BRAND NAMES
- International: Exforge
- Other: Dafiro
 MECHANISM OF ACTION
Amlodipine, a dihydropyridine calcium channel blocker. See Amlodipine mechanism of action
Valsartan is an angiotensin II receptor blocker (ARB). See Valsartan mechanism of action
Treatment of hypertension, to lower blood pressure:
- In patients not adequately controlled on monotherapy
- As initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals.
Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.
Amlodipine/Valsartan tablets may be administered with or without food.
Amlodipine/Valsartan tablets may be administered with other antihypertensive agents.
Majority of effect attained within 2 weeks
- Add-on Therapy: Amlodipine/Valsartan tablets May be used as add-on therapy for patients not controlled on monotherapy with amlodipine (or another dihydropyridine calcium-channel blocker) alone or with valsartan (or another angiotensin II receptor blocker) alone. A patient who experiences dose-limiting adverse reactions on either component alone may be switched to Amlodipine/Valsartan tablets containing a lower dose of that component in combination with the other to achieve similar blood pressure reductions. The clinical response to Amlodipine/Valsartan tablets should be subsequently evaluated and if blood pressure remains uncontrolled after 3 to 4 weeks of therapy, the dose may be titrated up to a maximum of 10/320 mg
- May be substituted for titrated components: For convenience, patients receiving amlodipine and valsartan from separate tablets may instead wish to receive tablets of Exforge containing the same component doses.
- Initial therapy: When used as initial therapy, Initiate with 5/160 mg once daily. The dosage can be increased after 1 to 2 weeks of therapy to a maximum of one 10/320mg once daily as needed to control blood pressure. The majority of the antihypertensive effect is attained within 2 weeks after initiation of therapy or a change in doses.
- Do not use in patients with known hypersensitivity to any component.
- Do not coadminister aliskiren with Amlodipine/Valsartan tablets in patients with diabetes
 WARNINGS AND PRECAUTIONS
- Pregnancy: When pregnancy is detected, discontinue Amlodipine/Valsartan tablets as soon as possible, Pregnancy Category: D
- Hypotension: Excessive hypotension was seen in 0.4% of patients with uncomplicated hypertension treated with Amlodipine/Valsartan tablets. Correct volume depletion prior to initiation. If excessive hypotension occurs with Amlodipine/Valsartan tablets , the patient should be placed in a supine position and, if necessary, given an intravenous infusion of normal saline.
- Risk of Myocardial Infarction or Increased Angina : Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease.
- Renal function: Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on Amlodipine/Valsartan tablets. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Amlodipine/Valsartan tablets.
- Potassium: Drugs that inhibit the renin-angiotensin system can cause hyperkalemia. Monitor serum electrolytes periodically. Some patients with heart failure have developed increases in potassium with valsartan therapy. These effects are usually minor and transient, and they are more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of Amlodipine/Valsartan tablets may be required
- If simvastatin is coadministered with amlodipine, do not exceed doses greater than 20 mg daily of simvastatin
- When amlodipine and sildenafil (Viagra) were used in combination, each agent independently exerted its own blood pressure lowering effect
- CYP3A4 Inhibitors: Coadministration with CYP3A4 inhibitors (moderate and strong) result in increased systemic exposure to amlodipine warranting dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A4 inhibitors to determine the need for dose adjustment.
- NSAID use may lead to increased risk of renal impairment and loss of anti-hypertensive effect, especially in patients who are elderly, volume-depleted (including those on diuretic therapy), or with
compromised renal function. Monitor renal function periodically in patients receiving valsartan and NSAID therapy.
- Dual inhibition of the renin-angiotensin system (RAS): : Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and
changes in renal function (including acute renal failure) compared to monotherapy. Closely monitor blood pressure, renal function, and electrolytes in patients on Exforge and other agents that affect the RAS.
- Potassium: Concomitant use of valsartan with other agents that block the renin-angiotensin system, potassium sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium and in heart failure patients to increases in serum creatinine. If co-medication is considered necessary, monitoring of serum potassium is advisable.
- Lithium: Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists, including valsartan. Monitor serum lithium
levels during concomitant use.
 PREGNANCY AND LACTATION
- Pregnancy Category D (US): 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 Exforge as soon as possible
- Nursing Mothers: a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
 SIDE EFFECTS
Peripheral edema (0.4%), vertigo (0.2%), nasopharyngitis and orthostatic hypotension.
