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Pharmacological properties

tonorma is a combined antihypertensive drug containing atenolol, nifedipine and chlortalidone. the antihypertensive effect of the drug is due to the mechanism of action of its components and, first of all, the main of them - atenolol.

Atenolol - cardioselective β blocker1-adrenoreceptors. It has antihypertensive, antianginal and antiarrhythmic effects. It has no internal sympathomimetic activity and membrane stabilizing action. It mainly blocks the β-adrenergic receptors of the heart and reduces the stimulating effect on the heart of the sympathetic nervous system and catecholamines circulating in the blood, as a result of which the automatism of the sinus node, heart rate decreases, AV conductivity slows down, myocardial contractility decreases, myocardial oxygen demand decreases.

Chlortalidone is a long-acting thiazide-like diuretic. It blocks the reabsorption of sodium ions, chlorine and, accordingly, liquid in the distal tubules of the nephron. Increases the excretion of potassium, magnesium ions from the body. Delays the excretion of calcium and uric acid ions. It reduces blood pressure by reducing bcc, lowering cardiac output, as well as reducing OPSS with prolonged use.

Nifedipine is a 1,4-dihydropyridine type calcium antagonist. It inhibits the transmembrane flow of calcium ions through slow calcium channels into the cell. It acts on the cells of the myocardium and smooth muscles of the coronary arteries and peripheral vessels. In the heart, nifedipine dilates coronary arteries, especially large blood vessels, and even intact segments of the walls of partially stenotic vessels. In addition, nifedipine reduces the tone of the smooth muscles of the coronary arteries, which leads to an increase in coronary blood flow and prevents angiospasm. With prolonged use, it prevents the development of atherosclerotic plaques in the vessel wall. Reduces myocardial oxygen demand by reducing afterload. It reduces the tone of the smooth muscles of arterioles, thereby reducing the increased resistance of peripheral vessels, which leads to a decrease in blood pressure. Nifedipine increases the excretion of sodium and water from the body. The antihypertensive effect is especially pronounced in patients with hypertension.

Pharmacokinetics The active ingredients of the drug do not interact with each other, so the metabolism of each component goes its own way. After oral administration, its main component, atenolol, is absorbed in the digestive tract in an amount of 50-60%. 5% of the drug binds to blood plasma proteins, the distribution volume is 0.7 l / kg. Penetrates through the placental barrier and into breast milk. Atenolol practically does not penetrate the BBB. T½ is 6–9 hours and may be prolonged in case of impaired renal function. The pharmacological effect of atenolol lasts a long period - up to 24 hours. 85% of the dose taken is excreted unchanged in the urine.

Nifedipine is rapidly absorbed by oral administration. Cmax in blood plasma is achieved 30 minutes after administration. T½ is 3-4 hours. Approximately 80% is excreted by the kidneys in the form of inactive metabolites, ≈15% - with feces.

Chlortalidone is well absorbed by oral administration, in the systemic circulation is absorbed on the surface of red blood cells, less associated with plasma proteins. The diuretic effect begins 2–4 hours after ingestion and lasts for ≥1 days, sometimes up to 3 days. T½ long - 30–40 hours. Excreted in urine (≈25%) and feces (≈75%). A characteristic feature of the action of chlortalidone is the relative duration of the diuretic effect, due to its slow excretion by the kidneys.


Ag, if therapy with one or two components of the drug is ineffective.


The drug is used by adults inside during or after a meal, without chewing, mainly at the same time. the dose and duration of treatment are determined by the doctor individually. the average adult dose is 1-2 tablets per day.


Hypersensitivity to atenolol, chlortalidone, nifedipine, to other dihydropyridines and β-adrenergic blockers or other components of the drug.

Myocardial infarction and the first month after myocardial infarction.

Unstable angina pectoris.

Acute heart failure.

Heart Failure (NYHA III – IV).

Sick sinus syndrome.

Sinus bradycardia (heart rate 50 beats / min).

AV block II and III degree.

Sinoatrial block.

Clinically significant aortic stenosis.

Arterial hypotension (systolic blood pressure 90 mm RT. Art.).

Cardiogenic shock.

Severe peripheral circulation disorders.

AD, bronchial obstructive syndrome.

Metabolic acidosis.

Untreated pheochromocytoma.

Ileostomy, colostomy.

Severe hepatic and / or renal failure (glomerular filtration rate of 30 ml / min), anuria.

Concomitant use with lithium preparations, MAO inhibitors (with the exception of MAO-B inhibitors), rifampicin.

The drug is contraindicated in patients who have taken verapamil in the last 48 hours.

Side effects

Cardiac disorders: bradycardia, tachycardia, palpitations, worsening heart failure, impaired av-conduction, angina pectoris, hot flashes, edema.

Vascular disorders: cold extremities, vasodilation, arterial hypotension, orthostatic hypotension, syncope, increased intermittent claudication in patients with Raynauds syndrome. In patients with malignant hypertension and hypovolemia undergoing hemodialysis, a significant decrease in blood pressure due to vasodilation can occur.

