- ACRONYMS AND DEFINITIONS
- AHA/ACC - American Heart Assoc / American College of Cardiology
- ER - Extended-release
- IR - Immediate-release
- NTG - Nitroglycerin
- SL - Sublingual
- VASODILATORS
Hydralazine (Apresoline®)
Dosage forms
Tablet
- 10 mg
- 25 mg
- 50 mg
- 100 mg
Dosing
Hypertension
- Starting: 40 - 100 mg/day given in 3 - 4 divided doses
- Maintenance: 100 - 200 mg/day given in 3 - 4 divided doses
- Max: 300 mg/day
- Increase dose at an interval of 3 - 5 days
- Food increases absorption. Take consistently either with or without food. [2,3]
Heart failure
- In the V-HeFT I and II trials, hydralazine was dosed 37.5 mg four times a day for 2 weeks, then 75 mg four times a day
- In the A-HeFT trial, hydralazine was initially dosed 37.5 mg three times a day, then increased to 75 mg three times a day if tolerated
- Food increases absorption. Take consistently either with or without food. [2,3]
Generic / Price
- YES/$Minoxidil (Loniten®)
Dosage forms
Tablet
- 2.5 mg
- 10 mg
Dosing
Hypertension
- Starting: 5 mg once daily
- Maintenance: 10 - 40 mg/day
- Max: 100 mg/day
- May be given in 1 or 2 divided doses
- Increase dose at intervals of 3 days
- May take without regard to food
Generic / Price
- YES/$Other
- It is recommended that minoxidil be taken with a diuretic and beta blocker because of its side effects
- QUICK-ACTING NITRATES
Nitroglycerin aerosol spray (Nitromist®)
Dosage forms
Aerosol
- 0.4 mg/spray
- Comes in 4.1g (90 sprays) and 8.5g (230 sprays) bottle
Dosing
Acute angina (chest pain)
- 1 - 2 sprays on or under the tongue at the onset of pain. May repeat in 5 minutes if needed.
- No more than 3 sprays are recommended within a 15-minute period
- See quick-acting nitroglycerin dosing
- May take without regard to food
Prevention of angina
- 1 spray 5 - 10 minutes prior to engaging in activity
- May take without regard to food
Generic / Price
- NO/$$$$Other
- Do not shake container
- Spray onto or under the tongue
- Prime bottle with 10 sprays initially. It will remain primed for 6 weeks. May be re-primed with 2 sprays if not used within 6 weeks.
- Do not rinse mouth for 5 - 10 minutes following spray
Nitroglycerin SL powder (GoNitro™)
Dosage forms
Sublingual powder
- 400 mcg per packet
- Comes in box with 12, 36, or 96 packets
Dosing
Acute angina (chest pain)
- Administer one or two packets (400 mcg of NTG) under the tongue at the onset of an attack
- One additional packet may be administered every five minutes as needed
- No more than three packets are recommended within a 15-minute period
- See quick-acting nitroglycerin dosing
Prevention of angina
- 1 packet 5 - 10 minutes prior to engaging in activity
Generic / Price
- NO/$$$$Other
- Administer at rest, ideally in the sitting position
- To administer, empty the contents of a packet under the tongue, close mouth and breath normally. Allow powder to dissolve without swallowing.
- Do not rinse or spit for 5 minutes after dosing
Nitroglycerin SL tablet (Nitrostat®)
Dosage forms
Sublingual tablet
- 0.3 mg
- 0.4 mg
- 0.6 mg
- Comes in bottle with 25 tablets
Dosing
Acute angina (chest pain)
- 1 tablet every 5 minutes up to a total of 3 tablets
- See quick-acting nitroglycerin dosing
- May take without regard to food
Prevention of angina
- 1 tablet 5 - 10 minutes prior to engaging in activity
- May take without regard to food
Generic / Price
- YES/$Other
- Store in original container with cap screwed on tightly
- Drug will lose potency when exposed to light and air
Nitroglycerin spray (Nitrolingual®)
Dosage forms
Spray
- 0.4 mg/spray
- Comes in 4.9g (60 sprays) and 12g (200 sprays) bottle
Dosing
Acute angina (chest pain)
- 1 - 2 sprays onto or under the tongue at the onset of pain. May repeat in 5 minutes if needed.
- No more than 3 sprays are recommended within a 15-minute period
- See quick-acting nitroglycerin dosing
- May take without regard to food
Prevention of angina
- 1 spray 5 - 10 minutes prior to engaging in activity
- May take without regard to food
Generic / Price
- YES/$$-$$$Other
- Do not shake container
- Spray onto or under the tongue
- Avoid swallowing immediately after spray
- Prime bottle with 5 sprays. It will remain primed for 6 weeks.
