Zamplify 40/5/Zamplify 40/10/Zamplify 80/5/Zamplify 80/10

40 mg/5 mg: Oblong uncoated bilayered tablets, white to off-white with debossed 'C6' on one side and blue plain on the other side of the tablet.
Each tablet contains: Telmisartan 40 mg, Amlodipine (as besilate) 5 mg.
40 mg/10 mg: Oblong uncoated bilayered tablets, white to off-white with debossed 'C7' on one side and blue plain on the other side of the tablet.
Each tablet contains: Telmisartan 40 mg, Amlodipine (as besilate) 10 mg.
80 mg/5 mg: Oblong uncoated bilayered tablets, white to off-white with debossed 'C8' on one side and blue plain on the other side of the tablet.
Each tablet contains: Telmisartan 80 mg, Amlodipine (as besilate) 5 mg.
80 mg/10 mg: Oblong uncoated bilayered tablets, white to off-white with debossed 'C9' on one side and blue plain on the other side of the tablet.
Each tablet contains: Telmisartan 80 mg, Amlodipine (as besilate) 10 mg.

Pharmacology: Pharmacodynamics: Telmisartan + Amlodipine have been shown to be effective in lowering blood pressure. Telmisartan + Amlodipine is a combination of two drugs with antihypertensive properties: a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker), amlodipine besylate, and an angiotensin II receptor blocker, telmisartan.
Both telmisartan and amlodipine, lower blood pressure by reducing peripheral resistance but through complementary mechanisms.
Telmisartan: In normal volunteers, a dose of telmisartan 80 mg inhibited the pressor response to an intravenous infusion of angiotensin II by about 90% at peak plasma concentrations with approximately 40% inhibition persisting for 24 hours.
Plasma concentration of angiotensin II and plasma renin activity (PRA) increased in a dose-dependent manner after single administration of telmisartan to healthy subjects and repeated administration to hypertensive patients. The once-daily administration of up to 80 mg telmisartan to healthy subjects did not influence plasma aldosterone concentrations. In multiple dose studies with hypertensive patients, there were no clinically significant changes in electrolytes (serum potassium or sodium), or in metabolic function (including serum levels of cholesterol, triglycerides, HDL, LDL, glucose, or uric acid).
In 30 hypertensive patients with normal renal function treated for 8 weeks with telmisartan 80 mg or telmisartan 80 mg in combination with hydrochlorothiazide 12.5 mg, there were no clinically significant changes from baseline in renal blood flow, glomerular filtration rate, filtration fraction, renovascular resistance, or creatinine clearance.
Amlodipine: Following administration of therapeutic doses to patients with hypertension, amlodipine produces vasodilation resulting in a reduction of supine and standing blood pressures. These decreases in blood pressure are not accompanied by a significant change in heart rate or plasma catecholamine levels with chronic dosing. Although the acute intravenous administration of amlodipine decreases arterial blood pressure and increases heart rate in hemodynamic studies of patients with chronic stable angina, chronic oral administration of amlodipine in clinical trials did not lead to clinically significant changes in heart rate or blood pressures in normotensive patients with angina.
With chronic once daily administration, antihypertensive effectiveness is maintained for at least 24 hours. Plasma concentrations correlate with effect in both young and elderly patients. The magnitude of reduction in blood pressure with amlodipine is also correlated with the height of pretreatment elevation; thus, individuals with moderate hypertension (diastolic pressure 105 to 114 mmHg) had about a 50% greater response than patients with mild hypertension (diastolic pressure 90 to 104 mmHg). Normotensive subjects experienced no clinically significant change in blood pressure (+1/-2 mmHg).
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.
As with other calcium channel blockers, hemodynamic measurements of cardiac function at rest and during exercise (or pacing) in patients with normal ventricular function treated with amlodipine have generally demonstrated a small increase in cardiac index without significant influence on dP/dt or on left ventricular end diastolic pressure or volume. In hemodynamic studies, amlodipine has not been associated with a negative inotropic effect when administered in the therapeutic dose range to intact animals and man, even when co-administered with beta-blockers to man. Similar findings, however, have been observed in normal or well-compensated patients with heart failure with agents possessing significant negative inotropic effects.
