Combination Treatments for Hypertension
| COMBINATION TREATMENTS FOR HYPERTENSION | ||||
|---|---|---|---|---|
| Generic | Brand & Company | Strengths | Formulation | Usual Adult Dose |
| **ACE INHIBITOR + THIAZIDE DIURETIC | ||||
| benazepril + HCTZ | LOTENSIN HCT
(Novartis) |
5mg/6.25mg
10mg/12.5mg 20mg/12.5mg 20mg/25mg |
scored tabs | To switch from benazepril monotherapy: see literature. Or, titrate individual components. |
| captopril + HCTZ | CAPOZIDE
(Par) |
25mg/15mg
25mg/25mg 50mg/15mg 50mg/25mg |
scored tabs | Take 1 hr before meals. As initial therapy: one 25/15 tab daily; adjust at 6 wk intervals. Previously titrated: use same doses as individual components. Usual max 150mg captopril, 50mg HCTZ daily. |
| enalapril + HCTZ | VASERETIC
(Valeant) |
5mg/25mg | tabs | Switching from monotherapy with either component: start with Vaseretic 10–25 once daily, then adjust; max 20mg enalapril/day and 50mg HCTZ/day. Allow 2–3 weeks for titration of HCTZ component. Or, substitute for individually titrated components. |
| lisinopril + HCTZ | PRINZIDE
(Merck) |
10mg–12.5mg
20mg–12.5mg 20mg–25mg |
tabs | Not for initial therapy. Usual maintenance: 1–2 tabs of 20–12.5 or 20–25 once daily, or 1 tab of 10–12.5 once daily. |
| ZESTORETIC
(AstraZeneca) |
Switching from monotherapy with either component: start with Zestoretic 10–12.5 or 20–12.5 once daily, then adjust. Allow 2–3 weeks for titration of HCTZ component. If on diuretic: if possible, suspend diuretic for 2–3 days, then adjust. Or, substitute for individually titrated components. | |||
| moexipril + HCTZ | UNIRETIC
(UCB) |
7.5mg/12.5mg
15mg/12.5mg 15mg/25mg |
scored tabs | Not for initial therapy. Take 1 hour 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
(Pfizer) |
10mg/12.5mg†
20mg/12.5mg† 20mg/25mg |
tabs
(† = scored) |
Not for initial therapy. Previously titrated: use same doses as individual components. Switching from quinapril monotherapy: initially one Accuretic 10/12.5 tab or one Accuretic 20/12.5 tab once daily; allow 2–3 weeks before increasing HCTZ component. Switching from HCTZ 25mg/day monotherapy: initially one Accuretic 10/12.5 tab daily or one Accuretic 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
(AbbVie) |
1mg/240mg
2mg/180mg 2mg/240mg 4mg/240mg |
tabs | Not for initial therapy. Titrate individual components. Take with food. ≥18yrs: 1 tab daily. |
| **ANGIOTENSIN II RECEPTOR BLOCKER + CALCIUM CHANNEL BLOCKER (DIHYDROPYRIDINE) | ||||
| telmisartan + amlodipine | TWYNSTA
(Boehringer Ingelheim) |
40mg/5mg
40mg/10mg 80mg/5mg 80mg/10mg |
tabs | Take once daily. Initial therapy: 40/5mg or 80/5mg; may titrate at 2-week intervals to max 80/10mg. Add-on therapy: may be used if not controlled on monotherapy; if dose-limiting adverse reactions with amlodipine 10mg, switch to 40/5mg 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). |
| ANGIOTENSIN II RECEPTOR BLOCKER + CALCIUM CHANNEL BLOCKER (DIHYDROPYRIDINE) + THIAZIDE DIURETIC | ||||
| olmesartan + amlodipine + HCTZ | TRIBENZOR
(Daiichi Sankyo) |
20mg/5mg/12.5mg
40mg/5mg/12.5mg 40mg/5mg/25mg 40mg/10mg/12.5mg 40mg/10mg/25mg |
tabs | One tablet 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
(Takeda) |
40mg/12.5mg
40mg/25mg |
tabs | Initially 40/12.5mg once daily. May increase to 40/25mg after 2–4 weeks as needed. Max: 40/25mg. Patients titrated to the individual components: may give corresponding dose of Edarbyclor. See literature. |
| candesartan + HCTZ | ATACAND HCT
(AstraZeneca) |
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 Atacand HCT 16–12.5 tab once daily. BP not controlled on candesartan 32mg per day: initially one Atacand HCT 32–12.5 tab once daily; may increase to 32–25 once daily. CrCl ≤30mL/min: not recommended. |
| eprosartan + HCTZ | TEVETEN HCT
(AbbVie) |
600mg/12.5mg
600mg/25mg |
tabs | Not for initial therapy. May be substituted for titrated components. One Teveten HCT 600mg/12.5mg tab once daily; after 2–3 weeks may increase to one Teveten HCT 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
