Telmisartan + Amlodipine

Oral
Hypertension

Mild to moderate: Max: 40 mg of telmisartan component. Severe: Contraindicated.

May be taken with or without food.

Biliary obstructive disorders, cardiogenic shock. Severe hepatic impairment. Pregnancy and lactation. Concomitant use w/ ACE inhibitors or aliskiren-containing products in patients w/ DM or renal impairment (GFR <60 mL/min).

Patient w/ Na- or volume-depletion, idiopathic or hereditary angioedema, primary hyperaldosteronism, severe obstructive coronary artery disease, heart failure, recent MI, mitral or aortic stenosis, hypertrophic cardiomyopathy w/ outflow tract obstruction, DM. Patient undergoing surgery or dialysis. Renal (e.g. unilateral/bilateral renal artery stenosis) and mild to moderate hepatic impairment.

Significant: Hypotension, angina, acute renal failure, hyperkalaemia, peripheral oedema. Rarely, angioedema.
Nervous: Dizziness, somnolence, migraine, fatigue, flu-like symptoms, headache, malaise, insomnia, vertigo, paraesthesia, hypoaesthesia, anxiety, depression, tremor, peripheral neuropathy.
CV: Orthostatic hypotension, oedema, syncope, chest pain, flushing, bradycardia, palpitation.
GI: Diarrhoea, nausea, dyspepsia, abdominal pain, constipation, gastritis, vomiting, dry mouth, hemorrhoids, gastroenteritis, gastroesophageal reflux, dysgeusia.
Resp: Sinusitis, pharyngitis, cough.
Hepatic: Increased hepatic enzymes.
Genitourinary: UTI, cystitis, micturition frequency, nocturia.
Endocrine: Impotence, hypercholesterolaemia, erectile dysfunction.
Musculoskeletal: Back pain, myalgia, arthralgia, muscle spasm, gout.
Ophthalmologic: Abnormal vision, conjunctivitis.
Otic: Tinnitus, earache.
Dermatologic: Hyperhidrosis, dermatitis, rash, eczema, pruritus.
Others: Pain.

PO: D

This drug may cause syncope, somnolence, dizziness, or vertigo, if affected, do not drive or operate machinery.

Monitor electrolyte panels at baseline and periodically, urinalysis, BP, heart rate, liver and renal (e.g. serum creatinine, BUN, urinalysis) functions. Monitor for signs and symptoms for peripheral oedema, symptomatic hypotension.

Increased hypotensive effects w/ other antihypertensive agents and agents w/ BP lowering potential (e.g. baclofen, amifostine). Orthostatic hypotension may be aggravated by barbiturates, narcotics, or TCAs. Reduced therapeutic effect w/ corticosteroids.
Telmisartan: Reduced antihypertensive effect and risk of acute renal insufficiency w/ NSAIDs. May cause reversible increase in serum lithium concentration and toxicity. Increased risk of hyperkalaemia w/ K-sparing diuretics, K supplements or K-containing salt substitutes. 
Amlodipine: Increased exposure CYP3A4 enzyme inhibitors (e.g. protease inhibitors, azole antifungals, erythromycin, diltiazem). Decreased plasma concentration w/ CYP3A4 enzyme inducers (e.g. rifampicin). May increase systemic exposure of ciclosporin or tacrolimus.
Potentially Fatal: Dual blockade of the renin-angiotensin-aldosterone system (RAAS) by concomitant use w/ ACE inhibitors (e.g. ramipril) or aliskiren may cause an increased risk of hypotension, hyperkalaemia, and acute renal failure (esp in patients w/ DM or renal impairment).

Food may decrease rate and extent of absorption. Alcohol may aggravate orthostatic hypotension.
Amlodipine: Increased BP-lowering effects w/ grapefruit or grapefruit juice. Decreased plasma concentration w/ St. John’s wort.

Description: Telmisartan, a nonpeptide tetrazole derivative, is an angiotensin II type 1 (AT₁) receptor antagonist producing its BP lowering effects by selectively blocking the binding of angiotensin II to angiotensin type 1 (AT₁) receptors, thereby reducing angiotensin II-induced vasoconstriction, aldosterone release, and Na reabsorption.
Amlodipine, a dihydropyridine Ca channel blocker, reduces peripheral vascular resistance and BP by producing a relaxation of vascular smooth muscle and coronary vasodilation through inhibition of Ca ion transmembrane influx into cardiac and vascular smooth muscles.
Pharmacokinetics:
Absorption: Telmisartan: Rapidly absorbed from the GI tract. Absolute bioavailability: Dose dependent: 42% after 40 mg dose; 58% after 160 mg dose. Time to peak plasma concentration: Approx 0.5-1 hr.
Amlodipine: Well absorbed. Bioavailability: 60-65%. Time to peak plasma concentration: 6-12 hr.
Distribution: Telmisartan: Plasma protein binding: >99.5%, mainly albumin and α₁ acid-glycoprotein.
Amlodipine: Volume of distribution: Approx 21 L/kg. Plasma protein binding: Approx 98%.
Metabolism: Telmisartan: Undergoes first-pass metabolism via conjugation to acylglucuronide.
Amlodipine: Extensively metabolised in the liver to inactive metabolites.
Excretion: Telmisartan: Mainly via faeces, as unchanged drug; urine (<1%). Terminal elimination half-life: Approx 24 hr.
Amlodipine: Via urine (<10% as unchanged drug, 60% as metabolites). Terminal elimination half-life: 30-50 hr.

Source: National Center for Biotechnology Information. PubChem Database. Telmisartan, CID=65999, https://pubchem.ncbi.nlm.nih.gov/compound/Telmisartan (accessed on Jan. 23, 2020)

Source: National Center for Biotechnology Information. PubChem Database. Amlodipine, CID=2162, https://pubchem.ncbi.nlm.nih.gov/compound/Amlodipine (accessed on Jan. 20, 2020)

Store at 25°C. Protect from moisture and 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.

Anon. Telmisartan and Amlodipine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 03/08/2017.

Buckingham R (ed). Amlodipine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/08/2017.

Buckingham R (ed). Telmisartan. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/08/2017.

Telmisartan and Amlodipine Tablet (Lupin Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 03/08/2017.