Telsat AM

Telmisartan, amlodipine.

TELSAT AM 40/5: Each tablet contains: Telmisartan 40 mg, Amlodipine besilate equivalent to amlodipine 5 mg.
TELSAT AM 80/5: Each tablet contains: Telmisartan 80 mg, Amlodipine besilate equivalent to amlodipine 5 mg.
TELSAT AM 80/10: Each tablet contains: Telmisartan 80 mg, Amlodipine besilate equivalent to amlodipine 10 mg.

Pharmacology: TELSAT AM combines two antihypertensive compounds with complementary mechanisms to control blood pressure in patients with essential hypertension: an angiotensin II receptor antagonist, telmisartan, and a dihydropyridine calcium channel blocker, amlodipine. The combination of these substances has an additive antihypertensive effect, reducing blood pressure to a greater degree than either component alone.
TELSAT AM once daily produces effective and consistent reductions in blood pressure across the 24-hours therapeutic dose range.
Telmisartan: Telmisartan is an orally effective and specific angiotensin II receptor (type AT1) antagonist. Telmisartan displaces angiotensin II with very high affinity from its binding site at the AT1 receptor subtype, which is responsible for the known actions of angiotensin II. Telmisartan does not exhibit any partial agonist activity at the AT1 receptor. Telmisartan selectively binds the AT1 receptor. The binding is long lasting.
Telmisartan does not show affinity for other receptors, including AT2 and other less characterized AT receptors. The functional role of these receptors is not known, nor is the effect of their possible overstimulation by angiotensin II, whose levels are increased by telmisartan. Plasma aldosterone levels are decreased by telmisartan. Telmisartan does not inhibit human plasma renin or block ion channels. Telmisartan does not inhibit angiotensin converting enzyme (kininase II), the enzyme which also degrades bradykinin. Therefore it is not expected to potentiate bradykinin-mediated adverse effects.
In patients with hypertension, telmisartan reduces both systolic and diastolic blood pressures without affecting pulse rate. The contribution of the medicinal product's diuretic and natriuretic effect to its hypotensive activity has still to be defined.
The antihypertensive efficacy of telmisartan is comparable to that of agent representative of other classes of antihypertensive drugs such as amlodipine, atenolol, enalapril, hydrochlorothiazide, losartan, lisinopril, ramipril, and valsartan.
Upon abrupt cessation of treatment with telmisartan, blood pressure gradually returns to pretreatment values over a period of several days without evidence of rebound hypertension.
The incidence of dry cough was significantly lower in patients treated with telmisartan than in those given angiotensin converting enzyme inhibitors.
Amlodipine: Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group (slow channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle.
The mechanism of the antihypertensive action of amlodipine is due to a direct relaxant effect on vascular smooth muscle, leading to reductions in peripheral vascular resistance and in blood pressure. Amlodipine binds to both dihydropyridine and non-dihydropyridine binding sites. Amlodipine is relatively vessel-selective, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells.
In patients with hypertension, once daily dosing provides clinically significant reductions of blood pressure in both the supine and standing positions throughout the 24 hours interval. Due to the slow onset of action, acute hypotension is not a feature of amlodipine administration.
In hypertensive patients with normal renal function, therapeutic doses of amlodipine resulted in a decrease in renal vascular resistance and an increase in glomerular filtration rate and effective renal plasma flow, without change in filtration fraction or proteinuria.
Amlodipine has not been associated with any adverse metabolic effects or changes in plasma lipids and is suitable for use in patients with asthma, diabetes, and gout.
Use in patients with heart failure: Amlodipine did not lead to clinical deterioration as measured by exercise tolerance, left ventricular ejection fraction, and clinical symptomatology in NYHA class II-IV heart failure patients.
Amlodipine did not lead to an increase in risk of mortality or combined mortality and morbidity with heart failure in patients with NYHA class III-IV heart failure that receiving digoxin, diuretics, and ACE inhibitors.
In patients with NYHA class III and IV heart failure without clinical symptoms or objective findings suggestive or underlying ischemic disease, on stable doses of ACE inhibitors, digitalis, and diuretics, amlodipine had no effect on total cardiovascular mortality. In this same population amlodipine was associated with increased reports of pulmonary edema.
Pharmacokinetics: Telmisartan/amlodipine 80/10 mg fixed-dose combination (TELSAT AM) tablet has been studied in an open-label, randomized, single-dose, three-period, three-sequence, partial replicated study under fasting conditions which included 31 healthy adult male subjects (18-55 years). The pharmacokinetic parameters assessed in this study were AUC_0-72h, C_max, t_max and t_½. These parameters were determined from plasma concentrations of telmisartan and amlodipine.
After oral administration of TELSAT AM, the mean (SD) AUC_0-72h of telmisartan and amlodipine were 3110.65 (1845.67) ng·hour/ml and 385.04 (130.99) ng·hour/ml, respectively. The mean (SD) maximum plasma concentration (C_max) of telmisartan and amlodipine were 546.06 (334.49) ng/ml and 11.46 (3.41) ng/ml, respectively. Cmax of telmisartan and amlodipine reached within 0.75 (0.50-2.00) hours and 8.00 (6.00-12.00) hours, respectively. The mean (SD) elimination half-lives (t_½) of telmisartan and amlodipine were 24.89 (8.26) hours and 33.64 (8.18) hours, respectively.
The geometric mean ratios (90% confidence intervals) of telmisartan were 99.10% (92.02-106.73%) for AUC_0-72h and 91.99% (78.64-107.61%) for C_max. The geometric mean ratios (90% confidence intervals) of amlodipine were 100.60% (95.03-106.49%) for AUC_0-72h and 104.21% (99.41-109.24%) for C_max. The result of this study showed that the pharmacokinetic parameters of TELSAT AM tablet were within the acceptance range for bioequivalence, therefore, TELSAT AM tablet was similar or bioequivalent to the reference drug.
Pediatric patients (age below 18 years): No pharmacokinetic data are available in the pediatric population.
Gender effects: Gender differences in plasma concentrations of telmisartan were observed, C_max and AUC being approximately 3-and 2-fold higher, respectively, in females compared to males.
Elderly patients: The pharmacokinetics of telmisartan do not differ between younger and elderly patients.
Time to peak plasma amlodipine concentrations is similar in young and elderly patients. In elderly patients, amlodipine clearance tends to decline, causing increases in the area under the curve (AUC) and elimination half-life.
Patients with renal impairment: In patients with mild to moderate and severe renal impairment, doubling of plasma concentrations of telmisartan was observed. Lower plasma concentrations of telmisartan were observed in patients with renal insufficiency undergoing dialysis. Telmisartan is highly bound to plasma protein in renal-insufficient patients and cannot be removed by dialysis. The elimination half-life is not changed in patients with renal impairment.
The pharmacokinetics of amlodipine is not significantly influenced by renal impairment.
Patients with hepatic impairment: Absolute bioavailability of telmisartan increases up to nearly 100% in patients with hepatic impairment. The elimination half-life is not changed in patients with hepatic impairment.
Patients with hepatic insufficiency have decreased clearance of amlodipine with resulting increase of approximately 40-60% in AUC.

