Combination Hypertension Treatments

COMBINATION HYPERTENSION TREATMENTS
RECOMMENDATION FOR DRUG COMBINATION IN
UNCOMPLICATED HYPERTENSION†

*Preferred Combination

• ACEI + thiazide

• ACEI + dihydropyridine
CCB

• ARB + thiazide

• ARB + dihydropyridine
CCB

Acceptable
 
Combination

• CCB + thiazide

• Thiazide + K+-sparing
diuretic

• Aliskiren + thiazide or
CCB

• β-blocker + diuretic or
dihydropyridine CCB

NOT Preferred
 
Combination

• ACEI + ARB

• β-blocker + ACEI or ARB

• β-blocker +
nondihydropyridine CCB

• β-blocker + central acting
(clonidine, etc)

Generic Brand Strength Form Usual Adult Dose
*ACE INHIBITOR + THIAZIDE DIURETIC
benazepril/
HCTZ
Lotensin HCT 5mg/6.25mg,
10mg/12.5mg,
20mg/12.5mg,
20mg/25mg
scored tabs To switch from benazepril monotherapy: initially 10/12.5mg once daily. Or, titrate individual components.
captopril/
HCTZ
Capozide 25mg/15mg,
25mg/25mg,
50mg/15mg,
50mg/25mg
scored tabs Take 1hr before meals. As initial therapy: one 25/15 tab daily; adjust at 6wk intervals. Previously titrated: use same doses as individual components. Usual max 150mg captopril, 50mg HCTZ daily.
enalapril/
HCTZ
Vaseretic 10mg/25mg tabs Switching from monotherapy with either component: start with 10/25 once daily, then adjust; max 20mg enalapril/day and 50mg HCTZ/day. Allow 2−3wks for titration of HCTZ component. Or, substitute for individually titrated components.
lisinopril/
HCTZ
Prinzide 10mg/12.5mg,
20mg/12.5mg+
tabs Not for initial therapy. Initially 10mg/12.5mg or 20mg/12.5mg; increase HCTZ dose 2−3wks after. Max 80mg/50mg daily. CrCl <30mL/min: not recommended.
Zestoretic 10mg/12.5mg,
20mg/12.5mg,
20mg/25mg
tabs Switching from monotherapy with either component: initally 10/12.5 or 20/12.5 once daily, then after 2−3wks titrate HCTZ component. If on diuretic: if possible, suspend diuretic for 2−3 days, then adjust. Or, substitute for individually titrated components.
moexipril/
HCTZ
Uniretic 7.5mg/12.5mg,
15mg/12.5mg,
15mg/25mg
scored tabs Take 1hr before a meal. Switching from monotherapy with either component: 1 tab once daily; adjust at 2−3‑week intervals; usual max 30mg/50mg per day. Or, substitute for individually titrated components.
quinapril/
HCTZ
Accuretic 10mg/12.5mg+,
20mg/12.5mg+,
20mg/25mg
tabs Not for initial therapy. Previously titrated: use same doses as individual components. Switching from quinapril monotherapy: initially one 10/12.5 tab or one 20/12.5 tab once daily; allow 2−3wks before increasing HCTZ component. Switching from HCTZ 25mg/day monotherapy: initially one 10/12.5 tab daily or one 20/12.5 tab once daily. Adjust based on response and serum potassium. CrCl ≤30mL/min: not recommended.
ACE INHIBITOR + CALCIUM CHANNEL BLOCKER (DIPHENYLALKYLAMINE)
trandolapril/
verapamil (ext‑rel)
Tarka 1mg/240mg,
2mg/180mg,
2mg/240mg,
4mg/240mg
tabs Titrate individual components. Take with food. 1 tab daily.
ANGIOTENSIN II RECEPTOR BLOCKER + CALCIUM CHANNEL BLOCKER (DIHYDROPYRIDINE) + THIAZIDE DIURETIC
olmesartan/
amlodipine/
HCTZ
Tribenzor 20mg/5mg/
 
