Quinapril Hydrochloride and Tamoxifen Citrate

• Generic Name: quinapril
• Dosage Forms: n.a.
• Other Brand Names: Accupril

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

ACE inhibitors 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 angiotensin II receptor antagonists, calcium-channel blockers, 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 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 ACE inhibitors. 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.

ACE inhibitors may be preferred in hypertensive patients with heart failure, ischemic heart disease, diabetes mellitus, CKD, or cerebrovascular disease or post-MI.

Heart Failure

Management of heart failure, usually in conjunction with other agents such as cardiac glycosides, diuretics, and β-adrenergic blocking agents (β-blockers).

Some evidence indicates that therapy with an ACE inhibitor (enalapril) may be less effective than angiotensin receptor-neprilysin inhibitor (ARNI) therapy (e.g., sacubitril/valsartan) in reducing cardiovascular death and heart failure-related hospitalization.

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend that patients with chronic symptomatic heart failure and reduced left ventricular ejection fraction (LVEF) (NYHA class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality.

Diabetic Nephropathy

A recommended agent in the management of patients with diabetes mellitus and persistent albuminuria who have modestly elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours) levels of urinary albumin excretion; slows rate of progression of renal disease in such patients.

• Generic Name: tamoxifen
• Dosage Forms: n.a.
• Other Brand Names: Soltamox, Nolvadex

An adjuvant to surgery and radiation therapy for the treatment of breast cancer in women with negative or positive axillary lymph nodes. Also reduces the occurrence of contralateral breast cancer in these women.

Palliative treatment of metastatic breast cancer in women. An alternative to ovarian ablative therapy (oophorectomy or radiation) in premenopausal women. Patients with estrogen receptor-positive tumors are more likely to respond.

Reduction of risk of invasive breast cancer in patients with DCIS following surgery and radiation therapy. Base decision regarding use on an individualized assessment of potential benefits and risks of therapy.

Reduction in the incidence of breast cancer in women at high risk for developing the disease. Base decision regarding use on an individualized assessment of potential benefits and risks of preventive therapy.

ASCO considers tamoxifen an option in premenopausal or postmenopausal women ≥35 years of age with either a 5-year projected risk for developing breast cancer of ≥1.67% (based on Gail risk model) or a history of lobular carcinoma in situ (LCIS).

Data regarding effect on breast cancer incidence in women with inherited mutations (e.g., BRCA1, BRCA2) are insufficient to support recommendations regarding tamoxifen use.

Palliative treatment of metastatic breast cancer in men.

Adjunct to surgery in the treatment of breast cancer in men with positive axillary lymph nodes; used alone or in conjunction with combination chemotherapy.

The high frequency of hormone receptors in tumors of men may explain the high response rate of male breast carcinoma to endocrine therapy. Treatment to date has been similar to that for women with breast cancer; however, experience in men is very limited.

Variations in genes responsible for tamoxifen metabolism may affect treatment decision (e.g., alternative drug or dosage requirement).

Exposure to endoxifen (major active metabolite of tamoxifen) is strongly associated with CYP2D6 metabolizer phenotype, and low endoxifen concentrations are associated with increased risk for disease recurrence in women receiving adjuvant tamoxifen therapy for breast cancer; however, the validity of CYP2D6 metabolizer phenotype as a predictor of the outcome of tamoxifen therapy is controversial.

Although some experts do not recommend use of CYP2D6 genotyping to guide treatment decisions in patients with hormone receptor-positive breast cancer based on available evidence, the Clinical Pharmacogenetics Implementation Consortium (CPIC) and other experts recommend that women with CYP2D6 poor-, intermediate-, or normal/intermediate-metabolizer phenotypes (activity scores of 0–1) receive adjuvant endocrine therapy with an alternative agent (e.g., aromatase inhibitor in postmenopausal women; aromatase inhibitor plus ovarian suppression in premenopausal women). If an aromatase inhibitor is contraindicated, CPIC and these experts state that an increased tamoxifen dosage of 40 mg daily may be considered, but endoxifen concentrations may still be suboptimal in those with a CYP2D6 poor-metabolizer phenotype.

Has been used to reduce the frequency of vaginal bleeding episodes and to reduce the rate of increase in bone age in girls with Albright syndrome (also known as McCune-Albright syndrome) and precocious puberty.

Long-term effects beyond one year not established. (See Pediatric Use under Cautions.)