Fenigidin-zdorov'ya

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PHENIHYDIN-ZDOROVYE

Composition:

Active substance: nifedipine;

1 ml (30 drops) of the preparation contains 20 mg of nifedipine;

Excipients: ethanol 96%, polyethylene glycol.

Medicinal form. Oral solution, drops.

Main physicochemical properties: a clear yellow or greenish-yellow viscous liquid with a faint alcoholic odor.

Pharmacotherapeutic group. Selective calcium antagonists with predominant vascular effect. ATC code C08CA05.

Pharmacological properties.

Pharmacodynamics. Nifedipine exerts antianginal and antihypertensive effects. It blocks the influx of calcium ions into cardiomyocytes and smooth muscle cells of coronary and peripheral arteries through slow potential-dependent calcium channels in cell membranes. It relaxes vascular smooth muscles, relieves spasms, and dilates coronary and peripheral arteries, thereby reducing peripheral vascular resistance, afterload, and myocardial oxygen demand. It slightly decreases myocardial contractility and moderately reduces platelet aggregation.

Pharmacokinetics. After oral administration, nifedipine is well absorbed from the gastrointestinal tract; its bioavailability is 40–60%. The effect develops particularly rapidly (within 5–10 minutes) when administered sublingually. The maximum effect is usually observed within 30–40 minutes. Food intake does not significantly affect the rate of drug absorption. The hemodynamic effect persists for 4–6 hours. Approximately 90% of nifedipine is bound to plasma proteins. It is metabolized in the liver and excreted from the body predominantly as inactive metabolites. Total clearance of nifedipine ranges from 0.4 to 0.6 L/kg/hour. The elimination half-life is 2–4 hours. In elderly patients and in patients with liver cirrhosis, nifedipine metabolism is slowed, resulting in nearly a twofold prolongation of the elimination half-life. Therefore, dosage reduction and increased dosing intervals are required in these patients. Nifedipine does not accumulate in the body. It crosses the blood-brain and placental barriers in insignificant amounts and is excreted into breast milk.

Clinical characteristics.

Indications. Arterial hypertension (treatment of hypertensive crises).

Contraindications. Acute myocardial infarction (within the first 4 weeks), cardiogenic shock, severe aortic and mitral stenosis, unstable angina; not to be used for the treatment of angina attacks, secondary prevention of myocardial infarction; decompensated heart failure, arterial hypotension (systolic blood pressure (BP) below 90 mm Hg), ventricular tachycardias with broad QRS complex, sinoatrial node weakness syndrome, Wolff–Parkinson–White (WPW) syndrome, Lown–Ganong–Levine (LGL) syndrome, second- and third-degree AV block, porphyria, ileostomy established after proctocolectomy, hypersensitivity to nifedipine and other components of the drug, hypersensitivity to other dihydropyridines; do not take concomitantly with rifampicin.

Interaction with other medicinal products and other forms of interaction. Nifedipine may enhance the antihypertensive effect of concomitantly administered antihypertensive drugs such as diuretics, β-blockers, ACE inhibitors, AT1-receptor antagonists, other calcium antagonists, α-adrenergic blockers, PDE5 inhibitors, α-methyldopa.

When used together with β-blockers, not only may antihypertensive effects be enhanced, but heart failure may also develop.

Diltiazem slows the elimination of nifedipine from the body (if necessary, the dose of nifedipine should be reduced).

Amiodarone and quinidine may enhance the negative inotropic effect of nifedipine. In individual cases, plasma levels of quinidine may decrease.

Combination of nifedipine with cardiac glycosides and theophylline is generally well tolerated by patients; very rarely, an increase in plasma levels of digoxin and theophylline may occur (plasma levels of the latter should be monitored).

Nifedipine increases the serum concentration of carbamazepine and phenytoin. Cimetidine increases the plasma level of nifedipine.

Rifampicin accelerates the metabolism of nifedipine due to increased activity of liver enzymes, which may lead to reduced clinical effect of nifedipine (this combination is contraindicated).

Nifedipine treatment should be discontinued 36 hours before planned fentanyl anesthesia. Nifedipine may be used together with radiopaque substances.

Nifedipine in combination with intravenous administration of magnesium sulfate in pregnant women may cause neuromuscular blockade.