(Sanofi Aventis) |
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 1–2 weeks, then titrate as needed up to max 300/25mg. Maximum effects within 2–4 weeks after dose change. CrCl ≤30mL/min: not recommended. |
| losartan + HCTZ | HYZAAR
(Merck) |
50mg–12.5mg
100mg–12.5mg 100mg–25mg |
tabs | ≥18yrs: One 50–12.5mg tab once daily; may increase after about 3 weeks (2–4 weeks 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
(Daiichi Sankyo) |
20mg/12.5mg
40mg/12.5mg 40mg/25mg |
tabs | Not for initial therapy. May be substituted for titrated components. Individualize. ≥18yrs: BP not controlled on olmesartan or HCTZ alone: one tab once daily; may titrate at 2–4 week intervals; usual max 40mg/25mg once daily. CrCl ≤ 30mL/min: not recommended. Volume depleted: reduce dose. |
| telmisartan + HCTZ | MICARDIS HCT
(Boehringer Ingelheim) |
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 Micardis HCT 80mg/12.5mg tab once daily; may titrate to 160mg/25mg. BP not controlled on HCTZ 25mg/day: one Micardis HCT 80mg/12.5mg tab or 80mg/25mg tab once daily; may titrate to 160mg/25mg if BP uncontrolled after 2–4 weeks. BP controlled on HCTZ 25mg/day but hypokalemic: One Micardis HCT 80mg/12.5mg tab once daily. CrCl ≤30mL/min: not recommended. Hepatic insufficiency or biliary obstruction: initially one Micardis HCT 40mg/12.5mg tab once daily; monitor closely. Severe hepatic impairment: not recommended. |
| valsartan + HCTZ | DIOVAN HCT
(Novartis) |
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 1–2 weeks up to max 320mg/25mg. Replacement therapy: may be substituted for the titrated components. Maximum effects within 2–4 weeks after dose change. CrCl ≤30mL/min: not recommended. |
| β-BLOCKER + THIAZIDE DIURETIC | ||||
| atenolol + chlorthalidone | TENORETIC
(AstraZeneca) |
50mg/25mg†
100mg/25mg |
tabs
(†= scored) |
Switching from monotherapy: initially one Tenoretic 50 tab daily; may increase to one Tenoretic 100 tab daily. CrCl 15–35mL/min: max 50mg atenolol/day. CrCl <15mL/min: max 50mg atenolol every other day. |
| bisoprolol + HCTZ | ZIAC
(Teva) |
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 (20mg bisoprolol + 12.5mg HCTZ) once daily. |
| metoprolol tartrate + HCTZ | LOPRESSOR HCT
(Novartis) |
50mg/25mg
100mg/25mg 100mg/50mg |
scored tabs | Titrate individual components. |
| metoprolol succinate extended-release + HCTZ | DUTOPROL
(AstraZeneca) |
25mg/12.5mg
50mg/12.5mg 100mg/12.5mg |
tabs | Individualize. Take once daily. Titrate individual components. Severe renal impairment: not recommended. Moderate hepatic impairment: consider initiating with lower HCTZ component. |
| nadolol + bendroflumethiazide | CORZIDE
(King) |
40mg/5mg
80mg/5mg |
scored tabs | Titrate components. Renally impaired: increase dosing interval; see literature. |
| propranolol + HCTZ | INDERIDE
(Akrimax) |
40mg/25mg | scored tabs | Titrate individual components. |
| **CALCIUM CHANNEL BLOCKER (DIHYDROPYRIDINE) + ACE INHIBITOR | ||||
| amlodipine + benazepril | LOTREL
(Novartis) |
2.5mg/10mg
5mg/10mg 5mg/20mg 5mg/40mg 10mg/20mg 10mg/40mg |
caps | Not for initial therapy. Titrate components (amlodipine or another dihydropyridine CCB, or benazepril or another ACEI). CrCl ≤30mL/min per 1.73m²: not recommended. Hepatic impairment, or small, elderly, or frail patients: initially 2.5mg/10mg strength. |
| **CALCIUM CHANNEL BLOCKER (DIHYDROPYRIDINE) + ANGIOTENSIN II RECEPTOR BLOCKER | ||||
| amlodipine + olmesartan | AZOR
(Daiichi Sankyo) |
5mg/20mg
5mg/40mg 10mg/20mg 10mg/40mg |
tabs | Take once daily. Initial therapy: initially 5/20mg; may increase after 1–2 weeks 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 2 weeks after dose change. |
| amlodipine + valsartan | EXFORGE
(Novartis) |
5mg/160mg
5mg/320mg 10mg/160mg 10mg/320mg |
