Amlodipine, Telmisartan | Twinsta tablets 5 + 80 mg, 28 pcs.

Latin name

Twynsta

Release form

Tablets.

Packaging

28 tablets.

Pharmacological action

The Twinsta drug is a combined drug containing two antihypertensive substances with a complementary effect, which allow controlling blood pressure in patients with arterial (essential) hypertension: an angiotensin II receptor antagonist, telmisartan, and a “slow” calcium channel blocker

In patients with arterial hypertension and normal renal function, amlodipine at therapeutic doses resulted in a decrease in renal vascular resistance, an increase in glomerular filtration rate and an effective plasma blood flow in the kidneys, without changing filtration or proteinuria. Amlodipine does not lead to any metabolic adverse effects or changes in the content of blood plasma lipids, and therefore is 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 a negative inotropic effect (tolerance to physical activity does not decrease, the ejection fraction of the left ventricle does not decrease). Pharmacokinetics Pharmacokinetics of a combination of fixed doses. The rate and extent of absorption of the drug is equivalent to the bioavailability of telmisartan and amlodipine if used in separate tablets.

Pharmacokinetics

Pharmacokinetics of fixed-dose combinations

The rate and extent of absorption of the Twinst drug is equivalent to the bioavailability of telmisartan and amlodipine if they are used in separate tablets.

Pharmacokinetics of individual components

Telmisartan

Absorption

When taken orally, it is rapidly absorbed from the gastrointestinal tract. Bioavailability is 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). 3 hours after ingestion, the concentration in the blood plasma is leveled, regardless of the meal.

Distribution of

Binding to blood plasma proteins - 99.5%, mainly with albumin and alpha-1 glycoprotein. The average value of visible Vd at an equilibrium concentration of 500 l.

Metabolism

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

Excretion of

T1 / 2 - more than 20 hours. Cmax in blood plasma and, to a lesser extent, AUC increase disproportionately to the dose. There is no evidence of clinically significant accumulation of telmisartan. It is excreted through the intestine unchanged, excretion by the kidneys less than 2%. The total plasma clearance is high (900 ml / min) compared with hepatic blood flow (about 1500 ml / min).

Amlodipine

Absorption

After oral administration of amlodipine in therapeutic doses of Cmax in blood plasma is achieved after 6-12 hours. The absolute bioavailability is from 64% to 80%. Eating does not affect the bioavailability of amlodipine.

The distribution of

Vd 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 significantly (approximately 90%) metabolized in the liver to form inactive metabolites.

Excretion

The excretion of amlodipine from blood plasma occurs in two phases. T1 / 2 is approximately 30-50 hours. Stable plasma levels are achieved after continuous administration of the drug for 7-8 days. Amlodipine is excreted by the kidneys both unchanged (10%) and 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 a significant effect on efficacy.

The pharmacokinetics of telmisartan in elderly patients is not different from younger patients. Dose adjustment is not required. In elderly patients, there is a tendency to a decrease in clearance of amlodipine, which leads to an increase in AUC and T1 / 2.

Changing the dose of telmisartan in patients with renal failure 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.

Pharmacokinetic studies in patients with impaired liver function have shown that the absolute bioavailability of telmisartan increases to almost 100%. T1 / 2 in patients with impaired liver function does not change. In patients with hepatic insufficiency, amlodipine clearance decreased, which led to an increase in AUC by about 40-60%.

Indications

arterial hypertension (for patients whose AD is not adequately controlled with telmisartan or amlodipine in monotherapy)

arterial hypertension (for patients who are shown combination therapy)

for patients with arterial hypertension receiving telmisartan and amlodipine tablets, as a replacement for this therapy.

Contraindications

obstructive biliary tract disease

severe arterial hypotension

obstruction of the outgoing tract of the left ventricle (incl. high degree of aortic stenosis)

hemodynamically unstable heart failure after acute myocardial infarction

severe hepatic insufficiency

shock

fructose intolerance and glucose / galactose malabsorption syndrome or sucrose deficiency

breastfed up to 18 years old safety not established)

hypersensitivity to active ingredients or excipients

hypersensitivity to ugim dihydropyridine derivative.

Twinst should be prescribed with caution to patients with: obstructive biliary tract disease or hepatic insufficiency

with bilateral renal artery stenosis or stenosis of a single kidney artery

condition after kidney transplantation

reduced bcc and / or hyponatremia

double blockade of the renin-angiotensin-aldosterone system of the other state aldosteronism

stenosis of the aortic and mitral valve, obstructive hypertrophic cardiomyopathy

heart failure

g with hyperkalemia

diabetes mellitus with additional cardiovascular risk (i.e. concomitant coronary artery disease / IHD /)

after 1 month after acute myocardial infarction and unstable angina.