12.5mg,
40mg/5mg/
 
12.5mg,
40mg/5mg/
 
25mg,
40mg/10mg/
 
12.5mg,
40mg/10mg/
 
25mg
tabs One tab daily. Titrate at 2‑week intervals; max one 40/10/25mg tablet daily. Replacement therapy: may be substituted for individually titrated components. Add‑on/switch therapy: may be used to provide additional BP lowering for patients not adequately controlled on max tolerated, labeled or usual doses of any two antihypertensive classes: ARBs, CCBs, and diuretics.
*ANGIOTENSIN II RECEPTOR BLOCKER + THIAZIDE DIURETIC
azilsartan/
chlorthalidone
Edarbyclor 40mg/12.5mg,
40mg/25mg
tabs Initially 40/12.5mg once daily. May increase to 40/25mg after 2−4wks as needed. Max: 40/25mg. Patients titrated to the individual components: may give corresponding dose of Edarbyclor. See full labeling.
candesartan/
HCTZ
Atacand HCT 16mg/12.5mg,
32mg/12.5mg,
32mg/25mg
scored tabs Not for initial therapy. May be substituted for titrated components. BP not controlled on HCTZ 25mg once daily, or controlled but serum potassium decreased: one 16/12.5 tab once daily. BP not controlled on candesartan 32mg per day: initially one 32/12.5 tab once daily; may increase to 32/25 once daily. CrCl ≤30mL/min: not recommended.
eprosartan/
HCTZ
Teveten HCT 600mg/12.5mg,
600mg/25mg
tabs Not for initial therapy. May be substituted for titrated components. One 600mg/12.5mg tab once daily; after 2−3wks may increase to one 600mg/25mg tab once daily. May add eprosartan 300mg once daily in the PM if additional BP control is needed at trough.
irbesartan/
HCTZ
Avalide 150mg/12.5mg,
300mg/12.5mg
tabs Take once daily. Not controlled on monotherapy: initially 150/12.5mg, titrate to 300/12.5mg then 300/25mg if needed. Replacement therapy: may be substituted for titrated components. Initial therapy: start at 150/12.5mg for 1−2wks, then titrate as needed up to max 300/25mg. Maximum effects within 2−4wks after dose change. CrCl ≤30mL/min: not recommended.
losartan/
HCTZ
Hyzaar 50mg/12.5mg,
100mg/12.5mg,
100mg/25mg
tabs One 50/12.5mg tab once daily; may increase after about 3wks (2−4wks for severe HTN) to two 50/12.5mg tabs once daily or one 100/25mg tab once daily. Titrate components: see literature. HTN with LVH: switch from losartan monotherapy (see literature). CrCl<30mL/min: not recommended.
olmesartan/
HCTZ
Benicar HCT 20mg/12.5mg,
40mg/12.5mg,
40mg/25mg
tabs Not for initial therapy. May be substituted for titrated components. Individualize. BP not controlled on olmesartan or HCTZ alone: one tab once daily; may titrate at 2−4wk intervals; usual max 40mg/25mg once daily. CrCl ≤30mL/min: not recommended. Volume depleted: reduce dose.
telmisartan/
HCTZ
Micardis HCT 40mg/12.5mg,
80mg/12.5mg,
80mg/25mg
tabs Not for initial therapy. May be substituted for titrated components. BP not controlled on telmisartan 80mg/day: one 80mg/12.5mg tab once daily; may titrate to 160mg/25mg. BP not controlled on HCTZ 25mg/day: one 80mg/12.5mg tab or 80mg/25mg tab once daily; may titrate to 160mg/25mg if BP uncontrolled after 2−4wks. BP controlled on HCTZ 25mg/day but hypokalemic: One 80mg/12.5mg tab once daily. CrCl ≤30mL/min: not recommended. Hepatic insufficiency or biliary obstruction: initially one 40mg/12.5mg tab once daily; monitor closely. Severe renal or hepatic impairment: not recommended.
valsartan/
HCTZ
Diovan HCT 80mg/12.5mg,
160mg/12.5mg,
160mg/25mg,
320mg/12.5mg,
320mg/25mg
tabs Take once daily. Add‑on or initial therapy and not volume-depleted: Initially 160mg/12.5mg; may increase after 1−2wks up to max 320mg/25mg. Replacement therapy: may be substituted for the titrated components. Maximum effects within 2−4wks after dose change. CrCl ≤30mL/min: not recommended.
 
