Corvalazid

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT CORVALAZID (CORVALAZID)

Composition:

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

1 ml of the preparation contains ethyl ether of α-bromoisovaleric acid (calculated as 100% content) 20.0 mg; phenobarbital (calculated as 100% content) 18.26 mg; peppermint oil (Menthaoil) 1.42 mg;

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

Pharmaceutical form. Oral drops.

Main physicochemical characteristics: clear, colorless liquid with a characteristic aromatic odor.

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

Pharmacological properties.

Pharmacodynamics.

Corvalazid is a sedative and spasmolytic agent, whose action is determined by the components included in its formulation.

Ethyl ether of α-bromoisovaleric acid exerts a reflex sedative and spasmolytic effect due to stimulation primarily of oral and nasopharyngeal receptors, reduction of reflex excitability in central nervous system centers, enhancement of inhibitory processes in cortical and subcortical neurons of the brain, as well as reduction in 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 the flow of excitatory impulses to the cerebral cortex and subcortical structures. Reduction of these activating influences, depending on the dose, produces sedative, tranquilizing, or hypnotic effects. Corvalazid reduces excitatory influences on vasomotor centers and on coronary and peripheral blood vessels, thereby lowering general arterial pressure and relieving or preventing vascular spasms, especially in the heart.

Peppermint oil contains a large amount of essential oils, including approximately 50% menthol and 4–9% menthol 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, and exert a sedative and mild choleretic effect. Peppermint oil has antiseptic and spasmolytic properties and may help relieve flatulence. By stimulating receptors of the gastric and intestinal mucosa, it enhances intestinal peristalsis.

Pharmacokinetics.

After oral administration, absorption begins in the sublingual area; bioavailability of the components is high (approximately 60–80%). The effect develops particularly rapidly (within 5–10 minutes) when the tablet 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.

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 alkaline nature of urine. Approximately 30% of phenobarbital is excreted unchanged in urine, while only a small fraction is oxidized in the liver.

With prolonged use, the active substance accumulates in blood plasma, and hepatic enzyme induction also occurs. As a result of this induction, the metabolism of phenobarbital and other drugs is accelerated.

Bromide is eliminated from the body very slowly. With prolonged drug use, bromide accumulates in the central nervous system, potentially leading to chronic bromide intoxication.

In patients 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 patients and those with liver cirrhosis, metabolism of Corvalazid is reduced, resulting in prolonged elimination half-life, which necessitates dose reduction and longer intervals between drug administrations.

Clinical characteristics.

Indications.

Functional disorders of the cardiovascular system; sleep onset disturbances, insomnia; in complex therapy of hypertension and vegetative-vascular dystonia; pronounced coronary vessel spasms, tachycardia; neuroses accompanied by increased irritability and feelings of fear, psychosomatic anxiety, excited states with pronounced vegetative manifestations; intestinal spasms caused by neurovegetative disorders (as a spasmolytic agent).

Contraindications.

• Hypersensitivity to the components of the drug and bromine.
• Severe impairment of liver and/or kidney function.
• Acute hepatic porphyria.
• Severe heart failure.
• 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, alcoholism, narcotic and drug dependence (including in medical history), respiratory diseases with dyspnea, obstructive syndrome.
• Pregnancy and breastfeeding period.
• Pediatric age (under 18 years).

Interaction with other medicinal products and other forms of interaction.

Central nervous system depressants enhance the effect of Corvalazid; mutual enhancement 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 effect of Corvalazid and may increase its toxicity.

Phenobarbital induces liver enzymes and, accordingly, may accelerate the metabolism of certain medicinal products metabolized by liver enzymes (e.g., coumarin derivatives, antibiotics, sulfonamides, indirect anticoagulants, cardiac glycosides, antimicrobial, antiviral, antifungal, antiepileptic, anticonvulsant, psychotropic, oral hypoglycemic, hormonal, immunosuppressive, cytostatic, antiarrhythmic, antihypertensive drugs).

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, and tranquilizers. Corvalazid enhances the effect of antihypertensive drugs, the sedative effect of psychotropic agents, opioid analgesics, and anesthetic agents. Concurrent use with neurotropic and other agents that depress the central nervous system causes drowsiness.

