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 (angina pectoris);
angina caused by vasospasm (Prinzmetal’s angina, variant);
paroxysmal supraventricular tachycardia;
atrial fibrillation/flutter accompanied by tachyarrhythmia (except for WPW syndrome).

Pharmacological effect

Calcium channel blocker. Inhibits the transmembrane flow of calcium ions into smooth muscle cells of the myocardium and blood vessels. Has antianginal, antiarrhythmic and antihypertensive effects.

The antianginal effect is associated with a direct effect on the myocardium and an effect on peripheral hemodynamics (reduces the tone of peripheral arteries, peripheral arterial resistance). Blockade of the entry of calcium ions into the cell leads to a decrease in the transformation of energy contained in macroergic bonds of ATP into mechanical work and to a decrease in myocardial contractility.

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

The drug has a pronounced antiarrhythmic effect, especially effective for supraventricular arrhythmia. It delays the conduction of the impulse in the AV node, as a result of which sinus rhythm is restored and/or heart rate is normalized, depending on the type of arrhythmia. Normal heart rate does not change or decreases slightly.

Pharmacokinetics

Suction

When taken orally, it is quickly and almost completely absorbed in the small intestine. The degree of absorption is 90-92%. The average systemic bioavailability in healthy volunteers after a single dose of the drug is 22%. Studies in patients with atrial fibrillation or angina showed mean bioavailability levels of 35% and 24% after a single oral and IV dose, respectively. With repeated administration of the drug, bioavailability increases almost 2 times compared with a single dose (this effect is probably due to partial saturation of liver enzyme systems and/or a transient increase in blood circulation in the liver after a single dose of verapamil).

Distribution

In case of coronary artery disease and arterial hypertension, no correlation was found between the therapeutic effect and the concentration of the drug in the blood plasma; there is only a definite relationship between plasma drug levels and the effect on the PR interval.

After administration of a prolonged-release dosage form, the plasma concentration curve of verapamil stretches and becomes flatter than with the administration of normal-release dosage forms.

Plasma protein binding is 90%.

Penetrates the placental barrier; concentrations found in umbilical vein plasma were 20–92% of maternal plasma concentrations.

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

Metabolism

Verapamil undergoes a first-pass effect through the liver. Almost completely metabolized. The main metabolite is norverapamil, which has pharmacological activity; other metabolites are largely inactive.

Removal

T1/2 ranges from 3 to 7 hours after a single oral dose. With repeated doses, T1/2 of verapamil can increase almost 2 times compared to a single dose.

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

Pharmacokinetics in special clinical situations

In patients with hepatic impairment, compared with those with normal liver function, the bioavailability of verapamil was much higher and a prolongation of T1/2 was observed.

Recent results indicate that there is no difference in the pharmacokinetics of verapamil between subjects with normal renal function and those with end-stage renal disease.

Special instructions

Acute myocardial infarction: Isoptin® SR 240 should be used with caution in patients with acute myocardial infarction complicated by bradycardia, a marked decrease in blood pressure or left ventricular dysfunction.

Beta-blockers and antiarrhythmic drugs: mutually enhancing the effect on the cardiovascular system (high-degree atrioventricular blockade, significant decrease in heart rate, exacerbation of heart failure and marked decrease in blood pressure).

Asymptomatic bradycardia (36 beats/min) with migration of the rhythm through the atria was observed in a patient simultaneously taking timolol (a beta-blocker) in the form of eye drops and verapamil orally.

Digoxin: in case of simultaneous use of Isoptin® CP 240 with digoxin, the dose of digoxin should be reduced. Heart failure: in patients with mild to moderate heart failure and a left ventricular ejection fraction greater than 35%, it is necessary to achieve a stable condition before starting Isoptin® CP 240 and carry out appropriate therapy thereafter.

Neuromuscular transmission disorders: Isoptin® CP 240 should be used with extreme caution in patients with diseases affecting neuromuscular transmission (myasthenia gravis, Lambert-Eaton syndrome, Duchenne muscular dystrophy).

Renal impairment: Verapamil should be used with caution and close monitoring in patients with impaired renal function. Verapamil is not excreted during hemodialysis.

