Tenox^® (Tablets) Instructions for Use

ATC Code

C08CA01 (Amlodipine)

Active Substance

Amlodipine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Calcium channel blocker. Antianginal and antihypertensive drug.

Pharmacotherapeutic Group

BMCC (Bone Mineral Crystal Complex)

Pharmacological Action

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

The antianginal action of amlodipine is presumably associated with its ability to dilate peripheral arterioles; this leads to a decrease in total peripheral vascular resistance, with no reflex tachycardia occurring.

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.

Peak plasma concentration (C_max) 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 elimination half-life (T_1/2) averages 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 Tenox^® (amlodipine) orally once daily, with or without food.

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

For vasospastic angina (Prinzmetal’s) and unstable angina, the initial adult dose is 5 mg to 10 mg.

Adjust the dose based on therapeutic efficacy and patient tolerance.

The maximum recommended dose is 10 mg once daily.

Dose titration should proceed in 2.5 mg to 5 mg increments, with intervals of 7 to 14 days between adjustments.

For small, fragile, or elderly patients, initiate therapy at 2.5 mg once daily.

In patients with hepatic impairment, use a lower initial dose of 2.5 mg once daily.

Dosage adjustment is not typically required for patients with renal impairment.

Monitor patients closely during the titration period for blood pressure control and adverse effects.

Do not crush or chew the tablets; swallow whole with a glass of water.

If a dose is missed, take it as soon as remembered unless it is almost time for the next dose.

Do not double the dose to make up for a missed one.

The antihypertensive effect is sustained over the 24-hour dosing interval.

Adverse Reactions

From the cardiovascular system: peripheral edema, tachycardia, flushing of the skin; when used in high doses – arterial hypotension, arrhythmias, dyspnea.

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

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

Allergic reactions: skin rash, itching.

Other: with long-term use – pain in the extremities.

Contraindications

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

Use in Pregnancy and Lactation

The safety of using amlodipine 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 cases of impaired liver function.

Use in Renal Impairment

Use with caution in cases of 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 the use of 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.

Dosage changes 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 slow 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 severity of 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 dose of simvastatin should be limited to 20 mg.

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

With concomitant use of sympathomimetics and estrogens, a decrease in the antihypertensive effect is possible due to sodium retention in the body.

Antipsychotics and isoflurane enhance the antihypertensive effect of dihydropyridine derivatives.

Concomitant use of inhalational anesthetics may enhance the hypotensive effect.

With concomitant use of amiodarone, an enhancement of the antihypertensive effect is possible.

With concomitant use of lithium carbonate, manifestations of neurotoxicity are possible (including nausea, vomiting, diarrhea, ataxia, tremor and/or tinnitus).

With concomitant use, orlistat reduces the antihypertensive effect of amlodipine, which can lead to a significant increase in blood pressure and the development of a hypertensive crisis.

With concomitant use of indomethacin and other NSAIDs, a decrease in the antihypertensive effect of amlodipine is possible due to inhibition of prostaglandin synthesis in the kidneys and fluid retention under the influence of NSAIDs.

With concomitant use of quinidine, an enhancement of the antihypertensive effect is possible.

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

Concomitant use of diltiazem (an inhibitor of the CYP3A4 isoenzyme) at a dose of 180 mg and amlodipine at a dose of 5 mg in elderly patients (from 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 (from 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 an increase in amlodipine plasma concentrations to a greater extent than diltiazem.

Amlodipine and inhibitors of the CYP3A4 isoenzyme should be used with caution.

There are no data on the effect of inducers of the CYP3A4 isoenzyme on the pharmacokinetics of amlodipine.

Blood pressure should be carefully monitored when amlodipine and inducers of the CYP3A4 isoenzyme are used concomitantly.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°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.