Possible influence on blood concentration of phenytoin, as well as carbamazepine and clonazepam.

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

Monoamine oxidase inhibitors (MAOIs) prolong the effect of phenobarbital. Rifampicin may reduce the effect of phenobarbital. When used with gold preparations, the risk of kidney damage increases. With prolonged concurrent use of nonsteroidal anti-inflammatory drugs, there is a risk of gastric ulcer formation and bleeding. Concurrent use of medicinal products containing phenobarbital with zidovudine enhances the toxicity of both drugs. The drug increases methotrexate toxicity.

Special precautions for use.

During treatment with Corvalazid, it is not recommended to engage in activities requiring increased attention and rapid psychomotor reactions.

Concomitant use of alcohol should be avoided.

Due to the presence of phenobarbital in the medicinal product, there is a risk of developing toxic epidermal necrolysis and Stevens–Johnson syndrome, which is most likely during the first weeks of treatment. Skin reactions (e.g., progressive skin rash, often with blisters, mucosal lesions) should be closely monitored during treatment. If any of the above symptoms occur, treatment must 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. A better prognosis is associated with long-term discontinuation of the suspected medication.

If Stevens–Johnson syndrome or toxic epidermal necrolysis develops after taking the medicinal product, this drug must never be used again.

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

If chest pain does not subside after taking Corvalazid, medical advice should be sought to rule out acute coronary syndrome.

Use with caution in patients with arterial hypotension, persistent headache, hyperkinesia, hyperthyroidism, adrenal insufficiency, uncompensated heart failure, acute and chronic pain syndromes, and acute intoxication with medicinal products.

Harmful for patients with alcoholism. Caution is required when administering to patients with liver diseases and epilepsy.

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

Use during pregnancy or breastfeeding.

Do not use during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

The medicinal product contains phenobarbital and ethanol in its composition and may therefore cause impaired coordination, slowed psychomotor reactions, drowsiness, and dizziness during treatment. For this reason, it is not recommended to engage in activities requiring high concentration, including driving vehicles or operating machinery.

Dosage and Administration

Corvalazid is taken orally, independent of food intake, 2–3 times daily, 15–30 drops per dose, diluted with water or administered on a sugar cube. If necessary (pronounced tachycardia, coronary vessel spasm), the single dose may be increased to 40–50 drops. For insomnia and difficulty falling asleep, the single nighttime dose may be increased to 30 drops, taken 30 minutes before bedtime.

Children.

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

Overdose.

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.

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 rash.

Acute severe poisoning:

deep coma accompanied by tissue hypoxia, shallow breathing (initially rapid, 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, poisoning may result in death due to circulatory failure, respiratory paralysis, or pulmonary edema.

With prolonged use, bromide poisoning is possible.

Symptoms: central nervous system depression, confusion, depression, ataxia, apathy, rhinitis, cold-like symptoms, conjunctivitis, acne, or purpura, lacrimation.

Treatment.

Acute Corvalazid poisoning should be treated 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 require stabilization and normalization. Respiratory insufficiency is managed by artificial ventilation; shock is treated with plasma and plasma substitutes infusion. If a significant amount of time has passed since ingestion, gastric lavage is indicated (10 g of activated charcoal powder and sodium sulfate are introduced into the stomach). To accelerate barbiturate elimination, 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 administration of a large volume of sodium chloride solution along with saluretic agents.

In case of hypersensitivity reactions, desensitizing medications should be administered.

Side effects.

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 (≥1/10,000, <1/1000), very rare (<1/10,000), frequency not known (cannot be estimated based on available data).

With prolonged use, bromine poisoning is possible, characterized by the following symptoms: central nervous system depression, depressive mood, confusion, ataxia, apathy, conjunctivitis, rhinitis, lacrimation, acne, or purpura.

These phenomena resolve upon dose reduction or discontinuation of the drug.

Shelf life. 2 years and 6 months.

Storage conditions.

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

Packaging. 25 ml in a bottle in a carton.

Dispensing category. Over-the-counter.

Manufacturer/Applicant.

LLC "DKP "Pharmaceutical Factory".

Address of manufacturer and location of business activity/applicant's address.

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