Brinerdin (Tablets) Instructions for Use

Marketing Authorization Holder

Krka, D.D. (Slovenia)

ATC Code

C02LA51 (Reserpine and diuretics in combination with other drugs)

Active Substances

Reserpine (Rec.INN registered by WHO)

Clopamide (Rec.INN registered by WHO)

Dihydroergocristine (DCF adopted for use in France)

Dosage Form

Brinerdin

Film-coated tablets, 500 mcg+5 mg+100 mcg: 20 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets dark pink in color, round, biconvex, smooth, shiny.

Excipients: lactose, hydrogenated peanut oil, sucrose, microcrystalline cellulose, povidone, stearic acid, talc, corn starch, titanium dioxide, macrogol, cetyl alcohol, polyethylene glycol, colloidal silicon dioxide, iron oxide (E172).

10 pcs. – blisters (2) – cardboard boxes.

Clinical-Pharmacological Group

Antihypertensive drug

Pharmacotherapeutic Group

Antihypertensive agent, combination (alpha-adrenergic blocker + diuretic + sympatholytic)

Pharmacological Action

Combined antihypertensive agent.

Reserpine is a sympatholytic; penetrating into the presynaptic endings of postganglionic sympathetic fibers, it releases norepinephrine from vesicles while disrupting its reuptake and enhancing the inactivation process by MAO. It causes depletion of neurotransmitter stores and a persistent decrease in blood pressure. It helps reduce the concentration of dopamine, serotonin, and other neurotransmitters in neurons, exerting an antipsychotic effect. It weakens the influence of sympathetic innervation on the cardiovascular system, reduces heart rate and total peripheral vascular resistance; preserves the activity of the parasympathetic nervous system; deepens and enhances physiological sleep, inhibits interoceptive reflexes. It increases gastrointestinal motility, increases the production of hydrochloric acid in the stomach; slows down metabolic processes in the body; slows and deepens respiratory movements, causes miosis, hypothermia; reduces the intensity of metabolism. It has a positive effect on lipid and protein metabolism in patients with arterial hypertension and coronary atherosclerosis; increases renal blood flow, enhances glomerular filtration.

Clopamide is a medium-strength non-thiazide sulfonamide diuretic; it blocks sodium reabsorption at the level of the cortical segment of the loop of Henle, excreting sodium, potassium, chlorides, and water.

Dihydroergocristine is a dihydrogenated ergot alkaloid; it blocks alpha-adrenergic receptors, causes vasodilation, and reduces total peripheral vascular resistance.

The antihypertensive effect of this combination surpasses the antihypertensive effect of each component individually and the action of any combination of 2 components; the onset of action is on days 4-7, a persistent antihypertensive effect is achieved after 1-4 weeks.

Pharmacokinetics

Reserpine is approximately 30-40% absorbed, Clopamide – about 90%, and Dihydroergocristine – less than 25%. C_max in blood plasma is reached respectively: for reserpine – 1-3 hours, for clopamide – about 2 hours, for dihydroergocristine – about 1 hour.

Binding to plasma proteins: for reserpine – does not bind, Clopamide – about 46%, Dihydroergocristine – about 68%. Reserpine and Dihydroergocristine cross the blood-brain barrier and the placental barrier.

Reserpine and Dihydroergocristine are intensively metabolized in the liver to inactive metabolites. Clopamide does not undergo significant metabolism in the liver.

T_1/2 is long due to the presence of reserpine, for which T_1/2 in the first phase is 4.5 hours, and in the second phase is about 271 hours. The route of elimination is different for individual components: Reserpine and Dihydroergocristine – inactive metabolites are excreted in urine and feces, Clopamide – mainly by the kidneys.

Indications

Arterial hypertension.

ICD codes

Dosage Regimen

Administer orally. The initial adult dosage is one tablet per day, taken as a single dose.

Take the tablet at the same time each day, preferably in the morning with or after a meal to minimize potential gastrointestinal discomfort.

If the antihypertensive effect is insufficient after 1-4 weeks of therapy, the dosage may be increased to two tablets per day.