Amlodipine does not change sinoatrial nodal function or atrioventricular conduction in intact animals or man. In patients with chronic stable angina, intravenous administration of 10 mg did not significantly alter A-H and H-V conduction and sinus node recovery time after pacing. Similar results were obtained in patients receiving amlodipine and concomitant beta-blockers. In clinical studies in which amlodipine was administered in combination with beta-blockers to patients with either hypertension or angina, no adverse effects of electrocardiographic parameters were observed. In clinical trials with angina patients alone, amlodipine therapy did not alter electrocardiographic intervals or produce higher degrees of AV blocks.
Pharmacokinetics: Telmisartan: Following oral administration, peak concentrations (Cmax) of telmisartan are reached in 0.5 to 1 hour after dosing. Food slightly reduces the bioavailability of telmisartan, with a reduction in the area under the plasma concentration-time curve (AUC) of about 6% with the 40 mg tablet and about 20% after a 160 mg dose. The absolute bioavailability of telmisartan is dose dependent. At 40 and 160 mg the bioavailability was 42% and 58%, respectively. The pharmacokinetics of orally administered telmisartan are nonlinear over the dose range 20 to 160 mg, with greater than proportional increases of plasma concentrations (Cmax and AUC) with increasing doses. Telmisartan shows bi-exponential decay kinetics with a terminal elimination half life of approximately 24 hours. Trough plasma concentrations of telmisartan with once daily dosing are about 10% to 25% of peak plasma concentrations. Telmisartan has an accumulation index in plasma of 1.5 to 2.0 upon repeated once daily dosing.
Amlodipine: Peak plasma concentrations of amlodipine are reached 6 to 12 hours after administration of amlodipine alone. Absolute bioavailability has been estimated to be between 64% and 90%. The bioavailability of amlodipine is not altered by the presence of food.
Elimination of amlodipine from the plasma is biphasic with a terminal elimination half-life of about 30 to 50 hours. Steady state plasma levels of amlodipine are reached after 7 to 8 days of consecutive daily dosing.
Distribution: Telmisartan: Telmisartan is highly bound to plasma proteins (>99.5%), mainly albumin and α1-acid glycoprotein. Plasma protein binding is constant over the concentration range achieved with recommended doses. The volume of distribution for telmisartan is approximately 500 liters indicating additional tissue binding.
Amlodipine: The apparent volume of distribution of amlodipine is 21 L/kg. Approximately 93% of circulating amlodipine is bound to plasma proteins in hypertensive patients.
Metabolism and Elimination: Telmisartan: Following either intravenous or oral administration of 14C-labeled telmisartan, most of the administered dose (>97%) was eliminated unchanged in feces via biliary excretion; only minute amounts were found in the urine (0.91% and 0.49% of total radioactivity, respectively). Telmisartan is metabolized by conjugation to form a pharmacologically inactive acylglucuronide; the glucuronide of the parent compound is the only metabolite that has been identified in human plasma and urine. After a single dose, the glucuronide represents approximately 11% of the measured radioactivity in plasma. The cytochrome P450 isoenzymes are not involved in the metabolism of telmisartan.
Total plasma clearance of telmisartan is >800 mL/min. Terminal half-life and total clearance appear to be independent of dose.
Amlodipine: Amlodipine is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine.
Special Populations: Renal Insufficiency: Telmisartan: No dosage adjustment is necessary in patients with decreased renal function. Telmisartan is not removed from blood by hemofiltration.
Amlodipine: The pharmacokinetics of amlodipine are not significantly influenced by renal impairment. Patients with renal failure may therefore receive the usual initial dose.
Hepatic Insufficiency: Telmisartan: In patients with hepatic insufficiency, plasma concentrations of telmisartan are increased, and absolute bioavailability approaches 100%.
Amlodipine: Patients with hepatic insufficiency have decreased clearance of amlodipine with a resulting increase in AUC of approximately 40% to 60%. Therefore, start with a low initial dose of amlodipine.
Gender: Plasma concentrations of telmisartan are generally 2 to 3 times higher in females than in males. In clinical trials, however, no significant increases in blood pressure response or in the incidence of orthostatic hypotension were found in women. No dosage adjustment is necessary.
Geriatric Patients: Telmisartan: The pharmacokinetics of telmisartan do not differ between the elderly and those younger than 65 years.
Amlodipine: Elderly patients have decreased clearance of amlodipine with a resulting increase in AUC of approximately 40% to 60%. Therefore, start with a low initial dose of amlodipine.