From the blood and lymphatic systems: thrombocytopenia, agranulocytosis, leukopenia, purpura, neutropenia, pancytopenia.

Neurological disorders: headache, vertigo, migraine, dizziness, tremor, syncope, paresthesia / dysesthesia, hypesthesia, drowsiness.

Mental disorders: sleep disturbances, insomnia, anxiety, mood changes (including depression), nightmares, confusion, psychosis, agitation, aggressiveness, hallucinations, impaired concentration.

From the side of the organ of vision: visual impairment, decreased secretion of lacrimal fluid, conjunctivitis, dry eyes, sensation of pain in the eyes.

From the respiratory system, chest and mediastinal organs: nosebleeds, nasal congestion, dyspnea, symptoms of bronchial obstruction; history of bronchospasm in patients with AD.

From the gastrointestinal tract: gastrointestinal disorders, constipation, diarrhea, abdominal pain, nausea, dyspepsia, flatulence, dry mouth, gum hyperplasia, vomiting, gastroesophageal sphincter insufficiency, dysphagia, bezoar, intestinal obstruction, intestinal ulcer.

From the hepatobiliary system: hepatotoxicity, including hepatitis, intrahepatic cholestasis, a transient increase in the activity of liver enzymes, jaundice, pancreatitis (mainly in women).

From the urinary system: polyuria, dysuria, difficulty urinating, interstitial nephritis.

From the musculoskeletal system and connective tissue: muscle cramps, joint swelling, arthralgia, myalgia.

From the side of metabolism and metabolism: hypoglycemia in patients with diabetes mellitus, hyperglycemia, impaired tolerance to carbohydrates.

From the reproductive system: impaired libido, erectile dysfunction, impotence, gynecomastia.

From the immune system, skin and subcutaneous tissue: hypersensitivity reactions, including allergic edema (including laryngeal edema), anaphylactic / anaphylactoid reactions, hyperemia, itching, rash, urticaria, Quincke edema, dermatitis; alopecia, psoriasis-like skin reactions, exacerbation of psoriasis, photosensitivity, purpura, toxic epidermal necrolysis, exfoliative dermatitis.

Laboratory studies: hyperuricemia, hyponatremia, hypomagnesemia, hypercalcemia, hypercholesterolemia, hypertriglyceridemia, increased levels of antinuclear antibodies.

Others: general weakness, increased fatigue, malaise, nonspecific pain, chills, increased sweating, fever.

special instructions

Treatment with the drug should be carried out under the supervision of a physician.

When used with other antihypertensive agents, postural arterial hypotension may occur. Patients should be monitored for blood pressure.

The drug reduces heart rate. In case of a slowdown in heart rate, a dose adjustment should be made.

Drug withdrawal should be carried out gradually, since angina pectoris may worsen and, in some cases, the onset of myocardial infarction (withdrawal syndrome) may accelerate.

The drug is used with caution in patients with impaired liver and kidney function, AV blockade блок degree, heart failure (NYHA ΙΙ), impaired peripheral circulation (Raynauds syndrome, obliterating diseases of the vessels of the lower extremities), Prinzmetal angina, impaired water-electrolyte balance, gout psoriasis, depression; in elderly patients.

The drug is used with caution in patients with congestive heart failure. At the first signs of decompensation of heart failure, you should stop using the drug and consult a doctor.

The drug is used with caution in people with diabetes because of the possibility of masking the symptoms of hypoglycemia. Plasma glucose should be monitored.

The drug is used with caution in patients with a pronounced narrowing of the gastrointestinal tract due to the possibility of symptoms of obstruction. Bezoars may occur that may require surgical intervention.

The drug is used with caution in patients with severe history of hypersensitivity and those receiving desensitizing therapy to reduce adrenergic counteraction.

The drug is used with caution in patients with malignant hypertension and hypovolemia undergoing hemodialysis, since a significant decrease in blood pressure due to vasodilation can occur.

When prescribing the drug to patients with pheochromocytoma, it is necessary to prescribe α-adrenoreceptor blockers in advance to prevent the development of a hypertensive crisis.

In most cases, before surgery with general anesthesia, there is no need to stop taking the drug. However, the drug should be used with caution in combination with drugs for anesthesia due to a decrease in the severity of reflex tachycardia and an increased risk of developing arterial hypotension.

The drug should not be used in patients with bronchial obstructive syndrome, other bronchospastic diseases and acute attacks of stable angina pectoris.

It is necessary to periodically determine the levels of electrolytes in blood plasma and urine to identify possible electrolyte imbalance, this is especially important for patients with indomitable vomiting or when injecting fluid parenterally.

Potassium levels should be periodically determined, especially in the elderly, in patients taking digitalis for the treatment of heart failure, in patients with an unbalanced diet, or in patients with complaints of digestive tract disorders.

If in vitro fertilization attempts are unsuccessful, in the absence of other explanations, calcium antagonists, such as nifedipine, may be considered as a possible cause of this phenomenon.

The use of the drug can lead to false positive results in an X-ray examination using a barium contrast medium (for example, filling defects are interpreted as a polyp).

When using the drug, a positive doping test reaction is possible.