tabs | Take once daily. Initial therapy and not volume depleted: Initially 5/160mg; may increase after 1–2 weeks up to max 10/320mg. Add-on therapy: may be used if not controlled on monotherapy; if inadequate response after 3–4 weeks, may titrate up to max 10/320mg. Replacement therapy: may be substituted for the titrated components. Maximum effects within 2 weeks after dose change. |
| CENTRAL α-AGONIST + THIAZIDE DIURETIC | ||||
| methyldopa + HCTZ | ALDORIL
(Merck) |
250mg/15mg
250mg/25mg |
tabs | Titrate individual components. Initially 1 Aldoril 15 tab 2–3 times daily or 1 Aldoril 25 tab twice daily or 1 Aldoril D30 tab once daily or 1 Aldoril D50 tab once daily. |
| ALDORIL D
(Merck) |
500mg/30mg
500mg/50mg |
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| DIRECT RENIN INHIBITOR + ANGIOTENSIN II RECEPTOR BLOCKER | ||||
| aliskiren + valsartan | VALTURNA
(Novartis) |
150mg/160mg
300mg/320mg |
tabs | Take consistently with regard to meals. 1 tablet once daily. Add-on or initial therapy and not volume-depleted: initially 150/160mg; may increase after 2–4 weeks to max 300/320mg. Replacement therapy: substitute for the titrated components. |
| DIRECT RENIN INHIBITOR + CALCIUM CHANNEL BLOCKER (DIHYDROPYRIDINE) | ||||
| aliskiren + amlodipine | TEKAMLO
(Novartis) |
150mg/5mg
150mg/10mg 300mg/5mg 300mg/10mg |
tabs | Give once daily, consistently with regard to meals. Initial therapy: 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 to 4-week intervals (slow titration in hepatic impairment or heart failure); max one 300mg/10mg tablet daily. |
| DIRECT RENIN INHIBITOR + CALCIUM CHANNEL BLOCKER (DIHYDROPYRIDINE) + THIAZIDE DIURETIC | ||||
| aliskiren + amlodipine + HTCZ | AMTURNIDE
(Novartis) |
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 tablet 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. ≥75 years or severe hepatic impairment: initially amlodipine 2.5mg/day (not available). Concomitant simvastatin: see Interactions. |
| DIRECT RENIN INHIBITOR + THIAZIDE DIURETIC | ||||
| aliskiren + HCTZ | TEKTURNA HCT
(Novartis) |
150mg/12.5mg
150mg/25mg 300mg/12.5mg 300mg/25mg |
tabs | Take consistently with regard to meals (absorption reduced by high-fat meals). ≥18yrs: 1 tablet once daily. Add-on or initial therapy and not volume-depleted: initially 150mg/12.5mg; may increase after 2–4 weeks up to max 300mg/25mg. Replacement therapy: substitute for the titrated components. Max effect usually seen at 4 weeks. |
| DIURETIC COMBINATION (K+ SPARING + THIAZIDE) | ||||
| amiloride + HCTZ | (Various) | 5mg/50mg | scored tabs | Initially 1 tab daily with food. May increase to 2 tabs daily in single or divided doses. |
| spironolactone + HCTZ | ALDACTAZIDE
(Pfizer) |
25mg/25mg
50mg/50mg† |
tabs
(†= scored) |
Usual maintenance: 50–100mg each of spironolactone and HCTZ daily in single or divided doses. |
| triamterene + HCTZ | DYAZIDE
(GSK) |
37.5mg/25mg | caps | 1–2 caps once daily. |
| MAXZIDE
(Bertek) |
37.5mg/25mg
75mg/50mg |
scored tabs | 1–2 tab(s) of 37.5/25 daily or 1 tab of 75/50 daily. | |
| NOTES | ||||
|
Caps = capsules; tabs = tablets; ext-rel = extended-release; HCTZ = hydrochlorothiazide. Regimens shown are from manufacturer's suggested guidelines. Doses should be individualized. Some of the products listed above have additional indications. See Alphabetical and Section indexes. |
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| RECOMMENDATION FOR DRUG COMBINATION IN UNCOMPLICATED HYPERTENSION¹ | ||||
| **Preferred Combination
• ACEI + thiazide • ACEI + dihydropyridine CCB • ARB + thiazide • ARB + dihydropyridine CCB |
Acceptable Combination
• CCB + thiazide • Thiazide + potassium-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) |
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|
ACEI = angiotensin-converting enzyme inhibitor; CCB = calcium channel blocker; ARB = angiotensin II receptor blocker ¹Adapted 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. 4/2013) |
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