- Do not rinse mouth for 5 - 10 minutes following spray
- LONG-ACTING NITRATES
Isosorbide dinitrate IR (Isordil®)
Dosage forms
Tablet
- 5 mg
- 10 mg
- 20 mg
- 30 mg
- 40 mg
Dosing
Prevention of angina
- Starting: 5 - 20 mg two to three times a day
- Maintenance: 10 - 40 mg two to three times a day
- Max: 160 mg/day
- Daily dose free interval of at least 14 hours is advised to minimize tolerance
- May take without regard to food
Heart failure
- In the V-HeFT I and II trials, isosorbide dinitrate was dosed 20 mg four times a day for 2 weeks, then 40 mg four times a day
- In the A-HeFT trial, isosorbide dinitrate was initially dosed 20 mg three times a day, then increased to 40 mg three times a day if tolerated
- May take without regard to food
Generic / Price
- YES/$ (#90 tablets)Isosorbide dinitrate ER (Dilatrate-SR®)
Dosage forms
Capsule, extended-release
- 40 mg
Dosing
Prevention of angina
- Dosing: 40 mg once daily
- Max: 160 mg/day
- Twice daily dosing with doses given 6 hours apart has been used in some studies
- Daily dose free interval of at least 18 hours is advised to minimize tolerance
- May take without regard to food
Generic / Price
- NO/$$$Isosorbide mononitrate IR | Monoket® | ISMO®
Dosage forms
Tablet, immediate-release
- 10 mg
- 20 mg
Dosing
Prevention of angina
- Dosing: 20 mg twice a day with the doses given 7 hours apart
- Max: 40 mg/day
- May take without regard to food
Generic / Price
- YES/$Other
- A starting dose of 5 mg twice a day may be appropriate in smaller patients. This dose should be increased to 10 mg by the second or third day of therapy.
- Tablets are scored
Isosorbide mononitrate ER (IMDUR®)
Dosage forms
Tablet, extended-release
- 30 mg
- 60 mg
- 120 mg
Dosing
Prevention of angina
- Starting: 30 - 60 mg once daily
- Maintenance: 60 - 120 mg once daily
- Max: 240 mg/day
- May take without regard to food
Generic / Price
- YES/$Other
- Take dose in morning
- Tablets should not be chewed or crushed
- 30 and 60 mg tablets are scored
Nitroglycerin ointment (Nitro-bid®)
Dosage forms
Ointment
- 2% ointment
- Comes in 30g and 60g tube
- Comes in box of 48 one gram foilpacs (one pack is equivalent to one inch)
Dosing
Prevention of angina
- Starting: Apply 1/2 inch over area of truncal skin in morning and 6 hours later
- Max: 2 inches per dose
- Effective for about 7 hours
- A 10 - 12 hour nitrate-free interval per day is recommended to prevent tolerance
Generic / Price
- Tube - NO/$
- Foilpac (#48) - NO/$$
Other
- One foilpac is equivalent to 1 inch of ointment
- Do not rub into the skin
- Typically applied to chest
- Coverage of an area approximately the size of the dose measuring applicator (3 1/2" by 2 1/4") should be sufficient to obtain the desired clinical effects. A larger area may be used.
- Tape applicator into place
- Ointment may stain clothing
Nitroglycerin patch | Minitran® | Nitro-Dur®
Dosage forms
Patch
- 0.1 mg/hr
- 0.2 mg/hr
- 0.3 mg/hr
- 0.4 mg/hr
- 0.6 mg/hr
- 0.8 mg/hr
- Comes in carton of 30 patches
Dosing
Prevention of angina
- Starting: 0.2 - 0.4 mg/hr patch applied for 12 - 14 hours a day
- Max: 0.8 mg/hr patch
- A 10 - 12 hour patch-free interval per day is recommended to prevent tolerance
Generic / Price
- 0.1, 0.2, 0.4, 0.6 mg/hr - YES/$
- 0.3, 0.8 mg/hr - NO/$$$$
Other
- Apply to reasonably hair-free site
- Typically applied to trunk. Avoid extremities below the knee or elbow, skin folds, scar tissue, burned or irritated areas
- After removing patch, skin may feel warm and appear red. This is normal.
