Трипликсам
Трипликсам Uses, Dosage, Side Effects, Food Interaction and all others data.
Amlodipine is a Dihydropyridine Calcium antagonist that inhibits the transmembrane influx of Calcium ions into cardiac and vascular smooth muscle. It has greater affinity towards vascular smooth muscle than on cardiac muscle. Amlodipine is peripheral vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and thereby reduces blood pressure. Amlodipine reduces tone, decreases coronary vasoreactivity and lowers cardiac oxygen demand by reducing after load.
General pharmacodynamic effects
Amlodipine has a strong affinity for cell membranes, modulating calcium influx by inhibiting selected membrane calcium channels. This drug's unique binding properties allow for its long-acting action and less frequent dosing regimen , .
Hemodynamic effects
Perindopril is an ACE inhibitor. It works by blocking the action of angiotensin converting enzyme (ACE). ACE produces angiotensin II, as part of the body's natural control of blood pressure. Angiotensin II causes blood vessels to constrict and narrow, which increases the pressure within the blood vessels. Perindopril blocks the action of ACE, it reduces the production of angiotensin II, thus allows the blood vessels to relax and widen. The overall effect of this is a drop in blood pressure.
Trade Name | Трипликсам |
Generic | Amlodipine + Indapamid + Perindopril Arginine |
Type | |
Therapeutic Class | |
Manufacturer | |
Available Country | Russia |
Last Updated: | September 19, 2023 at 7:00 am |
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Uses
Patients with mild to moderate hypertension (alone or in combination with other antihypertensives).
The treatment of chronic stable and vasospastic angina.
Raynaud\'s disease.
Perindopril is a long-acting ACE (Angiotensin Converting Enzyme) inhibitor and is used for-
- Essential hypertension,
- Stable coronary artery disease,
- Congestive heart failure.
Трипликсам is also used to associated treatment for these conditions: Anginal Pain, Cardiovascular Events, Chronic Stable Angina Pectoris, Coronary Artery Disease (CAD), High Blood Pressure (Hypertension), Homozygous Familial Hypercholesterolemia, Hypertension,Essential, Mixed Dyslipidemias, Primary Hypercholesterolemia, Vasospastic Angina
How Трипликсам works
Mechanism of action on blood pressure
Amlodipine is considered a peripheral arterial vasodilator that exerts its action directly on vascular smooth muscle to lead to a reduction in peripheral vascular resistance, causing a decrease in blood pressure. Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the influx of calcium ions into both vascular smooth muscle and cardiac muscle. Experimental studies imply that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites, located on cell membranes. The contraction of cardiac muscle and vascular smooth muscle are dependent on the movement of extracellular calcium ions into these cells by specific ion channels. Amlodipine blocks calcium ion influx across cell membranes with selectivity. A stronger effect of amlodipine is exerted on vascular smooth muscle cells than on cardiac muscle cells . Direct actions of amlodipine on vascular smooth muscle result in reduced blood pressure .
Mechanism of action in angina
The exact mechanism by which amlodipine relieves the symptoms of angina have not been fully elucidated to this date, however, the mechanism of action is likely twofold:
Amlodipine has a dilating effect on peripheral arterioles, reducing the total peripheral resistance (afterload) against which the cardiac muscle functions. Since the heart rate remains stable during amlodipine administration, the reduced work of the heart reduces both myocardial energy use and oxygen requirements .
Dilatation of the main coronary arteries and coronary arterioles, both in healthy and ischemic areas, is another possible mechanism of amlodipine reduction of blood pressure. The dilatation causes an increase in myocardial oxygen delivery in patients experiencing coronary artery spasm (Prinzmetal's or variant angina) and reduces coronary vasoconstriction caused by smoking .
Dosage
Трипликсам dosage
For treatment of both hypertension and angina pectoris, the usual initial dose is 5 mg once daily. If the desired therapeutic effect cannot be achieved within 2-4 weeks, the dose may be increased to a maximum dose of 10 mg once daily. Amlodipine 10 mg once daily provides symptomatic improvement in patients with Raynaud's disease.
Use in children: Use of Amlodipine in children (under 12 years of age) is not recommended.
Hypertension: One Perindopril 4 tablet once daily preferably in the morning. If necessary, the dose may be increased to 8 mg after 1 month of treatment. Perindopril should be taken before food.