During treatment, stop drinking alcohol.

Use during pregnancy and lactation. The drug is contraindicated during pregnancy and lactation.

Children. The drug is not used in children.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. During treatment, caution should be exercised when driving vehicles or working with machinery, and in case of dizziness, refrain from potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.


With simultaneous use with other drugs, it is possible:

with anesthetics, antiarrhythmic drugs, slow calcium channel blockers, β-adrenergic blockers - increased severity of negative chrono-, foreign and dromotropic effects;

with cardiac glycosides - the occurrence of tachy- or bradycardia, arrhythmias, as well as increased hypokalemia; with the simultaneous use of these drugs, laboratory indicators should be monitored;

with dihydropyridines - increased hypotensive effect, heart failure in patients with chronic heart failure;

with reserpine, guanethidine, guanfacin, clonidine - the occurrence of bradycardia. With the simultaneous use of these drugs, clonidine can be stopped only a few days after discontinuation of the drug;

with methyldopa - increased hypotensive effect and the occurrence of bradycardia;

with NSAIDs, estrogens, α- and β-adrenergic agonists - a decrease in the severity of the effect of atenolol, which is part of the drug;

with inhibitors of the cytochrome P450 3A4 system (in particular macrolide antibiotics, HIV protease inhibitors, antimycotics of the azole group, fluoxetine, nefazodone, cisapride, valproic acid, diltiazem, cimetidine, quinupristine / dalphopristine) - increased nifedine effect; with the simultaneous use of these drugs, blood pressure should be monitored; azithromycin, which is structurally similar to representatives of the macrolide antibiotic class, does not inhibit cytochrome P450 3A4;

with inductors of the cytochrome P450 3A4 system (in particular phenytoin, carbamazepine, phenobarbital) - weakening the effect of nifedipine;

with antihypertensive agents of different groups, ACE inhibitors, AT antagonists1-receptors, diuretics, peripheral vasodilators (PDE-5 inhibitors), nitrates, tricyclic antidepressants, antiepileptic drugs, barbiturates, phenothiazines, narcotic drugs, baclofen, magnesium sulfate - increased hypotensive effect;

with antidepolarizing muscle relaxants - increased effect of the latter;

with adrenaline, norepinephrine - increased effect of the latter;

with sympathomimetic agents - a decrease in bronchodilator activity;

with indirect anticoagulants - potentiation of the effect of the latter;

with oral hypoglycemic agents, insulin - increased effect of the latter; with the simultaneous use of these drugs, glucose levels in blood plasma should be monitored;

with lidocaine - a decrease in its excretion and an increased risk of toxic effects;

with tacrolimus, theophylline - an increase in the concentration of the latter in blood plasma; their plasma concentration should be carefully monitored and the dose adjusted if necessary;

with quinidine - a decrease in the concentration of the latter in blood plasma; with the simultaneous use of these drugs, blood pressure should be monitored; after discontinuation of the drug, it is necessary to carefully monitor the concentration of quinidine and, if necessary, adjust the dose.

Grapefruit juice inhibits the cytochrome P450 3A4 system. The simultaneous use of the drug with the use of grapefruit juice leads to an increase in the concentration of nifedipine in blood plasma and prolongation of its effect due to a decrease in metabolism.This can lead to increased hypotensive effect.

The use of nifedipine can cause falsely elevated spectrophotometric values ​​of vanillyl mindic acid in blood plasma. However, when determining by high performance liquid chromatography, this effect is not observed.

Ethyl alcohol potentiates the effect of the drug.

Quitting smoking increases the therapeutic effect of atenolol as a result of a decrease in its metabolism and an increase in the level of the drug in the blood.


Symptoms: the clinical picture depends on the degree of intoxication and is manifested mainly by disorders of the cardiovascular system and central nervous system.

An overdose can lead to arterial hypotension, bradycardia, heart failure and cardiogenic shock. In severe cases, respiratory failure, bronchospasm, vomiting, impaired consciousness, up to coma, hyperglycemia, metabolic acidosis, hypoxia, cardiogenic shock, which is accompanied by pulmonary edema, tachycardia are observed; extremely rarely - generalized convulsive attacks.

Treatment: in case of overdose or with an alarming decrease in heart rate and / or blood pressure, drug treatment is stopped. In intensive care units, careful monitoring of vital signs should be carried out and, if necessary, corrected.

If necessary, appoint:

  • atropine (0.5–2 mg iv in the form of a bolus);
  • glucagon: initial dose of 1–10 mg iv (jet), then 2–2.5 mg / h as a continuous infusion;
  • sympathomimetics depending on body weight and effect (dopamine, dobutamine, isoprenaline, oxyprenaline or adrenaline).

If drug treatment for bradycardia is ineffective, pacing is possible.

With bronchospasm, β is prescribed2sympathomimetics in the form of an aerosol (in case of insufficiency of the effect also in / in) or aminophylline in / in.

With generalized seizures, a slow intravenous administration of diazepam is prescribed.

Storage conditions

In the original packaging at a temperature not exceeding 25 ° C.

Tags: Atenolol, Nifedipine, Chlortalidone