Use during pregnancy and lactation

There have been no special studies of Tweenst during pregnancy and during lactation. The effects associated with the individual components of the drug are described below.

Pregnancy

Telmisartan

The use of angiotensin II receptor antagonists (ARA II) is contraindicated during pregnancy. When diagnosing pregnancy, the drug should be stopped immediately. If necessary, alternative therapy should be prescribed.

known that the use of ARA II during the II and III trimesters of pregnancy has a fetotoxic effect (decreased renal function, oligohydramnios, delayed ossification of the fetal skull), and neonatal toxicity (renal failure, arterial hypotension, and hyperkalemia).

Amlodipine

Limited evidence of exposure to amlodipine or other calcium receptor antagonists does not indicate adverse effects on the fetus. However, there is a risk of a slowdown in the birth process.

Breastfeeding Period

No specific studies have been performed on the isolation of telmisartan and / or amlodipine with breast milk in women. Animal studies have shown that telmisartan is excreted in the milk of lactating animals. Given possible adverse reactions, a decision to continue breastfeeding or to discontinue therapy should be made taking into account its importance to the mother. Studies on the effects on human fertility have not been conducted.

Composition

1 tablet contains:

active substances: amlodipine besilate 6.935 mg, which corresponds to the content of amlodipine 5 mg, telmisartan 40 and 80 mg

excipients: sodium hydroxide, povidone K25, meglumine, sorbitol, magnesium stearate, microcrystalline cellulose, pregelatinized starch, corn starch, colloidal silicon dioxide, a mixture of dyes *.

composition of the dye mixture: iron oxide black (E172) - 76%, iron oxide yellow (E172) - 4%, FD&C blue No. 1 (diamond blue FCF aluminum varnish), aluminum pigment (E133) - 20%

Dosage and administration of

Twinst should be taken 1 time / day, by mouth, regardless of the meal.

Tweenst may be prescribed to patients receiving the same doses of telmisartan and amlodipine in separate tablets, for ease of therapy and increased adherence to treatment.

Twinst can be prescribed to patients in whom the use of amlodipine alone or telmisartan alone does not lead to adequate control of blood pressure. Patients taking amlodipine at a dose of 10 mg, in which there are adverse reactions that limit the use of the drug, for example, peripheral edema, can switch to taking Twinst at a dose of 40/5 mg 1 time / day, which will reduce the dose of amlodipine, but will not reduce the overall expected antihypertensive effect.

Treatment of arterial hypertension in a patient may begin with the use of the Twinst drug in the case when it is assumed that achieving blood pressure control with any one drug is unlikely. The usual initial dose of Twinst is 40/5 mg 1 time / day. Patients who need a more significant decrease in blood pressure can start taking Twinst at a dose of 80/5 mg 1 time / day.

If an additional decrease in blood pressure is required after at least 2 weeks of treatment, the dose may be gradually increased to a maximum dose of 80/10 mg 1 time / day. Twindst

may be used in conjunction with other antihypertensive drugs.

Impaired renal function

In patients with impaired renal function, including in patients on hemodialysis, changes in the dosage of the drug are not required. Amlodipine and telmisartan are not removed from the body during hemodialysis.

Impaired liver function

In patients with mild to moderate hepatic impairment, Twinst should be used with caution. The dose of telmisartan should not exceed 40 mg 1 time / day.

Elderly patients

Dosage regimen does not require changes.

Peculiarities of the action of the drug at the first dose or when it is canceled

After the first dose of telmisartan, the antihypertensive effect gradually develops over the first 3 hours and the effect of the drug persists for 24 hours and remains significant for up to 48 hours.

In case of abrupt cancellation of telmisartan blood pressure gradually returns to its original level without the development of withdrawal syndrome.

Side effects

expected based on experience with telmisartan

expected based on experience with amlodipine

expected with simultaneous use of telmisartan and amlodipine

The following categories are used within systemic organ classes for the frequency 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 (frequency unknown (cannot be calculated according to the available data.)

