Expiration date: 03/2025
Feature: release form, composition
Tablet Twynsta oval, biconvex, uncoated, bilayer, one layer of white to almost white, the other gray-blue color on a white surface - the company's logo and engraved "A1", the other side of pill is smooth.
1 tablet contains:
is amlodipine besylate 6.935 mg, respectively. the content of amlodipine 5 mg
- telmisartan 40 mg
Auxiliary substances: sodium hydroxide 3.36 mg, povidone K25 12 mg, meglumin 12 mg, sorbitol - 168.64 mg, magnesium stearate 6 mg, microcrystalline cellulose - 125.765 mg, starch prezentatsionnyy - 53 mg, corn starch - 10 mg colloidal silicon dioxide 2 mg, mixture of dyes* - 0.3 mg.
Tablet Twynsta oval, biconvex, uncoated, bilayer, one layer of white to almost white, the other gray-blue color on a white surface - the company's logo and engraved "A2", the other side of pill is smooth.
1 tablet contains:
- besylate amlodipine 13.87 mg, respectively. the content of amlodipine 10 mg
- telmisartan 40 mg
Auxiliary substances: sodium hydroxide 3.36 mg, povidone K25 12 mg, meglumin 12 mg, sorbitol - 168.64 mg, magnesium stearate 6 mg, microcrystalline cellulose - 118.83 mg, starch prezentatsionnyy - 53 mg, corn starch - 10 mg colloidal silicon dioxide 2 mg, mixture of dyes* - 0.3 mg.
Tablet Twynsta oval, biconvex, uncoated, bilayer, one layer of white to almost white, the other gray-blue color on a white surface - the company's logo and engraved "A3", the other side of pill is smooth.
1 tablet contains:
is amlodipine besylate 6.935 mg, respectively. the content of amlodipine 5 mg
- telmisartan 80 mg
Auxiliary substances: sodium hydroxide 6.72 mg, povidone K25 - 24 mg, meglumin 24 mg, sorbitol - 337.28 mg, magnesium stearate 10 mg, microcrystalline cellulose - 125.765 mg, starch prezentatsionnyy - 53 mg, corn starch - 10 mg colloidal silicon dioxide 2 mg, mixture of dyes* - 0.3 mg.
Tablet Twynsta oval, biconvex, uncoated, bilayer, one layer of white to almost white, the other gray-blue color on a white surface - the company's logo and engraved "A4", the other side of pill is smooth.
1 tablet contains:
- besylate amlodipine 13.87 mg, respectively. the content of amlodipine 10 mg
- telmisartan 80 mg
Auxiliary substances: sodium hydroxide 6.72 mg, povidone K25 - 24 mg, meglumin 24 mg, sorbitol - 337.28 mg, magnesium stearate 10 mg, microcrystalline cellulose - 118.83 mg, starch prezentatsionnyy - 53 mg, corn starch - 10 mg colloidal silicon dioxide 2 mg, mixture of dyes* - 0.3 mg.
* Composition of mixture of dyes: iron oxide black (E172) - 76%, iron oxide yellow (E172) - 4%, FD&C blue No. 1 (brilliant blue FCF aluminum varnish), aluminum pigment (E133) - 20%.
Pharm group: Antihypertensive drug.
Formdata: TWISTA - combination drug containing two antihypertensive substances with complementary effects, allowing control of AD in patients with arterial (essential) hypertension: the antagonist receptor of angiotensin II, telmisartan, the blocker of slow calcium channels, derived digidropiridina, amlodipine. The combination of these ingredients has an additive antihypertensive effect, reducing blood pressure to a greater degree than each individual component. Drug Twynsta®, taken 1 time/day, leads to effective and sustainable reduction in blood pressure within 24 hours.
- Telmisartan:
Telmisartan is a specific antagonist of the angiotensin II receptor (type AT1), effective when administered. Has a high affinity to a subtype of AT1-angiotensin II receptor, through which is realized the action of angiotensin II. Displaces angiotensin II from the receptor, not having the action of agonist for this receptor. Telmisartan binds only to a subtype of AT1-angiotensin II receptor. The relationship is a long. Has no affinity for other receptors, including AT2-receptor. Reduces the concentration of aldosterone in the blood, does not inhibit the renin in the blood plasma and does not block ion channels. Telmisartan does not inhibit angiotensin converting enzyme (ACE, kininase II) (an enzyme that also breaks down bradykinin). Therefore, the enhancement of bradykinin-induced side effects are not expected.
