Isoptin SR 240: instructions for using the medicine, structure, Contraindications

Active material: Verapamil
When ATH: C08DA01
CCF: Kalьcievыh channel blocker
ICD-10 codes (testimony): I10, i20, I20.1, I47.1, i48
When CSF: 01.03.01
Manufacturer: ABBOTT GmbH & Co. KG (Germany)

Isoptin SR 240: DOSAGE FORM, COMPOSITION AND PACKAGING

Sustained-release tablets, coated light green, kapsulovidnoy form, with transverse risks on both sides, on one side are shown two signs “D”.

Excipients: microcrystalline cellulose, sodium alginate, povidone, magnesium stearate, Purified water, gipromelloza, macrogol 400, macrogol 6000, talc, Titanium dioxide, quinoline yellow, indigotin, Mining glycol wax.

10 PC. – blisters (2) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (5) – packs cardboard.
10 PC. – blisters (10) – packs cardboard.
15 PC. – blisters (2) – packs cardboard.
15 PC. – blisters (3) – packs cardboard.
15 PC. – blisters (5) – packs cardboard.
15 PC. – blisters (10) – packs cardboard.

Isoptin SR 240: pharmachologic effect

Kalьcievыh channel blocker. It inhibits the transmembrane current of calcium ions into smooth muscle cells of the myocardium and blood vessels. It has antianginalnoe, antiarrhythmic and antihypertensive action.

Antianginal effect is due to a direct effect on the myocardium and the impact on peripheral hemodynamics (It lowers the tone of the peripheral arteries, PR). Blockade of flow of calcium ions into the cell leads to a reduction in transformation energy bonds contained in ATP energy into mechanical work, and a reduction in myocardial contractility.

The antihypertensive effect of the drug due to a decrease in peripheral vascular resistance without increasing the heart rate as a reflex response. BP begins to fall directly on the first day of treatment and this effect is maintained in the long-term therapy.

The drug has a vasodilatory, negative ino- and chronotropism.

The drug has a pronounced antiarrhythmic effect, It is particularly effective in supraventricular arrhythmias. Delays in carrying out pulse AV-node, resulting in sinus rhythm is restored and / or heart rate to normal, depending on the type of arrhythmia. A normal heart rate is unchanged or slightly reduced.

Isoptin SR 240: pharmacokinetics

Absorption

When ingestion rapidly and almost completely absorbed from the small intestine. The extent of absorption 90-92%. Bioavailability in healthy volunteers following a single dose of the drug is 22%. Studies in patients with atrial fibrillation and angina showed, that the average levels of bioavailability is 35% and 24% After receiving a single dose of the drug inside and I / dose, respectively. Repeated taking the drug increases the bioavailability of nearly 2 times compared to single dose (This effect, probably, due to the partial liver enzymes saturation systems or transient increase in blood flow in the liver after a single dose of verapamil).

Distribution

When coronary artery disease and hypertension is not correlation between the therapeutic effect and the concentration of drug in blood plasma; there is only a definite relationship between the level of drug in the blood and the effect on PR interval.

Upon receiving the long-acting dosage form of verapamil concentration curve in plasma expands and becomes flatter, than when administered dosage forms with a normal release.

Plasma protein binding is 90%.

It penetrates through the placental barrier; concentration, found in umbilical venous plasma, were 20-92% plasma concentrations of maternal blood.

Return with breast milk, but when using therapeutic doses so low concentration, that the clinical effect is unlikely in newborns.

Metabolism

Verapamil undergoes effect “first pass” through the liver. Almost completely metabolized. The major metabolite is norverapamil, having pharmacological activity; Other metabolites, primarily, inactive.

Deduction

T_1/2 It is between 3 to 7 h after a single oral administration. With repeated admission T_1/2 verapamil increases by almost half compared with single dose.

Verapamil and its metabolites are excreted primarily in the urine (3-4% in unchanged form). During 24 h output 50% of the administered dose, during 48 no – 55-60%, during 5 days – 70%. To 16% excreted in the feces.

Pharmacokinetics in special clinical situations

Patients with hepatic impairment compared to individuals with normal liver function bioavailability of verapamil was much higher, and elongation was observed T_1/2.

Recent results indicate that, that there are no differences in the pharmacokinetics of verapamil in persons with normal renal function and in patients with end-stage renal failure.

