Twinsta® (Twynsta®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceAmlodipine + TelmisartanAmlodipine + Telmisartan
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  • Twinsta®
    pills inwards 
    Boehringer Ingelheim International GmbH     Germany
  • Telsartan® AM
    pills inwards 
    Dr. Reddy's Laboratories Ltd.     India
    • Dosage form: & nbsppills
    Composition:

    1 tablet contains: active ingredients:

    amlodipine besylate * 6.935 mg

    telmisartan 40 mg

    * equivalent to 5 mg of amlodipine

    Excipients: sodium hydroxide 3,360 mg; Povidone K25 12,000 mg; meglumine 12,000 mg; sorbitol 168,640 mg; magnesium stearate 6,000 mg; cellulose microcrystalline 125.765 mg; pregelatinized starch 53,000 mg; corn starch 10,000 mg; silicon colloid dioxide 2,000 mg; mixture of dyes 0.300 mg **.

    Or:

    active ingredients:

    amlodipine besylate * 13,870 mg

    telmisartan 40 mg

    * equivalent to 10 mg of amlodipine

    Excipients: sodium hydroxide 3,360 mg; Povidone K25 12,000 mg; meglumine 12,000 mg; sorbitol 168,640 mg; magnesium stearate 6,000 mg; cellulose microcrystalline 118.830 mg; pregelatinized starch 53,000 mg; corn starch 10,000 mg; silicon colloid dioxide 2,000 mg; mixture of dyes 0.300 mg **.

    Or:

    active ingredients:

    Amlodipine besylate * 6.935 mg

    telmisartan 80 mg

    * equivalent to 5 mg of amlodipine

    Excipients: sodium hydroxide 6,720 mg; Povidone K25 24,000 mg; meglumine 24,000 mg; sorbitol 337.280 mg; magnesium stearate 10,000 mg; cellulose microcrystalline 125.765 mg; starchpregelatinized 53,000 mg; corn starch 10,000 mg; silicon colloid dioxide 2,000 mg; mixture of dyes 0.300 mg **.

    Or:

    active ingredients:

    amlodipine besylate * 13.870 mg

    telmisartan 80 mg

    * equivalent to 10 mg of amlodipine

    Excipients: sodium hydroxide 6,720 mg; Povidone K25 24,000 mg; meglumine 24,000 mg; sorbitol 337.280 mg; magnesium stearate 10,000 mg; cellulose microcrystalline 1 18.830 mg; pregelatinized starch 53,000 mg; corn starch 10,000 mg; silicon colloid dioxide 2,000 mg; mixture of dyes 0.300 mg **.

    ** A mixture of dyes consists of 76% iron oxide black (E172, name in NF: iron oxide), 4% iron oxide yellow (E172, name in NF: iron oxide) and 20% FD&C blue # 1 (brilliant blue FCF aluminum lacquer) (E133).

    Description:

    Oval-shaped, biconvex, two-layer tablets, without shell. One layer from white to almost white, another layer of gray-blue color. The white surface of the tablets contains the company logo and engraving "A1" (for a dosage of 5 mg + 40 mg), "A2" (for a dosage of 10 mg + 40 mg), "AZ" (for a dosage of 5 mg + 80 mg), "A4 "(for a dosage of 10 mg + 80 mg), the other side of the tablet is smooth.

    Pharmacotherapeutic group:antihypertensive agent combined (blocker of "slow" calcium channels + angiotensin II receptor antagonist)
    ATX: & nbsp

    C.08.C.A.01   Amlodipine

    C.09.C.A.07   Telmisartan

    Pharmacodynamics:

    TWINSTA is a combination drug containing two antihypertensive substances with a complementary effect that allows controlling blood pressure in patients with arterial (essential) hypertension: an angiotensin II receptor antagonist (ARA II), telmisartan, and a "slow" calcium channel blocker (BCCC), a dihydropyridine derivative, amlodipine.

    The combination of these substances has an additive antihypertensive effect, reducing arterial pressure more than each individual component.

    The drug TWINSTA, taken once a day, leads to an effective and steady decrease in blood pressure within 24 hours.

    TELMISARTAN

    Telmisartan is a specific ARA II (type AT1), effective when ingested. Has a high affinity for the subtype AT | receptors 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 AT1 subtype of the angiotensin II receptor. Communication is of a lasting nature.Has no affinity for other receptors, including AT2 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 angiotensin-converting enzyme (kininase II is an enzyme that also breaks down bradykinin). Therefore, the enhancement of bradykinin-induced side effects is not expected.