In patients telmisartan dose of 80 mg completely blocks the hypertensive effect of angiotensin II. The beginning of the hypotensive effect observed during the 3 h after the first dose of telmisartan. The effect of the drug lasts for 24 hours and remains significant up to 48 h Pronounced hypotensive effect usually develops within 4-8 weeks after regular use.
In patients with hypertension telmisartan reduces systolic and diastolic blood pressure, without affecting heart rate.
In the case of abrupt cancellation of telmisartan AD slowly returns to the original level without the development of withdrawal syndrome.
- Amlodipine:
Amlodipine is dihydropyridine derivative that belongs to the class of blockers of slow calcium channels. It inhibits the transmembrane influx of calcium ions in and cardiomiotita gladkomyshechne cells receptacles. Mechanism of antigipertenzivnogo action of amlodipine is associated with direct relaxing effect on vascular smooth muscle cells, which leads to a decrease in peripheral vascular resistance and reduction in blood pressure.
In patients with arterial hypertension use of amlodipine 1 times per day. provides a clinically significant decrease AD over 24 h.
Orthostatic hypotension is not characteristic during the application of amlodipine because of the slow beginning of action of the drug. In patients with arterial hypertension and normal renal function amlodipine in therapeutic doses resulted in a decrease in vascular resistance of the kidney to increase glomerular filtration rate and effective blood plasma in the kidney, without changing the filter or proteinuria.
Amlodipine does not lead to any adverse metabolic effects or changes in the content of lipids of blood plasma and is therefore suitable for use in patients with asthma, diabetes and gout. The use of amlodipine in patients with heart failure is not accompanied by negative inotropic effects (no reduced tolerance to physical load is not reduced ejection fraction of the left ventricle).
Pharmacokinetics: the Pharmacokinetics of combination of fixed doses:
The rate and extent of drug absorption of Twynsta® equivalent to the bioavailability of telmisartan and amlodipine in the case of their application in the form of separate tablets.
The pharmacokinetics of the individual components
- Telmisartan:
If ingestion is rapidly absorbed from the gastrointestinal tract. Bioavailability of 50%. When taken in conjunction with food reduction AUC ranged from 6% (at a dose of 40 mg) to 19% (at the dose of 160 mg). After 3 h after ingestion, the concentration in the plasma is, regardless of the meal.
Linking blood plasma proteins is 99.5%, mainly to albumin and alpha-1 glycoprotein. The average value of the apparent Vd in the equilibrium concentration of 500 L.
Telmisartan is metabolized by conjugation with glucuronic acid. Metabolites pharmacologically inactive.
T1/2 20 h Cmax in blood plasma and, to a lesser extent AUC increase disproportionately the size of the dose. Data on clinically significant accumulation of telmisartan is not available. Eliminated through the intestines unchanged, renal excretion, less than 2%. The total plasma clearance is high (900 ml/min) compared with hepatic blood flow (about 1,500 ml/min).
- Amlodipine:
After taking amlodipine orally in therapeutic doses, Cmax in plasma is reached after 6-12 h. the Value of absolute bioavailability is 64% to 80%. Eating does not affect the bioavailability of amlodipine.
Vd amlodipine is approximately 21 l/kg. In vitro studies showed that patients with arterial hypertension approximately 97.5% of circulating amlodipine is bound to plasma proteins the blood.
Amlodipine largely (approximately 90%) metabolised in the liver to form inactive metabolites.
Elimination of amlodipine from the plasma of blood is biphasic. T1/2 is approximately 30-50 h Sustainable levels in plasma are reached after continuous administration of the drug for 7-8 days. Amlodipine is excreted by the kidneys in unchanged form (10%) and as metabolites (60%).
Pharmacokinetics in special clinical cases:
There is a difference in plasma concentrations in men and women. Cmax and AUC were approximately 3 and 2 times, respectively, higher in women compared with men without significant effect on the efficiency.
Pharmacokinetics of telmisartan in elderly patients is not different from younger patients. Dose adjustment is not required. In patients of advanced age there is a trend for decrease in clearance of amlodipine, which leads to an increase in AUC and T1/2.
Changing doses of telmisartan in patients with renal insufficiency not required, including patients, on hemodialysis. Telmisartan is not removed by hemodialysis.
The pharmacokinetics of amlodipine in patients with impaired renal function does not change significantly.
Pharmacokinetics studies conducted in patients with impaired liver function showed that the absolute bioavailability of telmisartan is increased almost to 100%.T1/2 in patients with impaired liver function is not changed. In patients with hepatic impairment, clearance of amlodipine is reduced, leading to increased values of AUC of approximately 40-60%.