Treatment of essential hypertension.
Replacement therapy: Patients receiving telmisartan and amlodipine from separate tablets may instead receive TELSAT AM containing the same component doses.
Add on therapy: TELSAT AM is indicated in patients whose blood pressure is not adequately controlled on amlodipine monotherapy.

Dosage: Adult: TELSAT AM should be taken once daily.
The maximum recommended dose is one tablet 80 mg telmisartan/10 mg amlodipine per day. TELSAT AM is indicated for long term treatment.
Replacement therapy: Patients receiving telmisartan and amlodipine from separate tablets can instead receive TELSAT AM containing the same component doses in one tablet once daily, e.g. to enhance convenience or compliance.
Add on therapy: TELSAT AM 40/5 mg tablets may be administered in patients whose blood pressure is not adequately controlled with amlodipine 5 mg alone. Individual dose titration with the components (i.e. amlodipine and telmisartan) is recommended before changing to the fixed dose combination. When clinically appropriate, direct change from monotherapy to the fixed combination may be considered. Patients treated with 10 mg amlodipine who experience any dose-limiting adverse reactions such as edema, may be switched to TELSAT AM 40/5 mg once daily, reducing the dose of amlodipine without reducing the overall expected antihypertensive response.
TELSAT AM can be administered with other antihypertensive drugs.
Special populations: Renal impairment: No posology adjustment is required for patients with renal impairment. Limited experience is available in patients with severe renal impairment or hemodialysis. Caution is advised when using TELSAT AM in such patients as amlodipine and telmisartan are not dialyzable.
Hepatic impairment: In patients with mild to moderate hepatic impairment, TELSAT AM should be administered with caution. For telmisartan the posology should not exceed 40 mg once daily. TELSAT AM is contraindicated in patients with severe hepatic impairment.
Elderly: No dose adjustment is necessary for elderly patients.
Pediatric population: TELSAT AM is not recommended for use in patients aged below 18 years due to a lack of data on safety and efficacy.
Method of administration: Tablet for oral administration.
TELSAT AM may be taken with or without food.

