Betaxolol Hydrochloride and Digoxin Immune Fab (Ovine)

• Generic Name: betaxolol
• Dosage Forms: n.a.
• Other Brand Names: Kerlone

Management of hypertension (alone or in combination with other classes of antihypertensive agents).

β-Blockers generally not preferred for first-line therapy of hypertension according to current evidence-based hypertension guidelines, but may be considered in patients who have a compelling indication (e.g., prior MI, ischemic heart disease, heart failure) for their use or as add-on therapy in those who do not respond adequately to the preferred drug classes (ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, or thiazide diuretics). A 2017 ACC/AHA multidisciplinary hypertension guideline states that β-blockers used for ischemic heart disease that are also effective in lowering BP include bisoprolol, carvedilol, metoprolol succinate, metoprolol tartrate, nadolol, propranolol, and timolol.

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).

The 2017 ACC/AHA 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) <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, chronic kidney disease (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.

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to β-blockers. However, diminished response to β-blockers is largely eliminated when administered concomitantly with a thiazide diuretic.

• Generic Name: digoxin immune fab
• Dosage Forms: n.a.
• Other Brand Names: DigiFab, Digibind

Treatment of life-threatening or potentially life-threatening digoxin toxicity or overdosage.

Has been used for treatment of life-threatening overdosage of digitoxin (no longer commercially available in US) or lanatoside C (not commercially available in US) intoxication; designated an orphan drug by FDA for treatment of potentially life-threatening cardiac glycoside (digitalis) intoxication refractory to conventional management.

Not indicated for treatment of non-life-threatening cardiac glycoside intoxication; limited experience and consequences of repeated exposure to the immune Fab not known.

Indicated in acute ingestions (e.g., known suicidal or accidental consumption) of ≥10 mg of digoxin in previously healthy adults or 4 mg (or >0.1 mg/kg) of digoxin in previously healthy children.

Minimum toxic or lethal acute doses of digoxin not well established; acute digoxin ingestions of >10 mg in previously healthy adults or >4 mg in previously healthy children often result in cardiac arrest.

Indicated in acute ingestions resulting in steady-state serum digoxin concentrations >10 ng/mL or chronic ingestions resulting in steady-state serum digoxin concentrations >6 ng/mL in adults or >4 ng/mL in children; ingestions resulting in steady-state serum digoxin concentrations >10 ng/mL often result in cardiac arrest.

Indicated when there are manifestations of life-threatening digoxin toxicity, including severe ventricular arrhythmias (e.g., ventricular tachycardia or fibrillation), progressive bradycardia (e.g., second- or third-degree heart block not responsive to atropine), or serum potassium concentrations >5–5.5 mEq/L in adults or >6 mEq/L in children with rapidly progressive signs and symptoms of digoxin toxicity.

Progressive hyperkalemia treated by conventional supportive and symptomatic measures without digoxin immune Fab (ovine) has poor prognosis. Also consider other potential causes of hyperkalemia, especially if digoxin immune Fab (ovine) does not appear to substantially decrease serum potassium concentrations.

Has been used for treatment of poisonings involving ingestion of certain cardiotoxic plants, including common or pink oleander (Nerium oleander), yellow oleander (Thevetia peruviana), and Indian hemp (Apocynum cannabinum). Has reversed or improved cardiotoxicity in some individuals; additional study needed.

Has not been effective in poisonings involving ingestion of foxglove extract or yew berry.

Reversed or improved cardiotoxicity associated with ingestion of toad venom. Toad venom has been identified in illicit street drugs marketed as aphrodisiacs; contains several cardioactive steroids (bufadienolides), including bufalin, cinobufagin, cinobufotalin, and resibufogenin.

Has been used with some success for management of severe preeclampsia or eclampsia; designated an orphan drug by FDA for treatment of severe preeclampsia and eclampsia.

Severe preeclampsia and eclampsia are major causes of maternal and fetal morbidity and mortality. There is some evidence that increased concentrations of endogenous cardiotonic steroids, including endogenous digitalis-like factors (EDLFs), in maternal and/or cord blood may contribute to pathogenesis of preeclampsia, particularly elevated BP; additional study needed to evaluate use of digoxin immune Fab (ovine).