    Patients telmisartan in 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 drug remains for 24 hours and remains significant up to 48 hours. The expressed hypotensive effect usually develops in 4-8 weeks after the regular reception.

    In patients with hypertension telmisartan reduces systolic and diastolic blood pressure (BP), without affecting the heart rate (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 dihydropyridine derivative, belongs to the BCCC class.It inhibits transmembrannoe intake of calcium ions in cardiomyocytes and smooth muscle cells of blood vessels.

    The mechanism of hypotensive 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 per day provides a clinically significant decrease in blood pressure during 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 led to a decrease in the resistance of the blood vessels of the kidneys, an increase in the glomerular filtration rate and an 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 speed and degree of absorption of the drug TWINSTA are equivalent to the bioavailability of telmisartan and amlodipine in the case of their use as separate tablets.

    Pharmacokinetics of individual components:

    TELMISARTAN

    Suction

    When ingested quickly absorbed from the gastrointestinal tract. Bioavailability - 50%. When taken simultaneously with food, a decrease in the area under the concentration-time curve (AUC) varies from 6% (at a dose of 40 mg) to 19% (with a dose of 160 mg). After 3 hours after ingestion, the concentration in the blood plasma levels out regardless of food intake.

    Distribution

    Communication with plasma proteins is 99.5%, mainly with albumin and alpha-1 glycoprotein. The average value of the apparent volume of distribution in the equilibrium concentration is 500 liters.

    Metabolism

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

    Excretion

    The half-life (T1/2) is more than 20 hours. The maximum concentration in the blood plasma (CmOh) and to a lesser extent AUC increase disproportionately to the magnitude of the dose. There are no data on the clinically significant accumulation of telmisartan.

    Output through the intestine in an unchanged form, excretion by the kidneys - less than 2%. The total plasma clearance is high (900 ml / min) compared with the "hepatic" blood flow (about 1500 ml / min).

    AMLODIPINE

    Suction

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

    Distribution

    The volume of distribution of amlodipine is approximately 21 l / kg. In studies in vitro It is 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, T1 / 2 is about 30-50 hours. Stable levels in 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 of telmisartan in men and women. FROMmah and AUC were approximately 3 and 2 times, respectively, higher in women than in men without significant effect on efficacy.

    Have elderly patients

    The pharmacokinetics of telmisartan in elderly patients does not differ from young patients. Patients in the elderly have a tendency to decrease the clearance of amlodipine, which leads to an increase AUC and T1 / 2.

    Patients with renal insufficiency

    Telmisartan binds to blood plasma proteins and is not removed during hemodialysis in patients with renal insufficiency. Also lower concentrations of telmisartan in blood plasma are observed, T1 / 2 does not change. The pharmacokinetics of amlodipine in patients with impaired renal function does not change significantly.

    Patients with hepatic insufficiency

    Studies of pharmacokinetics performed in patients with impaired hepatic function showed that the absolute bioavailability of telmisartan increases almost to 100%. T1 / 2 in patients with impaired liver function does not change. In patients with hepatic insufficiency, the clearance of amlodipine decreased, which led to an increase in the value AUC by about 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 hypertension receiving telmisartan and amlodipine in the form of individual tablets as a substitute for this therapy.

    Contraindications:

    - Hypersensitivity to active components or excipients

    - Hypersensitivity to other dihydropyridine derivatives

    - Pregnancy

    - Breastfeeding period

    - 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

    - Simultaneous use with aliskiren in patients with diabetes mellitus or impaired renal function (GFR less than 60 mL / min / 1.73 m)

    - Fructose intolerance and glucose / galactose absorption disorder or sugarase / isomaltase deficiency

    - Age to 18 years (effectiveness and safety not established).

    Carefully:

    Care must be taken with the following conditions.

    Impaired liver function

    Dosage recommendations for patients with impaired liver function have not been developed, so caution should be exercised in such clinical cases.

    Renovascular hypertension

    In patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney taking medications that affect the renin-angiotensin-aldosterone system (RAAS), there is an increased risk of developing severe hypotension and renal failure.

    Primary aldosteronism

    In patients with primary aldosteronism, antihypertensive drugs, whose mechanism of action is inhibition of RAAS, are usually not effective. Thus, the use of telmisartan in such cases is not recommended.

