Epirubicin Hydrochloride and Propranolol Hydrochloride

• Generic Name: epirubicin
• Dosage Forms: n.a.
• Other Brand Names: Ellence, Pharmorubicin Pfs, Pharmorubicin RDF

A component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast carcinoma; efficacy was established in combination with cyclophosphamide and fluorouracil.

• Generic Name: propranolol
• Dosage Forms: n.a.
• Other Brand Names: Inderal LA, InnoPran XL, Hemangeol, Inderal XL, InnoPran XL, Inderal

Management of hypertension, alone or in combination with other antihypertensive agents. Not indicated for the treatment of hypertensive emergencies.

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). Propranolol is one of several β-blockers (including bisoprolol, carvedilol, metoprolol succinate, metoprolol tartrate, nadolol, and timolol) recommended by a 2017 ACC/AHA multidisciplinary hypertension guideline as first-line therapy for hypertension in patients with stable ischemic heart disease/angina.

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 a BP of ≥130/80 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.

Chronic Stable Angina

Long-term management of chronic stable angina pectoris.

β-Blockers are recommended as first-line anti-ischemic drugs in most patients with chronic stable angina; despite differences in cardioselectivity, intrinsic sympathomimetic activity, and other clinical factors, all β-blockers appear to be equally effective for this use.

Supraventricular Arrhythmias

Treatment of supraventricular tachycardia (SVT) (e.g., atrial flutter, junctional tachycardia, focal atrial tachycardia, paroxysmal supraventricular tachycardia [PSVT]).

Vagal maneuvers and/or IV adenosine are considered first-line interventions for acute treatment of SVT when clinically indicated; if such measures are ineffective or not feasible, may consider an IV β-blocker. Oral β-blockers may be used for ongoing management. Although evidence of efficacy is limited, experts state that overall safety of β-blockers warrants use.

Used to slow ventricular rate in patients with atrial fibrillation or flutter when ventricular rate cannot be controlled by standard measures.

Ventricular Arrhythmias

Generally less effective in the management of ventricular arrhythmias than supraventricular arrhythmias, but may be considered when cardioversion or other drugs not effective.

May be used in the treatment of persistent premature ventricular complexes.

β-Blockers have been used in patients with cardiac arrest precipitated by ventricular fibrillation or pulseless VT; however, routine administration after cardiac arrest is potentially harmful and not recommended.

β-Blockers may be useful in the management of certain forms of polymorphic VT (e.g., associated with acute ischemia).

Tachyarrhythmias Associated with Cardiac Glycoside Intoxication or Catecholamine Excess

Management of supraventricular or ventricular tachyarrhythmias associated with cardiac glycoside toxicity when AV block is not present.

Management of resistant tachyarrhythmias associated with catecholamine excess during anesthesia; use with extreme caution and constant ECG and central venous pressure monitoring. More effective and less hazardous therapy, such as lessening the depth of anesthesia or improving ventilation, is preferred.

Hypertrophic Subaortic Stenosis

Management of exertional or other stress-induced angina, vertigo, syncope, and palpitation in patients with hypertrophic subaortic stenosis; clinical improvement may be temporary.

Pheochromocytoma

Management of symptoms resulting from excessive β-receptor stimulation in patients with inoperable or metastatic pheochromocytoma, as an adjunct to α-adrenergic blocking agents. Initiate therapy with an α-adrenergic blocking agent prior to treatment of pheochromocytoma.

Management of tachycardia prior to or during surgery in patients with pheochromocytoma, as an adjunct to α-adrenergic blocking agents. Initiate therapy with an α-adrenergic blocking agent prior to treatment of pheochromocytoma.

Thyrotoxicosis

Short-term (2–4 weeks) adjunctive therapy of tachycardia and supraventricular arrhythmias in patients with thyrotoxicosis when these symptoms are distressful or hazardous, or when immediate therapy is necessary.

Vascular Headache

Prophylaxis of common migraine headache; not recommended for the treatment of a migraine attack that has already started.

MI

Secondary prevention following acute MI to reduce the risk of cardiovascular mortality.

Administration within 5–21 days following MI associated with reductions in overall and cardiovascular mortality.

Experts recommend β-blocker therapy in all patients with left ventricular systolic dysfunction and prior MI; a β-blocker with proven mortality benefit (bisoprolol, carvedilol, or metoprolol succinate) is preferred. Although benefits of long-term β-blockade in patients with normal left ventricular function are less well established, experts recommend continued β-blocker therapy for at least 3 years in such patients.

Essential Tremor

Management of essential (familial, hereditary) tremor.

Not indicated for tremor associated with Parkinsonism.