NiCARdipine Hydrochloride and Saxagliptin Hydrochloride

• Generic Name: nicardipine
• Dosage Forms: n.a.
• Other Brand Names: Cardene IV, Cardene SR, Cardene

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

Therapy with extended-release capsules generally is preferred because of less frequent dosing, potentially smoother BP control, and concerns raised by experience with short-acting (conventional, immediate-release) nifedipine.

Calcium-channel blockers are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics. While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.

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 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 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.

Calcium-channel blockers may be beneficial in hypertensive patients with certain coexisting conditions (e.g., ischemic heart disease) and in geriatric patients, including those with isolated systolic hypertension.

Calcium-channel blockers may be particularly useful in black patients with hypertension; such patients generally respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to other antihypertensive drug classes (e.g., ACE inhibitors, angiotensin II receptor antagonists). However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.

IV, short-term management of hypertension when oral therapy is not feasible or desirable.

IV management of hypertensive crises (e.g., emergencies) in adults.

IV, rapid reduction of BP in the management of acute severe hypertension and life-threatening symptoms in children and adolescents.

Angina

Management of chronic stable angina pectoris (alone or in combination with other antianginal agents).

• Generic Name: saxagliptin
• Dosage Forms: n.a.
• Other Brand Names: Onglyza

Used as monotherapy as an adjunct to diet and exercise for management of type 2 diabetes mellitus in patients whose hyperglycemia cannot be controlled by diet and exercise alone.

Used in combination with metformin (separately or as fixed combination of saxagliptin and extended-release metformin), a sulfonylurea, a thiazolidinedione (e.g., a peroxisome proliferator-activated receptor-γ [PPAR-γ] agonist) or insulin for management of type 2 diabetes mellitus in patients who do not achieve adequate glycemic control with diet, exercise, and metformin, sulfonylurea, thiazolidinedione monotherapy, and/or insulin. Patients initially receiving an oral antidiabetic agent will eventually require multiple oral antidiabetic agents of different therapeutic classes and/or insulin for adequate glycemic control because of declining β2-cell function with disease progression.

The fixed combination of saxagliptin and dapagliflozin is used as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.

American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) suggests a DPP-4 inhibitor as one of several alternatives for initial monotherapy in patients with metformin contraindications (e.g., renal disease, hepatic disease, GI intolerance, risk of lactic acidosis). DPP-4 inhibitors also recommended as part of combination therapy, particularly with both postprandial and fasting plasma glucose elevations.

Not indicated for type 1 diabetes mellitus or diabetic ketoacidosis; insulin is required in these conditions.