Universal reference book for medicines
Product name: TWINSTA ® (TWYNSTA ® )

Active substance: amlodipine, telmisartan

Type: Antihypertensive drug

Manufacturer: BOEHRINGER INGELHEIM INTERNATIONAL (Germany) manufactured by CIPLA (India)
Composition, form of production and packaging
Tablets
are oval, biconvex, without shell, two-layer, one layer from white to almost white, the other - gray-blue;
on the white surface - the company logo and engraving "A1", the other side of the tablet is smooth.
1 tab.

amlodipine besylate 6.935 mg,

which corresponds to the content of amlodipine 5 mg

telmisartan 40 mg

[PRING] sodium hydroxide - 3.36 mg, povidone K25 - 12 mg, meglumine - 12 mg, sorbitol - 168.64 mg, magnesium stearate - 6 mg, microcrystalline cellulose - 125.765 mg, pregelatinized starch - 53 mg, starch corn - 10 mg, silicon colloidal dioxide - 2 mg, a mixture of dyes * - 0.3 mg.

7 pcs.
- blisters (2) - packs of cardboard.
7 pcs.
- blisters (4) - packs of cardboard.
Tablets are oval, biconvex, without shell, two-layer, one layer from white to almost white, the other - gray-blue;
on the white surface - the company logo and engraving "A2", the other side of the tablet is smooth.
1 tab.

amlodipine besylate 13.87 mg,

which corresponds to the content of amlodipine 10 mg

telmisartan 40 mg

[PRING] sodium hydroxide - 3.36 mg, povidone K25 - 12 mg, meglumine - 12 mg, sorbitol - 168.64 mg, magnesium stearate - 6 mg, microcrystalline cellulose - 118.83 mg, pregelatinized starch - 53 mg, corn starch - 10 mg, silicon colloidal dioxide - 2 mg, a mixture of dyes * - 0.3 mg.

7 pcs.
- blisters (2) - packs of cardboard.
7 pcs.
- blisters (4) - packs of cardboard.
Tablets are oval, biconvex, without shell, two-layer, one layer from white to almost white, the other - gray-blue;
on the white surface - the company logo and engraving "A3", the other side of the tablet is smooth.
1 tab.

amlodipine besylate 6.935 mg,

which corresponds to the content of amlodipine 5 mg

telmisartan 80 mg

[PRING] sodium hydroxide - 6.72 mg, povidone K25 - 24 mg, meglumine - 24 mg, sorbitol - 337.28 mg, magnesium stearate - 10 mg, cellulose microcrystalline - 125.765 mg, pregelatinized starch - 53 mg, corn starch - 10 mg, silicon colloidal dioxide - 2 mg, a mixture of dyes * - 0.3 mg.

7 pcs.
- blisters (2) - packs of cardboard.
7 pcs.
- blisters (4) - packs of cardboard.
Tablets are oval, biconvex, without shell, two-layer, one layer from white to almost white, the other - gray-blue;
on the white surface - the company logo and engraving "A4", the other side of the tablet is smooth.
1 tab.

amlodipine besylate 13.87 mg,

which corresponds to the content of amlodipine 10 mg

telmisartan 80 mg

[PRING] sodium hydroxide - 6.72 mg, povidone K25 - 24 mg, meglumine - 24 mg, sorbitol - 337.28 mg, magnesium stearate - 10 mg, microcrystalline cellulose - 118.83 mg, pregelatinized starch - 53 mg, corn starch - 10 mg, silicon colloidal dioxide - 2 mg, a mixture of dyes * - 0.3 mg.

7 pcs.
- blisters (2) - packs of cardboard.
7 pcs.
- blisters (4) - packs of cardboard.
* The composition of the mixture of dyes: iron oxide black (E172) - 76%, iron oxide yellow (E172) - 4%, FD & C blue No. 1 (diamond blue FCF aluminum lacquer), aluminum pigment (E133) - 20%.

INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2014.