Organ-organ class Side effect Frequency of occurrence of

Infections and invasions Cystitis 3) Rarely

Urinary tract infections 1) Infrequently

Upper respiratory infections 1) Infrequently

Sepsis, fatal 1) Rarely

Psychotic disorders Depression3), anxiety3), insomnia3) Rarely

Lability of mood2), confused consciousness2) Frequency unknown

Disorders of the nervous system Dizziness 3) Often

Drowsiness 3), migraine 3) sensitivity or resistance to external factors3), taste disorder3), fainting3), tremor3), peripheral neuropathy3)

Rarely

Immune system disorders Anaphylactic reaction1) Rarely

Hypersensitivity1), 2) Rarely1),

Frequency unknown1)

Visual impairment 3) Rarely srdl3 Hearing) Frequency unknown

Disorders of the

cardiovascular

system Bradycardia3), palpitations3) Infrequent

Tachycardia1) Infrequently

Myocardial infarction2) Rarely

Arrhythmia2), ventricular tachycardia2) redserdiy2) Frequency unknown

Marked reduction AD3) ortostasticheskaya gipotenziya3) Infrequently

Disorders of the respiratory sistemyKashel3) Infrequently

Odyshka1) 2) Infrequently1)

Frequency unknown2)

Rhinitis2) Frequency unknown

Disorders of the

of the gastrointestinal

tract Abdominal pain3), diarrhea3), nausea3), flatulence1) Infrequently

Discomfort3) Changes in the rhythm of defecation2), pancreatitis2), gastritis2) Frequency unknown

Liver dysfunction1) Rarely

Hepatitis2), jaundice2) Frequency unknown

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

Increased 3 levels of liver

Violations of the skin and subcutaneous tissue Eczema3), erythema3), rash1), 3), drug rash1), toxic rash1) Rarely

Skin itching3) Infrequently

Angioedema1), 2) Rarely1), frequency 2) ) Infrequently1), frequency unknown2)

Urticaria1), 2) Rarely1), frequency unknown2)

Alopecia2), purpura2), skin discoloration2), erythema multiforme2), exfoliative dermatitis2), Stevens-Johnson syndrome2), photosensitivity reaction2) unknown from the musculoskeletal system Arthralgia 3), back pain 3), muscle spasms (cramps of the calf muscles) 3), myalgia 3) Infrequent

Pain in the lower extremities 3), tendon pain (symptoms resembling tendinitis) 1) Rarely

Urogenital disorders Nocturia systems3) Rarely

Narush renal function, including acute renal failure 1), impaired urination 2), frequent urination 2)

Frequency unknown

Erectile dysfunction 3) Infrequent

General disorders Peripheral edema 3) Often

Asthenia (weakness) 3), chest pain3), increased fatigue3), swelling3) Infrequent

Malaise3), flu-like syndrome1), a feeling of a rush of blood to the face3), gum hypertrophy3), dry mucous membrane of the oral cavity3) Rarely

Pain2), weight gain2), weight loss body2), gynecomastia2) Frequency unknown

Reactions detected during

special

studies Increased uric acid concentration in the blood3), increased creatinine in the blood1) and creatine phosphokinase (CPK) 1),

decreased hemoglobin1) (anemia, weakness patient in with diabetes mellitus) 1), eosinophilia1) Rarely

Leukopenia2), hyperglycemia2) Frequency unknown

Hyperkalemia1) Infrequent

Thrombocytopenia1), 2) Rarely1), frequency unknown 2)

Additional information regarding individual components srd previously reported when using one of the components of the drug (amlodipine or telmisartan), may be enhanced with the use of the Twinst drug, even if they were not observed in clinical trials or during the post-marketing period.

Additional information regarding 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 often than in patients who received only amlodipine.

Drug Interaction

No interaction has been observed between the two active components included in the fixed doses of this drug in clinical trials.

No specific studies have been conducted on the drug interactions of the Twinn drug with other drugs.

Combination of active components

The following information should be taken into account when using the Twinn drug with the drugs listed below.

Other antihypertensive drugs

When used in conjunction with other antihypertensive drugs, the antihypertensive effect of the Twinst may be increased.

Drugs that can reduce BP

Some drugs, such as baclofen and amifostine, can be expected to be due to their pharmacological properties, will enhance the antihypertensive effect of all antihypertensive agents, including the Twinst drug. In addition, orthostatic hypotension mcan be enhanced with ethanol, barbiturates, narcotics or antidepressants.

Corticosteroids (systemic use)

Decrease in antihypertensive effect.

Telmisartan

With the use of telmisartan with: other antihypertensive agents: increased antihypertensive effect. In one study, when combined with telmisartan and ramipril, an increase of AUC0-24 and Cmax of ramipril and ramipril was 2.5-fold increased. The clinical significance of this interaction has not been established.

digoxin, warfarin, hydrochlorothiazide, glibenclamide, simvastatin and amlodipine: no clinically relevant interaction was found. An increase in the average concentration of digoxin in the blood plasma by an average of 20% (in one case by 39%) was noted. With the simultaneous administration of telmisartan and digoxin, it is advisable to periodically determine the concentration of digoxin in the blood.

with lithium drugs: there was a reversible increase in the concentration of lithium in the blood, accompanied by toxic effects when taking ACE inhibitors. In rare cases, such changes have been reported with the appointment of angiotensin II receptor antagonists, in particular telmisartan. With the simultaneous administration of lithium and angiotensin II receptor antagonists, it is recommended to determine the lithium content in the blood.

