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Tarca® [Verapamil, Trandolapril]

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Clinical Pharmacology

Tarka - a combination drug, which consists of verapamil prolonged action and trandolapril.

Trandolapril is an ethyl ester (prodrug) of a non-sulfhydryl ACE inhibitor trandolaprilat.

Verapamil hydrochloride is a slow calcium channel blocker (BMCC).

Trandolapril

Trandolapril inhibits the activity of the renin-angiotensin-aldosterone system in blood plasma. Renin is an enzyme that is synthesized by the kidneys and enters the bloodstream, where it causes the conversion of angiotensinogen to angiotensin I (low-active decapeptide). The latter is transformed under the action of ACE (peptidyl dipeptidase) into angiotensin II, a powerful vasoconstrictor that causes arterial constriction and an increase in blood pressure, and also stimulates the secretion of aldosterone by the adrenal glands.

Inhibition of ACE leads to a decrease in plasma angiotensin II concentration, which is accompanied by a decrease in vasopressor activity and aldosterone secretion. Although aldosterone production is not significantly reduced, a slight increase in serum potassium concentration can be observed in combination with sodium and water loss.

The decrease in the concentration of angiotensin II by the feedback mechanism leads to an increase in the activity of renin in the blood plasma. Another function of ACE is the destruction of kinins (bradykinin), which have potent vasodilator properties, to inactive metabolites. In this regard, the suppression of ACE leads to an increase in circulating and tissue concentrations of the kallikrein-kinin system, which contributes to the expansion of blood vessels due to the activation of the prostaglandin system. This mechanism may partly determine the hypotensive effect of ACE inhibitors and is the cause of some side effects.

In patients with arterial hypertension, the use of ACE inhibitors leads to a comparable decrease in blood pressure in the "lying" and "standing" without a compensatory increase in heart rate. OPSS decreases, cardiac output does not change or increases, renal blood flow increases, and the glomerular filtration rate usually does not change. Abrupt cessation of therapy was not accompanied by a rapid increase in blood pressure.

The antihypertensive effect of trandolapril manifests itself 1 hour after ingestion and persists for at least 24 hours. In some cases, optimal control of blood pressure can be achieved only a few weeks after the start of treatment. With prolonged therapy, the hypotensive effect persists. Trandolapril does not worsen the circadian blood pressure profile.

Verapamil

Verapamil inhibits the flow of calcium ions through the "slow" calcium channel of the membranes of vascular smooth muscle cells, conductive and contractile cardiomyocytes. Verapamil causes a decrease in blood pressure, both at rest and during exercise due to the expansion of peripheral arterioles. As a result of a reduction in round focal disease (afterload), myocardial oxygen demand and energy consumption decrease. Verapamil reduces myocardial contractility. The negative inotropic effect of the drug can be offset by a decrease in OPSS. Cardiac index does not decrease, except for patients with left ventricular dysfunction.

Verapamil does not affect the sympathetic regulation of cardiac activity, since it does not block the β-adrenergic receptors. bronchial asthma and bronchospastic states are not a contraindication to veralamil.

Tarka

In studies on healthy volunteers, there were no signs of interaction between verapamil and trandolapril at the level of pharmacokinetic parameters or RAAS. Consequently, the synergism of the two drugs reflects their complementary pharmacodynamic effects. In clinical studies, the drug Tarka reduced blood pressure to a greater extent than both drugs separately.

Indications

Essential arterial hypertension (in patients for whom combination therapy is indicated).

Composition

1 tab.

2 mg;

verapamil hydrochloride - 180 mg.

Excipients:verapamil hydrochloride layer - microcrystalline cellulose - 59.1 mg, sodium alginate - 240 mg, povidone K30 - 36 mg, magnesium stearate - 2.4 mg, water - 22.5 mg;trandolapril layer - corn starch - 74.3 mg, lactose monohydrate - 107 mg, povidone K25 - 10.7 mg, hypromellose 6 MPa * s (type 2910) - 4 mg, sodium fumarate - 2 mg.