Nifedipine is metabolized via the cytochrome P450 3A4 system located in the intestinal mucosa and liver. Therefore, drugs that inhibit or induce this enzyme system may alter the first-pass effect (after oral administration) or clearance of nifedipine. Concomitant use of macrolide antibiotics (e.g., erythromycin), anti-HIV protease inhibitors (e.g., ritonavir), azole antifungals (e.g., ketoconazole), fluoxetine, nefazodone, quinupristin/dalfopristin, cimetidine, cisapride, and nifedipine may lead to increased plasma concentrations of nifedipine.

It is known that valproic acid increases plasma concentrations of the structurally similar calcium channel blocker nimodipine due to inhibition of enzymes. Therefore, an increase in plasma concentration and efficacy of nifedipine cannot be excluded.

It is known that tacrolimus is metabolized via the cytochrome P450 3A4 system.

Published data indicate that in individual cases, the dose of tacrolimus may be reduced when used concomitantly with nifedipine. When using both drugs concomitantly, monitoring of tacrolimus plasma concentration is recommended, and dose reduction of tacrolimus should be considered if necessary.

Grapefruit juice inhibits the cytochrome P450 3A4 system. Consumption of grapefruit juice during nifedipine administration leads to increased drug plasma concentration and prolonged duration of action due to reduced first-pass metabolism or decreased clearance. As a result, the antihypertensive effect of the drug may be enhanced. After regular consumption of grapefruit juice, this effect may persist for at least 3 days after the last juice intake.

Therefore, during nifedipine therapy, consumption of grapefruit/grapefruit juice should be avoided.

Administration of nifedipine may lead to false-positive elevation in spectrophotometric determination of vanillylmandelic acid concentration in urine (however, this effect is not observed when using high-performance liquid chromatography).

Special precautions for use

The drug should be administered under strict clinical supervision in patients with unstable angina, severe heart failure, severe aortic stenosis, severe pulmonary hypertension, hypertrophic cardiomyopathy, severe cerebral circulation disorders, diabetes mellitus, hepatic or renal dysfunction, and in elderly patients. In elderly patients, a more pronounced reduction in cerebral blood flow may occur due to sudden peripheral vasodilation.

In patients with malignant arterial hypertension and hypovolemia undergoing hemodialysis, significant hypotension may occur during nifedipine therapy. Hypotension may especially develop at the beginning of treatment and when β-blockers are co-administered; some patients tolerate this poorly. Such patients require close monitoring. In patients receiving β-blockers, symptoms of congestive heart failure may appear at the start of treatment. In patients with severe coronary insufficiency, reflex tachycardia may worsen the course of ischemic heart disease and increase the frequency of angina attacks. Nifedipine should be used cautiously in patients with angina and in those who have had a myocardial infarction. If chest pain develops during nifedipine therapy, the drug should be discontinued. Alcohol consumption and smoking should be avoided during nifedipine treatment.

Dosages of other drugs used concomitantly with nifedipine should be individually adjusted. Cardiac glycosides may be administered together with nifedipine. During nifedipine therapy, false elevations in spectrophotometric measurements of urinary vanillylmandelic acid concentration may occur.

Patients with impaired liver function require careful monitoring and, in severe cases, a reduced dose of the drug.

Nifedipine is metabolized via the cytochrome P450 3A4 system. Therefore, drugs that inhibit or induce this enzyme system may alter the first-pass effect or clearance of nifedipine (see section "Interaction with other medicinal products and other forms of interaction").

When nifedipine is used concomitantly with such drugs, blood pressure should be monitored, and if necessary, a dose reduction of nifedipine should be considered.

Some in vitro experiments have shown an association between the use of calcium antagonists, particularly nifedipine, and reversible biochemical changes in spermatozoa that impair their fertilizing capacity. If in vitro fertilization attempts fail without other explanations, calcium antagonists, particularly nifedipine, may be considered as a possible cause.

This medicinal product contains a small amount of ethanol (alcohol), less than 100 mg per dose.

Use during pregnancy or breast-feeding. Nifedipine is contraindicated during pregnancy. Nifedipine passes into breast milk; therefore, breastfeeding should be discontinued during treatment with this drug.

Ability to influence reaction rate while driving or operating machinery. Patients should refrain from potentially hazardous activities requiring increased attention (such as driving vehicles or operating machinery) while taking this medication.

Dosage and Administration

To accurately measure the dose of the medication, the bottle should be held vertically with the opening facing downward.

Nifedipine is used for the treatment of hypertensive crisis as a rapid-acting agent. It is not recommended to use this medication in this dosage form for long-term therapy.