    Stenosis of aortic and mitral valves, hypertrophic obstructive cardiomyopathy

    In patients with aortic or mitral stenosis, or with obstructive hypertrophic cardiomyopathy, the use of the drug TWINSTA, as well as other vasodilators, requires extreme caution.

    Heart failure

    The clinical study found that the use of amlodipine in patients with cardiac insufficiency of non-ischemic etiology III and IV functional class by classification NYHA was accompanied by a more frequent development of pulmonary edema (despite the absence of a significant difference in the incidence of worsening heart failure compared with placebo).

    Diabetes

    In patients with diabetes mellitus (DM) with an additional cardiovascular risk (i.e., concomitant ischemic heart disease), the risk of fatal myocardial infarction and sudden cardiovascular death may be increased when treated with antihypertensive agents, such as ARA II and adenosine-converting enzyme (ACE inhibitors).

    Unstable angina, acute myocardial infarction

    There is no data on the use of the drug TWINSTA in patients with unstable angina, in the acute period and within one month after myocardial infarction.

    Disorders of kidney function and condition after kidney transplantation

    The experience of using the drug TWINSTA in patients who have recently undergone kidney transplantation is absent. Amlodipine and telmisartan not removed during hemodialysis. Patients with impaired renal function are encouraged to periodically monitor potassium and creatinine levels in the blood serum.

    Reduced circulating blood volume (BCC) and / or hyponatraemia

    Due to the restriction of consumption of table salt, intensive therapy with diuretics, diarrhea or vomiting, symptomatic arterial hypotension may develop, especially after taking the first dose of the drug. Before applying the drug TWINSTA, such conditions require correction.

    Hyperkalemia

    During treatment with drugs that affect RAAS, especially if there are abnormalities in kidney function and / or heart failure, hyperkalemia may occur.

    Other states characterized by activation of RAAS

    In cases of vascular tone and kidney function, mainly from RAAS activity (for example, in patients with chronic heart failure or kidney disease, including renal artery stenosis), the administration of drugs that affect this system can be accompanied by the development of acute arterial hypotension, hyperaemia, oliguria, and, in rare cases, acute renal failure.
    Pregnancy and lactation:

    Special studies of the drug TWINSTA during pregnancy and during lactation were not carried out. Effects associated with individual components of the drug are described below.

    Pregnancy

    TELMISARTAN

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

    Preclinical studies of telmisartan did not reveal teratogenic properties, but found the presence of fetotoxicity.

    It is known that the use of ARA II during the second and third trimesters of pregnancy has a fetotoxic effect (decreased kidney function,oligohydramnion, slowing ossification of the fetal skull), and neonatal toxicity (renal failure, arterial hypotension and hyperkalemia) is observed.

    In patients planning a pregnancy, ARA II should be replaced with other antihypertensive drugs that are characterized by an established safety profile when used during pregnancy (unless continued treatment with ARA II is considered necessary).

    If ARA II is used during pregnancy, then starting with the second trimester of pregnancy, ultrasound is recommended to monitor kidney function and skull conditions. Newborns whose mothers received ARA II should be carefully monitored for the development of arterial hypotension.

    AMLodipin

    Available limited data on the effects of amlodipine or other BCCs do not indicate the presence of adverse effects on the fetus. However, there is a risk of slowing the delivery process.

    Breastfeeding period

    Special studies on the isolation of telmisartan and / or amlodipine in breast milk have not been conducted in women. In animal studies, it was found that telmisartan is excreted with the milk of lactating animals.Taking into account possible adverse reactions, the decision to continue breastfeeding or to abolish therapy should be made taking into account its importance for the mother.

    Studies of the impact on human fertility have not been conducted.

    Dosing and Administration:

    The drug must be taken once a day.

    Inside, regardless of food intake.

    TVINSTA 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.

    TWINTHTA can be administered to patients in whom the use of one amlodipine or one telmisartan does not lead to adequate control of blood pressure.

    Patients receiving amlodipine in a dose of 10 mg, in which there are side effects that limit the intake of the drug, for example, peripheral edema, can switch to taking TWINSTA in a dose of 40/5 mg once a day, which will reduce the dose of amlodipine, but will not reduce the overall expected hypotensive effect .

    Treatment of hypertension in a patient can begin with the use of the drug TWINSTA in the event that 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 TWINSTA is 40/5 mg once a day.Patients who need a more significant reduction in blood pressure, can start taking the drug TWINSTA in a dose of 80/5 mg 1 time per 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 a day.

    TVINSTA 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 Do not remove from the body during hemodialysis.