Symptoms: There is no experience of overdose with TELSAT AM. Signs and symptoms of overdose are expected to be in line with exaggerated pharmacological effects. The most prominent manifestations of telmisartan overdosage were hypotension, tachycardia; bradycardia, dizziness, increase in serum creatinine, and acute renal failure have also been reported. Overdose with amlodipine may result in excessive peripheral vasodilatation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal outcome may occur.
Therapy: Supportive treatment should be instituted. Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. Telmisartan and amlodipine are not removed by hemodialysis.
The patients should be closely monitored, and the treatment should be symptomatic and supportive. Management depends on the time since ingestion and the severity of the symptoms.
Suggested measures include induction of emesis and/or gastric lavage. Activated charcoal may be useful in the treatment of overdose of both telmisartan and amlodipine.
Serum electrolytes and creatinine should be monitored frequently. If hypotension occurs, the patients should be placed in a supine position with elevation of extremities, with salt and volume replacement given quickly.

Hypersensitivity to the active substances, or to any of the excipients.
Hypersensitivity to dihydropyridine derivatives.
Second and third trimesters of pregnancy.
Lactation.
Biliary obstructive disorders.
Severe hepatic impairment.
Shock (including cardiogenic shock).
Severe hypotension.
Obstruction of the outflow tract of the left ventricle (e.g. high grade aortic stenosis).
Hemodynamically unstable heart failure after acute myocardial infarction.
The concomitant use of TELSAT AM with aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (GFR <60 ml/minute/1.73 m²).