Indicated for the treatment of hypertension, alone or with other antihypertensive agents.
Telmisartan + Amlodipine may also be used as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals. Base the choice of Telmisartan + Amlodipine as initial therapy for hypertension on an assessment of potential benefits and risks including whether the patient is likely to tolerate the starting dose of Telmisartan + Amlodipine.
Patients with moderate or severe hypertension are at relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. Consider the patient's baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared with monotherapy when deciding whether to use Telmisartan + Amlodipine as initial therapy. Individual blood pressure goals may vary based upon the patient's risk.

General Considerations: Telmisartan is an effective treatment of hypertension in once daily doses of 20 to 80 mg while amlodipine is effective in doses of 2.5 to 10 mg. Dosage must be individualized and may be increased after at least 2 weeks. Most of the antihypertensive effect is apparent within 2 weeks and maximal reduction is generally attained after 4 weeks. The maximum recommended dose of Telmisartan + Amlodipine is 80/10 mg once daily. The adverse reactions of telmisartan are uncommon and independent of dose; those of amlodipine are a mixture of dose-dependent phenomena (primarily peripheral edema) and dose-independent phenomena, the former much more common than the latter.
Telmisartan + Amlodipine may be taken with or without food.
Replacement Therapy: Patients receiving amlodipine and telmisartan from separate tablets may instead receive Telmisartan + Amlodipine containing the same component doses once daily. When substituting for individual components, increase the dose of Telmisartan + Amlodipine if blood pressure control has not been satisfactory.
Add-on Therapy for Patients with Hypertension Not Adequately Controlled on Antihypertensive Monotherapy: Telmisartan + Amlodipine may be used to provide additional blood pressure lowering for patients not adequately controlled with amlodipine (or another dihydropyridine calcium channel blocker) alone or with telmisartan (or another angiotensin receptor blocker) alone.
Patients treated with 10 mg amlodipine who experience any dose-limiting adverse reactions such as edema, may be switched to Telmisartan + Amlodipine 40/5 mg tablets once daily, reducing the dose of amlodipine without reducing the overall expected antihypertensive response.
Initial Therapy: A patient may be initiated on Telmisartan + Amlodipine if it is unlikely that control of blood pressure would be achieved with a single agent. The usual starting dose of Telmisartan + Amlodipine is 40/5 mg once daily. Patients requiring larger blood pressure reductions may be started on Telmisartan + Amlodipine 80/5 mg once daily.
Initial therapy with Telmisartan + Amlodipine is not recommended in patients ≥75 years old or with hepatic impairment.
Correct imbalances of intravascular volume- or salt-depletion, before initiating therapy with Telmisartan + Amlodipine.
Dosing in Specific Populations: Renal Impairment: No initial dosage adjustment is required for patients with mild or moderate renal impairment. Titrate slowly in patients with severe renal impairment.
Hepatic Impairment: In most patients, initiate amlodipine therapy at 2.5 mg. Titrate slowly in patients with hepatic impairment.
Patients 75 Years of Age and Older: In most patients, initiate amlodipine therapy at 2.5 mg. Titrate slowly in patients 75 years of age and older.

Telmisartan: Limited data are available with regard to overdosage in humans. The most likely manifestations of overdosage with telmisartan tablets would be hypotension, dizziness, and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Telmisartan is not removed by hemodialysis.
Amlodipine: Single oral doses of amlodipine maleate equivalent to 40 mg/kg and 100 mg/kg amlodipine in mice and rats, respectively, caused deaths. Single oral doses equivalent to 4 or more mg/kg amlodipine in dogs (11 or more times the maximum recommended human dose on a mg/m2 basis) caused a marked peripheral vasodilation and hypotension.
Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension. In humans, experience with intentional overdosage of amlodipine is limited. Reports of intentional overdosage include a patient who ingested 250 mg and was asymptomatic and was not hospitalized; another (120 mg) who was hospitalized underwent gastric lavage and remained normotensive; the third (105 mg) was hospitalized and had hypotension (90/50 mmHg) which normalized following plasma expansion. A case of accidental drug overdose has been documented in a 19-month-old male who ingested 30 mg amlodipine (about 2 mg/kg). During the emergency room presentation, vital signs were stable with no evidence of hypotension, but a heart rate of 180 bpm. Ipecac was administered 3.5 hours after ingestion and on subsequent observation (overnight) no sequelae was noted.
If massive overdose should occur, active cardiac and respiratory monitoring should be instituted. Frequent blood pressure measurements are essential. Should hypotension occur, cardiovascular support including elevation of the extremities and the judicious administration of fluids should be initiated. If hypotension remains unresponsive to these conservative measures, administration of vasopressors (such as phenylephrine) should be considered with attention to circulating volume and urine output. Intravenous calcium gluconate may help to reverse the effects of calcium entry blockade. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.

