescription only – 50 ml.

Manufacturer.

Krewel Meuselbach GmbH.

Manufacturer's address and place of business.

Krewelstrasse 2, 53783 Eitorf, Germany.