TELSAT AM tablets should not be divided into halves as no studies have been performed on halved tablets.
Hepatic impairment: Telmisartan is mostly eliminated in the bile. Patients with biliary obstructive disorders or hepatic insufficiency can be expected to have reduced clearance. Furthermore as with all calcium antagonists, amlodipine half-life is prolonged in patients with impaired liver function and dosage recommendations have not been established. TELSAT AM should therefore be used with caution in these patients.
Renovascular hypertension: There is an increased risk of severe hypotension and renal insufficiency when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with medicinal products that affect the renin-angiotensin-aldosterone system.
Renal impairment and kidney transplant: When TELSAT AM is used in patients with impaired renal function, a periodic monitoring of potassium and creatinine serum levels is recommended. There is no experience regarding the administration of TELSAT AM in patients with a recent kidney transplant.
Telmisartan and amlodipine are not dialyzable.
Intravascular hypovolemia: Symptomatic hypotension, especially after the first dose, may occur in patients who are volume and/or sodium depleted by e.g. vigorous diuretic therapy, dietary salt restriction, diarrhea, or vomiting. Such conditions should be corrected before the administration of TELSAT AM. If hypotension occurs with TELSAT AM, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. Treatment can be continued once blood pressure has been stabilized.
Dual blockade of the renin-angiotensin-aldosterone system: As a consequence of inhibiting the renin-angiotensin-aldosterone system, hypotension and changes in renal function (including acute renal failure) have been reported in susceptible individuals, especially if combining medicinal products that affect this system. TELSAT AM can be administered with other antihypertensive drugs, however dual blockade of the renin-angiotensin-aldosterone system (e.g. by adding an ACE inhibitor or the direct renin-inhibitor aliskiren to an angiotensin II receptor antagonist) is not recommended in patients with already controlled blood pressure and should therefore be limited to individually defined cases with close monitoring of renal function (see Contraindications).
Other conditions with stimulation of the renin-angiotensin-aldosterone system: In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with medicinal products that affect this system has been associated with acute hypotension, hyperazotemia, oliguria, or rarely acute renal failure.
Primary aldosteronism: Patients with primary aldosteronism generally will not respond to antihypertensive medicinal products acting through inhibition of the renin-angiotensin system. Therefore, the use of telmisartan is not recommended.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy: As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.
Unstable angina pectoris, acute myocardial infarction: There are no data to support the use of TELSAT AM in unstable angina pectoris and during or within one month of a myocardial infarction.
Heart failure: In a long-term, amlodipine was associated with increased reports of pulmonary edema in patients with NYHA III and IV heart failure of nonischemic etiology.
Hyperkalemia: The use of medicinal products that affect the renin-angiotensin-aldosterone system may cause hyperkalemia. Hyperkalemia may be fatal in the elderly, in patients with renal insufficiency, in diabetic patients, in patients concomitantly treated with other medicinal products that may increase potassium levels, and/or in patients with intercurrent events.
Before considering the concomitant use of medicinal products that affect the renin-angiotensin-aldosterone system, the benefit risk ratio should be evaluated.
The main risk factors for hyperkalemia to be considered are: Diabetes mellitus, renal impairment, age (>70 years).
Combination with one or more other medicinal products that affect the renin-angiotensin-aldosterone system and/or potassium supplements. Medicinal products or therapeutic classes of medicinal products that may provoke hyperkalemia are salt substitutes containing potassium, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, nonsteroidal anti-inflammatory medicinal products (NSAIDs, including selective COX-2 inhibitors), heparin, immunosuppressives (ciclosporin or tacrolimus), and trimethoprim.
Intercurrent events, in particular dehydration, acute cardiac decompensation, metabolic acidosis, worsening of renal function, sudden worsening of the renal condition (e.g. infectious diseases), cellular lysis (e.g. acute limb ischemia, rhabdomyolysis, extend trauma).
Serum potassium should be monitored closely in these patients.
Diabetes mellitus: In diabetic patients with an additional cardiovascular risk, i.e. patients with diabetes mellitus and coexistent coronary artery disease (CAD), the risk of fatal myocardial infarction and unexpected cardiovascular death may be increased when treated with blood pressure lowering agents such as ARBs or ACE inhibitors. In patients with diabetes mellitus CAD may be asymptomatic and therefore undiagnosed. Patients with diabetes mellitus should undergo appropriate diagnostic evaluation, e.g. exercise stress testing, to detect and to treat CAD accordingly before initiating treatment with TELSAT AM.
Other: TELSAT AM was effective when treating blackpatients (usually a low-renin population).
As with any antihypertensive agent, excessivereduction of blood pressure in patients with ischemiccardiopathy or ischemic cardiovascular disease couldresult in a myocardial infarction or stroke.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed. However, patients should be advised that they may experience undesirable effects such as syncope, somnolence, dizziness, or vertigo during treatment. Therefore, caution should be recommended when driving a car or operating machinery.
If patients experience these adverse experiences, they should avoid potentially hazardous tasks such as driving or operating machinery.
Use in Pregnancy & lactation: See USE IN PREGNANCY & LACTATION section for further information.

Pregnancy: Telmisartan: The use of angiotensin II receptor antagonists is not recommended during the first trimester of pregnancy and should not be initiated during pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started.
The use of angiotensin II receptor antagonists is contraindicated during the second and third trimester of pregnancy.
Telmisartan do not indicate teratogenic effect, but have shown fetotoxicity.
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with angiotensin II receptor antagonist, similar risks may exist for this class of medicinal products.
Angiotensin II receptor antagonists exposure during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation), and neonatal toxicity (renal failure, hypotension, hyperkalemia).
Unless continued angiotensin II receptor antagonist therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. Should exposure to angiotensin II receptor antagonists have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for hypotension.
Amlodipine: The safety of amlodipine in human pregnancy has not been established. In animal studies, reproductive toxicity was observed at high doses. Data on a limited number of exposed pregnancies do not indicate that amlodipine or other calcium receptor antagonists have a harmful effect on the health of the fetus. However, there may be a risk of prolonged delivery.
Lactation: It is not known whether telmisartan is excreted in human milk. Nonclinical studies have shown excretion of telmisartan in breast milk. Amlodipine has been identified in breastfed infants of treated women. The effect of amlodipine on infants is unknown. Because of the potential adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue therapy, taking into account the importance of this therapy for the mother (see Contraindications).
Fertility: No data with the fixed dose combination or with the individual components are available.
Separate reproductive toxicity studies with the combination of telmisartan and amlodipine have not been conducted.
No effects of telmisartan on male and female were observed.
Similarly, no effects on male and female fertility were reported for amlodipine.