Amlodipine/Valsartan tablets rarely cause palpitations, tachycardia, ear pain, diarrhea, nausea, constipation, dyspepsia, abdominal pain, gastritis, vomiting, flatulence, hemorrhoids, dry mouth, toothache, colitis, fatigue, chest pain, asthenia, pitting edema, pyrexia, pain, seasonal allergies, sinusitis, influenza, bronchitis, pharyngitis, urinary tract infections, gastroenteritis, bronchitis acute, viral infection, tooth abscesses, cystitis, gout, non-insulin dependent diabetes mellitus, hypercholesterolemia, arthralgia, back pain, muscle spasms, pain in extremities, myalgia, osteoarthritis, joint swelling, musculoskeletal chest pain, headache, sciatica, parasthesia, cerviocobrachial syndrome, carpal tunnel syndrome, hypoaesthesia, sinus headache, somnolence, insomnia, anxiety, depression, hematuria, nephrolithiasis, pollakiuria, erectile dysfunction, cough, pharyngolaryngeal pain and sinusitis
 RELATED LINKS
|ACE inhibitors||Benazepril (Lotensin) • Captopril (Capoten) • Cilazapril • Delapril • Enalapril (Renitec, Vasotec) • Fosinopril (Monopril) • Lisinopril (Prinivil, Zestril) • Moexipril (Univasc) • Perindopril (Aceon) • Quinapril (Accupril) • Ramipril (Altace, Triatec) • Trandolapril (Mavik) • Zofenopril (Bifril, Zopranol)|
|Angiotensin II receptor antagonist||Azilsartan (Edarbi) • Candesartan (Atacand) • Eprosartan (Teveten) • Irbesartan (Aprovel, Avapro, Karvea) • Losartan (Cozaar) • Olmesartan (Benicar, Olmetec) • Telmisartan (Micadis) • Valsartan (Diovan, Tareg)|
|Renin inhibitors||Aliskiren (Rasilez, Tekturna)|
|Alpha-1 blockers||Doxazosin (Cardura) • Prazosin (Minipress) • Terazosin (Hytrin)|
|Alpha-2 agonists (centrally acting)||Clonidine (Oral route) • Clonidine (Transdermal) (Catapresan) • Guanfacine (Tenex) • Methyldopa (Aldomet)|
|Calcium channel blockers||Dihydropyridines||Amlodipine (Norvasc) • Barnidipine (Vasexten) • Felodipine (Plendil) • Isradipine (Dynacirc) • Lacidipine (Lacipil, Motens) • Lercanidipine (Zanidip) • Manidipine • Nicardipine • Nifedipine (Adalat) • Nisoldipine • Nitrendipine|
|Benzothiazepine||Diltiazem (Cardizem, Taztia XT, Tiazac, Tildiem)|
|Phenylalkylamine||Gallopamil • Verapamil (Calan)|
|Beta blockers||Beta1 selective (cardioselective)||Acebutolol (Sectral) • Atenolol (Tenormin) • Betaxolol (Kerlon) • Bisoprolol (Concor) • Celiprolol (Cordiax) • Metoprolol (Betaloc, Lopressor, Toprol-XL) • Nebivolol (Bystolic, Lobivon, Nebilox)|
|Nonselective (Beta1 and Beta2 blockers)||Oxprenolol (Trasitensin) • Propranolol (Inderal) • Timolol (Blocadren)|
|Nonselective (Beta1, Beta2 and Alpha1 blockers)||Carvedilol (Dilatrend) • Labetalol (Trandate)|
|Beta blocker with intrinsic sympathomimetic activity (ISA)||Acebutolol (Sectral) • Celiprolol (Cordiax)|
|Lipophilic Beta blockers||Propranolol (Inderal) • Metoprolol (Betaloc, Lopressor, Toprol-XL) • Oxprenolol (Trasitensin)|
|Diuretics||Carbonic anhydrase inhibitors||Acetazolamide (Diamox)|
|Loop diuretics||Bumetanide • Etacrynic acid • Furosemide (Lasix) • Piretanide • Torasemide (Demadex)|
|Thiazide diuretics||Chlorothiazide (Diuril) • Hydrochlorothiazide (Esidrex)|
|Thiazide-like diuretics||Chlortalidone (Hygroton) • Indapamide (Lozol, Lozide) • Metolazone|
|Potassium-sparing diuretics|| Epithelial sodium channel blockers: Amiloride (Midamor) • Triamterene (Dyrenium) |
Aldosterone receptor antagonists: Potassium canrenoate • Eplerenone (Inspra) • Spironolactone (Aldactone)
|Combination therapy||Amiloride/Hydrochlorothiazide (Moduretic) • Spironolactone/Hydrochlorothiazide (Aldactazide)|