Indications: — arterial hypertension (in patients, for the AD of insufficiently controlled with telmisartan or amlodipine in monotherapy)
— arterial hypertension (in patients, which shows the combined therapy),
— patients with arterial hypertension receiving telmisartan and amlodipine as separate tablets, as a replacement for the therapy.
Category effects on the fetus: investigation of drug Twynsta® during pregnancy and lactation have not been conducted. Effects associated with individual ingredients of the preparation described below.
Pregnancy:
Telmisartan
The use of receptor antagonists of angiotensin II (ARA II) are contraindicated during pregnancy. When the diagnosis of pregnancy the drug should be discontinued immediately. If necessary, should be administered an alternative therapy.
It is known that the use of ARA II in the II and III trimesters of pregnancy has fetotoksicheskoe effect (decrease in kidney function, oligohydramnios, slow ossification of the skull of the fetus), and also observed neonatal toxicity (renal failure, hypotension and hyperkalemia).
Amlodipine
The limited data available regarding the effects of amlodipine or other calcium receptor antagonists, do not indicate adverse effects on the fetus. However, the potential risk of slowing down the birth process.
The breast-feeding period:
Special studies on the allocation of telmisartan and/or amlodipine with breast milk in women was conducted. In animal studies revealed that telmisartan is excreted in milk of lactating animals. Given the possible adverse reactions, the decision to continue breast-feeding or about the abolition of therapy should take into account its significance for the mother. Studies of the effect on fertility in humans have not been conducted.
Contraindications: obstructive disease of the biliary tract,
— severe hypotension,
— obstruction of the outlet tract of the left ventricle (including a high degree of aortic stenosis),
— hemodynamically unstable heart failure after acute myocardial infarction
— severe hepatic insufficiency,
— shock,
— fructose intolerance and malabsorption syndrome glucose/galactose or a deficit sucrase/isomaltase,
— pregnancy,
— lactation,
— the age 18 years (effectiveness and safety have not been established),
— hypersensitivity to active ingredients or auxiliary substances,
— hypersensitivity to other derivative of dihydropyridine.
Drug Twynsta should be administered with caution to patients with:
— obstructive diseases of the biliary tract or hepatic insufficiency,
— bilateral renal artery stenosis or stenosis of artery only kidneys,
— the condition after kidney transplantation,
— reduced BCC and/or hyponatremia,
— dual blockade of the renin-angiotensin-aldosterone system (RAAS),
— other conditions characterized by activation of the RAAS
— primary aldosteronism,
— stenosis of aortic and mitral valve, obstructive hypertrophic cardiomyopathy,
— heart failure
such as hyperkalemia,
— diabetes with an additional cardiovascular risk (ie, concomitant disease of the coronary arteries /coronary artery disease/),
— after 1 month after acute myocardial infarction and unstable angina.
Dosing: Adults
Drug Twynsta® should be taken 1 time/day, inside, regardless of meals.
Twynsta® may be prescribed to patients receiving the same dose of telmisartan and amlodipine as separate tablets, for the convenience of the therapy and increase commitment to treatment.
Twynsta® may be prescribed to patients who have the use of one one of telmisartan or amlodipine does not lead to adequate control of AD. Patients taking amlodipine at a dose of 10 mg, who observed adverse reactions, limiting the drug, for example, peripheral edema, can go to the drug of Twynsta® in the dose is 40/5 mg 1 time/day, that will allow to reduce the dose of amlodipine, but will not reduce the overall expected antihypertensive effect.
Treatment of hypertension the patient may begin with the drug Twynsta® in the case where it is assumed that achievement of BP control with any single drug unlikely. The usual initial dose of Twynsta® - 40/5 mg 1 times/day. Patients who need more significant decrease in blood pressure, can start taking the drug of Twynsta® dose 80/5 mg 1 times/day.
If, at least, after 2 weeks of treatment will require further reduction in blood pressure, the dose can be gradually increased to a maximum dose of 80/10 mg 1 times/day.
Twynsta® can be used together with other antihypertensive drugs.
The human kidney:
In patients with impaired renal function, including patients on hemodialysis, changes in drug dosing is not required. Amlodipine and telmisartan are not removed from the body during hemodialysis.
The human liver:
In patients with mild or moderate degree of liver dysfunction drug Twynsta® should be used with caution. The dose of telmisartan is 40 mg 1 time/day.
Elderly patients:
The dosage regimen requires no changes.
Peculiarities of action of the medicinal product at first use or withdrawal thereof:
After the first dose of telmisartan, the antihypertensive effect gradually develops over the first 3 h and the drug action lasts for 24 hours and remains significant up to 48 h.