Fixed dose combination: The most common adverse reactions include dizziness and peripheral edema. Serious syncope may occur rarely (less than 1 case per 1,000 patients).
Adverse reactions have been ranked under headings of frequency using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).
Adverse reactions reported with telmisartan plus amlodipine are shown below according to system organ class: see table.


Click on icon to see table/diagram/image


Additional information on the combination: Peripheral edema, a recognized dose dependent adverse reaction of amlodipine, was generally observed at a lower incidence in patients who received the telmisartan/amlodipine combination than in those who received amlodipine alone.
Additional information on individual components: Adverse reactions previously reported with one of the individual components (amlodipine or telmisartan) may be potential adverse reactions with TELSAT AM as well.
Telmisartan: Infections and infestations: Uncommon: urinary tract infections, upper respiratory tract infections.
Rare: sepsis including fatal outcome.
Blood and lymphatic system disorders: Uncommon: anemia.
Rare: eosinophilia, thrombocytopenia.
Immune system disorders: Rare: anaphylactic reaction, hypersensitivity.
Metabolism and nutrition disorders: Uncommon: hyperkalemia.
Rare: hypoglycemia (in diabetic patients).
Eye disorders: Rare: visual disturbance.
Cardiac disorders: Rare: tachycardia.
Respiratory, thoracic, and mediastinal disorders: Uncommon: dyspnea.
Gastrointestinal disorders: Uncommon: flatulence.
Rare: stomach discomfort.
Hepatobiliary disorders: Rare: hepatic function abnormal, liver disorder.
*Most cases of hepatic function abnormal/liver disorder from postmarketing experience with telmisartan occurred in patients in Japan, who are more likely to experience these adverse reactions.
Skin and subcutaneous tissue disorders: Uncommon: hyperhidrosis.
Rare: angioedema (with fatal outcome), urticaria, drug eruption, toxic skin eruption.
Musculoskeletal and connective tissue disorders: Rare: tendon pain (tendinitis like symptoms).
Renal and urinary disorders: Uncommon: renal impairment including acute renal failure.
General disorders: Rare: influenza-like illness.
Investigations: Uncommon: blood creatinine increased.
Very rare: blood creatine phosphokinase (CPK) increased, hemoglobin decreased.
Amlodipine: Blood and lymphatic system disorders: Very rare: thrombocytopenia, leukopenia.
Immune system disorders: Very rare: hypersensitivity.
Metabolism and nutrition disorders: Very rare: hyperglycemia.
Psychiatric disorders: Uncommon: mood change.
Rare: confusional state.
Nervous system disorders: Very rare: extrapyramidal disorder.
Eye disorders: Uncommon: visual impairment.
Ear and labyrinth disorders: Uncommon: tinnitus.
Cardiac disorders: Very rare: myocardial infarction, arrhythmia, ventricular tachycardia, atrial fibrillation.
Vascular disorders: Very rare: vasculitis.
Respiratory, thoracic, and mediastinal disorders: Uncommon: dyspnea, rhinitis.
Gastrointestinal disorders: Uncommon: change of bowel habit.
Very rare: pancreatitis, gastritis.
Hepatobiliary disorders: Very rare: hepatitis, jaundice, hepatic enzyme elevations (mostly consistent with cholestasis).
Skin and subcutaneous tissue disorders: Uncommon: alopecia, purpura, skin discoloration, hyperhidrosis.
Very rare: angioedema, erythema multiforme, urticaria, exfoliative dermatitis, Stevens-Johnson syndrome, photosensitivity reaction.
Renal and urinary disorders: Uncommon: micturition disorder, pollakiuria.
Reproductive system and breast disorders: Uncommon: gynecomastia.
General disorders: Uncommon: pain.
Investigations: Uncommon: weight increased, weight decreased.

