Exforge HCT

Essential HTN.

Adult 1 tab daily, may be increased after 2 wk. Max recommended dose: Amlodipine 10 mg, valsartan 320 mg, HCTZ 25 mg. Patient w/ hepatic impairment, elderly ≥65 yr Consider starting w/ amlodipine 5 mg.

May be taken with or without food.

Hypersensitivity to amlodipine, valsartan, HCTZ or other sulfonamide-derived medicinal products. Patients w/ anuria. Concomitant use w/ ARBs or ACE inhibitors w/ aliskiren in type 2 diabetes patients. Pregnancy.

Immediately discontinue use in patients who develop angioedema, & do not re-administer. Symptomatic hypotension may occur in severely Na- &/or vol-depleted patients eg, those receiving high doses of diuretics. May precipitate azotemia in patients w/ CKD. Risk of worsening angina pectoris & acute MI after starting or increasing amlodipine dose, particularly in patients w/ severe obstructive CAD. Perform periodic determinations of serum electrolytes at appropriate intervals to detect possible electrolyte imbalance. May exacerbate or activate SLE; alter glucose tolerance & raise serum levels of cholesterol, triglycerides & uric acid; cause or exacerbate hyperuricemia & precipitate gout in susceptible patients; decrease urinary Ca excretion & may cause mild elevation of serum Ca. Hypersensitivity reactions to hydrochlorothiazide are more likely in patients w/ allergy & asthma. Risk of non-melanoma skin cancer; regularly check the skin for any new & suspicious skin lesions. Patients w/ unilateral or bilateral renal artery stenosis, stenosis to a solitary kidney; serious CHF (NYHA functional class III-IV); aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy. Dual blockade of the renin-angiotensin system eg, w/ ACEIs or aliskiren. Avoid use w/ aliskiren in patients w/ severe renal impairment (GFR <30 mL/min). No experience w/ use in patients w/ recent kidney transplantation. Patients w/ hepatic impairment or biliary obstructive disorders; severe renal impairment (GFR <30 mL/min). Not to be used in women planning to become pregnant. Not advisable to use during breast-feeding. Not recommended in patients <18 yr.

Amlodipine: Headache, somnolence, dizziness; palpitations; flushing; abdominal pain, nausea; oedema, fatigue. HCTZ: Hypokalemia, increased blood lipids. Hyponatraemia, hypomagnesaemia, hyperuricaemia, decreased appetite; orthostatic hypotension; mild nausea & vomiting; urticaria & other forms of rash; erectile dysfunction.

Reversible increases in serum lithium conc & toxicity. Amlodipine: Increased exposure to simvastatin. Plasma conc may be increased w/ strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir). Increased exposure w/ grapefruit juice. Monitor for adequate clinical effect when co-administered w/ CYP3A4 inducers (eg, rifampicin, Hypericum perforatum). Valsartan: Increased incidence of hypotension, hyperkalemia, & changes in renal function w/ ARBs, ACE inhibitors or aliskiren. Concomitant use w/ K supplements, K-sparing diuretics, salt substitutes containing K, or other drugs that may increase K levels (eg, heparin). Attenuation of antihypertensive effect w/ NSAIDs including selective COX-2 inhibitors. Increased risk of worsening renal function w/ NSAIDs in patients who are elderly, vol-depleted or have compromised renal function. Systemic exposure to valsartan may be increased w/ inhibitors of OATP1B1 (eg, rifampin, ciclosporin) or MRP2 (eg, ritonavir). HCTZ: Potentiated antihypertensive action of other antihypertensive drugs (eg, guanethidine, methyldopa, β-blockers, vasodilators, Ca channel blockers, ACE inhibitors, ARBs, direct renin inhibitors). Potentiated action of skeletal muscle relaxants (eg, curare derivatives). Increased hypokalemic effect w/ kaliuretic diuretics, corticosteroids, ACTH, amphotericin, carbenoxolone, penicillin G, carbenoxolone, salicylic acid derivatives or antiarrhythmics. Intensified hyponatremic effect w/ antidepressants, antipsychotics, antiepileptics. Dose of insulin & oral antidiabetics may need adjustment due to altered glucose tolerance w/ thiazides. Thiazide-induced hypokalemia or hypomagnesemia may occur, favoring onset of digitalis-induced cardiac arrhythmias. Diuretic & antihypertensive activity may be weakened w/ NSAIDs & COX-2 selective inhibitors. Co-administration of thiazide diuretics may increase incidence of hypersensitivity reactions to allopurinol. Co-administration of thiazide diuretics may increase risk of adverse effects caused by amantadine. May reduce renal excretion of cytotoxic agents (eg, cyclophosphamide & MTX) & enhance myelosuppressive effects. Increased bioavailability w/ anticholinergic agents (eg, atropine, biperiden). Decreased bioavailability w/ prokinetic drugs (eg, cisapride). Decreased absorption w/ cholestyramine or colestipol. Administration w/ vit D or Ca salts may potentiate the rise in serum Ca. May increase risk of hyperuricemia & gout-type complications w/ ciclosporin. Concomitant use w/ Ca salts may lead to hypercalcemia. May enhance hyperglycemic effect of diazoxide. Reports of hemolytic anemia w/ methlydopa. May potentiate orthostatic hypotension w/ alcohol, barbiturates or narcotics. May reduce response to pressor amines eg, noradrenaline.

Angiotensin II Antagonists / Calcium Antagonists / Diuretics

C09DX01 - valsartan, amlodipine and hydrochlorothiazide ; Belongs to the class of angiotensin II receptor blockers (ARBs), other combinations. Used in the treatment of cardiovascular disease.

Rx