Amlodipine + Valsartan


Concise Prescribing Info
Indications/Uses
HTN.
Dosage/Direction for Use
Adult : PO Each tab contains amlodipine (mg)/valsartan (mg): 5/80, 5/160, 5/320, 10/160, or 10/320: Recommended dose: 1 tab once daily, may be titrated as needed.
Dosage Details
Oral
Hypertension
Adult: Each tab contains amlodipine (mg)/valsartan (mg): 5/80, 5/160, 5/320, 10/160, or 10/320: Individualised dosing according to patient condition. Recommended dose: 1 tab once daily, may be titrated as needed.
Hepatic Impairment
Mild to moderate: Valsartan: 80 mg. Severe: Contraindicated.
Administration
May be taken with or without food.
Contraindications
Biliary cirrhosis or cholestasis, severe hypotension, shock (i.e. cardiogenic shock). Severe hepatic impairment. Pregnancy. Concomitant use w/ ACE inhibitors or aliskiren-containing product in patients w/ DM or renal impairment (CrCl <60 mL/min).
Special Precautions
Patient w/ Na- or volume-depletion, idiopathic or hereditary angioedema, biliary obstructive disorders, primary hyperaldosteronism, severe obstructive coronary artery disease, severe CHF, recent MI, mitral or aortic stenosis, hypertrophic cardiomyopathy w/ outflow tract obstruction, DM. Patient undergoing surgery or dialysis. Renal (e.g. chronic kidney disease, unilater/bilateral renal artery stenosis) and mild to moderate hepatic impairment. Lactation.
Adverse Reactions
Significant: Hypotension, angina, acute renal failure, hyperkalaemia, peripheral oedema. Rarely, angioedema.
Nervous: Headache, anxiety, somnolence, syncope, vertigo, fatigue, asthenia, dizziness, paraesthesia.
CV: Orthostatic hypotension, tachycardia, palpitations.
GI: Nausea, abdominal pain, diarrhoea, anorexia, constipation, dry mouth.
Resp: Nasopharyngitis, upper resp tract infection, cough.
Genitourinary: Increased BUN.
Dermatologic: Pitting and facial oedema, rash, erythema,
Immunologic: Influenza.
Patient Counseling Information
This drug may cause dizziness, headache, fatigue, or nausea, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor electrolyte panels at baseline and periodically, urinalysis, BP, heart rate, and renal and liver functions. Monitor serum K periodically and during dose titration esp in patients w/ heart failure.
Drug Interactions
Increased risk of hypotension w/ TCAs, diuretics, α-blockers. Increased exposure of amlodipine w/ moderate or strong CYP3A4 enzyme inhibitors (e.g. protease inhibitors, azole antifungals, erythromycin, clarithromycin, verapamil, diltiazem). Decreased plasma concentration of amlodipine w/ CYP3A4 enzyme inducers (e.g. rifampicin). Valsartan may cause a reversible increase in serum lithium concentration and toxicity. Concomitant use of valsartan w/ NSAIDs may cause an attenuation of antihypertensive effects, worsen renal function, and increase serum K. Increased risk of hyperkalaemia w/ K-sparing diuretics, K supplements or K-containing salt substitutes w/ valsartan. Concomitant admin of organic anion transporter protein (OATP) 1B1 (e.g. ciclosporin, rifampicin) or multidrug resistance protein (MRP2) (e.g. ritonavir) inhibitors may increase systemic exposure of valsartan.
Potentially Fatal: Dual blockade of the renin-angiotensin-aldosterone system (RAAS) by concomitant use w/ ACE inhibitors or aliskiren may cause an increased risk of hypotension, hyperkaelemia, and acute renal failure.
Food Interaction
Increased BP-lowering effects of amlodipine w/ grapefruit or grapefruit juice. Decreased plasma concentration of amlodipine w/ St. John’s wort. Food may decrease rate and extent of absorption.
Action
Description: Amlodipine, a dihydropyridine Ca channel blocker, reduces peripheral vascular resistance and BP by producing peripheral arterial vasodilation through inhibition of Ca ion transmembrane influx into cardiac and vascular smooth muscles. Valsartan, a nonpetide 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 on numerous tissues including vascular smooth muscles and the adrenal gland, thereby resulting in antagonism of AT1-induced vasoconstriction, aldosterone synthesis and release, cardiac stimulation, and Na renal reabsorption.
Pharmacokinetics:
Absorption: Amlodipine: Well absorbed. Bioavailability: 64-80%. Time to peak plasma concentration: 6-12 hr. Valsartan: Rapidly absorbed. Food may decrease rate and extent of absorption. Bioavailability: 23%. Time to peak plasma concentration: 2-4 hr.
Distribution: Amlodipine: Volume of distribution: Approx 21 L/kg. Plasma protein binding: Approx 97.5%. Valsartan: Plasma protein binding: 94-97%, mainly to albumin.
Metabolism: Amlodipine: Extensively metabolised in the liver to inactive metabolites. Valsartan: Minimal metabolism by CYP2C9 enzyme.
Excretion: Amlodipine: Via urine (60% as metabolites, 10% as unchanged drug). Terminal elimination half-life: 30-50 hr. Valsartan: Via faeces (83%) and urine (13%). Terminal elimination half-life: 6 hr.
Chemical Structure

Chemical Structure Image
Amlodipine

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


Chemical Structure Image
Valsartan

Source: National Center for Biotechnology Information. PubChem Database. Valsartan, CID=60846, https://pubchem.ncbi.nlm.nih.gov/compound/Valsartan (accessed on Jan. 20, 2020)

Storage
Store below 30°C. Protect from moisture.
ATC Classification
C09DB01 - valsartan and amlodipine ; Belongs to the class of angiotensin II receptor blockers (ARBs) and calcium channel blockers. Used in the treatment of cardiovascular disease.
References
Anon. Amlodipine and Valsartan. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 13/06/2017.

Anon. Valsartan. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 13/06/2017.

Buckingham R (ed). Amlodipine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 13/06/2017.

Buckingham R (ed). Valsartan. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 13/06/2017.

Exforge Tablet, Film Coated (Novartis Pharmaceuticals Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 13/06/2017.

Joint Formulary Committee. Amlodipine with Valsartan. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 13/06/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Amlodipine Besylate. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 13/06/2017.

Disclaimer: This information is independently developed by MIMS based on Amlodipine + Valsartan from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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