Stable coronary artery disease: Perindopril 4 once daily for two weeks, then increased to 8 mg once daily, depending on renal function and provided that the 4 mg dose is well tolerated. Elderly patients should receive Perindopril 2 mg once daily for one week, then Perindopril 4 once daily the next week, before increasing the dose up to 8 mg once daily, depending on renal, function. The dose should be increased only if the previous lower dose is well tolerated.
Congestive heart failure: Perindopril should be started under close medical supervision at a starting dose of 2 mg in the morning. If necessary dose may be increased to 4 mg.
Elderly patients: Start at low daily dose (4 mg or less) and titrate slowly as needed. Experience with doses exceeding 8 mg is limited.
Side Effects
Amlodipine is generally well tolerated. The most commonly observed side effects are headache, peripheral oedema, palpitations, flushing, dizziness, nausea, abdominal pain.
Rare and mild: usually at the start of treatment cough, fatigue, asthenia, headache, disturbances of mood and/or sleep have been reported.
Less often: Taste impairment, epigastric discomfort, nausea, abdominal pain and rash. Reversible increase in blood urea and creatinine may be observed. Proteinuria has occurred in some patients.
Rarely: Angioneurotic edema and decrease in hemoglobin, red cells and platelets have been reported.
Toxicity
Acute oral toxicity (LD50): 37 mg/kg (mouse) .
Overdose
An overdose of amlodipine could result in a high degree of peripheral vasodilatation with a possibility of reflex tachycardia. Significant and prolonged hypotension leading to shock and fatal outcomes have been reported .
Carcinogenesis, mutagenesis, impairment of fertility
Rats and mice treated with amlodipine maleate in the diet on a long-term basis for up to 2 years demonstrated no evidence of a carcinogenic effect of the drug. For the mouse, the highest dose was comparable to the maximum recommended human dose of 10 mg amlodipine per day. For the rat, the highest dose was measured to be about twice the maximum recommended human dose .
Mutagenicity studies using amlodipine maleate showed no drug-related gene or chromosomal effects .
There was no impact on the fertility of rats given oral amlodipine maleate (males for 64 days and females for 14 days before mating) at doses up to 10 mg amlodipine/kg/day (8 times the maximum recommended human dose) .
Use in pregnancy
The safety of amlodipine in human pregnancy or lactation has not been proven. Amlodipine is therefore considered a pregnancy category C drug . Use amlodipine only if the potential benefit justifies the potential risk .
Use in nursing
Discontinue when administering amlodipine .
Precaution
Hypotension: Since the vasodilUse in renal failure
Although Amlodipine is excreted primarily via kidney, mild renal impairment does not appear to have an effect on the plasma concentrations. Severe renal impairment may however require a dosage reduction. Amlodipine is not dialyzable.
Use in patients with impaired hepatic function
Amlodipine half-life is prolonged in patient with impaired hepatic function. Amlodipine should therefore be administered at lower (5mg) initial dose in these patients.
Use in heart failure
An increased number of pulmonary oedema has been reported.atation induced by Amlodipine is gradual in onset, acute hypotension has rarely been reported after oral administration of Amlodipine. Nonetheless, caution should be exercised when administering the drug with any other peripheral vasodilator particularly in patients with severe aortic stenosis.
Cardiac failure: Patients with heart failure should be treated with caution. Calcium channel blockers, including Amlodipine, should be usedwith caution in patients with congestive heart failure, as they may increase the risk of future cardiovascular events and mortality.
Beta blocker withdrawal: Amlodipine gives no protection against the danger of abrupt beta blocker withdrawal; any such withdrawal should be gradualreduction of the dose of beta blocker.
Hepatic failure: The half-life of amlodipine is prolonged and AUC values are higher in patients with impaired liver function. Amlodipine should therefore be initiated at the lower end of the dosing range and caution should be used, both on initial treatment and when increasing the dose. Slow dose titration and careful monitoring may be required in patients with severe hepatic impairment.
In the following cases, Perindopril should be used with caution:
- Renovascular hypertension
- Surgery/Anesthesia
- Renal failure: The dose should be cautiously adjusted in accordance with the creatinine clearance
- Symptomatic hypotension is rarely seen, but is more likely in volume-depleted patients, those receiving diuretics, or with the first two doses
- In diuretic-treated patients: stop the diuretic 3 days before starting Perindopril. A diuretic may later be given in combination if necessary; potassium-sparing diuretics are not recommended
- Combination with neuroleptics or imipramine-type drugs may increase the hypotensive effect. Serum lithium concentrations may rise during lithium therapy
Interaction
Use of Amlodipine together with thiazide diuretics or angiotensin-converting-enzyme inhibitors in the treatment of hypertension is additive. There are no hazardous interaction of Amlodipine with Digoxin, Cimetidine, Warfarin and food.