PHARMACHOLOGIC EFFECT

Combination drug containing two antihypertensive substances with a complementary effect that allows controlling blood pressure in patients with arterial (essential) hypertension: angiotensin II receptor antagonist, telmisartan, and slow calcium channel blocker, dihydropyridine derivative, amlodipine.
The combination of these substances has an additive antihypertensive effect, reducing arterial pressure more than each individual component. The drug Twistast ® , taken 1 time / day, leads to an effective and steady decrease in blood pressure within 24 hours.
Telmisartan

Telmisartan is a specific angiotensin II receptor antagonist (type AT 1 ), effective when ingested.
Has a high affinity for the AT 1 -receptor of angiotensin II, through which the action of angiotensin II is realized. It displaces angiotensin II from the bond to the receptor, not having the action of an agonist for this receptor. Telmisartan binds only to the subtype of AT 1 -receptor angiotensin II. Communication is of a lasting nature. Does not have an affinity for other receptors, incl. to the AT 2 receptor.Reduces the concentration of aldosterone in the blood, does not inhibit renin in the blood plasma and does not block the ion channels. Telmisartan does not inhibit the angiotensin-converting enzyme (ACE, kininase II) (an enzyme that also breaks down bradykinin). Therefore, the enhancement of bradykinin-induced side effects is not expected.
In patients, telmisartan at a dose of 80 mg completely blocks the hypertensive effect of angiotensin II.
The onset of hypotensive action is noted within 3 hours after the first administration of telmisartan. The effect of the drug persists for 24 hours and remains significant until 48 hours. The pronounced antihypertensive effect usually develops 4-8 weeks after regular administration.
In patients with arterial hypertension, telmisartan reduces systolic and diastolic blood pressure without affecting the heart rate.

In the case of a sharp withdrawal of telmisartan, blood pressure gradually returns to the baseline without the development of withdrawal syndrome.

Amlodipine

Amlodipine - a derivative of dihydropyridine, belongs to the class of blockers of slow calcium channels.
It inhibits transmembrannoe intake of calcium ions in cardiomyocytes and smooth muscle cells of blood vessels. The mechanism of antihypertensive action of amlodipine is associated with a direct relaxing effect on the smooth muscle cells of the vessels, which leads to a decrease in peripheral vascular resistance and a decrease in blood pressure.
In patients with arterial hypertension, the use of amlodipine 1 time / day provides a clinically significant reduction in blood pressure for 24 hours.

Orthostatic arterial hypotension is not characteristic during the application of amlodipine due to the slow onset of the drug.
In patients with arterial hypertension and normal renal function, amlodipine in therapeutic doses reduced the resistance of the kidney vessels, increased glomerular filtration rate and the effective blood flow in the kidneys, without altering the filtration or proteinuria.
Amlodipine does not lead to any metabolic adverse effects or changes in plasma lipids, and is therefore suitable for use in patients with bronchial asthma, diabetes and gout.
The use of amlodipine in patients with heart failure is not accompanied by a negative inotropic effect (exercise tolerance does not decrease, the left ventricular ejection fraction does not decrease).
PHARMACOKINETICS

Pharmacokinetics of a combination of fixed doses

The rate and degree of absorption of the Twanna® preparation are equivalent to the bioavailability of telmisartan and amlodipine when administered as separate tablets.

Pharmacokinetics of individual components

Telmisartan

Suction

When ingested quickly absorbed from the digestive tract.
Bioavailability - 50%. When taken concomitantly with food, the decrease in AUC ranges from 6% (at a dose of 40 mg) to 19% (at a dose of 160 mg). After 3 hours after ingestion, the concentration in the blood plasma levels out, regardless of food intake.
Distribution

Binding to plasma proteins is 99.5%, mainly with albumin and alpha-1 glycoprotein.
The average value of the apparent V d at an equilibrium concentration of 500 liters.
Metabolism

Metabolized telmisartan by conjugation with glucuronic acid.
Metabolites are pharmacologically inactive.
Excretion

