Twinsta, tablets 5 mg+80 mg 28 pcs

Twinsta is a combination drug containing two hypotensive agents with complementary actions to control blood pressure in patients with arterial (essential) hypertension: an angiotensin II receptor antagonist, telmisartan, and a “slow” calcium channel blocker, a dihydropyridine derivative, amlodipine. The combination of these substances has an additive hypotensive effect, lowering blood pressure to a greater extent than each individual component. The drug, taken once a day, results in an effective and sustained reduction of blood pressure within 24 hours.

Telmisartan is a specific angiotensin II receptor antagonist (type AT1) that is effective when taken orally. It has high affinity for the AT1 subtype of angiotensin II receptors, through which the action of angiotensin II is realized. It displaces angiotensin II from binding to the receptor, having no agonist effect against this receptor. Telmisartan binds only to the AT1 subtype of the angiotensin II receptor. The binding is long-lasting. It has no affinity for other receptors, including the AT2 receptor. Reduces blood aldosterone concentration, does not inhibit plasma renin and does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (kinininase I) (an enzyme that also degrades bradykinin). Therefore, an increase in bradykinin-induced side effects is not expected. In patients, telmisartan at a dose of 80 mg completely blocks the hypertensive effects of angiotensin II.

The onset of hypotensive action is noted within 3 hours after the first dose of telmisartan. The action of the drug persists for 24 hours and remains significant up to 48 hours. A pronounced hypotensive effect usually develops 4 to 8 weeks after regular use. In patients with arterial hypertension, telmisartan reduces systolic and diastolic blood pressure (BP) without affecting heart rate (HR). In case of abrupt telmisartan withdrawal BP gradually returns to baseline levels without development of “withdrawal” syndrome.

Amlodipine is a dihydropyridine derivative and belongs to the class of “slow” calcium channel blockers. It inhibits transmembrane entry of calcium ions into cardiomyocytes and vascular smooth muscle cells. The mechanism of antihypertensive action of amlodipine is associated with a direct relaxant effect on vascular smooth muscle cells, which leads to a decrease in peripheral vascular resistance and BP. In patients with arterial hypertension, administration of amlodipine once daily provides clinically significant BP reduction for 24 hours. Orthostatic arterial hypotension is not typical during the use of amlodipine due to the slow onset of action of the drug.

In patients with arterial hypertension and normal renal function, amlodipine at therapeutic doses resulted in decreased renal vascular resistance, increased glomerular filtration rate and effective renal plasma blood flow, without changes in filtration or proteinuria. Amlodipine does not lead to any metabolic adverse effects or changes in plasma lipid content and is therefore suitable for use in patients with bronchial asthma, diabetes mellitus and gout. The use of amlodipine in patients with heart failure is not accompanied by negative inotropic effect (does not reduce exercise tolerance and left ventricular ejection fraction). Pharmacokinetics. Pharmacokinetics of fixed-dose combination. The rate and degree of drug absorption are equivalent to the bioavailability of telmisartan and amlodipine when used as separate tablets.

Pharmacokinetics

Pharmacokinetics of fixed-dose combination

The rate and degree of absorption of Twinsta is equivalent to the bioavailability of telmisartan and amlodipine when used as separate tablets.

Pharmacokinetics of individual components

Telmisartan

Intake

It is rapidly absorbed from the gastrointestinal tract when taken orally. Bioavailability is 50%. When taken concomitantly with food, AUC reduction ranges from 6% (at a dose of 40 mg) to 19% (at a dose of 160 mg). In 3 hours after oral administration, plasma concentrations level off, regardless of food intake.

Distribution

Binding to plasma proteins is 99.5%, mainly to albumin and alpha-1 glycoprotein. Average apparent V_d at an equilibrium concentration of 500L.

Metabolism

Telmisartan is metabolized by conjugation with glucuronic acid. Metabolites are pharmacologically inactive.

Excretion

T_1/2 – more than 20 h. C_max in plasma and, to a lesser extent, AUC increase disproportionately to dose. There are no data on clinically significant accumulation of telmisartan. It is excreted unchanged in the intestine, renal excretion is less than 2%. Total plasma clearance is high (900 ml/min) compared to hepatic blood flow (about 1500 ml/min).

Amlodipine

Intake

After oral administration of amlodipine at therapeutic doses, C_max in plasma is reached after 6-12 hours. Absolute bioavailability ranges from 64% to 80%. Food intake does not affect bioavailability of amlodipine.

Distribution

V_d amlodipine is approximately 21 l/kg. In in vitro studies, approximately 97.5% of circulating amlodipine has been shown to bind to plasma proteins in patients with arterial hypertension.

Metabolism

Amlodipine is largely (approximately 90%) metabolized in the liver to form inactive metabolites.

Elevation

Elevation of amlodipine from blood plasma is biphasic. T_1/2 is approximately 30-50 h. Stable plasma levels are reached after continuous drug administration for 7-8 days. Amlodipine is excreted by the kidneys both as unchanged (10%) and as metabolites (60%).

Pharmacokinetics in special clinical cases:

There is a difference in plasma concentrations in males and females. C_max and AUC were approximately 3 and 2 times higher in women compared to men, respectively, with no significant effect on efficacy.

The pharmacokinetics of telmisartan in elderly patients do not differ from younger patients. No dose adjustment is required. Amlodipine clearance tends to decrease in elderly patients, resulting in increased AUC and T_1/2.

Telmisartan dose changes are not required in patients with renal impairment, including patients on hemodialysis. Telmisartan is not eliminated by hemodialysis.

