Corvalol®

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

Composition:

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

1 capsule contains ethyl ether of α-bromoisovaleric acid 11 mg, phenobarbital 10.2 mg, peppermint oil (Mentha oil) 0.8 mg;

Excipients: colloidal anhydrous silicon dioxide, glycerol monostearate, sunflower oil;

Capsule shell composition: gelatin (150 bloom), glycerin, methylparaben (E 218), propylparaben (E 216), titanium dioxide (E 171), purified water.

Pharmaceutical form. Soft capsules.

Main physicochemical properties: soft oval-shaped gelatin capsules of white or almost white color. The capsule contents — oily suspension with a characteristic 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 its constituent components.

The ethyl ether of α-bromoisovaleric acid exerts reflex sedative and spasmolytic effects due to stimulation primarily of sensory nerve receptors in the mucous membranes of 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 the activating influence of the reticular formation centers of the midbrain and medulla oblongata on the cerebral cortex, thereby reducing excitatory impulses directed toward the cerebral cortex and subcortical structures. This reduction in activating input results in sedative or hypnotic effects, depending on the dose. Corvalol® reduces the excitatory influence 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 high amount of essential oils, including approximately 50% menthol and 4–9% menthol esters. These components can stimulate sensory "cold" nerve receptors in the mucous membranes of the oral cavity, inducing reflex dilation primarily of heart and cerebral blood vessels, relieving spasms of smooth muscle, and exerting sedative and mild choleretic effects. Peppermint oil also has antiseptic and spasmolytic properties and relieves flatulence. By stimulating receptors in the mucous membranes of the stomach and intestines, it enhances intestinal peristalsis.

Pharmacokinetics.

After oral administration, the effect develops within 15 minutes.

The duration of action lasts 3–6 hours. In individuals previously treated with barbituric acid derivatives, the 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® 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 hypertensive disease and vegetative-vascular dystonia;
• mild coronary vessel spasms, 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;
• 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 and obstructive syndrome.

Interaction with other medicinal products and other types of interactions.

Central nervous system depressants enhance the effect of Corvalol®; mutual potentiation of sedative and hypnotic effects is possible, which may be accompanied by respiratory depression. The effect of the drug is enhanced when used concomitantly with valproic acid preparations. Alcohol enhances the drug's effect 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, and 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, antifungal agents (azole group), griseofulvin, glucocorticoids, and oral contraceptives due to possible reduction in efficacy of these 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. Prolonged concurrent use with nonsteroidal anti-inflammatory drugs increases the risk of gastric ulceration and bleeding. Simultaneous administration of drugs containing phenobarbital and zidovudine enhances the toxicity of both agents. The drug increases methotrexate toxicity.

Special precautions for use.

During treatment with Corvalol®, activities requiring increased attention and rapid psychomotor reactions should be avoided.

Concomitant use of alcoholic beverages should be avoided.

The presence of phenobarbital in the medicinal product may cause Stevens–Johnson syndrome and Lyell's syndrome, most likely 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 must be discontinued.

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 improved by prompt withdrawal of the suspected drug.

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

Prolonged use of the medicinal product is not recommended due to the risk of drug dependence, bromide accumulation in the body, and bromide poisoning.

If chest pain does not subside after taking the drug, 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.

Corvalol® contains methylparaben and propylparaben, which may cause allergic reactions (possibly delayed).

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 in its composition, which may cause impaired coordination, slowed psychomotor reactions, drowsiness, and dizziness during treatment. Therefore, activities requiring high attention, including driving and operating machinery, should be avoided.

Dosage and Administration.

Corvalol®, capsules, should be taken orally, regardless of food intake, 2–3 times daily, 1–2 capsules per dose.

If necessary (in cases of pronounced tachycardia and coronary vessel spasm), the single dose may be increased to 3 capsules.

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 medication in children; therefore, the drug should not be used in pediatric practice.

Overdose.

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

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

Severe acute poisoning: deep coma accompanied by tissue hypoxia, shallow breathing, initially rapid and later slowed respiration, tachycardia, cardiac arrhythmia, low blood pressure, bradycardia, vascular collapse, diminished or absent reflexes, nystagmus, headache, nausea, weakness, cardiac disturbances, decreased body temperature, slowed pulse, reduced urine output.

If left untreated, poisoning may result in death 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 bromism, characterized by the following symptoms: confusion, ataxia, apathy, depressive mood, conjunctivitis, cold-like symptoms, acne, or purpura.

Treatment.

Cases of acute poisoning should be managed as 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 is managed by artificial ventilation; shock is treated with plasma and plasma substitutes. If a significant amount of time has passed since ingestion, gastric lavage is indicated (10 g of activated charcoal powder and sodium sulfate are 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 bromide poisoning: elimination of bromide ions from the body can be accelerated by administering a large volume of sodium chloride solution along with diuretic agents.

In case of hypersensitivity reactions, desensitizing agents should be prescribed.

Adverse reactions.

Corvalolum® 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 angioedema, dyspnea, facial swelling;

Skin and mucous membranes: allergic reactions, including skin rash, pruritus. 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: dyspnea;

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, bromism may develop. Symptoms include: 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.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of drug efficacy via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

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.

10 capsules in a blister. 1 or 3 blisters per carton.

Availability. Over-the-counter.

Manufacturer.

JSC "Farmak".

Manufacturer's location and address of business activity.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.