    Dysfunction of the liver

    In patients with mild or moderate degree of liver function abnormalities, the drug must be used with caution. The dose of telmisartan should not exceed 40 mg once a day.

    Elderly patients

    Dosing regimen does not require any changes.

    The features of the action of the drug at the first admission or with its cancellation

    Telmisartan:

    After the first dose of telmisartan, the hypotensive effect gradually develops within the first 3 hours and the effect of the drug persists for 24 hours and remains significant up to 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 effects:

    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

    Inside 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 (> 1/10000, <1/1000); very rarely (<1/10000); frequency is unknown (can not be calculated from available data).

    System-Organ Class

    By-effect

    Frequency of occurrence

    Infections and invasions

    Urinary tract infections1), upper respiratory tract infections1)

    Infrequently


    Cystitis3), sepsis, including fatalities1)

    Rarely

    Mental disorders

    Depression3), anxiety3), insomnia3)

    Rarely


    Lability of mood2), confused consciousness2)

    Frequency unknown

    Disturbances from the nervous system

    Dizziness3)

    Drowsiness3), migraines3), headache3), paresthesia3)

    Often

    Infrequently


    Lowering

    sensitivity or resistance to external factors3), a taste disorder3), fainting3), tremor3), peripheral neuropathy3)

    Rarely

    Immune system disorders

    Anaphylactic reaction1)

    Hypersensitivity1 )’2)

    Rarely

    Rarely1),

    Frequency unknown 2)

    Vision disorders

    Visual disorders 1), Reduced vision2)

    Rarely

    Frequency unknown

    Hearing impairments

    Vertigo3)

    Noise in ears2)

    Infrequently

    Frequency unknown

    Infringements from

    cardiovascular

    systems

    Bradycardia3), a feeling of heartbeat3), a marked decrease in blood pressure3), orthostatic arterial hypotension3)

    Infrequently


    Tachycardia1)

    Rarely


    Heart Attack

    arrhythmia2),

    tachycardia2),

    atria2)

    myocardium2)

    ventricular

    fibrillation

    Frequency unknown


    Disturbances from the respiratory system

    Cough3)

    Dyspnea1),2)


    Infrequently

    Infrequently1),

    frequency unknown 2)




    Rhinitis25


    Frequency unknown


    Infringements from

    gastrointestinal

    tract

    Abdominal pain3), diarrhea3), nausea3), flatulence1), increased activity of "hepatic" enzymes 3)

    Infrequently




    Vomiting3),

    discomfort

    stomach 1)

    dyspepsia3), in area

    Rarely




    Violations of the function of the liver1)

    Rarely




    Hepatitis2),

    change

    defecation2),

    gastritis2),

    activity

    transaminase

    manner

    cholestasis)2)

    jaundice2)

    rhythm

    pancreatitis2),

    rise

    "hepatic"

    (the main

    reflecting the

    Frequency unknown


    Disturbances from the skin and subcutaneous tissue

    Itchy skin3)

    Eczema3), erythema3), skin rash3), drug rash1), toxic rash1)

    Infrequently

    Rarely




    Hyperhidrosis1),2)

    Infrequently1), frequency unknown 2)




    Angioedema 1),2)

    Rarely1), the frequency is unknown 2)




    Urticaria1),2)

    Rarely1), the frequency is unknown 2)




    Alopecia2), purple2), discoloration of the skin2), erythema multiforme2), exfoliative dermatitis2), Stevens-Johnson syndrome2), the photosensitization reaction2), vasculitis2)

    Frequency unknown


    Violations from

    hand

    Arthralgia3),

    muscle spasms

    Infrequently


    musculoskeletal system

    (spasms of calf muscles)3), myalgia3)

    Pain in lower limbs3), pain in the tendons (symptoms resembling tendonitis) 1), back pain3).

    Rarely


    Disorders from the genitourinary system

    erectile disfunction3)

    Infrequently



    Nocturia3)

    Rarely



    Impaired renal function, including acute renal failure1), urination disorders2), frequent urination2)

    Frequency unknown


    Common violations

    Peripheral edema3)

    Often



    Asthenia (weakness)3), chest pain3), increased fatigue3), swelling3), a feeling of a tide of blood to the face3)

    Infrequently



    Malaise3), influenza-like syndrome1), gingival hypertrophy3), dryness of the oral mucosa3)

    Rarely



    Pain2), weight gain2), weight loss2), gynecomastia2)

    Frequency unknown


    Reactions identified by

    Hyperkalemia1), anemia1),

    Infrequently


    special

    increase in concentration



    research

    creatinine in the blood1)




    Increase in the concentration of uric acid in the blood3), increased activity of creatine phosphokinase (CK) in the blood1), a decrease in hemoglobin1), hypoglycemia (in patients with diabetes mellitus) 1), eosinophilia1)

    Rarely



    T rhombocytopenia1),2)

    Rarely1), the frequency

    unknown2)



    Leukopenia2)

    hyperglycemia2)

    Frequency unknown


    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 the drug TWINSTA, even if they were not observed in clinical studies 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 only amlodipine.

