The flexibility to customize dosing
for your patients

From the EXFORGE Prescribing Information2

EXFORGE Dosage Information – General Considerations

  • Amlodipine is an effective treatment of hypertension in once-daily dosages of 2.5 mg to 10 mg while valsartan is effective in dosages of 80 mg to 320 mg. In clinical trials with once-daily EXFORGE using amlodipine dosages of 5 mg to 10 mg and valsartan dosages of 160 mg to 320 mg, the antihypertensive effects increased with increasing dosages.
  • The hazards of valsartan are generally 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.
  • The majority of the antihypertensive effect is attained within 2 weeks after initiation of therapy or a change in dosage. The dosage can be increased after 1 to 2 weeks of therapy to a maximum of one 10/320-mg tablet once daily as needed to control blood pressure.
  • EXFORGE may be administered with or without food.
  • EXFORGE may be administered with other antihypertensive agents.
  • Elderly patients: Because of decreased clearance of amlodipine, therapy should usually be initiated at 2.5 mg.
  • 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: No initial dosage adjustment is required for patients with mild or moderate liver insufficiency. Titrate slowly in patients with hepatic impairment.

Add-on Therapy

  • A patient whose blood pressure is not adequately controlled with amlodipine (or another dihydropyridine calcium channel blocker) alone or with valsartan (or another angiotensin II receptor blocker) alone may be switched to combination therapy with EXFORGE.
  • A patient who experiences dose-limiting adverse reactions on either component alone may be switched to EXFORGE containing a lower dose of that component in combination with the other to achieve similar blood pressure reductions. The clinical response to EXFORGE should be subsequently evaluated and if blood pressure remains uncontrolled after 3 to 4 weeks of therapy, the dosage may be titrated up to a maximum of 10/320 mg.

Replacement Therapy

  • 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

  • A patient may be initiated on EXFORGE if it is unlikely that control of blood pressure would be achieved with a single agent. The usual starting dosage is EXFORGE 5/160 mg once daily in patients who are not volume-depleted.

From the EXFORGE HCT Prescribing Information3

Exforge HCT Dosage Information – General Considerations

  • Dose once daily. The dosage may be increased after 2 weeks of therapy. The full blood pressure-lowering effect was achieved 2 weeks after being on the maximal dosage of EXFORGE HCT. The maximum recommended dose of EXFORGE HCT is 10/320/25 mg.
  • EXFORGE HCT may be administered with or without food.
  • No initial dosage adjustment is required for elderly patients.
  • Renal impairment: The usual regimens of therapy with EXFORGE HCT may be followed if the patient's creatinine clearance is >30 mL/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so avoid use of
    EXFORGE HCT.
  • Hepatic impairment: Avoid EXFORGE HCT in patients with severe hepatic impairment. In patients with lesser degrees of hepatic impairment, monitor for worsening of hepatic or renal function and adverse reactions.

Add-on/Switch Therapy

  • EXFORGE HCT is not indicated for the initial therapy of hypertension.
  • EXFORGE HCT may be used for patients not adequately controlled on any two of the following antihypertensive classes: calcium channel blockers, angiotensin receptor blockers, and diuretics.
  • A patient who experiences dose-limiting adverse reactions to an individual component while on any dual combination of the components of EXFORGE HCT may be switched to EXFORGE HCT containing a lower dose of that component to achieve similar blood pressure reductions.

Replacement Therapy

  • EXFORGE HCT may be substituted for the individually titrated components.

INDICATIONS

EXFORGE and EXFORGE HCT are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake.

EXFORGE may be used for patients not adequately controlled on monotherapy with an angiotensin receptor blocker (ARB) or a dihydropyridine calcium channel blocker (DHP-CCB).

EXFORGE may also be used as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals. The choice of EXFORGE as initial therapy for hypertension should be based on an assessment of potential benefits and risks including whether the patient is likely to tolerate the lowest dose of EXFORGE, the baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination product compared to monotherapy.

EXFORGE HCT is not indicated for the initial therapy of hypertension.

EXFORGE HCT may be used for patients not adequately controlled on any two of the following antihypertensive classes: CCBs, ARBs, and diuretics.

IMPORTANT SAFETY INFORMATION

WARNING: FETAL TOXICITY

  • When pregnancy is detected, discontinue EXFORGE or EXFORGE HCT as soon as possible. (5.1)
  • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. (5.1)

Contraindications: Do not use in patients with known hypersensitivity to any component of either product. In addition, EXFORGE HCT is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.
Do not coadminister aliskiren with EXFORGE or EXFORGE HCT in patients with diabetes.