The composition of the film shell: hypromellose 6 MPa * s (type 2910) - 11.608 mg, hypromellose 15 MPa * s - 1.152 mg, hyprolosis 7 MPa * s - 1.152 mg, macrogol 400 - 1.8 mg, macrogol 6000 - 0.322 mg, talc - 1.878 mg, colloidal silicon dioxide - 0.03 mg, sodium dusate - 0.03 mg, titanium dioxide (E171) - 1.912 mg, iron dye red oxide (E172) - 0.112 mg, iron dye yellow oxide (E172) - 0.002 mg, iron dye black oxide (E172) - 0.002 mg.

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Dosage and Administration

Adults appoint 1 caps. 1 time / day The drug should be taken orally, preferably in the morning after a meal. The capsule is swallowed whole with water.

Adverse reactions

The following are side effects that have had a possible or probable connection with taking the drug Tark during clinical trials.

Nervous system disorders: often (≥1 / 100 to <1/10): headache, dizziness.

Violations of the cardiovascular system:often (from ≥1 / 100 to <1/10): AV blockade I degree.

Disorders of the respiratory system, organs of the chest and mediastinum: (from ≥1 / 100 to <1/10): cough.

Violations of the gastrointestinal tract: (from ≥1 / 100 to <1/10): constipation.

Common disorders:often (≥1 / 100 to <1/10): asthenia.

In addition to the reactions identified during clinical studies, the following side effects were identified in the process of post-registration use:

Infectious diseases: bronchitis.

Violations of the blood and lymphatic system: leukopenia, thrombocytopenia.

Metabolic disorders: hyperkalemia.

Mental Disorders: anxiety, insomnia.

Nervous system disorders:imbalance, paresthesia, drowsiness, syncope.

Violations by the organ of vision: blurred vision, "veil" before the eyes.

Labyrinth disturbances:dizziness.

Violations of the cardiovascular system: complete AV block, rest angina, bradycardia, sensation
palpitations, tachycardia.

Vascular disorders: hypotension, hyperemia of the skin, blood flushes to the skin of the face.

Disorders of the respiratory system, organs of the chest and mediastinum:shortness of breath, nasal congestion.

Violations of the gastrointestinal tract: nausea, diarrhea, dryness of the oral mucosa.

Violations of the skin and subcutaneous tissues: Stevens-Johnson syndrome, angioedema, pruritus, rash.

Disorders of the musculoskeletal and connective tissues: arthralgia, myalgia.

Kidney and urinary tract disorders:pollakiuria, polyuria.

Genital disorders: erectile disfunction.

Common disorders:chest pain, swelling, weakness.

Laboratory and instrumental data: increased LDH activity, alkaline phosphatase activity, creatinine concentration, urea concentration, ALT activity, blood AST.

Additional significant side effects that have been observed with verapamil are:

Immune system disorders: hypersensitivity.

Endocrine Disorders: hyperprolactinemia.

Heart disorders:AV-blockade I, II, III degree, sinus node arrest ("sinus arrest"), heart failure.

Disorders of the digestive system: gingival hyperplasia, abdominal pain, abdominal discomfort.

Violations of the skin and subcutaneous tissues: hives.

Breast disorders: gynecomastia, galactorrhea.

There are several separate reports of cases of paralysis (tetraparesis) associated with the combined use of verapamil and colchicine. This could be due to the penetration of colchicine through the BBB in connection with the suppression of the activity of CYP 3A4 and the P-glycoprotein by verapamil. The combined use of colchicine and verapamil is not recommended.

Additional significant side effects that have been observed with nitrandapril are:

Violations of the blood and lymphatic system: agranulocytosis.

Immune system disorders: hypersensitivity.

Violations of the gastrointestinal tract:vomiting, abdominal pain, pancreatitis.

Violations of the skin and subcutaneous tissues:alopecia.

Common disorders: fever.

The following are the side effects that have been reported with the use of other ACE inhibitors:

Violations of the blood and lymphatic system: pancytopenia.

Nervous system disorders:transient violation of cerebral circulation.

Heart disorders: myocardial infarction, cardiac arrest.

Vascular disorders: cerebral hemorrhage.

Disorders of the digestive system: intestinal angioedema.

Violations of the skin and subcutaneous tissues: erythema multiforme, toxic epidermal necrolysis.

Kidney and urinary tract disorders: acute renal failure.

Laboratory and instrumental data: decrease in hemoglobin and hematocrit.