    Overdose:

    Symptoms

    Cases of overdose have not been identified. Possible symptoms of an overdose consist of symptoms from the individual components of the drug. Telmisartan - tachycardia, possibly bradycardia, dizziness, increased serum creatinine concentration, acute renal failure. Amlodipine - marked decrease in blood pressure with the possible development of reflex tachycardia and symptoms of excessive peripheral vasodilation (risk of development of severe and persistent arterial hypotension, including with the development of shock and death).

    Treatment

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

    In order to counter blockade of calcium channels, intravenous administration of calcium gluconate may be beneficial.

    Overdose management methods such as induction of emesis, gastric lavage, the use of activated charcoal, the transfer of the patient to an "elevated leg" position and the introduction of plasma-substituting solutions in the case of pronounced blood pressure lowering may be used.

    Interaction:

    Interactions between the two active components that are included in fixed doses in the composition of this drug have not been revealed in clinical studies.Special studies of drug interactions of the drug TWINSTA with other drugs have not been conducted.

    COMBINATION OF ACTIVE COMPONENTS

    - Other antihypertensives

    With simultaneous use with other antihypertensive drugs, the antihypertensive effect of the drug TWINSTA can intensify.

    - Drugs that can reduce blood pressure

    It can be expected that some drugs, for example, baclofen and amifostine, due to their pharmacological properties, will enhance the antihypertensive effect of all antihypertensive drugs, including the drug TWINSTA, In addition, orthostatic arterial hypotension may strengthen ethanol, Barbiturates, narcotics or antidepressants.


    - Corticosteroids (systemic application)

    It is possible to reduce the hypotensive effect.

    TELMISARTAN


    - Other antihypertensives

    It is possible to intensify the hypotensive effect. In one study, combined use of telmisartan and ramipril showed an increase AUC0-24 and FROMmax ramipril and ramiprilata 2.5 times. The clinical significance of this interaction is not established.

    Double blockade of RAAS (for example, the combined use of ACE inhibitors or aliskiren, a direct inhibitor of renin with APA II) is not recommended because of possible renal dysfunction (including acute renal failure).


    - Lithium preparations

    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 were registered with the appointment of angiotensin II receptor antagonists, in particular telmisartan. When concomitant administration of lithium preparations and angiotensin II receptor antagonists, it is recommended to determine the content of lithium in the blood.

    - Nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid (in doses used as an anti-inflammatory drug), cyclooxygenase-2 (COX-2) inhibitors and nonselective NSAIDs

    Possible development of acute renal failure in patients with reduced BCC. Drugs that affect the activity of RAAS, including, telmisartan, may have a synergistic effect. In patients receiving NSAIDs and telmisartan, at the beginning of treatment should be compensated for BCC and kidney function monitoring performed.

    With the simultaneous use of NSAIDs and antihypertensive drugs like telmisartan, a reduction in hypotensive effect was reported by inhibiting the vasodilating effect of prostaglandins.


    - Other drugs

    There was no clinically significant interaction with digoxin, warfarin, hydrochlorothiazide, glibenclamide, simvastatin, ibuprofen, paracetamol and amlodipine. An increase in the average concentration of digoxin in the blood plasma was observed on average by 20% (in one case by 39%). With the simultaneous administration of telmisartan and digoxin, it is advisable to periodically determine the concentration of digoxin in the blood

    AMLODIPINE


    - Grapefruit and grapefruit juice

    The simultaneous use of the drug TWINSTA with grapefruit or grapefruit juice is not recommended, as in some patients, as a result of increasing the bioavailability of amlodipine, the antihypertensive effect may increase.


