Isoptin SR 240,240 mg 30 pcs

Calcium channel blocker. Inhibits transmembrane flow of calcium ions in myocardial and vascular smooth muscle cells. It has antianginal, antiarrhythmic and antihypertensive action.

The antianginal effect is related to the direct action on the myocardium and the effect on peripheral hemodynamics (reduces peripheral artery tone, PPS). Blockade of entry of calcium ions into the cell leads to a decrease of transformation of energy contained in ATP macroergic bonds into mechanical work and to a decrease of myocardial contractility.

The antihypertensive effect of the drug is due to decrease of peripheral vascular resistance without reflex increase of HR. Blood pressure begins to decrease immediately on the first day of treatment and this effect persists in long-term therapy. Isoptin SR 240 is indicated for the treatment of all types of arterial hypertension: for monotherapy of mild to moderate arterial hypertension, in combination with other antihypertensive agents, especially diuretics and (according to recent observations) ACE inhibitors The drug has a vasodilatory, negative and chronotropic effect.

The drug has a pronounced antiarrhythmic effect, especially effective in supraventricular arrhythmias. It inhibits the impulse conduction in the AV node, as a result of which the sinus rhythm is restored and/or the heart rate is normalized, depending on the type of arrhythmia. The normal HR is unchanged or slightly reduced.

Pharmacokinetics

Intake

In oral administration, it is quickly and almost completely absorbed in the small intestine. Absorption rate is 90-92%. Mean systemic bioavailability in healthy volunteers after a single drug administration is 22%. Studies in patients with atrial fibrillation or angina pectoris have shown that the average bioavailability levels are 35% and 24% after a single oral and IV dose of the drug, respectively. Bioavailability was increased by almost 2-fold with multiple doses compared to a single dose (this effect is probably due to partial saturation of hepatic enzyme systems and/or transient increase in blood flow in the liver after a single dose of verapamil).

Distribution

In CHD and arterial hypertension, no correlation between therapeutic effect and plasma concentration of the drug has been found; there is only some correlation between plasma levels of the drug and effect on the PR interval.

After administration of the sustained-release formulation, the plasma concentration curve for verapamil is longer and flatter than with normal-release formulations.

The binding to plasma proteins is 90%.

It penetrates the placental barrier; concentrations detected in umbilical vein plasma were 20-92% of maternal plasma concentrations.

It is excreted with breast milk, but with therapeutic doses its concentrations are so low that clinical effect in newborns is unlikely.

Metabolism

Verapamil undergoes a “first pass” effect through the liver. It is almost completely metabolized. The major metabolite is norverapamil, which has pharmacological activity; other metabolites are mostly inactive.

The T1/2 is 3 to 7 h after a single oral administration. The T1/2 of verapamil may be almost twice as long when administered multiple times compared to a single dose.

Verapamil and its metabolites are eliminated primarily through the kidneys (3-4% unchanged). Within 24 hours 50% of the administered dose is eliminated, within 48 hours – 55-60%, within 5 days – 70%. Up to 16% is excreted with the feces.

Pharmacokinetics in special clinical cases

The bioavailability of verapamil was much higher in patients with hepatic impairment compared to those with normal liver function and a prolongation of T1/2 was observed.

The recent results suggest that there are no differences in the pharmacokinetics of verapamil in individuals with normal renal function and in patients with end-stage renal failure.

Indications

• arterial hypertension;
• chronic stable angina pectoris (angina pectoris);
• angina pectoris due to vasospasm (Prinzmetal’s angina, variant);
• paroxysmal supraventricular tachycardia;
• atrial fibrillation/tripping accompanied by tachyarrhythmias (except WPW syndrome).

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Active ingredient

Verapamil

Composition

Active ingredient:

Verapamil hydrochloride 240 mg.

Excipients:

microcrystalline cellulose – 78.8 mg,

sodium alginate – 320.0 mg,

How to take, the dosage

Isoptin SR 240 is taken orally, without chewing, during or after a meal, with a small amount of liquid, 240-360 mg (dose adjusted individually).

In long-term therapy, the daily dose of Isoptin SR 240 should not exceed 480 mg. Usually 240 mg is prescribed in the morning. If a slow decrease in BP is desired, 120 mg is prescribed.

Interaction

In vitro metabolic studies indicate that verapamil is metabolized by CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18 cytochrome P450 isoenzymes.

Verapamil is an inhibitor of CYP3A4 and P-glycoprotein isoenzyme.

Clinically significant interactions were observed when concomitant use with CYP3A4 isoenzyme inhibitors, with an increase in plasma verapamil concentration, while CYP3A4 isoenzyme inducers decreased plasma verapamil concentration, Therefore, monitoring of patients for drug interactions is necessary.

HIV medications: some HIV medications, such as ritonavir, may inhibit verapamil metabolism, resulting in increased plasma concentrations. Caution should be exercised or the dose of verapamil should be reduced.