Contraindications

history of angioedema associated with taking ACE inhibitors;

- hereditary and idiopathic angioedema;

- cardiogenic shock;

- chronic heart failure of the III and IV functional class according to the NYHA classification;

- AV blockade of II and III degree (except for patients with an artificial pacemaker);

- sinoatrial block;

- acute myocardial infarction;

- SSS (except for patients with an artificial pacemaker);

- acute heart failure;

- Atrial fibrillation / flutter in patients with Wolff-Parkinson-White syndrome;

- severe bradycardia;

- severe hypotension;

- severe renal dysfunction (CC <30 ml="" min="" p="">

- pregnancy;

- breastfeeding period;

- age up to 18 years (efficacy and safety have not been established);

- simultaneous reception with colchicine and dantrolene;

- aortic stenosis or obstruction of the outflow tract of the left ventricle;

- hypertrophic obstructive cardiomyopathy;

- simultaneous use with beta-blockers (IV) (for
with the exception of patients undergoing treatment in the intensive care unit);

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (the product contains lactose);

- hypersensitivity to any component of the drug or to any other ACE inhibitor.

Carefully: hyperkalemia; abnormal liver function
and / or kidney function (CC more than 30 ml / min); with systemic
connective tissue diseases (including systemic lupus erythematosus, scleroderma) especially during treatment
corticosteroids and antimetabolites; risk of agranulocytosis and neutropenia; oppression of bone marrow hematopoiesis, AV-blockade of I degree; bradycardia; hypotension; conditions involving a decrease in the BCC (including diarrhea, vomiting), bilateral renal artery stenosis, single kidney artery stenosis (for example, after transplantation), a condition after kidney transplantation, diseases accompanied by neuromuscular transmission (myasthenia gravis, syndrome Lambert-Eaton, severe Duchenne muscular dystrophy); in patients on a diet with restricted salt; before the procedure of low-density lipoprotein apheresis (LDL), simultaneous
desensitization therapy with allergens (for example, hymenoptera poison) - the risk of anaphylactoid reactions (in some cases, life-threatening); surgical intervention (general anesthesia) - the risk of excessive
reduce blood pressure, hemodialysis using high-flow polyacrylonitrile membranes - the risk of anaphylactoid
reactions.

Drug interactions

Verapamil Interactions

In vitro studies indicate that verapamil is metabolized by the isoenzymes CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18.

Verapamil is an inhibitor of CYP3A4 and P-glycoprotein. Clinically significant interactions were observed with simultaneous use with CYP3A4 inhibitors, while there was an increase in plasma level of verapamil, while CYP3A4 inducers decreased plasma concentration of verapamil.Accordingly, with the simultaneous use of such funds should take into account the possibility of this interaction.

The table summarizes the data on drug interactions due to the content of verapamil.

. The table summarizes the data on drug interactions due to verapamil.

