General MedicationsORALBlack Box

Exforge HCT

AMLODIPINE VALSARTAN AND HYDROCHLOROTHIAZIDE

Standard Dose

2 DOSAGE AND ADMINISTRATION Dose once-daily. Titrate up to a maximum dose of 10/320/25 mg. ( 2.1 ) Exforge HCT may be used as add-on/switch therapy for patients not adequately controlled on any two of the following antihypertensive classes: calcium channel blockers, angiotensin receptor blockers, and diuretics. ( 2.2 ) Exforge HCT may be substituted for its individually titrated components. ( 2.3 ) 2.1 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 dose of Exforge HCT. The maximum recommended dose of Exforge HCT is 10/320/25 mg. 2.2 Add-on/Switch Therapy Exforge HCT may be used for patients not adequately controlled on any 2 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. 2.3 Replacement Therapy Exforge HCT may be substituted for the individually titrated components. 2.4 Use With Other Antihypertensive Drugs Exforge HCT may be administered with other antihypertensive agents.

Max Dose

See official label

Primary Use

1 INDICATIONS AND USAGE Exforge HCT (amlodipine, valsartan, and hydrochlorothiazide) is indicated for the treatment of hypertension, to lower blood pressure.

Summary

Indications and usage 1 INDICATIONS AND USAGE Exforge HCT (amlodipine, valsartan, and hydrochlorothiazide) is 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.

Structured Monograph

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE Exforge HCT (amlodipine, valsartan, and hydrochlorothiazide) is 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. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including amlodipine, hydrochlorothiazide, and the angiotensin II receptor blocker (ARB) class to which valsartan principally belongs. There are no controlled trials demonstrating risk reduction with Exforge HCT. 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. Many patients will require more than 1 drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (e.g., patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Limitations of Use Exforge HCT is not indicated for the initial therapy of hypertension [see Dosage and Administration (2)] . Exforge HCT is a combination tablet of amlodipine, a dihydropyridine calcium channel blocker (DHP CCB), valsartan, an angiotensin II receptor blocker (ARB), and hydrochlorothiazide, a thiazide diuretic. Exforge HCT is 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. ( 1 ) Limitations of Use Exforge HCT is not indicated for initial treatment of hypertension. ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION Dose once-daily. Titrate up to a maximum dose of 10/320/25 mg. ( 2.1 ) Exforge HCT may be used as add-on/switch therapy for patients not adequately controlled on any two of the following antihypertensive classes: calcium channel blockers, angiotensin receptor blockers, and diuretics. ( 2.2 ) Exforge HCT may be substituted for its individually titrated components. ( 2.3 ) 2.1 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 dose of Exforge HCT. The maximum recommended dose of Exforge HCT is 10/320/25 mg. 2.2 Add-on/Switch Therapy Exforge HCT may be used for patients not adequately controlled on any 2 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. 2.3 Replacement Therapy Exforge HCT may be substituted for the individually titrated components. 2.4 Use With Other Antihypertensive Drugs Exforge HCT may be administered with other antihypertensive agents. Warnings and cautions 5 WARNINGS AND PRECAUTIONS Hypotension: Correct volume depletion prior to initiation ( 5.2 ) Increased angina and/or myocardial infarction ( 5.3 ) Monitor renal function and potassium in susceptible patients ( 5.4 , 5.5 ) Exacerbation or

Boxed Warning

WARNING: FETAL TOXICITY When pregnancy is detected, discontinue 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) WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning. When pregnancy is detected, discontinue 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 )

Monitoring

• 5 WARNINGS AND PRECAUTIONS Hypotension: Correct volume depletion prior to initiation ( 5.2 ) Increased angina and/or myocardial infarction ( 5.3 ) Monitor renal function and potassium in susceptible patients ( 5.4 , 5.5 ) Exacerbation or activation of systemic lupus erythematosus ( 5.7 ) Observe for signs of fluid or electrolyte imbalance ( 5.9 ) Acute angle-closure glaucoma ( 5.10 ) 5.1 Fetal Toxicity Valsartan Exforge HCT can cause fetal harm when administered to a pregnant woman.
• 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.

Interaction Notes

• 7 DRUG INTERACTIONS No drug interaction studies have been conducted with Exforge HCT and other drugs, although studies have been conducted with the individual components.
• A pharmacokinetic drug-drug interaction study has been conducted to address the potential for pharmacokinetic interaction between the triple combination, Exforge HCT, and the corresponding 3 double combinations.
• No clinically relevant interaction was observed.
• Amlodipine Impact of Other Drugs on Amlodipine CYP3A Inhibitors Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction.