CORVALOL

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CORVALOL® (CorvalolUM®)

Composition:

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

1 ml of solution (26 drops) contains ethyl ether of α-bromoisovaleric acid, recalculated to 100 % substance ‒ 20 mg, phenobarbital ‒ 18.26 mg, peppermint oil (Mentha oil) ‒ 1.42 mg;

Excipients: stabilizer, ethanol 96 %, purified water.

Pharmaceutical form. Oral drops.

Main physicochemical properties: clear, colorless liquid with a specific odor.

Pharmacotherapeutic group.

Hypnotics and sedatives. Barbiturates in combination with other components. ATC code N05C B02.

Pharmacological properties.

Pharmacodynamics.

Corvalol® is a sedative and spasmolytic agent whose effects are determined by the components contained in its formulation.

The ethyl ether of α-bromoisovaleric acid exerts a reflex sedative and spasmolytic effect due to 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 cortical and subcortical neurons of the brain, as well as decreased activity of 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 excitatory inputs to the cerebral cortex and subcortical structures. Reduction of these activating influences results in sedative, tranquilizing, or hypnotic effects, depending on the dose. Corvalol® reduces excitatory influences on vasomotor centers and on coronary and peripheral blood vessels, thereby lowering overall arterial pressure and relieving or preventing vascular spasms, particularly in the heart.

Peppermint oil contains a large amount of essential oils, including approximately 50% menthol and 4–9% menthyl esters. These components can stimulate "cold" receptors in the oral cavity and reflexively dilate primarily cardiac and cerebral blood vessels, relieve spasms of smooth muscle, produce a calming effect, and exert mild choleretic action. Peppermint oil possesses antiseptic and spasmolytic properties and is capable of reducing flatulence. By stimulating receptors in the gastric and intestinal mucosa, it enhances intestinal peristalsis.

Pharmacokinetics.

When administered orally, absorption begins already 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 taken 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 derivatives, duration of action is shortened due to accelerated hepatic metabolism of phenobarbital, as barbiturates induce liver enzymes. In elderly individuals and in patients with liver cirrhosis, metabolism of Corvalol® is reduced, resulting in prolonged elimination half-life, which necessitates dose reduction and longer intervals between doses.

Clinical characteristics.

Indications.

• Neuroses with increased irritability;
• insomnia;
• as part of combination therapy for hypertension and vegetative-vascular dystonia;
• mild spasms of coronary vessels, tachycardia;
• intestinal spasms caused by neurovegetative disorders (as a spasmolytic agent).

Contraindications.

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

Interaction with other medicinal products and other types of interactions.

Central nervous system depressants enhance the effect of Corvalol®; mutual enhancement of sedative and hypnotic effects is possible, which may be accompanied by respiratory depression. The drug's effect is enhanced when used concomitantly with valproic acid preparations. Alcohol enhances the effect of the drug and may increase its toxicity.

Phenobarbital induces liver enzymes and thus may accelerate the metabolism of certain drugs metabolized by liver enzymes (e.g., coumarin derivatives, antibiotics, sulfonamides, antivirals, oral hypoglycemics, hormonal, immunosuppressive, cytostatic, antiarrhythmic, antihypertensive agents). Phenobarbital reduces the effect of paracetamol, indirect anticoagulants, metronidazole, tricyclic antidepressants, salicylates, cardiac glycosides (digoxin). Phenobarbital enhances the effect of analgesics, anesthetics, anesthetic agents, neuroleptics, tranquilizers. Possible influence on blood concentrations of phenytoin, as well as carbamazepine and clonazepam.

Unfavorable interaction of Corvalol® (due to phenobarbital content) with antiepileptic drugs (lamotrigine), thyroid hormones, doxycycline, chloramphenicol, antifungals (azole group), griseofulvin, glucocorticoids, oral contraceptives due to possible reduction in efficacy of the above-mentioned drugs.

Phenobarbital enhances the effect of analgesics and local anesthetics.

Monoamine oxidase inhibitors (MAOIs) 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 simultaneous use with nonsteroidal anti-inflammatory drugs, there is a risk of gastric ulceration and bleeding. Simultaneous administration of preparations containing phenobarbital and zidovudine enhances the toxicity of both drugs. The drug increases the toxicity of methotrexate.

