Calchek^® (Tablets) Instructions for Use

ATC Code

C08CA01 (Amlodipine)

Active Substance

Amlodipine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Calcium channel blocker

Pharmacotherapeutic Group

“Slow” calcium channel blocker

Pharmacological Action

A selective class II calcium channel blocker. The antihypertensive effect is due to a direct relaxing effect on vascular smooth muscles.

The antianginal effect of amlodipine is presumably associated with its ability to dilate peripheral arterioles; this leads to a reduction in total peripheral vascular resistance, without causing reflex tachycardia.

As a result, the myocardial oxygen demand and the energy consumption of the heart muscle are reduced.

On the other hand, Amlodipine appears to cause dilation of large coronary arteries and coronary arterioles in both intact and ischemic areas of the myocardium.

This ensures the supply of oxygen to the myocardium during coronary artery spasms.

Pharmacokinetics

When taken orally, it is absorbed slowly and almost completely from the gastrointestinal tract. C_max in plasma is reached within 6-9 hours.

Protein binding is 95-98%.

It undergoes minimal metabolism during the “first pass” through the liver and slow but significant hepatic metabolism to form metabolites with insignificant pharmacological activity.

The average T_1/2 is 35 hours and in arterial hypertension it can increase to an average of 48 hours, in elderly patients – up to 65 hours, and in cases of impaired liver function – up to 60 hours.

It is excreted mainly as metabolites: 59-62% by the kidneys, 20-25% via the intestine.

Indications

Arterial hypertension (as monotherapy or as part of combination therapy).

Stable angina, unstable angina, Prinzmetal’s angina (as monotherapy or as part of combination therapy).

ICD codes

Dosage Regimen

Take tablets orally with water, once daily.

For arterial hypertension and angina, the initial adult dose is 5 mg.

Increase the dose to 10 mg once daily based on individual therapeutic response and tolerability.

The maximum daily dose is 10 mg.

For geriatric patients, initiate therapy at the 5 mg dose; no initial dose adjustment is required.

In patients with hepatic impairment, use a 2.5 mg initial dose due to prolonged elimination half-life.

Exercise caution during dose titration in this patient population.

For renal impairment, no initial dose adjustment is necessary; standard dosing guidelines apply.

When co-administering with potent CYP3A4 inhibitors, consider using a lower starting dose.

Monitor for signs of hypotension and peripheral edema, particularly during the dose titration phase.

Discontinue treatment gradually; do not abruptly stop taking the medication.

Adverse Reactions

From the cardiovascular system: peripheral edema, tachycardia, skin flushing; with the use of high doses – arterial hypotension, arrhythmias, shortness of breath.

From the digestive system: nausea, abdominal pain; rarely – gingival hyperplasia.

From the CNS and peripheral nervous system: headache, fatigue, drowsiness, dizziness; with long-term use – paresthesia.

Allergic reactions: skin rash, itching.

Other: with long-term use – limb pain.

Contraindications

Severe arterial hypotension (systolic BP less than 90 mm Hg); obstruction of the left ventricular outflow tract (including severe aortic stenosis); hemodynamically unstable heart failure after myocardial infarction; children and adolescents under 18 years of age (efficacy and safety not established); hypersensitivity to amlodipine and other dihydropyridine derivatives.

Use in Pregnancy and Lactation

The safety of amlodipine use during pregnancy has not been established, so use is only possible if the intended benefit to the mother outweighs the potential risk to the fetus.

There are no data indicating the excretion of amlodipine in breast milk. However, it is known that other slow calcium channel blockers (dihydropyridine derivatives) are excreted in breast milk. In this regard, if it is necessary to use amlodipine during lactation, the issue of discontinuing breastfeeding should be considered.

Use in Hepatic Impairment

Use with caution in patients with impaired liver function.

Use in Renal Impairment

Use with caution in patients with impaired renal function.

Pediatric Use

There are no clinical data on the use of amlodipine in pediatrics.