In the case of abrupt cancellation of telmisartan AD slowly returns to the original level without the development of withdrawal syndrome.
Side effects: 1) anticipated based on the experiences of telmisartan
2) anticipated based on the experience of using amlodipine
3) expected with concomitant use of telmisartan and amlodipine
Inside the system-organ classes according to the frequency of side effects are used the following categories: very common (?1/10), often (?1/100, <, 1/10), infrequently (?1/1000, <, 1/100), rare (?1/10 000, <, 1/1000), very rare (<,1/10 000),
frequency unknown (cannot be estimated according to the available data).
Additional information in respect of individual components:
Side effects previously reported with one of the components of the drug (amlodipine or telmisartan) may be aggravated by the use of the drug of Twynsta®, even if not observed in clinical trials or during post marketing period.
Additional information regarding the combinations of components:
Peripheral edema, dose-dependent side effect of amlodipine, was observed in patients who received a combination of telmisartan and amlodipine, less often than patients who received only amlodipine.
Overdose: Symptoms:
Cases of overdose have not been identified. Possible overdose symptoms consist of symptoms of the individual components of the drug.
Telmisartan - expressed lower AD, tachycardia, possibly bradycardia, dizziness, increased creatinine concentration in blood serum, acute renal failure.
Amlodipine - excessive peripheral vasodilatation and possibly reflex tachycardia. You may experience severe and probably prolonged systemic hypotension up to development of shock with fatal outcome.
Treatment:
Hemodialysis is not effective. Monitoring the patient's condition, treatment should be symptomatic and supportive.
To counter the blockade of calcium channels may be useful to intravenous calcium gluconate.
Can be used the treatment of overdose, such as induction of vomiting, gastric lavage, administration of activated charcoal, the transfer of the patient to position "lying down with raised legs" and the introduction of plasma-substituting solutions in case of expressed lower AD.
Interactions: no Interactions between the two active components included in the fixed dose composition of this drug, in clinical studies were observed.
Special studies drug interactions drug Twynsta® with other drugs have not been conducted.
The combination of active ingredients:
While the use of the drug Twynsta® with the following preparations should take into account the following information.
Other antihypertensive drugs:
With simultaneous use with other antihypertensive drugs the antihypertensive effect of the drug Twynsta® may increase.
Drugs that can reduce blood pressure:
It can be expected that some drugs, such as baclofen and amifostine, due to its pharmacological properties, will increase the hypotensive effect of all antihypertensives including drug Twynsta®. In addition, orthostatic hypotension may increase with ethanol, barbiturates, narcotics or antidepressants.
Corticosteroids (systemic administration):
May reduce the hypotensive effect.
Telmisartan
While the use of telmisartan with:
— other antihypertensive agents: may increase hypotensive effect. In one study, the combined use of telmisartan and ramipril was an increase in AUC0-24 and Cmax of ramipril and ramiprilat in 2.5 times. The clinical significance of this interaction is not established.
digoxin, warfarin, hydrochlorothiazide, glibenclamide, simvastatin and amlodipine: not identified clinically significant interactions. The marked increase in the average concentration of digoxin in plasma in average by 20% (in one case by 39%). While the appointment of telmisartan and digoxin it is advisable to periodically determine the concentration of digoxin in the blood.
drugs lithium: marked reversible increase in the concentration of lithium in the blood, accompanied by toxic effects when taking ACE inhibitors. In rare cases, such change was in the appointment of antagonists of a receptor of angiotensin II, in particular, of telmisartan. While the appointment of lithium drugs and antagonists of the receptor of angiotensin II is recommended that the definition of lithium content in the blood.
— NSAIDs, including acetylsalicylic acid at doses used as anti-inflammatory agents, inhibitors of cyclooxygenase-2 (COX-2) and nonselective NSAIDs, can cause the development of acute renal failure in patients with reduced BCC. Drugs affecting the activity of the renin-angiotensin, including telmisartan, may have a synergistic effect. Patients receiving NSAIDs and telmisartan, in the beginning of treatment should be compensated BCC and monitoring of renal function.
While the use of NSAIDs and antihypertensive drugs, such telmisartan, reported the decrease of antihypertensive effect via inhibition of vasodilatory effect of prostaglandins.
Amlodipine
With simultaneous use of amlodipine with:
— grapefruit and grapefruit juice: odnovremenno the drug with grapefruit or grapefruit juice is not recommended because some patients by increasing the bioavailability of amlodipine can increase his antigipertenzivnye influence.
