Corvalol-darnitsa®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Korvalol-Darnytsia®

Composition:

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

1 ml of the preparation contains: ethyl ether of α-bromoisovaleric acid, recalculated to 100 % substance – 20.0 mg, phenobarbital – 18.26 mg, peppermint oil – 1.42 mg;

Excipients: ethanol 96 %, potassium isovalerate, purified water.

Pharmaceutical form. Oral solution (drops).

Main physicochemical properties: colourless clear liquid with a characteristic ethereal odour.

Pharmacotherapeutic group. Hypnotics and sedatives. Barbiturates in combination with other medicinal substances. ATC code N05C B02.

Pharmacological properties.

Pharmacodynamics.

Corvalol-Darnytsia® is a sedative and spasmolytic agent, whose action is determined by the components included in its formulation.

The ethyl ether of α-bromoisovaleric acid exerts a reflex sedative and spasmolytic effect, caused by stimulation primarily of receptors in the oral cavity and nasopharynx, reduction of reflex excitability in central parts of the nervous system, enhancement of inhibitory processes in neurons of the cerebral cortex and subcortical structures, as well as reduction of activity in central vasomotor centers and direct local spasmolytic action on smooth muscle of blood vessels.

Phenobarbital suppresses activating influences from the reticular formation centers of the midbrain and medulla oblongata on the cerebral cortex, thereby reducing streams of excitatory impulses to the cerebral cortex and subcortical structures. Reduction of activating influences results, depending on the dose, in sedative, tranquilizing, or hypnotic effects. Corvalol-Darnytsia® reduces excitatory influences on vasomotor centers and on coronary and peripheral blood vessels, thereby lowering overall arterial pressure, relieving and preventing vascular spasms, especially in the heart.

Peppermint oil contains a large amount of essential oils, among which approximately 50% is menthol and 4–9% are menthol esters. These components can stimulate "cold" receptors in the oral cavity and reflexively dilate primarily coronary and cerebral blood vessels, relieve spasms of smooth musculature, exert a sedative effect, and provide mild choleretic action. Peppermint oil also exerts antiseptic and spasmolytic effects and has the ability to reduce flatulence. By stimulating receptors in the mucosa of the stomach and intestine, it enhances intestinal peristalsis.

Pharmacokinetics.

When taken orally, absorption begins in the sublingual area, and bioavailability of the components is high (approximately 60–80%). The effect develops particularly rapidly (within 5–10 minutes) when the medication is held in the mouth (sublingual absorption) or administered on a sugar cube. The onset of action occurs within 15–45 minutes and lasts for 3–6 hours. In individuals previously exposed to barbituric acid drugs, duration of action is shortened due to accelerated hepatic metabolism of phenobarbital, as barbiturates induce liver enzymes. In elderly individuals and patients with liver cirrhosis, metabolism of Corvalol-Darnytsia® is reduced, resulting in prolonged elimination half-life, which necessitates dose reduction and extended intervals between doses.

Clinical characteristics.

Indications.

• Neuroses with increased irritability.
• Insomnia.
• As part of combination therapy for hypertensive disease and vegetative-vascular dystonia.
• Mild coronary vessel spasms, tachycardia.
• Intestinal spasms (as a spasmolytic agent).

Contraindications.

• Hypersensitivity to the components of the medicinal product or to bromine.
• Severe impairment of liver and/or kidney function.
• Acute hepatic porphyria.
• Severe heart failure.
• Medicinal products containing phenobarbital are contraindicated in marked arterial hypotension, acute myocardial infarction, diabetes mellitus, depression and depressive disorders with suicidal tendencies, myasthenia gravis, alcoholism, drug or medication dependence (including in medical history), respiratory disorders with dyspnea, obstructive syndrome.
• Pregnancy and breastfeeding period.
• Age under 18 years.

Interaction with other medicinal products and other types of interactions.

Concomitant use with drugs that depress the central nervous system (neuroleptics and tranquilizers) enhances the sedative and hypnotic effect of the medicinal product Korvalol-Darnitsa®, which may be accompanied by respiratory depression; whereas concomitant use with central nervous system stimulants reduces the effect of each component.

The effect of the medicinal product is enhanced when used concomitantly with valproic acid preparations and alcohol, which may increase its toxicity.

Since phenobarbital induces liver enzymes, concomitant use with certain medicinal products metabolized by liver enzymes (including indirect anticoagulants, coumarin derivatives, antibiotics, sulfonamides, griseofulvin, glucocorticoids, oral contraceptives, cardiac glycosides, antimicrobial, antiviral, antifungal agents (azole group), antiepileptic, anticonvulsant, psychotropic, oral hypoglycemic, hormonal, immunosuppressive, cytostatic, antiarrhythmic, antihypertensive drugs) is undesirable due to reduced efficacy resulting from increased metabolism.

Phenobarbital reduces the effect of paracetamol, indirect anticoagulants, metronidazole, tricyclic antidepressants, salicylates, and cardiac glycosides (digoxin). Phenobarbital enhances the effect of analgesics, anesthetics, anesthetic agents, neuroleptics, tranquilizers, and hypnotics. Possible influence on blood concentrations of phenytoin, as well as carbamazepine and clonazepam, may occur.

Concomitant use of Korvalol-Darnitsa® (due to phenobarbital content) with lamotrigine, thyroid hormones, doxycycline, and chloramphenicol is not recommended due to possible reduction of their efficacy.

Monoamine oxidase inhibitors (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. Prolonged concomitant use with nonsteroidal anti-inflammatory drugs increases the risk of gastric ulceration and bleeding. Concomitant use of medicinal products containing phenobarbital with zidovudine enhances the toxicity of both agents.

Korvalol-Darnitsa® increases the toxicity of methotrexate.

Special precautions for use.

During treatment, activities requiring increased attention and quick psychomotor reactions should be avoided.

Alcoholic beverages should be avoided during medication intake due to the potential increase in its toxicity.

The presence of phenobarbital in the drug composition may cause Stevens-Johnson syndrome and Lyell's syndrome, most commonly during the first weeks of treatment.

Patients should be warned about the signs and symptoms, and skin reactions should be closely monitored. If symptoms of Stevens-Johnson syndrome or toxic epidermal necrolysis occur (e.g., progressive skin rashes, often with blisters, and mucosal damage), treatment should be discontinued.

The best outcomes in treating Stevens-Johnson syndrome or toxic epidermal necrolysis are observed with early diagnosis and immediate discontinuation of any medication that may have caused these symptoms.

If a patient has developed Stevens-Johnson syndrome or toxic epidermal necrolysis while using Corvalol-Darnitsia®, this medication should not be used again in such patients.

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

If chest pain does not subside after taking the medication, medical advice should be sought to rule out acute coronary syndrome. Use with caution in severe arterial hypotension, hyperkinesia, hyperthyroidism, adrenal insufficiency, decompensated heart failure, acute and chronic pain syndromes, and acute intoxication with medicinal products.

Important information about excipients.

This medicinal product contains 56% v/v ethanol (alcohol).

The minimum dose of the drug (15 drops) contains 254 mg of ethanol, equivalent to 6.4 ml of beer or 2.7 ml of wine. Harmful for patients suffering from alcoholism. Caution should be exercised when administering to patients with liver disease or epilepsy.

This medicinal product contains potassium compounds. Caution is advised in patients with impaired kidney function or those on a potassium-controlled diet.

Use during pregnancy or breastfeeding.

Do not use during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Corvalol-Darnitsia® contains phenobarbital and ethanol in its composition and therefore may cause impaired coordination, reduced psychomotor reaction speed, drowsiness, and dizziness during treatment. For this reason, activities requiring high concentration, including driving vehicles or operating machinery, should be avoided.

Method of Administration and Dosage.

Corvalol-Darnytsia® should be taken orally regardless of food intake, 2–3 times daily, 15–30 drops diluted with water or administered on a piece of sugar. If necessary (in cases of pronounced tachycardia or coronary vessel spasm), the single dose may be increased to 40–50 drops.

The duration of treatment is determined by the physician depending on the clinical response and tolerability.

Children.

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

Overdose.

Overdose is possible with frequent or prolonged use of the medicinal product due to accumulation of its components. Long-term and continuous use may lead to dependence, withdrawal syndrome, and psychomotor agitation.

Symptoms.

Acute (mild to moderate severity) barbiturate poisoning: dizziness, fatigue, and even deep sleep from which the patient is very difficult to awaken.

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

Acute severe poisoning: respiratory depression, up to respiratory arrest; central nervous system depression, progressing to coma; hypoxia, shallow breathing (initially rapid, later slowed), tachycardia, cardiovascular depression including arrhythmias; decreased arterial blood pressure, up to collapse-like state, bradycardia, slowed pulse, diminished or absent reflexes, nystagmus, headache, nausea, weakness, hypothermia, decreased urine output.

Prolonged use of medicinal products containing bromide may lead to bromism, characterized by the following symptoms: confusion, ataxia, apathy, depressive mood, conjunctivitis, upper respiratory tract infections, acne, or purpura.

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

Treatment.

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

In case of hypersensitivity reactions, administer desensitizing agents.

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

Adverse Reactions

Corvalol-Darnytsia® is generally well tolerated. In individual cases, the following adverse effects may occur:

Eye disorders: conjunctivitis, lacrimation;

Respiratory, thoracic and mediastinal disorders: dyspnea;

Gastrointestinal disorders: constipation, feeling of heaviness in the epigastric region, nausea, vomiting; with prolonged use – liver function disturbances;

Nervous system disorders: asthenia, weakness, ataxia, impaired motor coordination, nystagmus, hallucinations, paradoxical excitation, fatigue, slowed reaction time, headache, cognitive disturbances, confusion, drowsiness, insomnia (in elderly patients), mild dizziness, decreased concentration;

Cardiac and vascular disorders: bradycardia, arterial hypotension;

Blood and lymphatic system disorders: anemia, megaloblastic anemia, thrombocytopenia, agranulocytosis;

Immune system disorders: hypersensitivity reactions, including angioneurotic edema, facial swelling, rhinitis;

Skin and subcutaneous tissue disorders: allergic reactions, including skin rash, pruritus. Serious skin adverse reactions reported with phenobarbital use: urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), acne, purpura;

Musculoskeletal and connective tissue disorders: with prolonged use of products containing phenobarbital, there is a risk of impaired osteogenesis. Cases of decreased bone mineral density, osteopenia, osteoporosis, and fractures have been reported in patients receiving long-term phenobarbital therapy. The mechanism of phenobarbital's effect on bone metabolism is unknown.

With prolonged use, bromide poisoning is possible. Symptoms: central nervous system depression, depression, ataxia, apathy, rhinitis, conjunctivitis, acne or purpura, lacrimation, confusion.

These phenomena resolve upon dose reduction or discontinuation of the medicinal product.

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions after medicinal product registration is an important procedure. It allows continuous monitoring of the benefit-risk ratio of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national reporting system.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze. Keep out of reach of children.

Packaging.

25 ml or 40 ml in a bottle; 1 bottle per carton.

Dispensing category.

25 ml bottle – available without prescription.

40 ml bottle – prescription only.

Manufacturer: JSC "Pharmaceutical Company "Darnitsya".

Manufacturer's address and location of business activity:

13, Borispilska Street, Kyiv, 02093, Ukraine.