Hepatic impairment: Use with extreme caution in patients with severe hepatic impairment.

Active ingredient

Verapamil

Composition

Active substance:

verapamil hydrochloride 240 mg.

Excipients:

microcrystalline cellulose – 78.8 mg,

sodium alginate – 320.0 mg,

povidone-KZO – 48.0 mg,

magnesium stearate – 3.2 mg,

water – 30.0 mg.

Film coating: hypromellose-2910 – 4.90 mg, macrogol-400 – 1.26 mg, macrogol-6000 – 0.84 mg, talc – 8.40 mg, titanium dioxide – 6.16 mg, aluminum varnish: quinoline yellow dye (E 104) + indigo carmine dye (E 132) – 0.14 mg, mountain glycolic wax – 0.30 mg.

Pregnancy

There is insufficient data on the use of Isoptin® CP 240 in pregnant women.

Isoptin® CP 240 can be used during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus/child.

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

Contraindications

hypersensitivity to the active substance or auxiliary components of the drug;
cardiogenic shock;
atrioventricular block II or III degree (except for patients with a functioning pacemaker);
sick sinus syndrome (except for patients with a functioning pacemaker);
heart failure with reduced ejection fraction of less than 35% and/or pulmonary artery wedge pressure of more than 20 mm Hg. Art. (with the exception of heart failure caused by supraventricular tachycardia, subject to treatment with verapamil);
atrial fibrillation/flutter in the presence of additional pathways (including in patients with Wolff-Parkinson-White syndrome, Lown-Ganong-Levin syndrome). These patients are at risk of developing ventricular tachyarrhythmia, incl. ventricular fibrillation when taking verapamil; use with ivabradine (see section “Interaction with other drugs”);
pregnancy;
breastfeeding period (efficacy and safety have not been established);
children under 18 years of age (efficacy and safety have not been established).

Side Effects

Dizziness, headache; bradycardia; “flushes” of blood to the skin of the face, a pronounced decrease in blood pressure; constipation, nausea; peripheral edema.

Interaction

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

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

Clinically significant interactions were observed when used simultaneously with inhibitors of the CYP3A4 isoenzyme, and an increase in the concentration of verapamil in the blood plasma was observed, while inducers of the CYP3A4 isoenzyme decreased the concentration of verapamil in the blood plasma. Therefore, monitoring patients for drug interactions is necessary.

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

Antihypertensives, diuretics, vasodilators: enhanced antihypertensive effect

Overdose

Symptoms of poisoning resulting from an overdose of Isoptin CP 240 depend on the amount of the drug taken, the time of detoxification measures and the contractility of the myocardium, which depends on age. Fatal cases resulting from overdose have been reported.

Symptoms: fall in blood pressure (in some cases to levels that cannot be measured), shock, loss of consciousness, 1st or 2nd degree AV block, often in the form of Wenckebach periods with or without escape rhythm, complete AV block with complete AV dissociation, escape rhythm, cardiac arrest; sinus bradycardia, sinus node arrest.

In case of an overdose of Isoptin CP 240, it must be borne in mind that the active substance is released and absorbed from the intestine within 48 hours after taking the drug orally. Depending on the time of taking the drug, individual conglomerates of swollen tablet residues, acting as active depots, will be located throughout the gastrointestinal tract.

Treatment: measures aimed at removing the drug are indicated (for example, induce vomiting, rinse the stomach and intestines in combination with endoscopic examination, prescribe laxatives, emetics). If there is no motility of the stomach and intestines (signs of peristalsis during auscultation), then it is advisable to perform gastric lavage even 12 hours after taking the drug orally. Common emergency resuscitation measures include chest compressions, artificial respiration, and electrical stimulation of the heart.

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

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

In the case of AV blockade of the second or third degree, sinus bradycardia, cardiac arrest, administration of atropine, isoprenaline, orciprenaline, and cardiac stimulation are indicated.

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

In case of persistent signs of myocardial failure, dopamine, dobutamine are administered, and, if necessary, additional calcium is administered.

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

1 year

Manufacturer

Famar A.V.E., Greece