T 1/2 - more than 20 hours C max in blood plasma and, to a lesser extent, AUC increase disproportionately to the dose value.
There are no data on the clinically significant accumulation of telmisartan. It is excreted through the intestine in unchanged form, excretion by the kidneys of less than 2%. The total plasma clearance is high (900 ml / min) compared with hepatic blood flow (about 1500 ml / min).
Amlodipine

Suction

After taking amlodipine inside in therapeutic doses, Cmax in blood plasma is reached after 6-12 hours. The absolute bioavailability is between 64% and 80%.
Eating food does not affect the bioavailability of amlodipine.
Distribution

V d of amlodipine is approximately 21 l / kg.
In vitro studies have shown that in patients with arterial hypertension, approximately 97.5% of circulating amlodipine binds to plasma proteins.
Metabolism

Amlodipine is metabolized to a significant extent (approximately 90%) in the liver with the formation of inactive metabolites.

Excretion

Removal of amlodipine from the blood plasma occurs biphasic.
T 1/2 is approximately 30-50 hours. Stable levels in the blood plasma are achieved after a constant intake of the drug for 7-8 days. Amlodipine is excreted by the kidneys both in unchanged form (10%) and in the form of 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 than in men without significant effect on efficacy.
The pharmacokinetics of telmisartan in elderly patients does not differ from young patients.
Dose correction is not required. In elderly patients there is a tendency to decrease the clearance of amlodipine, which leads to an increase in AUC and T 1/2 .
A change in the dose of telmisartan in patients with renal insufficiency is 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.

Studies of pharmacokinetics conducted in patients with impaired hepatic function showed that the absolute bioavailability of telmisartan increases to almost 100%. T1/2 in patients with impaired hepatic function does not change.
In patients with hepatic insufficiency, clearance of amlodipine decreased, which led to an increase in the AUC value by approximately 40-60%.
INDICATIONS

- arterial hypertension (for patients whose blood pressure is not adequately controlled by telmisartan or amlodipine in monotherapy);

- arterial hypertension (for patients who are shown combined therapy);

- patients with arterial hypertension receiving telmisartan and amlodipine in the form of individual tablets, as a substitute for this therapy.

DOSING MODE

Adults

The drug Twinast ® should be taken 1 time / day, inside, regardless of food intake.

Twistast® can be administered to patients receiving the same doses of telmisartan and amlodipine in separate tablets, for the convenience of therapy and increased adherence to treatment.

Twistast® may be administered to patients in whom the use of one amlodipine or one telmisartan does not lead to adequate control of blood pressure.
Patients taking amlodipine at a dose of 10 mg who have adverse drug-limiting reactions, such as peripheral edema, may switch to Twistast® at a dose of 40/5 mg once a day, which will reduce the dose of amlodipine, but not will reduce the overall expected antihypertensive effect.
Treatment of hypertension in a patient can begin with the use of the drug Twistast ® in the case where it is assumed that achieving the control of blood pressure with the help of any one drug is unlikely.
The usual initial dose of the drug Twistast ® is 40/5 mg 1 time / day. Patients who need a more significant reduction in blood pressure may start taking Twinst ® in a dose of 80/5 mg 1 time / day.
If, at least after 2 weeks of treatment, an additional reduction in blood pressure is required, the dose of the drug can be gradually increased to a maximum dose of 80/10 mg once / day.

Twistast ® can be used together with other antihypertensive drugs.

Renal impairment

In patients with impaired renal function, including patients on hemodialysis, there is no need to change the dosage of the drug.
Amlodipine and telmisartan are not removed from the body during hemodialysis.
Dysfunction of the liver

In patients with mild to moderate liver function disorder, the Twinst® preparation should be used with caution.
The dose of telmisartan should not exceed 40 mg 1 time / day.
Elderly patients

Dosing regimen does not require any changes.

Features of the drug during the first admission or when it is canceled

After the first dose of telmisartan, the hypotensive effect gradually develops during the first 3 hours and the effect of the drug persists for 24 hours and remains significant until 48 hours.

In the case of a sharp withdrawal of telmisartan, blood pressure gradually returns to the baseline without the development of withdrawal syndrome.

