Metoprolol Tartrate and Vinblastine Sulfate

• Generic Name: metoprolol
• Dosage Forms: n.a.
• Other Brand Names: Toprol XL, Lopressor, Kapspargo Sprinkle, Toprol-XL

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). Metoprolol succinate and metoprolol tartrate are two of several β-blockers (including bisoprolol, carvedilol, nadolol, propranolol, 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 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.

Chronic Stable Angina

Long-term management of stable angina pectoris.

β-Blockers are considered 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.

Non-ST-Segment-Elevation Acute Coronary Syndromes (NSTE ACS)

Used as part of the standard therapeutic measures for managing NSTE ACS, which include unstable angina and non-ST-segment-elevation MI (NSTEMI).

Expert guidelines recommend initiation of oral β-blocker therapy within the first 24 hours in patients who do not have manifestations of heart failure, evidence of low-output state, increased risk of cardiogenic shock, or any other contraindications to β-blocker therapy.

Continue β-blocker therapy for secondary prevention in patients with stabilized heart failure and reduced systolic function (preferably with bisoprolol, carvedilol, or metoprolol succinate because of proven mortality benefit).

Acute MI

Used during acute phase of MI to reduce cardiovascular mortality.

Expert guidelines recommend initiation of oral β-blocker therapy within the first 24 hours in patients who do not have manifestations of heart failure, evidence of low-output state, increased risk of cardiogenic shock, or any other contraindications to β-blocker therapy. Because of conflicting evidence of benefit and potential for harm (e.g., cardiogenic shock), experts recommend limiting use of IV β-blockers to patients with refractory hypertension or ongoing ischemia at time of presentation.

Continue β-blocker therapy for secondary prevention in post-MI patients with left ventricular systolic dysfunction (preferably with bisoprolol, carvedilol, or metoprolol succinate because of proven mortality benefit). Although benefits of long-term β-blockade in patients with normal left ventricular function are less well established, experts recommend continuing β-blocker therapy for at least 3 years in such patients.

Supraventricular Arrhythmias

Has been used in the 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-adrenergic blockers warrants use.

Used to slow ventricular rate in patients with atrial fibrillation or flutter.

Ventricular Arrhythmias

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).

Heart Failure

Management of mild to moderately severe (NYHA class II or III) heart failure of ischemic, hypertensive, or cardiomyopathic origin (in conjunction with other heart failure therapies [e.g., ACE inhibitors, diuretics, cardiac glycosides]). Used to increase survival and to reduce the risk of hospitalization.

The American College of Cardiology Foundation (ACCF), AHA, and the Heart Failure Society of America (HFSA) recommend therapy with an ACE inhibitor, angiotensin II receptor antagonist, or angiotensin receptor-neprilysin inhibitor (ARNI) in conjunction with a β-blocker, and an aldosterone antagonist in selected patients, to reduce morbidity and mortality in patients with symptomatic heart failure and reduced left ventricular ejection fraction (LVEF) (ACCF/AHA stage C heart failure).

Initiate a clinical-trial proven β-blocker (bisoprolol, carvedilol, extended-release metoprolol succinate) to reduce the risk of death in patients with chronic heart failure; benefits shown with these β-blockers not considered indicative of a β-blocker class effect.

Experts recommend that β-blockers be used in conjunction with ACE inhibitors in all patients with asymptomatic heart failure (i.e., structural heart disease but no signs or symptoms; ACCF/AHA stage B heart failure) with reduced LVEF.

Vascular Headache

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

• Generic Name: vinblastine
• Dosage Forms: n.a.
• Other Brand Names: Velban

In combination chemotherapy as first- or second-line therapy for Hodgkin’s disease.

Often used with doxorubicin, bleomycin, and dacarbazine (known as the ABVD regimen) as first-line therapy for Hodgkin’s disease.

Under investigated in other combination regimens (e.g., Stanford V regimen: doxorubicin, bleomycin, vinblastine, vincristine, mechlorethamine, etoposide, and prednisone) for the treatment of advanced Hodgkin's disease.

For the treatment of advanced nonseminomatous testicular carcinoma, combination chemotherapy regimens containing vinblastine, cisplatin, and bleomycin have been used; however, most clinicians recommend regimens containing cisplatin and bleomycin, in combination with etoposide rather than vinblastine, as first-line therapy, particularly because of the reduced risk of neuromuscular toxicity and evidence suggesting greater efficacy in poor-risk patients.

A regimen of cisplatin, ifosfamide, and either vinblastine or etoposide currently is considered by most clinicians to be the standard initial salvage (i.e., second-line) regimen in patients with recurrent testicular cancer.

Has been used alone or in combination chemotherapy for the palliative treatment of AIDS-related Kaposi’s sarcoma.

Single-agent therapy with vinblastine is considered an alternative regimen.

Combination chemotherapy with a vinca alkaloid (vinblastine or vincristine) also has been a preferred regimen, but many clinicians currently consider a liposomal anthracycline (doxorubicin or daunorubicin) the first-line therapy of choice for advanced AIDS-related Kaposi’s sarcoma.

Combination chemotherapy with conventional antineoplastic agents (e.g., bleomycin, conventional doxorubicin, etoposide, vinblastine, vincristine) has been used for more advanced disease (e.g., extensive mucocutaneous disease, lymphedema, symptomatic visceral disease).

A liposomal anthracycline for the treatment of advanced AIDS-related Kaposi’s sarcoma produces similar or higher response rates with a more favorable toxic effects profile than combination therapy with conventional chemotherapeutic agents.

Single-agent vinblastine has been used for the treatment of classic Kaposi's sarcoma.

In combination regimens with cisplatin and methotrexate, with or without doxorubicin, as first- or second-line therapy for invasive and advanced bladder cancer.

In combination with cisplatin and mitomycin (MVP) as an alternative regimen for the treatment of non-small cell lung cancer.

Currently preferred regimens for the treatment of advanced non-small cell lung cancer include the combination of cisplatin or carboplatin, with another agent, such as paclitaxel, docetaxel, vinorelbine, or gemcitabine.

Used in combination regimens (e.g., cisplatin, vinblastine, and dacarbazine, with or without interferon alfa and aldesleukin) for the treatment of metastatic melanoma.

Superiority of combination regimens compared with dacarbazine alone not established, and dacarbazine monotherapy currently is a systemic treatment of choice for metastatic melanoma.

In combination with cisplatin and bleomycin or as monotherapy (second-line) for the treatment of intracranial germ cell tumors.

Has been used in the treatment of immune thrombocytopenic purpura.

Slow IV infusions of vinblastine or the use of vinblastine-loaded platelets has reportedly been effective in some cases for the treatment of autoimmune hemolytic anemia.

Palliative treatment of non-Hodgkin’s lymphomas, including lymphocytic lymphoma (nodular and diffuse, poorly and well differentiated), histiocytic lymphoma, and advanced stages of mycosis fungoides; however, other agents currently are preferred.

Treatment of Letterer-Siwe disease.