NSAIDs, including acetylsalicylic acid at doses used as an anti-inflammatory agent, cyclooxygenase-2 (COX-2) inhibitors, and nonselective NSAIDs, may cause acute renal failure in patients with decreased BCC. Drugs, affecting the activity of the renin-angiotensin system, including telmisartan may have a synergistic effect. Patients receiving NSAIDs and telmisartan should be compensated for BCC at the start of treatment and renal function monitored.

The concomitant use of NSAIDs and telmisartan-like hypotensive drugs has been reported to reduce the antihypertensive effect by inhibiting the vasodilating effect of prostaglandins.

Amlodipine

When co-administered with amlodipine with: grapefruit and grapefruit juice: simultaneous use of the drug with grapefruit or grapefruit juice is not recommended since in some patients, as a result of increased bioavailability of amlodipine, its antihypertensive effects may increase.

CYP3A4 isoenzyme inhibitors: In a study in elderly patients, diltiazem was shown to inhibit the metabolism of amlodipine, possibly influencing CYP3A4 (blood plasma concentrations of amlodipine increase by about 50% and the effect of amlodipine increased). It cannot be excluded that more active CYP3A4 inhibitors (such as ketoconazole, itraconazole, ritonavir) may increase blood plasma concentrations of amlodipine more than diltiazem.

CYP3A4 isoenzyme inducers - anticonvulsants (eg, carbamazepine, phenobarbital, phenytoin, phosphenitoin, primidone), rifampicin, Hypericum perforatum, combined with Hypericum perforatum Regular medical observation is shown. While using CYP3A4 inducers, and also after their abolition, it is recommended (if possible) to change the dose of amlodipine.

co-administration of simvastatin at 80 mg with amlodipine, regardless of dose, contributes to an increase in simvastatin exposure of up to 77% compared with simvastatin alone. Therefore, the dose of simvastatin should not exceed 40 mg / day.

When using the following drugs at the same time, the following information should be considered:

When co-administered with amlodipine and sildenafil, that each drug had an independent antihypertensive effect.

Additional Information

Co-administration with 20 healthy volunteers of 240 ml grapefruit juice with a single dose of 10 mg orally administered amlodipine did not significantly affect the pharmacokinetic properties of amlodipine.

Co-administration of amlodipine with cimetidine had no significant effect on the pharmacokinetics of amlodipine.

The concomitant use of amlodipine with atorvastatin, digoxin, warfarin or cyclosporine did not significantly affect the pharmacokinetics or pharmacodynamics of these drugs.

Based on the experience of using other agents that affect RAAS, the simultaneous use of the Twinnst drug and potassium-sparing diuretics, potassium-containing additives, potassium-containing dietary salt, other agents, potassium boosters in the blood (eg, heparin) can lead to hyperkalemia, so this should be monitored in patients. Therefore, their co-administration with telmisartan requires caution.



overdose Symptoms of

Overdose has not been detected. Possible symptoms of overdose consist of the symptoms on the part of the individual components of the drug.

Telmisartan - marked decrease in blood pressure, tachycardia, possibly bradycardia, dizziness, increase in serum creatinine concentration, acute renal failure.

Amlodipine is excessive peripheral vasodilation and possibly reflex tachycardia. There may be pronounced and probably prolonged systemic hypotension, up to the development of a fatal shock.

Treatment for

Hemodialysis is not effective. Control of the patient's condition, therapy should be symptomatic and supportive.

Intravenous administration of calcium gluconate may be helpful to counteract calcium channel blockade.

Methods for treating overdose, such as induction of vomiting, gastric lavage, use of activated charcoal, transfer of the patient to a supine position with elevated legs, and the introduction of plasma replacement solutions in the event of a marked decrease in blood pressure, may be used.

Storage conditions

The drug should be stored in its original packaging, out of reach of children at a temperature not exceeding 25 РC.

Expiration

3 years.

Deystvuyuschee substances

amlodipine, Telmisartan

pharmacy prescription

pharmacy prescription s171product aprpfd445frdp4frdp4frdp4frdp4frdp4frd41pfdpfdpfpfp431

dosage form

dosage form

tablets

Cipla Ltd., India