Exforge5 mg+160 mg

Exforge is an FDA-approved fixed-dose combination indicated for the treatment of hypertension (high blood pressure) in adults.

• Established/FDA-approved use: Treatment of hypertension, either as initial therapy in patients likely to need multiple drugs to achieve blood pressure goals, or as substitution/add-on therapy in patients whose blood pressure is not adequately controlled on amlodipine or valsartan monotherapy, or on the two components given separately.
• Guideline-supported use: Major hypertension guidelines (e.g., ACC/AHA, ESC/ESH) support initial combination therapy with a calcium channel blocker plus a renin-angiotensin system blocker such as an ARB in patients with stage 2 hypertension or blood pressure substantially above goal.
• Cardiovascular risk reduction: Lowering blood pressure with Exforge reduces the risk of fatal and non-fatal cardiovascular events, primarily by reducing the incidence of stroke and myocardial infarction, a benefit demonstrated in controlled trials of the individual antihypertensive-drug classes that include amlodipine and valsartan.

Exforge is not indicated as first-line therapy in patients who do not require multiple drugs to control their blood pressure.

Amlodipine + Valsartan is a fixed-dose combination tablet containing two active ingredients:

• Amlodipine (as amlodipine besylate) - a dihydropyridine calcium channel blocker.
• Valsartan - an angiotensin II receptor blocker (ARB).

Amlodipine + Valsartan is available internationally as film-coated tablets in several fixed-dose strength combinations, commonly 5 mg/80 mg, 5 mg/160 mg, 10 mg/160 mg, and 10 mg/320 mg (amlodipine/valsartan); exact strengths marketed may vary by country and manufacturer.

Exforge combines a calcium channel blocker and an angiotensin II receptor blocker in a single tablet to treat high blood pressure. Combining two antihypertensive agents with complementary mechanisms allows more effective blood pressure control than either agent alone, often with fewer dose-dependent side effects than using a higher dose of a single agent.

Exforge is taken once daily for long-term (chronic) management of hypertension; it is not intended for acute blood pressure emergencies.

Exforge belongs to the therapeutic class of antihypertensive combination agents, combining a dihydropyridine calcium channel blocker with an angiotensin II receptor blocker (ARB).

Amlodipine + Valsartan lowers blood pressure through two independent and complementary mechanisms:

• Amlodipine inhibits the influx of calcium ions across vascular smooth muscle cell membranes, causing relaxation (vasodilation) of arterial smooth muscle and a reduction in peripheral vascular resistance.
• Valsartan selectively blocks the binding of angiotensin II to the AT1 receptor in vascular smooth muscle and the adrenal gland, blocking the vasoconstrictor and aldosterone-secreting effects of angiotensin II, without inhibiting ACE (kinase II), so it does not affect bradykinin metabolism.

Because the two components act on different blood-pressure-regulating pathways, the antihypertensive effects of Amlodipine + Valsartan are approximately additive.

Exforge tablets should be swallowed whole with a glass of water, with or without food, once daily, preferably at the same time each day.

• Do not crush, chew, or split the tablet unless advised by a physician or pharmacist.
• If a dose is missed, take it as soon as remembered unless it is almost time for the next dose; do not double the dose.
• Do not stop taking Exforge abruptly without consulting a physician, even if blood pressure appears well controlled, since hypertension is typically a lifelong condition requiring continuous therapy.
• Continue routine blood pressure monitoring and follow-up visits as advised by the prescribing physician.

Clinically significant interactions with Exforge include:

• Aliskiren: Combined use in patients with diabetes is contraindicated (see Contraindications); avoid combination in patients with renal impairment (GFR <60 mL/min) due to increased risk of hyperkalemia, hypotension, and renal dysfunction.
• Other RAAS blockers (ACE inhibitors, other ARBs): Dual blockade of the renin-angiotensin system increases the risk of hypotension, hyperkalemia, and changes in renal function compared to monotherapy; combined use is generally not recommended.
• NSAIDs (including selective COX-2 inhibitors): May reduce the antihypertensive effect of Exforge and worsen renal function, particularly in elderly, volume-depleted, or renally impaired patients.
• Potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes: May increase serum potassium; monitor levels if co-administration is necessary.
• Lithium: Increased serum lithium concentrations and lithium toxicity have been reported with ARBs; monitor lithium levels during concomitant use.
• Strong or moderate CYP3A4 inhibitors (e.g., certain azole antifungals, macrolide antibiotics, protease inhibitors): May increase amlodipine exposure, raising the risk of hypotension and edema.
• CYP3A4 inducers (e.g., rifampicin, St. John's Wort): May reduce amlodipine plasma concentration and antihypertensive effect; monitor blood pressure.
• Simvastatin: Amlodipine increases simvastatin exposure; limit simvastatin dose to 20 mg daily during concurrent use.