Isoptin SR 240: testimony

• arterial hypertension: mild or moderate – monotherapy, severe – in a combination therapy;
• stable angina (angina);
• angiospastic angina (Prinzmetal angina);
• paroxysmal supraventricular tachycardia;
• fibrilloflutter, accompanied tachyarrhythmia (except WPW syndrome).

Isoptin SR 240: dosing regimen

The average daily dose is 240-360 mg. Long-term treatment should not exceed the daily dose 480 mg; It may be a temporary increase in the dose above this level.

At CHD (stable angina, Prinzmetal angina) Isoptin SR 240 administered in a daily dose of 240-480 mg (by 1/2-1 tab. 2 times / day at intervals 12 no).

At hypertension (mild or moderate) Isoptin SR 240 appoint 240 mg (1 tab.) 1 time / day in the morning. If you prefer a slow decrease in blood pressure, the treatment should be started with a dose of 120 mg (1/2 tab. Isoptin SR 240). If you want to appoint more 1/2-1 tab. evening with an interval between doses of about 12 no. The dose should be increased every 2 week of treatment.

At paroxysmal supraventricular tachycardia, tahiaritmicheskoy fibrilloflutter Isoptin SR 240 appoint 120-240 mg (1/2-1 tab.) 2 times / day at intervals 12 no.

At abnormal liver function the effect of the drug is enhanced and becomes longer as a result of slow metabolism of verapamil, It is depending on the severity of liver dysfunction. In such cases, the dose should be mounted with extreme caution; treatment should begin with taking the drug at lower doses (t. it is. Patients with cirrhosis of prescribers Isoptinum 40 mg 2-3 times / day).

The tablets should be taken with food or immediately after meals, swallowing whole and with water.

Isoptin SR 240: side effects

Cardio-vascular system: sometimes (when taken in high doses or in the presence of cardiovascular disorders) – fibrillation against the background of bradycardia (sinusovaya bradycardia, sinoatrialynaya blockade, AV-block II and III degree of bradyarrhythmia or atrial fibrillation), hypotension, palpitations, tachycardia, development or worsening symptoms of heart failure.

From the central and peripheral nervous system: rarely – headache, dizziness, drowsiness, fatigue, Increased nervousness, tremor, paresthesia.

From the digestive system: often – constipation; rarely – nausea, vomiting, bowel obstruction, pain and discomfort in the abdomen; described reversible increase in liver enzymes and / or alkaline phosphatase; in some cases – giperplaziya right, fully reversible after discontinuation of the drug.

On the part of the musculoskeletal system: in some cases – myalgia and arthralgia.

Allergic reactions: rarely – rash, hives, angioedema, Stevens-Johnson syndrome.

On the part of the endocrine system: elevated prolactin levels; rarely (elderly patients in long-term therapy) – gynecomastia, fully reversible after discontinuation of the drug; in some cases – galactorrhea, impotence.

Other: rarely – swelling of lower legs, rodonalgia, tides.

Isoptin SR 240: Contraindications

Absolute contraindications

• cardiogenic shock;
• complicated acute myocardial infarction (bradycardia, severe hypotension, left ventricular failure);
• AV-blockade II or III degrees;
• SSS (bradycardia-tachycardia syndrome);
• sinoatrialynaya blockade.

Relative contraindications

• AV block I degrees;
• bradycardia (less 50 u. / min);
• hypotension (systolic blood pressure less than 90 mmHg.);
• atrial fibrillation/flutter with WPW syndrome (the risk of ventricular tachycardia);
• heart failure (if necessary, before starting treatment with Isoptin SR 240 prescribed cardiac glycosides).

Isoptin SR 240: Pregnancy and lactation

The appointment of the drug Isoptin SR 240 Pregnancy (especially in the I trimester) and during lactation is possible only in the case, the expected benefit to the mother outweighs the potential risk to the fetus.

If necessary, the appointment during lactation breastfeeding should be discontinued.

Isoptin SR 240: Special instructions

In severe hypertension medication Isoptin SR 240 should be used in combination with other antihypertensive drugs (Diuretics, ACE inhibitors).

Effects on ability to drive vehicles and management mechanisms

Depending on the individual response to the drug a patient's ability to control a car or operate machinery during its reception may be reduced. This is especially important during the initial treatment period, when translated into reception Isoptin SR 240 after administration of the other drug, and while receiving alcohol.

Isoptin SR 240: overdose

Symptoms of poisoning as a result of drug overdose Isoptin SR 240 depends on the adoption of the preparation, time events and detoxification of myocardial contractility, depending on age. Reported cases of fatal overdose.