Hypotensive agents, diuretics, vasodilators: increase antihypertensive effect

Special Instructions

Acute myocardial infarction: Isoptin® SR 240 should be used with caution in patients with acute myocardial infarction complicated by bradycardia, markedly reduced BP or left ventricular dysfunction.

Beta-adrenoblockers and antiarrhythmic agents: mutual enhancement of cardiovascular effects (high degree antrioventricular blockade, significant reduction of HR, exacerbation of heart failure and marked BP reduction).

Asymptomatic bradycardia (36 bpm) with atrial rhythm migration was observed in a patient simultaneously taking timolol (beta-adrenoblocker) in the form of eye drops and verapamil orally.

Digoxin: If Isoptin® SR 240 is taken concomitantly with digoxin, the dose of digoxin should be reduced. Heart failure: Patients with mild to moderate heart failure with left ventricular ejection fraction greater than 35% should be stabilized before starting Isoptin® SR 240 and appropriate therapy should be continued.

Disorders of neuromuscular transmission: Isoptin® SR 240 should be used with special caution in patients with diseases affecting neuromuscular transmission (myasthenia gravis, Lambert-Eaton syndrome, Duchenne muscular dystrophy).

With impaired renal function: Verapamil in patients with impaired renal function should be used with caution and under close supervision. Verapamil is not excreted by hemodialysis.

Hepatic impairment: should be used with caution in patients with severe hepatic impairment.

Synopsis

Light green oblong-shaped film-coated tablets. Both sides of the tablets have transverse ridges. On one side two “A” marks are engraved.

Contraindications

• high sensitivity to the active substance or excipients;
• cardiogenic shock;
• atrioventricular block of degree II or III (except for patients with a functioning pacemaker);
• Sinus node weakness syndrome (except in patients with a functioning pacemaker);
• heart failure with decreased ejection fraction less than 35% and/or pulmonary artery occlusion pressure greater than 20 mmHg. Tachycardia (except for heart failure due to supraventricular tachycardia to be treated with verapamil);
• atrial fibrillation/tripping with additional conduction pathways (including in patients with Wolff-Parkinson-White syndrome, Laun-Hanong-Levin syndrome). These patients are at risk of ventricular tachyarrhythmias, including ventricular fibrillation in case of verapamil administration; use with ivabradine (see section “Interaction with other drugs”).
• pregnancy
• breastfeeding (efficacy and safety not established)
• children under 18 years of age (efficacy and safety not established).
  

Side effects

Dizziness, headache; bradycardia; “rushes” of blood to the skin, marked BP decrease; constipation, nausea; peripheral edema.

Overdose

The symptoms of poisoning resulting from overdose of Isoptin SR 240 depend on the amount of the drug taken, the timing of detoxification measures and myocardial contractility, which depends on age. Fatal cases have been reported as a result of overdose.

Symptoms: drop in BP (in some cases to levels that cannot be measured), shock, loss of consciousness, grade I or II AV blockade, often as Wenckebach periods with or without a slipping rhythm, complete AV blockade with complete AV dissociation, slipping rhythm, cardiac arrest; sinus bradycardia, sinus node arrest.

In case of overdose of Isoptin SR 240, it should be borne in mind that the active substance is released and absorbed from the intestine within 48 hours after oral administration. Depending on the time of ingestion, individual conglomerates of swollen tablet residues acting as active depots will be located throughout the GI tract.

Treatment: measures aimed at elimination of the drug are indicated (e.g., inducing vomiting, gastric and bowel flushing in conjunction with endoscopic examination, prescribing laxatives, vomiting agents). If there is no gastric and intestinal motility (signs of peristalsis on auscultation), gastric lavage is appropriate even 12 h after ingestion. Routine emergency resuscitation measures include closed heart massage, artificial respiration, and electrical cardiac stimulation.

Effects associated with cardiac depression, arterial hypotension, and bradycardia should be excluded.

Calcium is a specific antidote: administer 10-30 ml of 10% calcium gluconate solution as an IV infusion (2.25-4.5 mmol), repeatedly if necessary or as a slow drip infusion (5 mmol/h).

In case of AV-blockade of II or III degree, sinus bradycardia, cardiac arrest atropine, isoprenaline, orciprenaline, cardiac stimulation is indicated.

In case of arterial hypotension, dopamine, dobutamine, norepinephrine (noradrenaline) are administered.

In case of persistent signs of myocardial insufficiency, administer dopamine, dobutamine, and additional calcium administration if necessary.

Pregnancy use

There are insufficient data on the use of Isoptin® SR 240 in pregnant women.

Isoptin® SR 240 should only be used during pregnancy if the benefit to the mother exceeds the potential risk to the fetus/infant.

Verapamil and its metabolites are excreted into the breast milk. Given the possibility of serious adverse effects in infants, Isoptin® SR 240 should only be used during breastfeeding if the benefit to the mother exceeds the potential risk to the child.

Similarities

Verapamil