Telmisartan + Amlodipine are contraindicated in patients with known hypersensitivity (e.g., anaphylaxis or angioedema) to telmisartan, amlodipine, or any other component of this product.

Hypotension: Telmisartan: In patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of therapy with Telmisartan + Amlodipine tablets. Either correct this condition prior to administration of Telmisartan + Amlodipine tablets, or start treatment under close medical supervision with a reduced dose.
If hypotension does occur, place the patient in the supine position and, if necessary, give an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.
Amlodipine: Since the vasodilation induced by amlodipine is gradual in onset, acute hypotension has rarely been reported after oral administration. Nonetheless, observe patients with severe aortic stenosis closely when administering amlodipine, as one should with any vasodilator.
Hyperkalemia: Telmisartan: Hyperkalemia may occur in patients 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. Consider periodic determinations of serum electrolytes to detect possible electrolyte imbalances, particularly in patients at risk.
Patients with Impaired Hepatic Function: Telmisartan: As the majority of telmisartan is eliminated by biliary excretion, patients with biliary obstructive disorders or hepatic insufficiency can be expected to have reduced clearance. Initiate telmisartan at low doses and titrate slowly in these patients.
Amlodipine: Amlodipine is extensively metabolized by the liver and the plasma elimination half-life (1/2) is 56 hours in patients with impaired hepatic impairment have decreased clearance of amlodipine, start amlodipine or add amlodipine at 2.5 mg in patients with hepatic impairment. The lowest dose of Telmisartan + Amlodipine is 40/5 mg; therefore, initial therapy with Telmisartan + Amlodipine tablets is not recommended in hepatically impaired patients.
Renal Function Impairment: Telmisartan: As a consequence of inhibiting the renin-angiotensin aldosterone system, anticipate changes in renal function in susceptible individuals. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure or renal dysfunction), treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. Similar results may be anticipated in patients treated with telmisartan.
In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen were observed. There has been no long term use of telmisartan in patients with unilateral or bilateral renal artery stenosis, but anticipate an effect similar to that seen with ACE inhibitors.
Dual Blockade of the Renin-Angiotensin-Aldosterone System: Telmisartan: As a consequence of inhibiting the renin-angiotensin aldosterone system, changes in renal function (including acute renal failure) have been reported. Dual blockade of the renin angiotensin-aldosterone system (e.g., by adding an ACE inhibitor to an angiotensin II receptor antagonist) should include close monitoring of renal function.
Risk of Myocardial Infarction or Increased Angina: Amlodipine: Uncommonly, patients, particularly those with severe obstructive coronary artery disease, have developed documented increased frequency, duration or severity of angina or acute myocardial infarction on starting calcium channel blocker therapy or at the time of dosage increase. The mechanism of this effect has not been elucidated.
Heart Failure: Amlodipine: Closely monitor patients with heart failure. There was no overall adverse effect on survival or cardiac morbidity (as defined by life-threatening arrhythmia, acute myocardial infarction, or hospitalization for worsened heart failure).
Use in Pregnancy & Lactation: See Use in Pregnancy & Lactation section for further information.

Pregnancy: Pregnancy Category D.
These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.
In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Telmisartan + Amlodipine, unless it is considered life-saving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Telmisartan + Amlodipine for hypotension, oliguria, and hyperkalemia.
Fetal Toxicity: Pregnancy Category D: Telmisartan: Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Telmisartan + Amlodipine as soon as possible.
Lactation: Telmisartan: It is not known whether telmisartan is excreted in human milk, but telmisartan was shown to be present in the milk of lactating rats. Because of the potential for adverse effects on the nursing infant, decide whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Amlodipine: It is not known whether amlodipine is excreted in human milk. In the absence of this information, it is recommended to discontinue nursing while amlodipine is administered.