A drug	Possible effect on verapamil or verapamil on another drug while applying
Alpha blockers
Prazosin	The increase in Cmax of prazosin (approximately 40%) does not affect T1 / 2 of prazosin.
Terazosin	Increased terazosin AUC (approximately 24%) and Cmax (approximately 25%).
Antiarrhythmic drugs
Flekainid	Minimal effect on plasma clearance of flecainide (<10%); does not affect plasma clearance of verapamil.
Quinidine	Reduced oral clearance of quinidine (approximately 35%).
Bronchodilators
Theophylline	Reduced oral and systemic clearance (approximately 20%). In smokers - a decrease of about 11%.
Anticonvulsants
Carbamazepine	Increased AUC of carbamazepine (approximately 46%) in patients with resistant partial epilepsy.
Antidepressants
Imipramine	An increase in imipramine AUC (approximately 15%) does not affect the level of the active metabolite, desipramine.
Oral hypoglycemic agents
Gliburide	Gliburide Cmax increases (approximately 28%), AUC (approximately 26%).
Antimicrobial agents
Clarithromycin	Possible increase in the level of verapamil.
Erythromycin	Possible increase in the level of verapamil.
Rifampicin	AUC (approximately 97%), Cmax (approximately 94%), bioavailability (approximately 92%) of verapamil decrease.
Telithromycin	Possible increase in the level of verapamil.
Antitumor agents
Doxorubicin	AUC (89%) and Cmax (61%) of doxorubicin are increased when taking verapamil orally in patients with small cell lung cancer. The introduction of verapamil IV patients with advanced tumors does not affect the plasma clearance of doxirubicin.
Barbiturates
Phenobarbital	The oral clearance of verapamil is increased approximately 5 times.
Benzodiazepines and other tranquilizers
Buspirone	The AUC and Cmax of buspirone increased 3.4 times.
Midazolam	AUC (approximately 3 times) and Cmax (approximately 2 times) midazolam increases.
Beta blockers
Metoprolol	AUC (approximately 32.5%) and Cmax (approximately 41%) of metoprolol are increased in patients with angina pectoris.
Propranolol	AUC (approximately 65%) and Cmax (approximately 94%) of propranolol are increased in patients with angina pectoris.
Cardiac glycosides
Digitoxin	Total clearance (approximately 27%) and extrarenal clearance (approximately 29%) of digitoxin decrease.
Digoxin	In healthy volunteers, Cmax (approximately 45-53%), Css (approximately 42%) and AUC (approximately 52%) of digoxin increase. Reducing the dose of digoxin.
Histamine H2 Receptor Blockers
Cimetidine	AUC of R- and S-verapamil increases (approximately 25% and 40%, respectively) with a decrease in clearance of R- and S-verapamil.
Immunosuppressants
Cyclosporine	Increased AUC, Css, Cmax (approximately 45%) of cyclosporine.
Sirolimus	Possible increase in sirolimus.
Tacrolimus	Possible increase in tacrolimus.
Everolimus	Increasing the level of everolimus is possible.
HMG-CoA reductase inhibitors
Atorvastatin	Perhaps an increase in atorvastatin levels, an increase in the level of verapamil by about 42.8% in plasma.
Lovastatin	Possible increase in lovastatin.
Simvastatin	AUC increases (approximately 2.6 times) and Cmax (approximately 4.6 times) simvastatin.
Serotonin Receptor Antagonists
Almotriptan	AUC (approximately 20%) and Cmax (approximately 24%) of almotriptan are increasing.
Urikozurichesky means
Sulfinpyrazon	Increased oral clearance of verapamil (about 3 times), a decrease in its bioavailability (approximately 60%).
Other
Grapefruit juice	Increased AUC of R- and S-verapamil (approximately 49% and 37%, respectively) and Cmax R- and S-verapamil (approximately 75% and 51%, respectively). T1 / 2 and renal clearance did not change.
Hypericum perforatum	AUC of R- and S-verapamil decreases (approximately 78% and 80%, respectively) with decreasing Cmax.

Other possible interactions of verapamil

With simultaneous use with the drug Tarka antiarrhythmic drugs and beta-blockers may increase the adverse effects on the cardiovascular system (more pronounced AV-blockade, a more significant reduction in heart rate, development of heart failure and increased arterial hypotension).

With simultaneous use of quinidine with the drug Tarka hypotensive effect is enhanced. Patients with hypertrophic obstructive cardiomyopathy may develop pulmonary edema.

With the simultaneous use of antihypertensive drugs, diuretics and vazodilatatorov drug Tarka increases the hypotensive effect.

With simultaneous use of the drug Tarka prazosin, terazosin increases the hypotensive effect.

With simultaneous use of the drug Tarka, some drugs for treating HIV infection (ritonavir) can inhibit the metabolism of verapamil, which leads to an increase in its concentration in blood plasma. With simultaneous use of the dose of verapamil should be reduced.

With the simultaneous use of carbamazepine with the drug Tarka, the level of carbamazepine in the blood plasma increases, which may be accompanied by side effects characteristic of carbamazepine - diplopia, headache, ataxia or dizziness.

With simultaneous use of lithium with the drug Tarka increases the neurotoxicity of lithium.

With the simultaneous use of rifampicin with the drug Tarka may decrease the hypotensive action of verapamil.

Colchicine is a substrate for CYP3A4 isoenzyme and P-glycoprotein. It is known that verapamil inhibits the activity of CYP3A isoenzyme and P-glycoprotein. Therefore, when used simultaneously with verapamil, the concentration of colchicine in the blood can increase significantly. The combined use of drugs is contraindicated.

Cases of hyperkalemia and suppression of myocardial function were noted in patients with coronary artery disease when prescribing verapamil after taking dantrolene. Joint use of drugs is contraindicated.

With simultaneous use of sulfinpirazon with the drug Tarka, a decrease in the hypotensive action of verapamil is possible.

