Overview
11 DESCRIPTION Amlodipine, valsartan and hydrochlorothiazide tablets, USP are a fixed combination of amlodipine, valsartan, and hydrochlorothiazide. Amlodipine, valsartan and hydrochlorothiazide tablets, USP contains the besylate salt of amlodipine, a dihydropyridine calcium channel blocker (CCB).
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The active ingredients of amlodipine, valsartan and hydrochlorothiazide tablets target 3 separate mechanisms involved in blood pressure regulation. Specifically, amlodipine blocks the contractile effects of calcium on cardiac and vascular smooth muscle cells; valsartan blocks the vasoconstriction and sodium retaining effects of angiotensin II on cardiac, vascular smooth muscle, adrenal and renal cells; and hydrochlorothiazide directly promotes the excretion of sodium and chloride in the kidney leading to reductions in intravascular volume. A more detailed description of the mechanism of action of each individual component follows.
Indications
- 1 INDICATIONS & USAGE Amlodipine, valsartan and hydrochlorothiazide tablets 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. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including amlodipine, hydrochlorothiazide, and the ARB class to which valsartan principally belongs.
Common Doses
- 25 mg
Dosage
2 DOSAGE & ADMINISTRATION • Dose once-daily. Titrate up to a maximum dose of 10/320/25 mg ( 2.1 ) • Amlodipine, valsartan and hydrochlorothiazide tablets 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 ). • Amlodipine, valsartan and hydrochlorothiazide tablets 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.
Black Box Warning
BOXED WARNING WARNING: FETAL TOXICITY • When pregnancy is detected, discontinue amlodipine, valsartan and hydrochlorothiazide tablets 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 amlodipine, valsartan and hydrochlorothiazide tablets as soon as possible. ( 5.1 ) • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
Contraindications
- 4 CONTRAINDICATIONS Do not use in patients with anuria, hypersensitivity to other sulfonamide-derived drugs, or hypersensitivity to any component of this product. Do not coadminister aliskiren with amlodipine, valsartan and hydrochlorothiazide tablets in patients with diabetes [see Drug Interactions ( 7 )]. • Anuria ( 4 ) • Hypersensitivity to sulfonamide-derived drugs ( 4 ) • Known hypersensitivity to any component ( 4 ) • Do not coadminister aliskiren with amlodipine, valsartan and hydrochlorothiazide tablets in patients with diabetes ( 4 )
Side Effects
- 6 ADVERSE REACTIONS Most common adverse events (≥2% incidence) are dizziness, peripheral edema, headache, dyspepsia, fatigue, muscle spasms, back pain, nausea and nasopharyngitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Macleods Pharma USA, Inc., at 1-888-943-3210 or or 1-855-926-3384 FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and...
Interactions
- 7 DRUG INTERACTIONS No drug interaction studies have been conducted with amlodipine, valsartan and hydrochlorothiazide tablets 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, amlodipine, valsartan and hydrochlorothiazide tablets, and the corresponding 3 double combinations. No clinically relevant interaction was observed.