Clinical Trials Experience: Because clinical studies are conducted under widely varying conditions, adverse reactions rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Telmisartan + Amlodipine: Adverse reactions have generally been mild and transient in nature and have only infrequently required discontinuation of therapy.
In the placebo-controlled factorial design study, the population treated with a telmisartan and amlodipine combination had a mean age of 53 years and included approximately 50% males, 79% were Caucasian, 17% Blacks, and 4% Asians. Patients received doses ranging from 20/2.5 mg to 80/10 mg orally, once daily.
The frequency of adverse reactions was not related to gender, age, or race.
The adverse reactions that occurred in the placebo-controlled factorial design trial in of patients treated with Telmisartan + Amlodipine and at a higher incidence in Telmisartan + Amlodipine treated patients than placebo-treated patients were peripheral edema dizziness and back pain. Edema (other than peripheral edema), hypotension, and syncope were reported in In the placebo-controlled factorial design trial, discontinuation due to adverse events occurred in 2.2% of all treatment cells of patients in the telmisartan/amlodipine treated patients and in 4.3% in the placebo-treated group. The most common reasons for discontinuation of therapy with Telmisartan + Amlodipine were peripheral edema, dizziness, and hypotension.
Peripheral edema is a known, dose-dependent adverse reaction of amlodipine, but not of telmisartan. In the factorial design study, the incidence of peripheral edema during the 8 week, randomized, double-blind treatment period was highest with amlodipine 10 mg monotherapy. The incidence was notably lower when telmisartan was used in combination with amlodipine 10 mg (see Table 1).

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Telmisartan: Adverse experiences have generally been mild and transient in nature and have only in frequently required discontinuation of therapy.
Adverse events occurring at an incidence of ≥1% in patients treated with telmisartan and at a greater rate than in patients treated with placebo, irrespective of their causal association, are upper respiratory tract infection, back pain, sinusitis, diarrhea, pharyngitis presented in Table 2. (See Table 2.)