Hypotension: Excessive hypotension was seen in 0.4% of patients treated with EXFORGE and, including orthostatic hypotension, in 1.7% of patients treated with EXFORGE HCT 10/320/25 mg in controlled trials. In patients with an activated renin-angiotensin-aldosterone system (RAAS), such as volume- and/or salt-depleted patients receiving high doses of diuretics, symptomatic hypotension may occur in patients receiving angiotensin receptor blockers. Correct this condition before administering EXFORGE or EXFORGE HCT. Caution should be observed when initiating therapy with EXFORGE in patients with heart failure or recent myocardial infarction and in patients undergoing surgery or dialysis. Do not initiate treatment with EXFORGE HCT in patients with aortic or mitral stenosis or obstructive hypertrophic cardiomyopathy.

Risk of MI or Increased Angina: Worsening angina and acute myocardial infarction (MI) can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease.

Renal Considerations: Changes in renal function, including acute renal failure, can be caused by drugs that inhibit the RAAS and by diuretics. Patients whose renal function may depend in part on the activity of the RAAS (eg, 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 EXFORGE HCT. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on EXFORGE or EXFORGE HCT.

Monitor renal function periodically in patients receiving valsartan and non-steroidal anti-inflammatory drugs (NSAIDs) who are also elderly, volume-depleted (including those on diuretics), or who have compromised renal function due to potential reversible deterioration of renal function, including acute renal failure. The antihypertensive effect of ARBs, including valsartan, may be attenuated by NSAIDs.

Avoid use of aliskiren with EXFORGE or EXFORGE HCT in patients with renal impairment (GFR <60 mL/min).

Potassium Abnormalities: In the controlled trial of EXFORGE HCT in moderate to severe hypertensive patients, the incidence of hypokalemia (serum potassium <3.5 mEq/L) at any time post-baseline with the maximum dose of EXFORGE HCT (10/320/25 mg) was 10% compared to 25% with HCTZ/amlodipine (25/10 mg), 7% with valsartan/HCTZ (320/25 mg), and 3% with amlodipine/valsartan (10/320 mg). One patient (0.2%) discontinued therapy due to an adverse event of hypokalemia in each of the EXFORGE HCT and HCTZ/amlodipine groups. The incidence of hyperkalemia (serum potassium >5.7 mEq/L) was 0.4% with EXFORGE HCT compared to 0.2-0.7% with the dual therapies.

Concomitant use of EXFORGE or EXFORGE HCT with other agents that block the RAAS, potassium-sparing diuretics, potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium. Monitor serum electrolytes periodically.

Important Considerations Due to the HCTZ Component of EXFORGE HCT: Hypersensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history. Thiazides have been reported to cause exacerbation or activation of systemic lupus erythematosus. Lithium generally should not be given with thiazides.

Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction resulting in transient myopia and angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Discontinue hydrochlorothiazide as rapidly as possible in these patients. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

Dual Blockade of the RAAS: Dual blockade of the RAAS with angiotensin receptor blockers, angiotensin-converting enzyme inhibitors (ACEIs), 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 or EXFORGE HCT and other agents that affect the RAAS.

Common Adverse Events: The most common adverse events that occurred more frequently with EXFORGE than placebo were peripheral edema (5% vs 3%), nasopharyngitis (4% vs 2%), upper respiratory tract infection (3% vs 2%), and dizziness (2% vs 1%).

The most frequent adverse events that occurred in ≥2% of patients treated with EXFORGE HCT were dizziness (8.2%), edema (6.5%), headache (5.2%), dyspepsia (2.2%), fatigue (2.2%), muscle spasms (2.2%), back pain (2.1%), nausea (2.1%) and nasopharyngitis (2.1%).

Please see accompanying full Prescribing Information, including Boxed WARNING, for EXFORGE and EXFORGE HCT.

References: 1. Data on file. Fingertip Formulary. January 2012. Novartis Pharmaceuticals Corp. 2.EXFORGE [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp.; 2012. 3. EXFORGE HCT [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp.; 2012.

* Source: National formulary data are provided by Fingertip Formulary and are accurate as of January 2012. Data from the Department of Veterans Affairs, Department of Defense, Indian Health Service, Kaiser Permanente, and HealthTrans are not included. Please note that formularies are subject to change and many health plans offer more than one formulary. Please check with the health plan directly to confirm coverage for individual patients. Tier status may include step edits and/or prior authorizations. Inclusion on formulary or formulary status does not imply superior clinical efficacy or safety. Includes plans listing products in any cost-sharing tier and certain plans may have quantity limits, prior authorizations, or step edits in place. Patient costs may vary significantly among plans.

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