Geriatric Use

No dose reduction is required for elderly patients.

Special Precautions

Use with caution in patients with hepatic insufficiency, chronic heart failure of non-ischemic etiology NYHA functional class III-IV, unstable angina, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after it), sick sinus syndrome (severe tachycardia, bradycardia), arterial hypotension, and when used concomitantly with inhibitors or inducers of the CYP3A4 isoenzyme.

During treatment with amlodipine in patients with chronic heart failure (NYHA class III and IV) of non-ischemic origin, an increased incidence of pulmonary edema was noted, despite the absence of signs of worsening heart failure.

In elderly patients, the T_1/2 of amlodipine may increase and its clearance may decrease. Dose adjustments are not required, but more careful monitoring of patients in this category is necessary.

The efficacy and safety of amlodipine in hypertensive crisis have not been established.

Although calcium channel blockers do not have a withdrawal syndrome, it is advisable to discontinue treatment with amlodipine gradually.

There are no clinical data on the use of amlodipine in pediatrics.

Drug Interactions

The antianginal and antihypertensive effects of slow calcium channel blockers may be enhanced when used concomitantly with thiazide and “loop” diuretics, ACE inhibitors, beta-blockers, and nitrates, and their antihypertensive effect may be enhanced when used concomitantly with alpha₁-blockers and antipsychotics.

Although a negative inotropic effect was not usually observed in studies of amlodipine, nevertheless, some slow calcium channel blockers may enhance the negative inotropic effect of antiarrhythmic drugs that cause QT interval prolongation (e.g., amiodarone and quinidine).

Concomitant multiple administration of amlodipine 10 mg and simvastatin 80 mg leads to a 77% increase in the bioavailability of simvastatin. In such cases, the simvastatin dose should be limited to 20 mg.

Antiviral drugs (e.g., ritonavir) increase the plasma concentrations of slow calcium channel blockers, including amlodipine.

Concomitant use of sympathomimetics and estrogens may reduce the antihypertensive effect due to sodium retention in the body.

Antipsychotics and isoflurane enhance the antihypertensive effect of dihydropyridine derivatives. Concomitant use with inhalation anesthetics may enhance the hypotensive effect.

Concomitant use with amiodarone may enhance the antihypertensive effect.

Concomitant use with lithium carbonate may lead to manifestations of neurotoxicity (including nausea, vomiting, diarrhea, ataxia, tremor and/or tinnitus).

Concomitant use with orlistat reduces the antihypertensive effect of amlodipine, which may lead to a significant increase in blood pressure and the development of a hypertensive crisis.

Concomitant use with indomethacin and other NSAIDs may reduce the antihypertensive effect of amlodipine due to inhibition of prostaglandin synthesis in the kidneys and fluid retention under the influence of NSAIDs.

Concomitant use with quinidine may enhance the antihypertensive effect.

Calcium supplements may reduce the effect of slow calcium channel blockers.

Concomitant use of diltiazem (a CYP3A4 isoenzyme inhibitor) 180 mg and amlodipine 5 mg in elderly patients (69 to 87 years) with arterial hypertension results in a 57% increase in the bioavailability of amlodipine.

Concomitant use of amlodipine and erythromycin in healthy volunteers (18 to 43 years) does not lead to significant changes in amlodipine exposure (22% increase in AUC). Although the clinical significance of these effects is not fully understood, they may be more pronounced in elderly patients.

Potent inhibitors of the CYP3A4 isoenzyme (e.g., ketoconazole, itraconazole) may lead to a greater increase in amlodipine plasma concentrations than diltiazem. Amlodipine and CYP3A4 isoenzyme inhibitors should be used with caution.

There are no data on the effect of CYP3A4 isoenzyme inducers on the pharmacokinetics of amlodipine. Blood pressure should be carefully monitored when amlodipine is used concomitantly with CYP3A4 isoenzyme inducers.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.