SIDE EFFECT

1) Expected on the basis of experience with telmisartan

2) Expected on the basis of experience with amlodipine

3) expected with simultaneous use of telmisartan and amlodipine

Within the system-organ classes, the following categories are used for the incidence of side effects: very often (? 1/10);
often (? 1/100, <1/10); infrequently (? 1/1000, <1/100); rarely (? 1/10 000, <1/1000); very rarely (<1/10 000);
frequency is unknown (can not be calculated from available data).

System-Organ Class Side Effect Frequency of occurrence

Infections and Infections Cystitis 3) Rarely

Urinary tract infection 1) Infrequently

Infections of the upper respiratory tract 1) Infrequently

Sepsis, incl.
with lethal outcome 1) Rarely
Psychotic disorders Depression 3) , anxiety 3) , insomnia 3) Rarely

Lability of mood 2) , confused consciousness 2) Frequency unknown

Disturbances from the nervous system Dizziness 3) Often

Drowsiness 3) , migraine 3) , headache 3) , paresthesia 3) Infrequently

Decrease in sensitivity or resistance to external factors 3) , taste disorder 3) , syncope 3) , tremor 3) , peripheral neuropathy 3) Rarely

Disturbances from the immune system Anaphylactic reaction 1) Rarely

Hypersensitivity 1), 2) Rarely 1) , Frequency unknown 1)

Impaired vision. 3) Rarely

Violations from Vertigo's hearing organs 3) Infrequently

Noise in the ears 2) Frequency unknown

Disturbances from the cardiovascular system Bradycardia 3) , palpitations 3) Infrequently

Tachycardia 1) Infrequently

Myocardial infarction 2) Rarely

Arrhythmia 2) , ventricular tachycardia 2) , atrial fibrillation 2) Frequency unknown

Pronounced decrease in blood pressure 3) , orthostatic hypotension 3) Infrequently

Respiratory system disorders Cough 3) Infrequently

Dyspnea 1), 2) Infrequently 1) Frequency is unknown 2)

Rhinitis 2) Frequency unknown

Disturbances from the gastrointestinal tract Pain in the abdomen 3) , diarrhea 3) , nausea 3) , flatulence 1) Infrequently

Vomiting 3) , dyspepsia 3) , discomfort in the stomach 1) Rarely

Changes in the rhythm of defecation 2) , pancreatitis 2) , gastritis 2) Frequency unknown

Dysfunction of the liver 1) Rarely

Hepatitis 2) , jaundice 2) Frequency unknown

Increased activity of hepatic transaminases (mainly reflecting cholestasis) 2) Frequency unknown

Increased level of hepatic enzymes 3) Rarely

Disturbances from the skin and subcutaneous tissue Eczema 3) , erythema 3) , rash 1), 3) , drug rash 1) , toxic rash 1) Rarely

Skin itching 3) Infrequently

Angioedema 1), 2) Rarely 1) , frequency unknown 2)

Hyperhidrosis 1), 2) Infrequently 1) , the frequency is unknown 2)

Urticaria 1), 2) Rarely 1) , the frequency is unknown 2)

Alopecia 2) , purpura 2) , skin discoloration 2) , erythema multiforme 2) , exfoliative dermatitis 2) , Stevens-Johnson syndrome 2) , photosensitivity reaction 2) , vasculitis 2) Frequency unknown

Disturbances from the musculoskeletal system of arthralgia 3) , back pain 3) , muscle spasms (gastrocnemius muscle cramps) 3) , myalgia 3) Infrequently

Pain in the lower extremities 3) , pain in the tendons (symptoms resembling tendonitis) 1) Rarely

Disorders from the genitourinary system of Nicturia 3) Rarely

Impaired renal function, including acute renal failure 1) , urination disorders 2) , frequent urination 2) Frequency unknown

3) Infrequently

Common disorders Peripheral edema 3) Often

Asthenia (weakness) 3) , pain in the chest 3) , increased fatigue 3) , swelling 3) Infrequently

Misery 3) , flu-like syndrome 1) , a feeling of flush to the face 3) , gingival hypertrophy 3) , dryness of the oral mucosa 3) Rarely

