Indinavir Sulfate and Methyldopate hydrochloride

• Generic Name: indinavir
• Dosage Forms: n.a.
• Other Brand Names: Crixivan

Treatment of HIV infection in adults, adolescents, and pediatric patients; used in conjunction with other antiretrovirals.

Experts state indinavir not recommended for initial treatment regimens in antiretroviral-naive adults and adolescents because of inconvenient dosing regimen, fluid requirements, and toxicities (e.g., nephrolithiasis, crystalluria).

Indinavir with low-dose ritonavir (ritonavir-boosted indinavir) not recommended for initial therapy in antiretroviral-naive adults and adolescents because of fluid requirements and toxicities (e.g., nephrolithiasis, crystalluria).

Indinavir (with or without low-dose ritonavir) not recommended for initial treatment regimens in antiretroviral-naive pediatric patients because of high incidence of hematuria, sterile leukocyturia, and nephrolithiasis in children.

• Generic Name: methyldopa
• Dosage Forms: n.a.
• Other Brand Names: Aldomet

Used alone or in combination with other classes of antihypertensive agents in the management of hypertension.

Not considered a preferred agent for initial management of hypertension according to current guidelines for the management of hypertension in adults, but may be used as add-on therapy if BP not adequately controlled with the recommended antihypertensive drug classes (i.e., ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, thiazide diuretics).

Generally reserved as a last-line treatment option because of the drug's ability to cause substantial adverse CNS effects, especially in geriatric patients.

May be more effective when used with a diuretic.

Use of a diuretic may prevent tolerance to methyldopa and permit reduction of methyldopa dosage.

Also has been used with other hypotensive agents, permitting a reduction in the dosage of each drug and, in some patients, minimizing adverse effects while maintaining BP control.

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 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. Consider initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes in patients with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.

Recommended by ACOG and other experts as an appropriate drug of choice in pregnant women who require antihypertensive therapy.

Hypertensive Crises

Has been used IV for the management of hypertensive crises. Because of the slow onset of action, other agents (e.g., labetalol, esmolol, fenoldopam, nicardipine, sodium nitroprusside) are preferred.