Divide the two-tablet dose, administering one tablet in the morning and one tablet in the evening.

Do not exceed the maximum recommended daily dose of two tablets.

The onset of the antihypertensive effect typically occurs within 4 to 7 days of initiating treatment.

A persistent therapeutic effect is usually achieved after 1 to 4 weeks of continuous therapy.

For elderly patients, use the same initial dosage, but exercise caution and monitor closely for orthostatic hypotension and electrolyte imbalances.

The drug is contraindicated in children and adolescents under 18 years of age.

Regularly monitor blood pressure, serum electrolytes, and kidney function during long-term treatment.

Adverse Reactions

From the nervous system: headache, dizziness, weakness, drowsiness, insomnia, anxiety, decreased ability to concentrate, paresthesia.

From the digestive system: dyspepsia, nausea, vomiting, diarrhea, abdominal pain, decreased appetite; thoracalgia; dryness of mucous membranes.

From the respiratory system: nasal congestion.

From the organ of vision: hyperemia of the conjunctiva, accommodation spasm.

From the cardiovascular system: orthostatic hypotension.

From the hematopoietic system: hypokalemia, hyponatremia, hyperuricemia, hyperglycemia, thrombocytopenia.

Allergic reactions: skin itching.

Other: decreased potency and/or libido, gynecomastia, urination disorders, myasthenia.

Contraindications

Hypersensitivity; hypokalemia; hyponatremia; hypochloremia; hepatic insufficiency; chronic renal failure; Addison’s disease; nephritis; arterial hypotension; uremia; chronic heart failure; atherosclerosis; nephrosclerosis; concomitant treatment with MAO inhibitors; subacute stage of myocardial infarction; epilepsy; Parkinson’s disease; depression; gastric and duodenal ulcer (in the acute phase); erosive gastritis; ulcerative colitis; bronchial asthma; pheochromocytoma; angle-closure glaucoma; bradycardia; AV block; intraventricular block; electroconvulsive therapy; blood diseases; pregnancy; lactation period; age under 18 years (efficacy and safety of use have not been established).

With caution

Diabetes mellitus, gout, elderly age.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Contraindications: hepatic insufficiency.

Use in Renal Impairment

Contraindications: chronic renal failure; nephritis; nephrosclerosis.

Pediatric Use

Contraindicated in children under 18 years of age (efficacy and safety of use have not been established).

Special Precautions

The drug should be discontinued 7 days before starting electroconvulsive therapy or a planned surgery; in case of emergency surgery, atropine should be administered beforehand.

During treatment, it is necessary to monitor the concentration of electrolytes and uric acid in the blood serum, the mental state of patients (possible development of depression), kidney function, blood glucose concentration (in patients with diabetes mellitus).

With long-term use, a diet high in potassium (fruits, vegetables, low-fat cheese, fish) or additional prescription of potassium supplements is recommended.

If the antihypertensive effect is insufficient with monotherapy with the drug, it can be combined with beta-blockers or vasodilators.

Caution should be exercised in patients with bronchial asthma and bronchospasms.

Influence on the ability to drive vehicles and mechanisms

During the treatment period, caution must be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions (possibility of developing orthostatic hypotension, myasthenia, fatigue).

Drug Interactions

Reduces the effectiveness of oral hypoglycemic agents, tricyclic antidepressants, anticoagulants; increases the plasma concentration of lithium (by slowing its excretion); weakens the effect of antiepileptic drugs and levodopa, anticholinergics, reduces the analgesic effect of morphine; enhances the effect of barbiturates, ethanol, agents for inhalation anesthesia, antihistamines; enhances the effect of adrenomimetics.

Barbiturates, ethanol, beta-blockers, peripheral vasodilators enhance the antihypertensive effect.

Corticosteroids, NSAIDs, laxatives reduce the diuretic, antihypertensive effects, and increase the risk of hypokalemia.

Against the background of treatment with MAO inhibitors – enhancement of the inhibitory effect on the central nervous system; or severe arterial hypertension, hyperpyrexia.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.