Pain 2) , weight gain 2) , weight loss 2) , gynecomastia 2) Frequency unknown

Reactions identified in special studies Increase in uric acid in the blood 3) , increase in the level of creatinine in the blood 1) and creatine phosphokinase (CK) 1) , decrease in hemoglobin 1) (anemia, weakness), hypoglycemia (in patients with diabetes mellitus) 1) , eosinophilia 1) Rarely

Leukopenia 2) , hyperglycemia 2) Frequency unknown

Hyperkalemia 1) Infrequently

Thrombocytopenia 1), 2) Rarely 1) , the frequency is unknown 2)

Further information on individual components

Side effects previously reported with the use of one of the components of the drug (amlodipine or telmisartan) may increase with the use of Twistast ® , even if they were not observed in clinical trials or during the postmarketing period.

Further information on the combination of components

Peripheral edema, a dose-dependent side effect of amlodipine, was observed in patients who received a combination of telmisartan and amlodipine, less frequently than patients receiving amlodipine alone.

CONTRAINDICATIONS

- Obstructive diseases of the biliary tract;

- severe arterial hypotension;

- Obstruction of the outgoing tract of the left ventricle (including a high degree of aortic stenosis);

- hemodynamically unstable heart failure after acute myocardial infarction;

severe hepatic impairment;

- shock;

- fructose intolerance and malabsorption syndrome glucose / galactose or deficit sucrase / isomaltase;
- Pregnancy;

- the period of breastfeeding;

- the age of 18 years (effectiveness and safety have been established);
- increased sensitivity to the active ingredients or excipients;
- Hypersensitivity to any other dihydropyridine derivatives.
The drug should be used with caution in patients with:
- obstructive diseases of the biliary tract or liver insufficiency;
- bilateral renal artery stenosis or stenosis of the artery to a solitary kidney;
- 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 the aortic and mitral valve, obstructive hypertrophic cardiomyopathy;
- heart failure;
- hyperkalemia;
- diabetes with additional cardiovascular risk (i.e. concomitant coronary artery disease / CHD /);
- after 1 month after acute myocardial infarction and unstable angina.
PREGNANCY AND LACTATION

Special studies of the drug Tvinsta ® have not been conducted during pregnancy and lactation. Effects related to individual components of the formulation are described below.
Pregnancy
Telmisartan
The use of angiotensin II receptor antagonists (ARA II) is contraindicated in pregnancy. In the diagnosis of pregnancy the drug should be discontinued immediately. If necessary, alternative therapy should be administered.
It is known that the use of ARA for II II and III trimester of pregnancy has fetotoksichicheskoe effect (reduction of renal function, oligohydramnios, fetal skull ossification retardation) and neonatal observed toxicity (renal failure, hypotension and hyperkalaemia).
Amlodipine
The limited data available on the effects of amlodipine and other calcium receptor antagonists, do not indicate the presence of adverse effects on the fetus. However, the possible risk of slowing down the process of childbirth.
Lactation
No specific studies on the allocation of telmisartan and / or amlodipine with breast milk in women was conducted. In animal studies showed that telmisartan is excreted in the milk of lactating animals. Given the possible adverse reactions, the decision to continue breastfeeding or cancellation of therapy should be made taking into account its importance to the mother. Studies on the effect on human fertility have not been conducted.
APPLICATION FOR FUNCTIONS OF THE LIVER

In patients with renal impairment, including patients on hemodialysis, the drug dosage change is required. Amlodipine and telmisartan are not removed from the body during hemodialysis.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Patients with mild or moderate impaired liver function Tvinsta preparation ® should be used with caution. Telmisartan dose should not exceed 40 mg 1 time / day.
APPLICATION FOR CHILDREN

Contraindicated in children and adolescents under 18 years.