If prolonged antihypertensive therapy is required, the choice of medication and dosage form should be determined by a physician.

In cases of sudden and significant increase in arterial pressure (AP), the initial single dose for adults is 3–5 drops (2–3.35 mg); for elderly patients, it should not exceed 3 drops (2 mg). The drops should be administered sublingually or onto a piece of dry cracker or sugar, and held in the mouth as long as possible. If the response is inadequate, the dose may be gradually increased until a clinically significant effect is achieved. Subsequently, in cases of elevated AP, this effective dose should be used as a reference. If necessary (when AP rises to 190/100–220/110 mm Hg), the single dose may be gradually increased in individual cases up to 10–15 drops (6.7–10 mg), taking into account individual changes in the patient's AP values.

Individual patient sensitivity to nifedipine must be considered. In such cases, the dose should be individually adjusted, starting with 3 drops, and gradually increased by 2–3 drops (1.34–2 mg) until the desired clinical effect is achieved.

Exceeding the initial dose of the medication may lead to a sudden drop in arterial pressure.

Children. The medication is not used for the treatment of children.

Overdose.

Symptoms of acute nifedipine intoxication: impaired consciousness up to coma, decreased arterial pressure, tachycardia/bradycardia, hyperglycemia, metabolic acidosis, hypoxia, cardiogenic shock associated with pulmonary edema.

Treatment. Emergency measures should primarily aim at eliminating the drug from the body and restoring stable hemodynamics.

After oral administration, gastric lavage is recommended; if necessary, in combination with intestinal lavage.

Due to nifedipine’s high degree of plasma protein binding and relatively small volume of distribution, hemodialysis is ineffective; however, plasmapheresis is recommended.

Bradycardia can be treated with β-sympathomimetics. In cases of life-threatening bradycardia, artificial cardiac pacing is recommended.

Arterial hypotension resulting from cardiogenic shock and vasodilation can be managed with calcium preparations (10–20 mL of 10% calcium chloride or calcium gluconate solution administered slowly intravenously, repeated if necessary). Serum calcium levels may reach the upper normal limit or become slightly elevated. If calcium administration is insufficiently effective, sympathomimetics such as dopamine or norepinephrine should be used. The doses of these agents should be titrated according to the therapeutic response.

Additional fluid administration should be approached with extreme caution, as it may increase the risk of cardiac overload.

Adverse Reactions

When the recommended application guidelines are followed, adverse reactions are usually mild and reversible, generally not requiring discontinuation of therapy.

With frequent and uncontrolled use, adverse reactions characteristic of drugs in this pharmacological group may occur.

Cardiovascular system: frequently – edema, vasodilation; infrequently – tachycardia, palpitations, arterial hypotension, syncope.

Central and peripheral nervous system: frequently – headache; infrequently – vertigo, migraine, dizziness, tremor, sleep disorders, anxiety; rarely – transient visual disturbances, excitement, paresthesia, dysesthesia.

Endocrine system: hyperglycemia (should be considered when administering to patients with diabetes mellitus).

Gastrointestinal system: frequently – constipation; infrequently, when higher doses are used – abdominal pain, dyspeptic symptoms, flatulence, nausea, vomiting (very rare), gingival hyperplasia (with prolonged use), dry mouth, transient increase in liver enzymes.

Urinary system: infrequently – polyuria, dysuria.

Hematopoietic system: rarely – anemia, leukopenia, thrombocytopenia.

Allergic reactions: infrequently – allergic reaction, allergic edema/angioedema (including laryngeal edema); rarely – itching, urticaria, rash; very rarely – anaphylactic/anaphylactoid reactions.

Other: frequently – malaise; infrequently – epistaxis, nasal congestion, erythema; rarely – muscle cramps, joint swelling, erectile dysfunction, nonspecific pain, fever, dyspnea.

Shelf life: 2 years.

Storage conditions: Store in the original packaging at a temperature not exceeding 25 °C.

The shelf life of the medication after opening the bottle is 28 days.

Keep out of reach of children.

Packaging: 10 ml or 20 ml in a bottle with a dropper cap and lid, in a box.

Prescription status: Prescription only.

Manufacturer: Limited liability company "Pharmaceutical Company "Zdorovia".

Manufacturer's address and place of business: 22, Shevchenka Street, Kharkiv, Kharkiv Oblast, 61013, Ukraine.