Click on icon to see table/diagram/image

In addition to the adverse events in the table, the following events occurred at a rate of ≥1% but were at least as frequent in the placebo group: influenza-like symptoms, dyspepsia, myalgia, urinary tract infection, abdominal pain, headache, dizziness, pain, fatigue, coughing, hypertension, chest pain, nausea, and peripheral edema. Discontinuation of therapy because of adverse events was required in 2.8% of 1455 patients treated with telmisartan tablets and 6.1% of 380 placebo patients in placebo-controlled clinical trials.
The incidence of adverse events was not dose-related and did not correlate with gender, age, or race of patients.
The incidence of cough occurring with telmisartan in 6 placebo-controlled trials was identical to that noted for placebo-treated patients (1.6%). In addition to those listed previously, adverse events that occurred in >0.3% of 3500 patients treated with telmisartan monotherapy in controlled or open trials are listed as follows. It cannot be determined whether these events were causally related to telmisartan tablets: Autonomic Nervous System: impotence, increased sweating, flushing; Body as a Whole: allergy, fever, leg pain, malaise; Cardiovascular: palpitation, dependent edema, angina pectoris, tachycardia, leg edema, abnormal ECG; CNS: insomnia, somnolence, migraine, vertigo, paresthesia, involuntary muscle contractions, hypoesthesia; Gastrointestinal: flatulence, constipation, gastritis, vomiting, dry mouth, hemorrhoids, gastroenteritis, enteritis, gastroesophageal reflux, toothache, nonspecific gastrointestinal disorders; Metabolic: gout, hypercholesterolemia, diabetes mellitus; Musculoskeletal: arthritis, arthralgia, leg cramps; Psychiatric: anxiety, depression, nervousness; Resistance Mechanism: infection, fungal infection, abscess, otitis media; Respiratory: asthma, bronchitis, rhinitis, dyspnea, epistaxis; Skin: dermatitis, rash, eczema, pruritus; Urinary: micturition frequency, cystitis; Vascular: cerebrovascular disorder; and Special Senses: abnormal vision, conjunctivitis, tinnitus, earache.
During initial clinical studies, a single case of angioedema was reported (among a total of 3781 patients treated).
Zamplify 40/5/Zamplify 40/10: The frequency of adverse reactions was not related to gender, age, or race.
In addition to those listed previously, adverse events that occurred in >0.3% of patients treated with telmisartan monotherapy in controlled or open trials are listed as previously mentioned. It cannot be determined whether these events were causally related to telmisartan tablets.
Clinical Laboratory Findings: In placebo-controlled clinical trials, clinically relevant changes in standard laboratory test parameters were rarely associated with administration of telmisartan tablets.
Hemoglobin: A greater than 2 g/dL decrease in hemoglobin was observed in 0.8% telmisartan patients compared with 0.3% placebo patients. No patients discontinued therapy due to anemia.
Creatinine: A 0.5 mg/dL rise or greater in creatinine was observed in 0.4% telmisartan patients compared with 0.3% placebo patients. One telmisartan-treated patient discontinued therapy due to increases in creatinine and blood urea nitrogen.
Liver Enzymes: Occasional elevations of liver chemistries occurred in patients treated with telmisartan; all marked elevations occurred at a higher frequency with placebo. No telmisartan-treated patients discontinued therapy due to abnormal hepatic function.
Amlodipine: Most adverse reactions reported during therapy with amlodipine were all mild or moderate severity. In controlled clinical trials directly comparing amlodipine in doses up to 10 mg to placebo, discontinuation of amlodipine due to adverse reactions was required in only about 1.5% of amlodipine-treated patients and was not significantly different from that seen in placebo-treated patients. The most common side effects were headache and edema.
Zamplify 40/5/Zamplify 40/10: Other adverse experiences which were not clearly dose related but which were reported with an incidence greater than 1% in placebo-controlled clinical trials are headache, fatigue, nausea, abdominal pain and somnolence.
The following events occurred in 0.1% of patients in controlled clinical trials or under conditions of open trials or marketing experience where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship: Cardiovascular: arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, hypotension, peripheral ischemia, syncope, tachycardia, postural dizziness, postural hypotension, vasculitis; Central and Peripheral Nervous System: hypoesthesia, neuropathy peripheral, paresthesia, tremor, vertigo; Gastrointestinal: anorexia, constipation, dyspepsia, dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia, change of bowel habit; General: allergic reaction, asthenia, back pain, hot flushes, malaise, pain, rigors, weight gain, weight decrease; Musculoskeletal System: arthralgia, arthrosis, muscle cramps, myalgia; Psychiatric: sexual dysfunction (male and female), insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalization, mood change; Respiratory System: dyspnea, epistaxis; Skin and Appendages: angioedema, erythema multiforme, pruritus, rash, rash erythematous, rash maculopapular; Special Senses: abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus; Urinary System: micturition frequency, micturition disorder, nocturia; Autonomic Nervous System: dry mouth, sweating increased; Metabolic and Nutritional: hyperglycemia, thirst; Hemopoietic: leukopenia, purpura, thrombocytopenia.
The following events occurred in <0.1% of patients: cardiac failure, pulse irregularity, extra systoles, skin discoloration, urticaria, skin dryness, alopecia, dermatitis, muscle weakness, twitching, ataxia, hypertonia, migraine, cold and clammy skin, apathy, agitation, amnesia, gastritis, increased appetite, loose stools, coughing rhinitis, dysuria, polyuria, parosmia, taste perversion, abnormal visual accommodation, and xerophthalmia.
Other reactions occurred sporadically and cannot be distinguished from medications or concurrent disease states such as myocardial infarction and angina. Amlodipine has not been associated with clinically significant changes in routine laboratory tests. No clinically relevant changes were noted in serum potassium, serum glucose, total triglycerides, total cholesterol, HDL cholesterol, uric acid, blood urea nitrogen, or creatinine.
Amlodipine has been used safely in patients with chronic obstructive pulmonary disease, well-compensated congestive heart failure, coronary artery disease, peripheral vascular disease, diabetes mellitus, and abnormal lipid profiles.
Zamplify 80/5/Zamplify80/10: The following events occurred in 0.1% of patients in controlled clinical trials or under conditions of open trials or marketing experience where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship: Cardiovascular: arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, hypotension, peripheral ischemia, syncope, tachycardia, postural dizziness, postural hypotension, vasculitis; Central and Peripheral Nervous System: hypoesthesia, neuropathy peripheral, paresthesia, tremor, vertigo; Gastrointestinal: anorexia, constipation, dyspepsia,** dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia, change of bowel habit; General: allergic reaction, asthenia,** back pain, hot flushes, malaise, pain, rigors, weight gain, weight decrease; Musculoskeletal System: arthralgia, arthrosis, muscle cramps,** myalgia; Psychiatric: sexual dysfunction (male** and female), insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalization, mood change; Respiratory System: dyspnea,** epistaxis; Skin and Appendages: angioedema, erythema multiforme, pruritus,** rash,** rash erythematous, rash maculopapular; Special Senses: abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus; Urinary System: micturition frequency, micturition disorder, nocturia; Autonomic Nervous System: dry mouth, sweating increased; Metabolic and Nutritional: hyperglycemia, thirst; Hemopoietic: leukopenia, purpura, thrombocytopenia.
The following events occurred in <0.1% of patients: cardiac failure, pulse irregularity, extrasystoles, skin discoloration, urticaria, skin dryness, alopecia, dermatitis, muscle weakness, twitching, ataxia, hypertonia, migraine, cold and clammy skin, apathy, agitation, amnesia, gastritis, increased appetite, loose stools, coughing rhinitis, dysuria, polyuria, parosmia, taste perversion, abnormal visual accommodation, and xerophthalmia.
Other reactions occurred sporadically and cannot be distinguished from medications or concurrent disease states such as myocardial infarction and angina.
Amlodipine has not been associated with clinically significant changes in routine laboratory tests. No clinically relevant changes were noted in serum potassium, serum glucose, total triglycerides, total cholesterol, HDL cholesterol, uric acid, blood urea nitrogen, or creatinine.
Amlodipine has been used safely in patients with chronic obstructive pulmonary disease, well-compensated congestive heart failure, coronary artery disease, peripheral vascular disease, diabetes mellitus, and abnormal lipid profiles.