Special precautions for use

During treatment with this medicinal product, activities requiring increased attention, quick mental and motor reactions should be avoided.

Concomitant use of alcoholic beverages should be avoided.

The presence of phenobarbital in the formulation may lead to the development of Stevens-Johnson syndrome and Lyell's syndrome, most likely during the first weeks of treatment.

Patients should be informed 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 must be discontinued immediately.

The best outcomes in treating Stevens-Johnson syndrome or toxic epidermal necrolysis have been observed with early diagnosis and immediate discontinuation of any suspected causative drug. Improved prognosis is associated with prompt withdrawal of the suspected medication.

If a patient has developed Stevens-Johnson syndrome or toxic epidermal necrolysis while taking Corvalol®, the medication must never be used again in such patients.

Prolonged use of the medication 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.

This medicinal product contains 56 vol.% ethanol (alcohol).

The minimum dose (15 drops) contains 254 mg of ethanol, equivalent to 6.4 ml of beer or 2.7 ml of wine. Potentially harmful for patients suffering from alcoholism. Should be used with caution in patients with liver disease and in those with epilepsy.

Use during pregnancy or breastfeeding

Do not use during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery

Corvalol® contains phenobarbital and ethanol in its formulation and may therefore cause impaired coordination, slowed psychomotor reactions, drowsiness, and dizziness during treatment. For this reason, activities requiring high concentration, including driving or operating machinery, should be avoided.

Dosage and Administration.

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

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

Children.

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

Overdose.

Symptoms.

Acute (mild to moderate severity) barbiturate poisoning: dizziness, fatigue, even deep sleep from which the patient cannot be awakened.

Hypersensitivity reactions may occur: angioneurotic edema, urticaria, itching, rash.

Acute severe poisoning: deep coma accompanied by tissue hypoxia, superficial respiration initially rapid and then slowed, tachycardia, cardiac arrhythmia, low blood pressure, bradycardia, vascular collapse, diminished or absent reflexes, nystagmus, headache, nausea, weakness, cardiac dysfunction, decreased body temperature, slowed pulse, reduced diuresis.

If untreated, fatal outcome may occur due to circulatory failure, respiratory paralysis, or pulmonary edema.

Overdose may occur with frequent or prolonged use of the drug due to accumulation of its components. Prolonged and continuous use may lead to dependence, withdrawal syndrome, and psychomotor agitation.

Long-term use of drugs containing bromine may lead to bromine poisoning, characterized by the following symptoms: confusion, ataxia, apathy, depressive mood, conjunctivitis, cold-like symptoms, acne, or purpura.

Treatment.

Cases of acute poisoning 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 is managed by artificial ventilation; shock is treated by infusion of plasma and plasma substitutes. If a significant time has passed since ingestion, gastric lavage should be performed (10 g of activated charcoal and sodium sulfate powder administered into the stomach). To accelerate the elimination of barbiturates from the body, forced alkaline diuresis, hemodialysis, and/or hemoperfusion may be performed.

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

In case of hypersensitivity reactions, administer desensitizing medications.

Adverse reactions.

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

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

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

Immune system: hypersensitivity reactions, including angioneurotic edema, difficulty breathing, facial swelling;

Skin and mucous membranes: allergic reactions, including skin rash, itching. Serious skin adverse reactions reported with phenobarbital use: Stevens–Johnson syndrome and toxic epidermal necrolysis (Lyell’s syndrome), urticaria, rhinitis, conjunctivitis, acne, purpura, lacrimation;

Blood system: megaloblastic anemia, anemia, thrombocytopenia, agranulocytosis;

Respiratory system: difficulty breathing;

Cardiovascular system: bradycardia, arterial hypotension;

Musculoskeletal system: with prolonged use of agents 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 by which phenobarbital affects bone metabolism is unknown.

With prolonged use, symptoms of bromine poisoning may develop. 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 drug.

Shelf life.

2 years and 6 months.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

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

Packaging.

25 ml or 50 ml in a bottle. 1 bottle per carton.

Prescription status.

25 ml bottle – over-the-counter.

50 ml bottle – prescription only.

Manufacturer: JSC "Farmak".

Manufacturer's location and address of operations.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.