Acular PF and Amiloride Hydrochloride

• Generic Name: ketorolac ophthalmic
• Dosage Forms: Ophthalmic Solution 0.5% Preservative-Free Sterile
• Other Brand Names: Acular, Acular LS, Acuvail, Acular PF

Ketorolac eye drops is used to treat itching caused by seasonal allergic conjunctivitis (an allergy that occurs at only certain times of the year). It is also used to treat pain, burning, and inflammation of the eye following cataract surgery or corneal refractive surgery. This medicine is a topical nonsteroidal anti-inflammatory drug (NSAID).

This medicine is available only with your doctor's prescription.

• Generic Name: amiloride
• Dosage Forms: n.a.
• Other Brand Names: Midamor

Amiloride should rarely be used alone, because such use may result in increased risk of hyperkalemia. Use alone only when persistent hypokalemia has been documented.

Hypokalemia Induced by Kaliuretic Diuretics

Treatment or prevention of hypokalemia induced by thiazide or other kaliuretic diuretics in patients with heart failure or hypertension.

May be particularly useful for preventing diuretic-induced hypokalemia in patients in whom the clinical consequences of hypokalemia represent an important risk, such as patients receiving cardiac glycosides or those with cardiac arrhythmias.

Also useful in patients with hypokalemia who do not respond to potassium supplements or those who cannot tolerate potassium supplements.

Potassium-sparing effect of amiloride generally persists during prolonged therapy with the drug, but may diminish with time in some patients.

Potassium-sparing effect of amiloride is additive with that of spironolactone. May be effective in some patients unresponsive to spironolactone; unlike spironolactone, diuretic effect of amiloride is independent of aldosterone concentrations.

Edema

Management of edema associated with heart failure, cirrhosis of the liver, or secondary hyperaldosteronism.

Generally, use in combination with other more effective, rapidly acting diuretics, such as thiazides, chlorthalidone, or loop diuretics (e.g., furosemide), to decrease potassium excretion caused by kaliuretic diuretics.

Used in fixed combination with hydrochlorothiazide for treatment of edema in patients who require a thiazide diuretic and in whom the development of hypokalemia cannot be risked.

Heart Failure

Management of edema associated with heart failure, generally used in conjunction with other more effective, rapidly acting diuretics (e.g., thiazides, chlorthalidone, loop diuretics).

Most experts state that loop diuretics (e.g., bumetanide, ethacrynic acid, furosemide, torsemide) are the diuretics of choice for most patients with heart failure.

Most experts state that all patients with symptomatic heart failure who have evidence for, or a history of, fluid retention generally should receive diuretic therapy in conjunction with moderate sodium restriction, an agent to inhibit the renin-angiotensin-aldosterone (RAA) system (e.g., ACE inhibitor, angiotensin II receptor antagonist, angiotensin receptor-neprilysin inhibitor [ARNI]), a β-adrenergic blocking agent (β-blocker), and in selected patients, an aldosterone antagonist.

Hypertension

Management of hypertension alone or in combination with other classes of antihypertensive agents; however, other agents (i.e., ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, thiazide diuretics) are preferred for initial management according to current evidence-based practice guidelines for the management of hypertension in adults.

Amiloride alone has mild hypotensive activity.

Used concomitantly with a thiazide diuretic mainly to prevent or treat diuretic-induced hypokalemia. The manufacturers state that amiloride produces little additive hypotensive activity when used concurrently with a thiazide diuretic.

Some experts state that amiloride may be useful as a component of combination therapy in the management of resistant hypertension.

Used in fixed combination with hydrochlorothiazide for treatment of hypertension in patients who require a thiazide diuretic and in whom the development of hypokalemia cannot be risked and in patients who develop hypokalemia during hydrochlorothiazide monotherapy.

Use the amiloride/hydrochlorothiazide fixed combination alone or as an adjunct to other antihypertensive agents (e.g., methyldopa, β-blocker).

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP. However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk. In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg. These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.

Other hypertension guidelines generally have based target BP goals on age and comorbidities. Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk, and have used higher BP thresholds and target BPs in elderly patients compared with those recommended by the 2017 ACC/AHA hypertension guideline.

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors. ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.

Adults with hypertension and diabetes mellitus, CKD, or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg. Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP. Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.

Hyperaldosteronism

Has been used to control hypertension and correct electrolyte abnormalities associated with primary hyperaldosteronism.

Also has been used for the management of secondary hyperaldosteronism (Bartter’s syndrome) to correct hypokalemia.

Diuretic-induced Metabolic Alkalosis

Has been used to correct the metabolic alkalosis produced by thiazides and other kaliuretic diuretics.

Calcium Nephrolithiasis

Has been used in combination with hydrochlorothiazide in patients with recurrent calcium nephrolithiasis.

Lithium-induced Polyuria

Has been used for the management of lithium-induced polyuria (secondary to lithium-induced nephrogenic diabetes insipidus).