Telmisartan, amlodipine besilate.
Each film-coated tablet contains: Telmisartan 40.0 mg, Amlodipine 5.0 mg.
Pharmacology: Pharmacodynamics: Telmisartan and Amlodipine are two hypertensive compounds with complimentary mechanism to control pressure in patients with essential hypertension. An angiotensin II receptor antagonist telmisartan and a dihydropyridine calcium channel blocker, amlodipine.
The combination of these substance has an additive antihypertensive effect reducing blood pressure to a greater degree than either component alone.
Pharmacokinetics: Absorption: Absorption of Telmisartan is rapid although the amount absorbed varies. The mean absolute bioavailability for Telmisartan is about 50%. When Telmisartan is taken with food, the reduction in the area under the plasma concentration-time curve (AUC) of Telmisartan varies from approximately 6% (40mg dose) to approximately 19% (160mg dose). By 3 hours after administration, plasma concentration are similar whether Telmisartan is taken fasting or with food.
After oral administration of therapeutic doses, amlodipine is well absorbed with peak blood levels between 6-12 hours post dose. Absolute bioavailability has been estimated to be between 64 and 80%. Amlodipine's bioavailability is not affected by food.
Distribution: Telmisartan is largely bound to plasma protein (>99.5%), mainly albumin and alpha-1 acid glycoprotein. The mean steady state apparently volume of distribution (Vdss) is approximately 500l.
The volume of distribution of amlodipine is approximately 21 l/kg.
Biotransformation: Telmisartan is metabolized by conjugation to the glucuronide of the patient compound. No pharmacological activity has been shown for the conjugate.
Amlodipine is extensively (approximately 90%) metabolized by the liver to inactive metabolites.
Elimination: Telmisartan is characterized by biexponential decay pharmacokinetics with a terminal elimination half life of >20 hours. The maximum plasma concentration (Cmax) and to a smaller extent, the area under the plasma concentration-time curve (AUC), increase disproportionately with dose. There is no evidence of clinically relevant accumulation of Telmisartan taken at the recommended dose. Telmisartan is nearly exclusively excreted with the faeces, mainly as unchanged compound. Cumulative urinary excretions <1% of dose. Total plasma clearance (Cltot) is high (approximately 1,000 ml/min) compared with hepatic blood flow (about 1,500 ml/min).
Used for the treatment of hypertension, and as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals.
Telmisartan: Recommended dose: 20 to 80mg once daily.
Amlodipine: Recommended dose: 2.5 to 10 mg once daily.
Dosage must be individual and may be increased after at least 2 weeks. Most of the anti-hypertensive effect is apparent within 2 weeks and maximal reduction is generally attained after 4 weeks, the maximum recommended dose of Telmisartan and Amlodipine tablet is 80/10mg once daily. Initial therapy with Telmisartan and Amlodipine is not recommended in patients >75 years old or with hepatic impairment.
The most prominent manifestations of telmisartan overdose were hypotension and tachycardia, bradycardia, dizziness, increase in serum creatinine, and acute renal failure have also been reported. Overdose with amlodipine may result in excessive peripheral vasodilation and possibly reflex tachycardia.
Telmisartan is not removed by haemodialysis. Suggested measures include induction of emesis and/or gastric lavage. If hypotension occurs, patient should be placed in supine position, with salt and volume replacement given quickly.
It is contraindicated in patients with hypersensitivity to the active substance telmisartan and amlodipine or any of the excipients used. It is also contraindicated in co-administration of aliskiren in patients with diabetes.
Hypotension: Telmisartan: In patients with an activated renin-angiotensin system, such as volume or salt-depleted patients, symptomatic hypotension occur alter initiation of therapy with Telmisartan.
Amlodipine: Symptomatic hypotension is possible particularly in patients with severe aortic stenosis.
Hyperkalemia: Telmisartan: Hyperkalemia may occur in plasma on ARBs particularly in patients with advanced renal impairment, heart failure, on renal replacement therapy, or on potassium supplements, potassium sparing diuretics, potassium-containing salt substitutes or other drugs that increase potassium levels.
Patients with Impaired Hepatic Function: Telmisartan: Patients with biliary obstructive disorders or hepatic insufficiency can be expected to have reduced clearance.
Amlodipine: Since patients with hepatic impairment have decreased clearance of amlodipine, start amlodipine or add amlodipine at 2.5mg in patients with hepatic impairment.
When pregnancy is diagnosed, treatment with Telmisartan and Amlodipine should be stopped immediately. Telmisartan and Amlodipine tablet is not recommended during breastfeeding.
The most commonly reported adverse reaction is dizziness and peripheral edema.
Telmisartan Drug Interactions: Lithium: Reversible increase in serum lithium concentration and toxicity have been reportedly during concomitant administration of lithium with angiotensin enzyme inhibitors, and with angiotensin II receptor antagonists, including telmisartan. If use of the combination proves necessary careful monitoring of serum lithium levels is recommended.
Aliskiren: Do not administered with Telmisartan and Amlodipine in patients with diabetes and renal impairment.
Digoxin: When telmisartan is co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed.
Amlodipine Drug Interactions: Simvastatin: Co-administration of multiple doses of 10mg of amlodipine with 80mg of simvastatin resulted in a 77% increases in exposure to simvastatin compared to simvastatin alone. Limit the dose of simvastatin in patients on amlodipine 20mg daily.
Store at temperature not exceeding 30°C. Protect from light and moisture.
Shelf-Life: 24 months.
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