With simultaneous use with the drug Tarka, the effect of muscle relaxants may increase.

With the simultaneous use of acetylsalicylic acid as an antiplatelet agent with verapamil, the tendency to bleeding may increase.

With simultaneous use with verapamil, the level of ethanol in the blood plasma increases.

Simultaneous use with verapamil can lead to an increase in the serum level of simvastatin / atorvastatin / lovastatin.

Patients receiving verapamil, treatment with HMG-CoA reductase inhibitors (i.e. simvastatin / atorvastatin / lovastatin) should be started with the lowest possible doses with their gradual increase during therapy. If, however, it is necessary to prescribe verapamil to patients already receiving HMG-CoA reductase inhibitors, then their doses should be revised and reduced accordingly to serum cholesterol concentrations.

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

Trandolapril interactions

Diuretics or other antihypertensive drugs can enhance the hypotensive effect of trandolapril.

Potassium-sparing diuretics (spironolactone, amiloride, triamterene) or potassium preparations increase the risk of hyperkalemia, especially in patients with renal insufficiency. Trandolapril can reduce potassium loss when used in conjunction with thiazide diuretics.

The simultaneous use of trandolapril (as well as any ACE inhibitors) by hypoglycemic agents (insulin or oral hypoglycemic agents) may enhance the hypoglycemic effect and lead to an increased risk of hypoglycemia.

Trandolapril may worsen lithium clearance. Need to control the level of lithium in the serum.

Other interactions

When high-flow polyacrylonitrile membranes were used in patients receiving ACE inhibitors during hemodialysis, anaphylactoid reactions were described. In patients receiving ACE inhibitors, the use of membranes of this type during hemodialysis should be avoided.

Non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the hypotensive effect of trandolapril, therefore, when you join NSAIDs to treatment with trandolapril or cancel them, you need a blood pressure control.

ACE inhibitors can enhance the hypotensive effect of certain agents for inhalation anesthesia.

Allopuripol, cytostatics, immunosuppressants and systemic corticosteroids or procainamide may increase the risk of leukopenia when treated with ACE inhibitors.

Aitacides can reduce the bioavailability of ACE inhibitors.

The antihypertensive effect of ACE inhibitors can be reduced by co-prescribing sympathomimetics. In such cases, careful monitoring is required.

As with the use of any other antihypertensive drugs, co-prescribing antipsychotics or tricyclic antidepressants increases the risk of orthostatic hypotension.

Pregnancy and Lactation

Pregnancy

The safety of the drug Tarka in pregnant women has not been established. Use during pregnancy is contraindicated.
There are separate observations on the development of lung hypoplasia in newborns, intrauterine growth retardation, open arterial duct and hypoplasia of the skull bones after the use of ACE inhibitors during
of pregnancy.

There is no information about the teratogenic or embryo / fetotoxic effects of ACE inhibitors in the first trimester of pregnancy, but this possibility cannot be completely ruled out. In patients planning pregnancy, antihypertensive drugs should be prescribed, for which the safety of use during pregnancy has been proven, except in cases where the use of ACE inhibitors is necessary. If pregnancy occurs in the process of taking an ACE inhibitor, it should be immediately canceled and a more suitable treatment prescribed.

It is known that the use of ACE inhibitors in the second and third trimester of pregnancy may be fetotoxic
the effect of drugs (impaired renal function, lack of water, slowing down ossification of the skull bones) and toxic effects on the newborn (renal failure, arterial hypotension, hyperkalemia). In the case of trandolapril, starting from the second trimester of pregnancy, ultrasound assessment of fetal kidney function and the state of the skull is recommended. Newborns whose mothers took ACE inhibitors during pregnancy should be monitored by a doctor to rule out arterial hypotension.

Breastfeeding period

The use of the drug Tarka during breastfeeding is contraindicated. Verapamil is excreted in breast milk.

Data on the use of trandolapril during breastfeeding is not available. Preference should be given to drugs with a studied safety profile for this group of patients, especially when feeding newborns and premature babies.

Special instructions

Liver dysfunction

Since trandolapril is metabolized in the liver to form an active metabolite, patients with impaired liver function should be prescribed the drug with caution and with careful observation of the physician.