— inhibitors of CYP3A4: in a study in elderly patients, it was shown that diltiazem inhibits metabolism of amlodipine, probably through its effect on CYP3A4 (concentration of amlodipine in plasma increased by about 50% and enhanced the effect of amlodipine). It is possible that more active inhibitors of CYP3A4 (such as ketoconazole, Itraconazole, ritonavir) may increase the concentration of amlodipine in plasma to a greater extent than diltiazem.
— CYP3A4 inducers - anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidon), rifampicin, St. John's wort (Hypericum perforatum): concomitant use may lead to lower concentrations of amlodipine in plasma. Shown regular medical supervision. While the use of inducers of CYP3A4, and also after their withdrawal recommended (possible) changes in dose of amlodipine.
— the combined use of simvastatin at a dose of 80 mg amlodipine, regardless of the dose, helps increase the exposure of simvastatin up to 77% compared to simvastatin monotherapy. Therefore, the dose of simvastatin should not exceed 40 mg/day.
While the use of the below drugs should take into account the following information
Installed safety joint use amlodipine with thiazide diuretics, beta-blockers, ACE inhibitors, long-acting nitrates, nitroglycerin (used sublingually), NSAIDs, antibiotics and hypoglycemic agents for oral administration.
With simultaneous use of amlodipine and sildenafil is shown that each drug has provided independent hypotensive effect.
Additional information:
Simultaneous application of 20 healthy volunteers with 240 ml of grapefruit juice with a single dose of amlodipine 10 mg, taken inside, not led to a significant influence on the pharmacokinetic properties of amlodipine.
The simultaneous use of amlodipine with cimetidine had no significant effect on the pharmacokinetics of amlodipine.
The simultaneous use of amlodipine with atorvastatin, digoxin, warfarin, or cyclosporine does not significantly affect pharmacokinetics or pharmacodynamics of these drugs.
Based on experience with other agents that affect the RAAS, the simultaneous use of the drug Twynsta® and potassium-sparing diuretics, potassium supplements, potassium-containing salt, other means that increase potassium levels (e.g. heparin) may lead to hyperkalemia, so monitor this indicator in patients. In this regard, their concurrent use with telmisartan requires caution.
Special instructions: the Drug Twynsta should be administered with caution when the patient has the following conditions:
— abnormal liver function,
— bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, severe renal dysfunction. Some patients, due to the suppression of the RAAS, especially when using a combination of tools operating on this system, impaired renal function (including acute renal failure). Therefore, therapy involving this kind of dual blockade of the RAAS, should be carried out strictly individually and with careful monitoring of renal function (including periodic monitoring of potassium and creatinine in the serum). In cases of dependence of vascular tone and renal function mainly from the activity of the RAAS (e.g., patients with congestive heart failure, or kidney disease, including stenosis of renal arteries or stenosis of artery only kidneys), drugs that affect this system may be accompanied by the development of acute arterial hypotension, giperazotemii, oliguria, and in rare cases, acute renal failure,
— the condition after kidney transplantation (experience of the missing),
— reduction of BCC and/or hyponatremia as a result of prior diuretic therapy, limit salt intake, diarrhea or vomiting,
— dual blockade of the RAAS
other condition characterized by activation of the RAAS
— primary aldosteronism,
— stenosis of aortic and mitral valve, idiopathic hypertrophic subaortic stenosis,
heart failure,
— hyperkalemia,
— hereditary fructose intolerance,
— patients with diabetes and additional cardiovascular risk, ie patients with diabetes and concomitant disease of the coronary arteries (coronary artery disease), risk of fatal myocardial infarction and sudden cardiovascular death may be increased with treatment of antihypertensives, such as receptor antagonists angiotensin II and ACE inhibitors. In patients with diabetes mellitus ischemic heart disease may be asymptomatic and thus cannot be diagnosed. Patients with diabetes should undergo appropriate diagnosis, for example, a sample with the physical load, for diagnosis and treatment of CHD, respectively, before treatment with a medication Twynsta®.
Other instructions
Twynsta® less effective in the treatment of patients of black race (in this population is usually reduced renin activity in the blood).
No data on the use of the drug Twynsta® in patients with unstable angina, acute myocardial infarction and in the period of one month after myocardial infarction.
Effects on ability to drive vehicles and management mechanisms
Study of the effect on the ability to drive vehicles and management mechanisms was carried out. However, one should take into consideration that during treatment may experience undesirable effects such as fainting, drowsiness or dizziness. Therefore, during the driving or mechanisms should be used with caution. If patients experience these feelings, they should avoid potentially dangerous actions like driving vehicles or operating machinery.