No interactions between the two components of this fixed dose combinations have been observed.
Interactions common to the combination: No drugs interaction studies have been performed with TELSAT AM and other medicinal products.
Concomitant use to be taken into account: Other antihypertensive agents: The blood pressure lowering effect of TELSAT AM can be increased by concomitant use of other antihypertensive medicinal products.
Agents with blood pressure lowering potential: Based on their pharmacological properties it can be expected that the following medicinal products may potentiate the hypotensive effects of all antihypertensives including TELSAT AM, e.g. baclofen, amifostine. Furthermore, orthostatic hypotension may be aggravated by alcohol, barbiturates, narcotics, or antidepressants.
Corticosteroids (systemic route): Reduction of the antihypertensive effect.
Interactions linked to telmisartan: Concomitant use not recommended: Potassium sparing diuretics or potassium supplements: Angiotensin II receptor antagonists such as telmisartan, attenuate diuretic induced potassium loss.
Potassium sparing diuretics e.g. spironolactone, eplerenone, triamterene, or amiloride, potassium supplements, or potassium-containing salt substitutes may lead to a significant increase in serum potassium. If concomitant use is indicated because of documented hypokalemia, they should be used with caution and with frequent monitoring of serum potassium.
Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting 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.
Concomitant use requiring caution: Nonsteroidal anti-inflammatory medicinal products (NSAIDs): Nonsteroidal anti-inflammatory medicinal products/NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors, and nonselective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.
In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the coadministration of angiotensin II receptor antagonists and medicinal products that inhibit cyclooxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be administered with the caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy and periodically thereafter.
Ramipril: The coadministration of telmisartan and ramipril led to an increase of up to 2.5 fold in the AUC_0-24 and C_max of ramipril and ramiprilat. The clinical relevance of this observation is not known.
Interactions linked to amlodipine: Concomitant use requiring caution: Grapefruit and grapefruit juice: Administration of TELSAT AM with grapefruit or grapefruit juice is not recommended since bioavailability may be increased in certain patients resulting in increased blood pressure lowering effects.
CYP3A4 inhibitors: With concomitant use with the CYP3A4 inhibitor erythromycin in young patients and diltiazem in elderly patients respectively, the plasma concentration of amlodipine increased 22% and 50% respectively. However, the clinical relevance of this finding is uncertain. It cannot be ruled out that strong inhibitors of CYP3A4 (i.e. ketoconazole, itraconazole, ritonavir) may increase the plasma concentrations of amlodipine to a greater extent than diltiazem. Amlodipine should be used with caution together with CYP3A4 inhibitors. However, no adverse events attributable to such interaction have been reported.
CYP3A4 inducers: There is no data available regarding the effect of CYP3A4 inducers on amlodipine. The concomitant use of CYP3A4 inducers (i.e. rifampicin, Hypericum perforatum) may lead to a lower plasma concentration of amlodipine.
Concomitant use to be taken into account: Simvastatin: Coadministration of multiple doses of amlodipine with simvastatin 80 mg resulted in an increase in exposure to simvastatin up to 77% compared to simvastatin alone. Therefore, limit the dose of simvastatin in patients on amlodipine to 20 mg daily.
Immunosuppressants: Amlodipine may increase the systemic exposure of ciclosporin or tacrolimus when coadministered. Frequent monitoring of trough blood levels of ciclosporin and tacrolimus and dose adjustment when appropriate is recommended.
Others: Amlodipine has been safely administered with digoxin, warfarin, atorvastatin, sildenafil, antiacid-medicinal products (aluminium hydroxide, magnesium hydroxide, and simeticone), cimetidine, ciclosporin, antibiotics, and oral hypoglycemic medicinal products. When amlodipine and sildenafil were used in combination, each agent independently exerted its own blood pressure lowering effect.
Additional information: Concomitant administration of 240 ml of grapefruit juice with a single oral dose of 10 mg amlodipine in healthy volunteers did not show a significant effect on the pharmacokinetic properties of amlodipine.

Store at temperature below 30°C, protect from light.

Angiotensin II Antagonists / Calcium Antagonists

C09DB04 - telmisartan and amlodipine ; Belongs to the class of angiotensin II receptor blockers (ARBs) and calcium channel blockers. Used in the treatment of cardiovascular disease.

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