Verogalid ER 240 (Tablets) Instructions for Use

Marketing Authorization Holder

Teva Pharmaceutical Industries, Ltd. (Israel)

Manufactured By

Pliva Hrvatska, d.o.o. (Croatia)

ATC Code

C08DA01 (Verapamil)

Active Substance

Verapamil (Rec.INN registered by WHO)

Dosage Form

Verogalid ER 240

Extended-release tablets, film-coated, 240 mg: 10, 30, or 100 pcs.

Dosage Form, Packaging, and Composition

Extended-release tablets, film-coated white with a yellowish tint, oblong, elongated, biconvex, with a score and marking on one side “73” (on one side of the score) and “00” (on the other side of the score); with two triangles facing each other – on the other.

Excipients: sodium alginate, microcrystalline cellulose, povidone, magnesium stearate.

Coating composition Opadry clear YS-1-7006 (hypromellose 6cP, macrogol (PEG 400), macrogol (PEG 8000)), Opadry yellow YS-5-12577 (hypromellose 3cP, hyprolose (hydroxypropylcellulose), titanium dioxide, macrogol (PEG 400), hypromellose 50cP, yellow lake dye).

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.
30 pcs. – plastic jars (1) – cardboard packs.
100 pcs. – plastic jars (1) – cardboard packs.

Clinical-Pharmacological Group

Calcium channel blocker

Pharmacotherapeutic Group

BMCC (Bone Mineral Crystal Complex)

Pharmacological Action

Slow calcium channel blocker. It has antihypertensive, antianginal, and antiarrhythmic action.

It inhibits the transmembrane transport of calcium ions to the contractile fibers of smooth muscle cells. The antianginal effect is associated both with a direct effect on the myocardium and with an effect on peripheral hemodynamics (reduces the tone of peripheral arteries and total peripheral vascular resistance). Blockade of calcium ion entry into the cell leads to a decrease in myocardial contractility and a reduction in myocardial oxygen demand.

Verapamil has a vasodilatory, antihypertensive, negative ino- and chronotropic effect, reduces conduction through the AV node, prolongs the refractory period, and suppresses sinus node automaticity.

Development of tolerance to verapamil is not observed.

Pharmacokinetics

Absorption

After oral administration of the drug, about 90% of the administered dose is absorbed from the gastrointestinal tract. C_max is 80-400 ng/ml and is reached after 5-7 hours. Bioavailability is approximately 20% due to intensive metabolism during the “first pass” through the liver.

Distribution

Plasma protein binding is more than 90%.

It crosses the placental barrier and is excreted in breast milk.

Metabolism

It is rapidly biotransformed in the liver by N-dealkylation and O-demethylation to form several metabolites, of which norverapamil is pharmacologically active. Accumulation of verapamil and its metabolites enhances the effect during course treatment.

Elimination

T_1/2 is 11 hours. It is excreted mainly in the urine and about 25% in the bile.

Indications

• Arterial hypertension;
• Prevention of angina attacks (including angiospastic);
• Prevention of supraventricular tachyarrhythmias.

ICD codes

Dosage Regimen

For the treatment of arterial hypertension, the drug is prescribed at an average dose of 240-360 mg. The maximum daily dose is 360 mg.

Usually, 240 mg is prescribed once/day in the morning, if necessary 240 mg in the morning and 120 mg in the evening with a 12-hour interval. Increasing the daily dose to 480 mg should be done only in a hospital setting.

For patients with impaired liver and kidney function, as well as elderly patients, the drug is prescribed at a lower initial dose (120 mg).

For the prevention of angina attacks, the drug is prescribed at 120 mg 1-2 times/day with a 12-hour interval. The maximum daily dose is 240 mg.

For the prevention of supraventricular tachyarrhythmias, the drug is prescribed at 120 mg 1-2 times/day.

The drug should be taken with meals, the tablets should be swallowed whole, without chewing, with a small amount of water.

Adverse Reactions

From the cardiovascular system sinus bradycardia, sinoatrial block, asystole, AV block II and III degree, bradyarrhythmic form of atrial fibrillation, arterial hypotension, development of heart failure, palpitations, tachycardia; rarely – angina pectoris, up to the development of myocardial infarction (especially in patients with severe obstructive coronary artery disease).

From the central and peripheral nervous system rarely – dizziness, lethargy, headache, drowsiness, feeling of fatigue, increased nervous excitability, paresthesia; rarely – fainting, anxiety, asthenia, depression, extrapyramidal disorders.

From the musculoskeletal system very rarely – myalgia, arthralgia.

From the digestive system constipation, nausea, vomiting, intestinal obstruction, pain or discomfort in the abdomen, increased activity of liver transaminases, alkaline phosphatase; rarely – diarrhea.

Allergic reactions exanthema, urticaria, angioedema, Stevens-Johnson syndrome.

From the reproductive system in some cases – galactorrhea, impotence, gynecomastia, which are reversible and disappear after drug withdrawal.

Other flushing, peripheral edema; rarely – weight gain; very rarely – agranulocytosis, gingival hyperplasia.