APPLICATION IN ELDERLY PATIENTS

The dosage regimen does not require modification.
SPECIAL INSTRUCTIONS

The drug should be used with caution if the patient has the following states:
- abnormal liver function;
- bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, severe renal dysfunction. In some patients, due to suppress the RAAS, especially when using combinations of means acting on this system is disturbed renal function (including acute renal failure). Therefore, therapy, followed by a similar dual RAAS blockade, must be carried out strictly individually and with careful monitoring of renal function (including periodic monitoring of potassium and creatinine in serum). In cases depending vascular tone and renal function primarily on the activity of the RAAS (e.g., patients with chronic heart failure, or kidney disease, including stenosis of renal arteries, or stenosis of the artery only kidneys), designation drugs affecting the system,It may be accompanied by the development of acute hypotension, hyperasotemia, oliguria, and in rare cases acute renal failure;
- condition after kidney transplantation (application no experience);
- reducing the BCC and / or hyponatremia due to prior therapy with diuretics, limiting reception salt, diarrhea or vomiting;
- dual blockade of the RAAS;
- other conditions characterized by activation of the RAAS;
- primary aldosteronism;
- stenosis of the aortic and mitral valve, idiopathic hypertrophic subaortic stenosis;
- heart failure;
- hyperkalemia;
- hereditary fructose intolerance;
- in patients with diabetes mellitus and additional cardiovascular risk, ie Patients with diabetes mellitus and associated coronary artery disease (CAD) risk of fatal myocardial infarction and sudden cardiovascular death may be increased when treating antihypertensives such as angiotensin II antagonists and ACE inhibitors. In patients with diabetes mellitus CHD may occur symptomless, whereby not be diagnosed. Patients with diabetes must receive appropriate diagnosis, for example, exercise tests, for diagnosing and treating coronary artery disease, respectively, before treatment with Tvinsta ® .
Further information
Tvinsta ®less effective in the treatment of patients blacks (in this population typically reduced activity of renin in the blood).
There are no data on the use of the drug Tvinsta ® in patients with unstable angina, acute myocardial infarction and in the period of one month after myocardial infarction.
Impact on the ability to drive vehicles and manage mechanisms

Studies of the effect on the ability to drive vehicles and management mechanisms have not been conducted. However, one should take into account that during the treatment may experience undesirable effects such as fainting, sleepiness or dizziness. Therefore, during road controls or mechanisms should be careful. If patients experience these sensations, they should avoid performing these potentially dangerous activities like driving a vehicle or operating machinery.
OVERDOSE

Symptoms of
overdose cases have been identified. Possible symptoms of an overdose are made up of symptoms of the individual components of the preparation.
Telmisartan - marked reduction of blood pressure, tachycardia, possibly bradycardia, dizziness, increase in serum creatinine concentration in the serum, acute renal failure.
Amlodipine - excessive peripheral vasodilatation and possibly reflex tachycardia. There may be severe and probably prolonged systemic hypotension up to the shock of death.
Treatment
Hemodialysis is not effective. Control over the condition of the patient, treatment should be symptomatic and supportive.
In order to counteract the blockade of calcium channels may be useful intravenous administration of calcium gluconate.
May be used overdose treatments such as induction of emesis, gastric lavage, administration of activated charcoal, patient transfer to the "lying with raised legs" and introduction plazmozameshchath solutions in case of significant decrease in blood pressure.
DRUG INTERACTION