Drug Interactions with Telmisartan + Amlodipine: The pharmacokinetics of amlodipine and telmisartan are not altered when the drugs are co-administered.
No drug interaction studies have been conducted with Telmisartan + Amlodipine and other drugs, although studies have been conducted with the individual amlodipine and telmisartan components of Telmisartan + Amlodipine, as described as follows: Drug Interactions with Telmisartan: Digoxin: When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed. It is, therefore, recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing telmisartan to avoid possible over-or under digitalization.
Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists including telmisartan. Therefore, monitor serum lithium levels during concomitant use.
Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors): In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including telmisartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving telmisartan and NSAID therapy.
The antihypertensive effect of angiotensin II receptor antagonists, including telmisartan may be attenuated by NSAIDS including selective COX-2 inhibitors.
Ramipril and Ramiprilat: Co-administration of telmisartan 80 mg once daily and ramipril 10 mg once daily to healthy subjects increases steady-state Cmax and AUC of ramipril 2.3- and 2.1-fold, respectively, and Cmax and AUC of ramiprilat 2.4- and 1.5-fold, respectively. In contrast, Cmax and AUC of telmisartan decrease by 31% and 16%, respectively. When co-administering telmisartan and ramipril, the response may be greater because of the possibly additive pharmacodynamic effects of the combined drugs, and also because of the increased exposure to ramipril and ramiprilat in the presence of telmisartan. Co-administration of telmisartan and ramipril is not recommended.
Other Drugs: Co-administration of telmisartan did not result in a clinically significant interaction with acetaminophen, amlodipine, glyburide, simvastatin, hydrochlorothiazide, warfarin, or ibuprofen. Telmisartan is not metabolized by the cytochrome P450 system and had no effects in vitro on cytochrome P450 enzymes, except for some inhibition of CYP2C19. Telmisartan is not expected to interact with drugs that inhibit cytochrome P450 enzymes; it is also not expected to interact with drugs metabolized by cytochrome P450 enzymes, except for possible inhibition of the metabolism of drugs metabolized by CYP2C19.
Drug Interactions with Amlodipine: In clinical trials, amlodipine has been safely administered with thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, non-steroidal anti-inflammatory drugs, antibiotics, and oral hypoglycemic drugs.
Simvastatin: Co-administration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.
The following have no clinically relevant effects on the pharmacokinetics of amlodipine: cimetidine, grapefruit juice, Maalox, sildenafil.
Amlodipine has no clinically relevant effects on the pharmacokinetics or pharmacodynamics of the following: atorvastatin, digoxin, warfarin.

Store at temperatures not exceeding 30°C.

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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