Generic Brand Strength Form Usual Adult Dose
BETA-BLOCKER + THIAZIDE DIURETIC
atenolol/
chlorthalidone
Tenoretic 50mg/25mg+,
100mg/25mg
tabs Switching from monotherapy: initially one 50mg/25mg tab daily; may increase to one 100mg/25mg tab daily. CrCl 15−35mL/min: max 50mg atenolol/day. CrCl <15mL/min: max 50mg atenolol every other day.
bisoprolol/
HCTZ
Ziac 2.5mg/6.25mg,
5mg/6.25mg,
10mg/6.25mg
tabs Initially one 2.5mg/6.25mg tab once daily. Adjust at 14‑day intervals; max two 10mg/6.25mg tabs once daily.
metoprolol tartrate/
HCTZ
Lopressor HCT 50mg/25mg,
100mg/25mg,
100mg/50mg
scored tabs Titrate individual components.
metoprolol succinate extended-release/
HCTZ
Dutoprol 25mg/12.5mg,
50mg/12.5mg,
100mg/12.5mg
tabs Individualize. Take once daily. Titrate as needed every 2wks up to max 200/25mg. Severe renal impairment: not recommended. Moderate hepatic impairment: consider initiating with lower HCTZ component.
nadolol/
bendroflu-
methiazide
Corzide 40mg/5mg,
80mg/5mg
scored tabs Titrate components. Renally impaired: increase dosing interval; see literature.
propranolol/
HCTZ
Inderide 40mg/25mg scored tabs Titrate individual components.
*CALCIUM CHANNEL BLOCKER (DIHYDROPYRIDINE) + ACE INHIBITOR
amlodipine/
benazepril
Lotrel 2.5mg/10mg,
5mg/10mg,
5mg/20mg,
5mg/40mg,
10mg/20mg,
10mg/40mg
caps Not adequately controlled with dihydropyridine CCB, ACE inhibitor, unable to achieve BP control with amlodipine without developing edema: Initially 2.5mg/10mg once daily; may titrate up to 10mg/40mg once daily if BP remains uncontrolled. Replacement therapy: may be substituted for titrated components. CrCl ≤30mL/min: not recommended.
*CALCIUM CHANNEL BLOCKER (DIHYDROPYRIDINE) + ANGIOTENSIN II RECEPTOR BLOCKER
amlodipine/
olmesartan
Azor 5mg/20mg,
5mg/40mg,
10mg/20mg,
10mg/40mg
tabs Take once daily. Initial therapy: initially 5/20mg; may increase after 1−2wks up to max 10mg/40mg; ≥75yrs old or hepatic impairment: not recommended. Replacement therapy: may be substituted for titrated components. Add‑on therapy: may be used if not controlled on monotherapy. Individualize; titrate at 2‑week intervals up to max 10/40mg once daily, usually by increasing dose of one or both components if BP not controlled on prior therapy. Maximum effects within 2wks after dose change.
amlodipine/
telmisartan
Twynsta 5mg/40mg,
5mg/80mg,
10mg/40mg,
10mg/80mg
tabs Take once daily. Initial therapy: 5/40mg or 5/80mg; may titrate at 2‑week intervals to max 10/80mg. Add‑on therapy: may be used if not controlled on monotherapy; if dose-limiting adverse reactions with amlodipine 10mg, switch to 5/40mg tab. Replacement therapy: may be substituted for the titrated components. Renal and/or hepatic impairment: titrate slower. ≥75yrs, or hepatic impairment: not for initial use (initially use amlodipine alone, or add amlodipine 2.5mg to telmisartan).
amlodipine/
valsartan
Exforge 5mg/160mg,
5mg/320mg,
10mg/160mg,
10mg/320mg