Hypotension

In patients with uncomplicated arterial hypertension after taking the first dose of trandolapril or increasing the dose of the drug, the development of arterial hypotension was observed, accompanied by clinical symptoms.The risk of arterial hypotension is higher when water and electrolyte imbalance is disturbed as a result of prolonged diuretic therapy, restriction of salt intake, dialysis, diarrhea or vomiting. In these patients, before starting treatment with tradolapril, diuretic therapy should be discontinued and the BCC and / or sodium content should be replenished.

Agranulocytosis / oppression of bone marrow hematopoiesis

When treating with ACE inhibitors, cases of agranulocytosis and bone marrow suppression are described. These phenomena more often
occur in patients with impaired renal function, especially with systemic connective tissue diseases. Have
such patients (for example, with systemic lupus erythematosus or scleroderma) it is advisable to regularly monitor
the number of leukocytes in the blood and the protein content in the urine, especially in violation of kidney function, treatment with corticosteroids and antimetabolites.

Angioedema

Trandolapril may cause angioedema of the face, tongue, pharynx, and / or larynx. There is evidence that ACE inhibitors are more likely to cause angioedema in patients of the Negroid race.

During treatment with ACE inhibitors, there were also cases of angioedema. This possibility should be taken into account in the development of abdominal pain (accompanied by nausea or vomiting, or without these symptoms) while receiving trandolapril.

Heart failure

The composition of the drug Tarka includes verapamil, so the use of the combined drug should be avoided in patients with severe dysfunction of the left ventricle (for example, with a ventricular ejection fraction less than 30%, an increase in the wedging pressure of the pulmonary capillaries more than 20 mm Hg or severe symptoms of chronic heart failure) and in patients with any degree of left ventricular dysfunction, if they receive beta-blockers.

Special patient groups

The drug Tarka has not been studied in children under 18 years old, so its use in this age group is not recommended.

General Precautions

In some patients receiving diuretics (especially in the first days of treatment), after administering trandolapril or increasing its dose, a sharp decrease in blood pressure is observed.

Renal dysfunction

When examining patients with arterial hypertension, renal function should always be assessed. In patients with QA less than 30 ml / min, lower doses of trandolapril are required.

In patients with impaired renal function, chronic heart failure, bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney (for example, after its transplantation), the risk of deterioration of renal function is increased. In some patients with arterial hypertension, without impairing the function of pochae, when administering trandolapril in combination with a diuretic, an increase in blood urea nitrogen and serum creatinine may be observed.

Hyperkalemia

In patients with arterial hypertension, especially with impaired renal function, the drug Tarka can cause hyperkalemia.

Surgical intervention / general anesthesia

For surgical interventions or general anesthesia with the use of drugs that cause hypotension, trandolapril can block the formation of angiotensin II, associated with compensatory renin release.

Desensitization

Patients receiving ACE inhibitors during a course of desensitization (for example, hymenoptera poison) may in rare cases develop life-threatening anaphylactic reactions.

LDL apheresis

During LDL apheresis in patients receiving ACE inhibitors, the development of life-threatening anaphylactic reactions was observed.

Influence on ability to drive motor vehicles and work with mechanisms

Care must be taken when driving and engaging in other potentially hazardous activities that require increased concentration and psychomotor speed, especially at the beginning of treatment. The drug Tarka can help to increase the blood alcohol content and slow down its elimination. In this regard, the effects of alcohol can be enhanced.

Overdosage

In clinical studies, the maximum dose of trandolapril was 16 mg. However, there were no signs of intolerance.

In case of an overdose of drug Tarka, the following symptoms caused by verapamil are possible: a marked decrease in blood pressure, AV-blockade, bradycardia, asystole. Overdose deaths have been reported.

In case of an overdose of drug Tarka, the following symptoms may be caused by tetrapol: marked reduction in blood pressure, shock, stupor, bradycardia, electrolyte disturbances, renal failure.

Treatment: symptomatic. Treatment of verapamil overdose includes parenteral administration of calcium supplements, the use of beta adrenomimetics and gastric lavage. Given the slow absorption of the drug of prolonged action, the patient’s condition should be monitored for 48 hours; hospitalization may be required during this period. Verapamil is not removed by hemodialysis.

Brand name: Tarka
Active ingredient: Verapamil, Trandolapril
Dosage form: pills with modified release, film-coated pink, oval, engraved with "Δ182" on one side.
Manufacturer: Pierre Fabre Medicament