    - Inhibitor inhibitors CYP3A4

    In a study in elderly patients, it was shown that diltiazem inhibits the metabolism of amlodipine, probably influencing the isoenzyme CYP3A4 (concentration of amlodipine in the blood plasma increases by approximately 50% and amplifies the effect of amlodipine). It can not be ruled out that the more active isoenzyme inhibitors CYP3A4 (such as ketoconazole, itraconazole, ritonavir) can increase the concentration of amlodipine in the blood plasma to a greater extent than diltiazem.


    - Inductors of isoenzyme CYP3A4 [Anticonvulsant drugs (eg, carbamazepine, phenobarbital, phenytoin, phosphenytoin, primidon), rifampicin, St. John's Wort (Hypericum perforatum)]

    Joint application can lead to a decrease in the concentration of amlodipine in the blood plasma. Regular medical supervision is shown. During application of isoenzyme inducers CYP3A4, and after their cancellation is recommended (if possible) a change in the dose of amlodipine.


    - Simvastatin

    The combined use of amlodipine with simvastatin at a dose of 80 mg led to an increase in the exposure of simvastatin to 77% compared with simvastatin monotherapy. Therefore, the dose of simvastatin should not exceed 20 mg per day.


    - Other drugs

    The safety of joint use of amlodipine with thiazide diuretics, beta-adrenoblockers, ACE inhibitors, long-acting nitrates, nitroglycerin (used sublingually), non-steroidal anti-inflammatory drugs, antibiotics and hypoglycemic agents for oral administration. With the simultaneous use of amlodipine and sildenafil, it was shown that each drug had an independent hypotensive effect.

    Additional Information:

    Simultaneous use in 20 healthy volunteers of 240 ml of grapefruit juice with a single dose of amlodipine 10 mg ingested did not significantly affect the pharmacokinetic properties of amlodipine. The simultaneous use of amlodipine with cimetidine did not significantly affect the pharmacokinetics of amlodipine. The simultaneous 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 drugs that affect RAAS, the simultaneous use of the drug TWINSTA and potassium-sparing diuretics, potassium-containing supplements, potassium-containing edible salt, other means that increase the potassium content in the blood (eg heparin) can lead to hyperkalemia, therefore, in patients.In this regard, their simultaneous use with telmisartan requires caution.

    Special instructions:During treatment with drugs that affect RAAS, especially if there are abnormalities in kidney function and / or heart failure, hyperkalemia may occur. These patients are recommended regular monitoring of potassium in the blood serum. Patients with impaired renal function are also encouraged to periodically monitor serum creatinine concentrations.

    In some patients, due to inhibition of RAAS, especially with the combination of agents acting on this system (for example, the addition of ACE inhibitors or aliskiren, a direct inhibitor of renin to APA II), kidney function (including acute renal failure) is impaired. Therapy, accompanied by such a double blockade of RAAS, is not recommended and therefore should be limited and carried out strictly individually with careful monitoring of kidney function.

    In patients with diabetes, coronary heart disease (CHD) can be asymptomatic, and therefore not be diagnosed. Patients with diabetes should undergo appropriate diagnosis, for example, a test with physical activity,for the diagnosis and treatment of IHD, respectively, before the start of treatment with the drug TWINSTA.

    Other instructions

    The drug TWINSTA is effective in treating patients of the Negroid race (in this population, renin activity in the blood is usually reduced).

    Effect on the ability to drive transp. cf. and fur:

    Studies of the impact on the ability to drive vehicles and control mechanisms have not been conducted. However, it should be appreciated that during treatment, undesirable effects such as syncope, drowsiness, or dizziness may be noted. Therefore, during the management of vehicles or mechanisms should be careful. If patients experience these feelings, they should avoid performing potentially dangerous activities, such as driving vehicles or controlling mechanisms.

    Form release / dosage:

    Tablets 5 mg + 40 mg, 10 mg + 40 mg, 5 mg + 80 mg, 10 mg + 80 mg.

    Packaging:

    7 tablets per blister of Al / Al foil.

    For 2 or 4 blisters together with instructions for use in a cardboard box.
    Storage conditions:

    Store at a temperature of no higher than 25 ° C in the original packaging.

    Keep out of the reach of children!

    Shelf life:

    3 years.

    The drug should not be used after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-002012
    Date of registration:25.02.2013
    The owner of the registration certificate:Boehringer Ingelheim International GmbHBoehringer Ingelheim International GmbH Germany
    Manufacturer: & nbsp
    Representation: & nbspBERINGER INGELCHAIM INTERNATIONAL GmbH BERINGER INGELCHAIM INTERNATIONAL GmbH Germany
    Information update date: & nbsp17.04.2014
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