Interactions between the two active components in fixed doses of the drug in clinical trials was not observed.
Special studies of drug interactions Tvinsta preparation ® been conducted with other drugs.
The combination of active ingredients
With simultaneous application Tvinsta preparation ® with the following preparations should take into account the following information.
Other antihypertensive drugs
With simultaneous use with other antihypertensive drugs hypotensive effect of the drug Tvinsta ® can be amplified.
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 effects of all antihypertensives including drug Tvinsta ® . Furthermore, orthostatic hypotension may be enhanced by ethanol, barbiturates, narcotics or antidepressants.
Corticosteroids (systemic administration)
may decrease the hypotensive effect.
Telmisartan
With simultaneous use of telmisartan with:
- other antihypertensive agents: may increase the hypotensive effect. In one study, the combined use of telmisartan and ramipril observed increase in AUC 0-24 and Cmaxramipril and ramiprilat 2.5 times. The clinical significance of this interaction has not been established.
- digoxin, warfarin, hydrochlorothiazide, glibenclamide, simvastatin and amlodipine: no clinically significant interaction. An increasing average digoxin concentration in the blood plasma of an average of 20% (in one case by 39%). When concomitant administration of telmisartan and digoxin advisable to carry out periodic determination of digoxin concentration in the blood.
- lithium therapy:mentioned reversible increase the concentration of lithium in the blood, accompanied by toxic phenomena when taking ACE inhibitors. In rare cases, such changes are registered in the appointment of angiotensin II receptor antagonists, in particular, of telmisartan. When concomitant administration of drugs lithium and angiotensin II receptor antagonists recommended determination of lithium in blood.
- NSAIDs, including aspirin in dosages employed as anti-inflammatory agents, cyclooxygenase-2 (COX-2) and non-selective NSAIDsCan cause the development of acute renal failure in patients with reduced BCC. Drugs affecting renin-angiotensin system, including telmisartan may have synergistic effect. In patients receiving NSAIDs and telmisartan, at the beginning of treatment should be compensated for BCC and conducted monitoring of renal function.
With simultaneous use of antihypertensive drugs and NSAIDs, such telmisartan, reported the reduction of the hypotensive effect by inhibiting prostaglandin vasodilator effect.
Amlodipine
In an application with amlodipine:
- Grapefruit and grapefruit juice:simultaneous application of grapefruit or grapefruit juice preparation is not recommended because some patients by increasing the bioavailability of amlodipine may increase the antihypertensive effect of it;
- inhibitors isoenzyme CYP3A4: the study in elderly patients, it was shown that amlodipine diltiazem inhibits metabolism, probably by influencing the CYP3A4 (plasma concentration of amlodipine increased by about 50% amlodipine and amplified effect). It is possible that more active inhibitors of CYP3A4 (such as ketoconazole, itraconazole, ritonavir) may increase amlodipine plasma concentration to a greater extent than diltiazem.
-Inductors isoenzyme CYP3A4 - anticonvulsants (eg, carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), rifampicin, St. John's wort (Hypericum perforatum): the combined use can lead to a reduction in plasma concentration of amlodipine. Displaying regular medical supervision. During the application of inducers of CYP3A4, as well as after their withdrawal is recommended (if possible) change the dose of amlodipine;
- combined use of simvastatin 80 mg amlodipine, regardless of dose, simvastatin helps to increase exposure to 77% compared to a monotherapy simvastatin. Therefore simvastatin dose should not exceed 40 mg / day.
With simultaneous use of the following preparations should take into account the following
established safety joint application of amlodipine with thiazide diuretics, beta-blockers, ACE inhibitors, long-acting nitrates, nitroglycerine (sublingual applicable), NSAIDs, antibiotics and hypoglycemic agents for oral administration.
With simultaneous use of amlodipine and sildenafil it showed that each formulation provided independent hypotensive effect.
Summary
The simultaneous use of 20 healthy volunteers, 240 ml grapefruit juice with amlodipine single dose of 10 mg taken by mouth without a significant effect on the pharmacokinetic properties of amlodipine.
Concomitant use of amlodipine with cimetidine had no significant effect on the pharmacokinetics of amlodipine.
Simultaneous use of amlodipine with atorvastatin, digoxin, cyclosporin warfarin or substantially no effect on the pharmacokinetics or pharmacodynamics of drugs.
Based on the experience of other means influencing the RAAS, the simultaneous use of the drug Tvinsta ® and potassium-sparing diuretics, potassium-containing additives, potassium-containing edible salt other means which increase in blood potassium content (e.g., heparin) can cause hyperkalemia, however should monitor the index patients. In this regard, their simultaneous application of telmisartan requires compliance with caution.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

TERMS AND CONDITIONS OF STORAGE

The drug should be stored in its original packaging, out of reach of children at or above 25 ° C. Shelf life - 3 years. The drug should not be used beyond the expiration date.
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