tabs Take once daily. Initial therapy and not volume depleted: Initially 5/160mg; may increase after 1−2wks up to max 10/320mg. Add‑on therapy: may be used if not controlled on monotherapy; if inadequate response after 3−4wks, may titrate up to max 10/320mg. Replacement therapy: may be substituted for the titrated components. Maximum effects within 2wks after dose change.
CENTRAL ALPHA-AGONIST + THIAZIDE DIURETIC
methyldopa/
HCTZ
250mg/15mg,
250mg/25mg
tabs Titrate individual components. Initially one 250mg/15mg tab 2−3 times daily or one 250mg/25mg tab 2 times daily.
DIRECT RENIN INHIBITOR + CALCIUM CHANNEL BLOCKER (DIHYDROPYRIDINE)
aliskiren/
amlodipine
Tekamlo 150mg/5mg,
150mg/10mg,
300mg/5mg,
300mg/10mg
tabs Take once daily, consistently with regard to meals. Initially one 150mg/5mg tablet daily. Add‑on: switch when BP is not controlled with aliskiren or any DHP CCB alone. Replacement therapy: switch from previously-titrated components. Titrate at 2−4‑week intervals (slow titration in hepatic impairment or heart failure); max one 300mg/10mg tab daily.
DIRECT RENIN INHIBITOR + CALCIUM CHANNEL BLOCKER (DIHYDROPYRIDINE) + THIAZIDE DIURETIC
aliskiren/
amlodipine/
HTCZ
Amturnide 150/5/12.5mg,
300/5/12.5mg,
300/5/25mg,
300/10/12.5mg,
300/10/25mg
tabs Take once daily. Titrate at 2‑week intervals; max one 300/10/25mg tab daily. Replacement: may substitute for individually titrated components. Add‑on/switch: if not adequately controlled on any two of the following: aliskiren, dihydropyridine CCB, thiazide diuretics. May switch with a lower dose of any component that causes dose-limiting ADRs. ≥75yrs or severe hepatic impairment: initially amlodipine 2.5mg/day (not available). Concomitant simvastatin: see Interactions.
DIRECT RENIN INHIBITOR + THIAZIDE DIURETIC
aliskiren/
HCTZ
Tekturna HCT 150mg/12.5mg,
150mg/25mg,
300mg/12.5mg,
300mg/25mg
tabs Take consistently with regard to meals. 1 tab once daily. Add‑on or initial therapy and not volume-depleted: initially 150mg/12.5mg; may increase after 2−4wks up to max 300mg/25mg. Replacement therapy: substitute for the titrated components.
K+ SPARING DIURETIC + THIAZIDE DIURETIC
amiloride/
HCTZ
5mg/50mg scored tabs Initially 1 tab daily with food. May increase to 2 tabs daily in single or divided doses.
spirono-
lactone/
HCTZ
Aldactazide 25mg/25mg,
50mg/50mg+
tabs Usual maintenance: 50/100mg each of spironolactone and HCTZ daily in single or divided doses.
triamterene/
HCTZ
Dyazide 37.5mg/25mg caps 1−2 caps once daily.
Maxzide 37.5mg/25mg,
75mg/50mg
scored tabs 1−2 tabs of 37.5/25 daily or 1 tab of 75/50 daily.
NOTES

Key: HCTZ = hydrochlorothiazide; + = scored.

Not an inclusive list of medications, official indications, and/or dosing details. Please see drug monograph at www.eMPR.com and/or contact company for full drug labeling.

REFERENCES

†Adapted from Gradman AH, Basile JN, Carter BL, et al. Combination therapy in hypertension. Journal of the American Society of Hypertension 2010; 4:42−50.

(Rev. 7/2015)

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