May enhance hypotensive effect with diuretics. Additive hyperkalaemic effect with K supplements, K-sparing diuretics, and other drugs (e.g. ciclosporin, heparin, indometacin). May increase serum levels and toxicity of lithium. Antihypertensive effect may be reduced by aspirin or other NSAIDs. Coadministration with NSAIDs may also increase the risk of renal impairment. Increased risk of hypoglycaemia with antidiabetic agents. Rarely, nitritoid reactions occur with concomitant use of gold (Na aurothiomalate).
Volume of Distribution
21 L/kg , .
Elimination Route
Amlodipine absorbed slowly and almost completely from the gastrointestinal tract. Peak plasma concentrations are achieved 6-12 hours after oral administration. The estimated bioavailability of amlodipine is 64-90%. Steady-state plasma amlodipine levels are achieved after 7-8 days of consecutive daily dosing. Absorption is not affected by food .
Half Life
The terminal elimination half-life of about 30–50 hours .
Plasma elimination half-life is 56 hours in patients with impaired hepatic function, titrate slowly when administering this drug to patients with severe hepatic impairment .
Clearance
Total body clearance (CL) has been calculated as 7 ± 1.3 ml/min/kg (0.42 ± 0.078 L/ h/kg) in healthy volunteers , .
Elderly patients show a reduced clearance of amlodipine with an AUC (area under the curve) increase of about 40–60%, and a lower initial dose may be required .
Elimination Route
Elimination from the plasma occurs in a biphasic with a terminal elimination half-life of about 30–50 hours. Steady-state plasma levels of amlodipine are reached after 7-8 days of consecutive daily dosing . Amlodipine is 10% excreted as unchanged drug in the urine. Amlodipine can be initiated at normal doses in patients diagnosed with renal failure , .
Pregnancy & Breastfeeding use
Pregnancy: Safety in pregnancy has not been established.
Lactation: It is not known whether Amlodipine is excreted in breast milk. It is advised to stop breastfeeding during treatment with Amlodipine.
Perindopril should not be used during pregnancy & lactation.
Contraindication
Amlodipine is contraindicated in patients with-
- Hypersensitivity to amlodipine, dihydropyridine derivatives or any of the excipients
- Shock (including cardiogenic shock)
- Obstruction of the outflow-tract of the left ventricle (e.g. high grade aortic stenosis)
- Unstable angina
- Hemodynamically unstable heart failure after acute myocardial infarction (during the first 28 days)
- Severe hypotension
Perindopril is contraindicated in patients with a history of hypersensitivity to Perindopril. This drug is contraindicated in case of management of hypertension of Children, during Pregnancy & Lactation.
Special Warning
Children with hypertension from 6 years to 17 years of age: 2.5 mg once daily as a starting dose, up-titrated to 5 mg once daily if blood pressure goal is not achieved after 4 weeks. Doses in excess of 5 mg daily have not been studied in pediatric patients.
Children under 6 years old: The effect of amlodipine on blood pressure in patients less than 6 years of age is not known.
Elderly: Amlodipine used at similar doses in elderly or younger patients is equally well tolerated. Normal dosage regimens are recommended in the elderly, but increase of the dosage should take place with care.
Renal impairment: Changes in amlodipine plasma concentrations are not correlated with degree of renal impairment, therefore the normal dosage is recommended. Amlodipine is not dialysable.
Hepatic impairment: Dosage recommendations have not been established in patients with mild to moderate hepatic impairment; therefore dose selection should be cautions and should start at the lower end of the dosing range. The pharmacokinetics of Amlodipine have not been studied in severe hepatic impairment. Amlodipine should be initiated at the lowest dose (2.5 mg once daily) and titrated slowly in patients with severe hepatic impairment.
Acute Overdose
There is no well documented experience with Amlodipine overdosage. In case of clinically significant hypotension due to Amlodipine over dosage, calls for active cardiovascular support including monitoring of cardiac and respiratory function, elevation of extremities and attention to circulating fluid volume and urine output. Since Amlodipine is highly protein-bound, dialysis is unlikely to be of benefit.
Storage Condition
Keep out of the reach of children. Store below 30° C. Keep in the original package in a cool & dry place in order to protect from light and moisture.
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.
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