The pharmacokinetics of amlodipine are not significantly altered in patients with impaired renal function.

Pharmacokinetics studies conducted in patients with hepatic impairment have shown that the absolute bioavailability of telmisartan increases to almost 100%.T_1/2 in patients with hepatic impairment does not change. In patients with hepatic impairment, the clearance of amlodipine was decreased, resulting in an increase in AUC of approximately 40-60%.

Indications

Active ingredient

Composition

1 tablet contains:

acting ingredients:

amlodipine besylate 6.935 mg, which corresponds to the content of amlodipine 5 mg, telmisartan 40 and 80 mg;

complementary substances:

sodium hydroxide,

povidone K25,

meglumine,

pregelatinized starch,

corn starch,

How to take, the dosage

Twinsta should be taken once daily, orally, regardless of meals.
Twinsta may be administered to patients receiving the same doses of telmisartan and amlodipine as separate tablets for ease of therapy and to increase adherence.

Twinsta may be administered to patients in whom amlodipine or telmisartan alone does not adequately control BP. Patients taking amlodipine at a dose of 10 mg who have adverse reactions that limit the drug, such as peripheral edema, may switch to taking Twinsta at a dose of 40/5 mg once daily, which will reduce the amlodipine dose but will not reduce the overall expected antihypertensive effect.

The treatment of arterial hypertension in a patient may be initiated with Twinst when it is believed that achieving BP control with any one drug is unlikely. The usual starting dose of Twinst is 40/5 mg once daily. Patients who require a greater decrease in BP may start Twinsta at a dose of 80/5 mg once daily.
If, after at least 2 weeks of treatment, additional BP reduction is required, the dose may be gradually increased to a maximum dose of 80/10 mg once daily.
Twinsta may be used with other hypotensive medications.

Kidney function disorders
In patients with impaired renal function, including patients on hemodialysis, no changes in dosing of the drug are required. Amlodipine and telmisartan are not eliminated from the body during hemodialysis.

Hepatic disorders
In patients with mild to moderate hepatic impairment, Twinsta should be used with caution. The dose of telmisartan should not exceed 40 mg once daily.

Elderly patients
The dosing regimen does not require changes.

Particulars of action of the drug at first administration or at its withdrawal
After the first dose of telmisartan, the hypotensive effect gradually develops within the first 3 h and the drug action persists for 24 h and remains significant until 48 h.
In case of abrupt withdrawal of telmisartan BP gradually returns to baseline levels without development of withdrawal syndrome.

Interaction

No interactions between the two active ingredients included in fixed doses in this drug have been observed in clinical trials.
No special studies of drug interactions of the drug Twinsta with other drugs have been conducted.

Combinations of active ingredients
The following information should be taken into account when concomitant use of the drug Twinsta with the following drugs.
Other hypotensive drugs
When used simultaneously with other hypotensive drugs, the hypotensive effect of the drug Twinsta may be enhanced.
Drugs that can reduce BP
Some drugs, such as baclofen and amifostine, can be expected to increase the hypotensive effects of all hypotensive drugs, including Twinsta, due to their pharmacological properties. In addition, orthostatic hypotension may be enhanced by ethanol, barbiturates, narcotics, or antidepressants.
Corticosteroids (systemic use)
The hypotensive effect may be reduced.

Telmisartan
When telmisartan is used concomitantly with:

In concomitant use of NSAIDs and hypotensive drugs like telmisartan, reduction of hypotensive effect through inhibition of vasodilatory prostaglandin effect has been reported.

Amlodipine
When amlodipine is used concomitantly with:

Special Instructions

The drug should be administered with caution if the patient has the following conditions:

Contraindications

Side effects

Overdose

Symptoms
No cases of overdose have been identified. Possible symptoms of overdose consist of symptoms of individual drug components.
Telmisartan – marked BP decrease, tachycardia, possibly bradycardia, dizziness, increased serum creatinine concentration, acute renal failure.
Amlodipine – excessive peripheral vasodilation and possibly reflex tachycardia. Severe and probably prolonged systemic hypotension, up to and including shock with fatal outcome may be observed.Treatment
Hemodialysis is not effective. The therapy should be symptomatic and supportive.
In order to counteract the calcium channel blockade, intravenous administration of calcium gluconate may be useful.
Methods of overdose treatment such as induction of vomiting, gastric lavage, activated charcoal, transfer of patient to the position “lying with elevated legs” and administration of plasma exchange solutions in case of marked BP decrease may be applied.

Pregnancy use

Twynsta has not been specifically studied during pregnancy and lactation. Effects associated with individual drug components are described below.

Pregnancy
Telmisartan
The use of angiotensin II receptor antagonists (ARA II) is contraindicated during pregnancy. If pregnancy is diagnosed, the drug should be stopped immediately. If necessary, alternative therapy should be prescribed.
It is known that the use of ARA II during the second and third trimesters of pregnancy has fetotoxic effects (decreased renal function, oligohydramnios, delayed fetal skull ossification) and neonatal toxicity (renal failure, arterial hypotension and hyperkalemia).
Amlodipine
The limited data available regarding the effects of amlodipine or other calcium receptor antagonists do not indicate any adverse effects on the fetus. However, there may be a risk of delayed labor.

Breast-feeding period
No special studies on excretion of telmisartan and/or amlodipine with breast milk in women have been conducted. Animal studies have shown that telmisartan is excreted with the milk of lactating animals. Given the possible adverse reactions, the decision to continue breastfeeding or to discontinue therapy should be made taking into account its relevance to the mother. Studies of the effect on human fertility have not been conducted.

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