The most common side effects of Exforge include:

• Peripheral (ankle/leg) edema - the most common dose-related adverse effect, mainly attributable to the amlodipine component
• Nasopharyngitis (cold-like symptoms)
• Upper respiratory tract infection
• Dizziness
• Headache
• Fatigue
• Flushing

Less common but important effects include hypotension, palpitations, and elevated liver enzymes. Rare but serious effects include angioedema and significant declines in renal function (see Precautions and Warnings). Patients should seek prompt medical attention for facial/throat swelling, difficulty breathing, severe dizziness, or fainting while taking Exforge.

Pregnancy: Exforge can cause fetal harm and is contraindicated once pregnancy is confirmed. Drugs that act directly on the renin-angiotensin system, such as the valsartan component, can cause injury and death to the developing fetus when used in the second and third trimesters, including oligohydramnios, fetal lung hypoplasia, skeletal deformations, and neonatal renal failure. When pregnancy is detected, Exforge should be discontinued as soon as possible, and the patient should consult her physician immediately about alternative antihypertensive therapy. Use only if clearly needed and no safer alternative exists, and only under close physician supervision.

Lactation: Amlodipine is present in human milk; it is not known whether valsartan is excreted in human milk. Because of the potential for serious adverse effects in a nursing infant, breastfeeding is generally not recommended during treatment with Exforge; a physician should be consulted to weigh the benefits of breastfeeding against the potential risk, or to consider an alternative agent.

Hypotension: Symptomatic hypotension may occur, particularly after the first dose or a dose increase, and especially in patients who are volume- or salt-depleted (e.g., from diuretic use, dietary salt restriction, dialysis, vomiting, or diarrhea). Correct volume depletion before starting Exforge, or begin under close medical supervision.

Hyperkalemia and renal function: As with other drugs affecting the renin-angiotensin system, Exforge can cause hyperkalemia and changes in renal function, including acute renal failure, particularly in patients with renal artery stenosis, pre-existing renal impairment, heart failure, or volume depletion. Periodic monitoring of serum potassium and renal function is advised in at-risk patients.

Angioedema: Angioedema, including swelling of the face, lips, throat, and/or tongue, has been reported rarely with valsartan and other ARBs; discontinue Exforge immediately if angioedema occurs and do not re-administer.

Peripheral edema: Dose-related peripheral edema, primarily due to amlodipine, is the most frequently reported adverse effect; it is usually mild to moderate and related to arteriolar vasodilation rather than fluid retention.

Worsening angina or myocardial infarction: Rarely, patients, particularly those with severe obstructive coronary artery disease, may develop increased frequency, duration, or severity of angina, or acute myocardial infarction, on starting therapy or at the time of dose increase.

Hepatic impairment: Use with caution, starting at a low dose, since amlodipine clearance is reduced (see Dosage and Administration).

Regular blood pressure monitoring and follow-up are recommended for all patients taking Exforge.

Overdose of Exforge may cause excessive peripheral vasodilation with marked and potentially prolonged hypotension, reflex tachycardia (or occasionally bradycardia), dizziness, and shock.

If an overdose is suspected, seek immediate medical attention or contact emergency services/a poison control center right away. Do not attempt to treat an overdose at home. Management is supportive and is provided by a physician in a medical facility, typically including cardiovascular monitoring and careful fluid administration; valsartan is not effectively removed by hemodialysis.

Store Exforge at room temperature (below 30°C), protected from light and moisture. Keep out of reach of children.

Elderly (65 years and older): No overall differences in effectiveness were observed compared with younger patients, but elderly patients may be more sensitive to the blood-pressure-lowering effect. Amlodipine clearance is reduced in older adults, increasing systemic exposure; treatment with Exforge should generally start at the lower end of the dosing range.

Renal impairment: No initial dose adjustment needed for mild-to-moderate impairment; use with caution and close monitoring in severe impairment or renal artery stenosis (see Precautions and Warnings).

Hepatic impairment: Not recommended for initial therapy; if required, initiate at the lowest dose with slow titration.

Pediatric patients: See Pediatric Uses.

Pregnant or breastfeeding women: See Pregnancy and Lactation.

Hypertension is typically a chronic, lifelong condition. Exforge is generally intended for long-term, continuous use as directed by a physician, with periodic reassessment of blood pressure control, kidney function, and electrolytes. Treatment should not be stopped abruptly without medical advice.

Amlodipine + Valsartan combines two drug classes:

• Dihydropyridine calcium channel blocker (amlodipine)
• Angiotensin II receptor blocker / ARB (valsartan)

Amlodipine + Valsartan acts through two complementary mechanisms: amlodipine blocks L-type calcium channels in vascular smooth muscle, reducing calcium influx and causing vasodilation; valsartan selectively blocks angiotensin II from binding to the AT1 receptor, preventing angiotensin II-mediated vasoconstriction and aldosterone release. Together, these mechanisms produce an additive reduction in blood pressure through both direct vascular relaxation and suppression of the renin-angiotensin-aldosterone system.

D

The safety and effectiveness of Exforge have not been established in pediatric patients under 18 years of age. Exforge should not be used in children unless specifically directed by a pediatric specialist, and is not recommended for routine pediatric use.