Symptoms: drop in blood pressure (in some cases to levels, which can not be measured), shock, loss of consciousness, AV block I or II degrees, often in the form of periods of the Wenckebach with or without slip rate, complete AV-block with complete AV-dissociation, slip rate, cardiac arrest; sinusovaya bradycardia, Stop sinus.

In overdose Isoptin SR 240 you need to keep in mind, that the active substance is released and absorbed from the intestine during 48 hours after oral administration. Depending on the time of dosing some conglomerates residues swollen tablets, acting as active depot, will be located throughout the gastrointestinal tract.

Treatment: It shows event, aimed at the elimination of the drug (eg, , induce vomiting, wash the stomach and small intestine in combination with endoscopic examination, appoint laxatives, emetics). If no motility of the stomach and intestine (signs peristalsis auscultation), it is advisable to carry out gastric lavage, even after 12 hours after oral administration. Typical activities include emergency resuscitation chest compressions, artificial respiration and electrical stimulation of the heart.

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

In the case of AV-block II or III degree, sinus bradycardia, heart failure shows atropine, isoprenaline, orciprenaline, holding a heart stimulation. If hypotension injected dopamine, doʙutamin, norepinephrine (noradrenaline).

In the case of steady signs of myocardial insufficiency administered dopamine, doʙutamin, if necessary, carry out additional calcium intake.

Isoptin SR 240: drug interaction

In vitro studies suggest that, that verapamil hydrochloride is metabolized with the participation isozymes CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. Clinically significant interaction was noted, while the use CYP3A4 inhibitors, which induced an increase in plasma levels of verapamil, while inducers of CYP3A4 reduces its concentration in plasma. Respectively, while the use of such funds should take into account the possibility of interaction.

The following table provides a list of possible drug interactions when taking Isoptin SR 240.

* in patsientov with progressiruyushtimi novoobrazovaniyami verapamil not affecting uroveny clearance or doxorubicin. In patients with small cell lung cancer verapamil reduced T_1/2 and C_max doxorubicin.

With the simultaneous use of the drug Isoptin SR 240 with antiarrhythmics, beta-blockers possible mutual reinforcement effects on the cardiovascular system (AV-occurrence of blockade, slowing of the heart rate, strengthening hypotension, development of heart failure).

Isoptin SR 240 can increase the effect of other antihypertensive drugs (incl. diuretics, vasodilators).

With the simultaneous use of the drug Isoptin SR 240 with prazosin, terazosin marked additive hypotensive effect.

Ritonavir and antiviral drugs can inhibit the metabolism of verapamil, thereby increasing its concentration in plasma. In this regard, the dose Isoptin SR 240 must be reduced.

With the simultaneous use of the drug Isoptin SR 240 with quinidine in patients with hypertrophic obstructive cardiomyopathy in some cases, seen the development of pulmonary edema.

With the simultaneous use of the drug Isoptin SR 240 with carbamazepine there is an increase in plasma levels of carbamazepine and strengthening its neurotoxicity. There may be inherent carbamazepine adverse reactions, such as diplopia, headache, ataxia or dizziness.

Isoptin SR 240 while the application increases the neurotoxicity of lithium.

The antihypertensive effect of Isoptin SR 240 may decrease while the use of rifampicin and sulfinpyrazone.

While the use of the drug Isoptin SR 240 effect of muscle relaxants may be enhanced.

In an application with acetylsalicylic acid can be observed an increase in bleeding.

While the use of the drug Isoptin SR 240 increased levels of ethanol in the plasma.

The simultaneous use of the drug Isoptin SR 240 It may lead to increased serum levels of simvastatin or lovastatin.

Patients, receiving verapamil, treatment of HMG-CoA reductase (simvastatin, lovastatin) It should start with the lowest possible dose, which further increase the. If you want to assign patients verapamil, already receiving HMG-CoA reductase, need to review and reduce their doses, the concentrations of serum cholesterol. This tactic should be followed, while the appointment of verapamil with atorvastatin (although there are no clinical data, confirming the interaction of atorvastatin and verapamil), because these are precisely known pharmacokinetic studies, confirmatory, verapamil in the same way that affects the level of atorvastatin.

Fluvastatin, pravastatin and rosuvastatin are not metabolized by the action of isozymes CYP3A4, therefore their interaction with verapamil least likely.

Isoptin SR 240: terms of dispensing from pharmacies

The drug is released under the prescription.

Isoptin SR 240: terms and conditions of storage

The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 3 year.