Contraindications

• Severe bradycardia;
• Arterial hypotension;
• Cardiogenic shock;
• Acute phase of complicated myocardial infarction (with bradycardia, severe arterial hypotension, left ventricular failure);
• Aortic stenosis;
• Morgagni-Adams-Stokes syndrome;
• AV block II and III degree;
• Sinoatrial block;
• WPW syndrome (Wolff-Parkinson-White);
• Sick sinus syndrome;
• Digitalis intoxication;
• IV administration of beta-blockers within the previous 2 hours;
• Pregnancy;
• Lactation (breastfeeding);
• Age under 18 years (efficacy and safety not established);
• Hypersensitivity to the drug components.

With caution the drug should be prescribed for impaired liver function, AV block I degree, chronic heart failure, arterial hypotension (systolic BP below 90 mm Hg), atrial fibrillation/flutter with WPW syndrome (risk of ventricular tachycardia).

Use in Pregnancy and Lactation

Use during pregnancy and lactation (breastfeeding) is possible only if the intended benefit to the mother outweighs the potential risk to the fetus and child.

Use in Hepatic Impairment

For patients with impaired liver function the drug is prescribed at a lower initial dose (120 mg).

Use in Renal Impairment

For patients with impaired kidney function the drug is prescribed at a lower initial dose (120 mg).

Pediatric Use

Contraindicated: age under 18 years (efficacy and safety not established).

Geriatric Use

Elderly patients are prescribed the drug at a lower initial dose (120 mg).

Special Precautions

Before using the drug, it is necessary to preliminarily compensate for heart failure.

To increase BP in hypertrophic cardiomyopathy, alpha-adrenomimetics (phenylephrine) should be prescribed; isoproterenol and epinephrine should not be used.

Sudden discontinuation of treatment is not recommended.

During treatment, the functions of the cardiovascular and respiratory systems, plasma glucose and electrolyte levels, circulating blood volume and the amount of urine output should be monitored.

Overdose

Symptoms severe bradycardia, AV block, severe arterial hypotension, heart failure, shock, asystole, sinoatrial block.

Treatment gastric lavage is recommended in all cases if no more than 12 hours have passed since drug intake, as well as at later times with reduced gastrointestinal motility (absence of bowel sounds on auscultation). Symptomatic treatment is carried out. For cardiac arrhythmias – IV isoprenaline, norepinephrine, atropine, 10% calcium gluconate solution (10-20 ml), artificial pacemaker; IV infusion of plasma-substituting solutions. Hemodialysis is ineffective. To increase BP in patients with hypertrophic cardiomyopathy, isoprenaline and norepinephrine should not be used.

Drug Interactions

When Verogalid ER 240 is co-administered with carbamazepine, the effect of the latter is enhanced and the risk of side effects in the form of toxic lesions of the nervous system increases.

Concomitant use with rifampicin or phenobarbital leads to a decrease in the effectiveness of Verogalid ER 240.

Cimetidine enhances the effect of Verogalid ER 240, as it increases the bioavailability of verapamil by 40-50% (due to reduced hepatic metabolism), which may necessitate a dose reduction of the latter.

Nicotine, by accelerating metabolism in the liver, leads to a decrease in the concentration of verapamil in the blood, which reduces the severity of the antianginal, antihypertensive and antiarrhythmic action.

When used concomitantly with inhalation anesthetics, the risk of bradycardia, AV block, and heart failure increases.

Combined use of Verogalid ER 240 with other antihypertensive drugs leads to an enhancement of their effect.

The combination of Verogalid ER 240 with beta-blockers may lead to potentiation of the negative inotropic effect, increased risk of AV conduction disorders, and bradycardia.

When Verogalid ER 240 is taken concomitantly with digoxin, theophylline, cyclosporine, and quinidine, their blood concentrations increase.

Prescribing Verogalid ER 240 to patients receiving long-term lithium preparations may lead to a decrease in serum lithium concentration.

When used concomitantly with hypolipidemic agents: with atorvastatin – an increase in serum atorvastatin level, with lovastatin – an increase in serum atorvastatin level, with simvastatin – an increase in the AUC of simvastatin by approximately 2.6 times and C_max of simvastatin by 4.6 times.

For patients receiving Verapamil, treatment with HMG-CoA reductase inhibitors should be started at the lowest possible doses, which are gradually increased. If it is necessary to prescribe Verapamil to patients already receiving HMG-CoA reductase inhibitors, their doses should be reviewed according to the serum cholesterol concentration.

Fluvastatin, pravastatin, and rosuvastatin are not metabolized by CYP3A4 isoenzymes, so their interaction is least likely.

When used concomitantly with almotriptan, an increase in AUC by approximately 20% and C_max of almotriptan by approximately 24% is possible.

When taken concomitantly with grapefruit juice, an increase in the AUC and C_max of verapamil is possible.

When used concomitantly with St. John’s wort, a decrease in the AUC of verapamil with a corresponding decrease in C_max is possible.

When used concomitantly with doxorubicin, the T_1/2 of doxorubicin decreases (by approximately 27%) and C_max (by approximately 38%). In patients with progressive neoplasms, Verapamil does not affect the level or clearance of doxorubicin. In patients with small cell lung cancer, Verapamil reduces the T_1/2 and C_max of doxorubicin.

When used concomitantly with glyburide, an increase in C_max of glyburide (by approximately 28%) and AUC (by approximately 26%) is possible.

When used concomitantly with acetylsalicylic acid, increased bleeding is possible.

Storage Conditions

The drug should be stored in a dry, light-protected place, out of the reach of children, at a temperature up to 25°C (77°F).

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

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.