- May shower with patch on
- HYDRALAZINE/ISOSORBIDE (BIDIL®)
Bidil® (hydralazine + isosorbide dinitrate)
Dosage forms
Tablet
- Isosorbide dinitrate - Hydralazine
- 20 mg - 37.5 mg
Dosing
Heart failure in black patients
- Starting: 1 tablet three times a day
- Target: 2 tablets three times a day
- Max: 2 tablets three times a day
- Titrate dose as tolerated
- See A-HeFT trial
- Effect of food on absorption is unknown
Generic / Price
- NO/$$$$Other
- Tablets are scored
- NITRATE PHARMACOKINETICS
Drug | Onset of action | Duration of effect |
---|---|---|
Nitroglycerin spray, tablet, powder | 1 - 3 minutes | around 25 minutes |
Isosorbide dinitrate | about 1 hour | up to 8 hours after one dose |
Isosorbide mononitrate | about 1 hour | up to 12 hours after one dose |
Nitroglycerin ointment | not rapid enough for acute angina | up to 12 hours |
Nitroglycerin patch | steady-state reached in 2 hours | up to 12 hours |
- QUICK-ACTING NITROGLYCERIN DOSING
- Overview
- Quick-acting nitroglycerin includes nitroglycerin tablet (Nitrostat®), sprays (Nitromist®, Nitrolingual®), and powder (GoNitro®)
- Quick-acting nitroglycerin is typically taken at the onset of chest pain
- AHA recommendations for quick-acting nitroglycerin
- Patients with chest pain should take 1 dose of quick-acting nitroglycerin
- If pain is not improved or worsening after 5 minutes, it is recommended that 9-1-1 be called, and further instructions should be taken from them
- If pain is significantly improved after 1 dose, then 2 more doses should be given five minutes apart (total of 3 doses), and 9-1-1 should be called if pain does not resolve completely [4]
- Prophylactically to prevent chest pain (angina)
- Quick-acting nitrates can help to prevent chest pain
- They should be taken 5 - 10 minutes prior to engaging in activities likely to cause chest pain [1]
- Kidney disease dosing
- Hydralazine
- In one study, severe kidney disease did not affect blood levels of hydralazine
- Manufacturer makes no specific dosage recommendations [32]
- Minoxidil
- Minoxidil should be used with caution in patients with significant kidney disease
- Lower doses should be used
- Manufacturer makes no specific dosage recommendations [1]
- Nitrates
- Adjustments are not necessary in patients with kidney disease
- Liver disease dosing
- Hydralazine
- Hydralazine undergoes extensive liver metabolism
- Liver disease would be expected to affect its clearance
- Manufacturer makes no specific dosage recommendations
- Isosorbide dinitrate
- Isosorbide dinitrate undergoes extensive first-pass liver metabolism
- Isosorbide dinitrate undergoes metabolism in the liver and at sites outside of the liver
- The manufacturer makes no specific dosage recommendations in liver disease
- Isosorbide mononitrate
- Isosorbide mononitrate is primarily metabolized by the liver, but unlike oral isosorbide dinitrate, it is not subject to first-pass metabolism
- Liver disease does not appear to affect the clearance of isosorbide mononitrate
- Minoxidil
- Lower doses should be used
- Manufacturer makes no specific dosage recommendations [1]
- Nitroglycerin
- Nitroglycerin undergoes metabolism in the liver and at sites outside of the liver
- The manufacturer makes no specific dosage recommendations in liver disease
- DRUG INTERACTIONS
- NOTE: Drug interactions presented here are NOT all-inclusive. Other interactions may exist. The interactions presented here are meant to encompass commonly prescribed medications and/or interactions that are well-documented. Always consult your physician or pharmacist before taking medications concurrently. CLICK HERE for more information on drug interactions.
- Hydralazine
- MAO inhibitors - MAO inhibitors should be used with caution in patients receiving hydralazine
- Nitrates
- Alcohol - beverage alcohol may potentiate the blood pressure-lowering effect of nitrates
- Aspirin - aspirin has been shown to significantly increase blood levels of nitroglycerin. Vasodilatory and hemodynamic properties of nitroglycerin may be enhanced when taken with aspirin.
- Calcium channel blockers - marked symptomatic orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used in combination
- Dihydroergotamine (Migranal®) - nitrates may increase blood levels of dihydroergotamine and they should not be taken together [20]
- Heparin - IV nitroglycerin may decrease the effect of heparin [25, 26]
- Phosphodiesterase type 5 inhibitors (Viagra®, Cialis®, sildenafil, etc.)- Erectile dysfunction (ED) medications and drugs used to treat pulmonary hypertension should not be taken with nitrates. Dangerously low blood pressure may occur.
- The AHA/ACC makes the following statements about nitrates and ED medications:
- Nitrates should not be taken within 24 hours of sildenafil (Viagra®)
- Nitrates should not be taken within 48 hours of tadalafil (Cialis®)
- The suitable time for the administration of nitrates after vardenafil (Levitra®) has not been determined [22]
- Avanafil (Stendra®) - the avanafil PI states that when nitrate administration is deemed medically necessary in a life-threatening situation, at least 12 hours should elapse after the last dose of avanafil before nitrate administration is considered
- Riociguat (Adempas®) - DO NOT USE nitrates in patients who are taking riociguat. Riociguat stimulates soluble guanylate cyclase (sGC), an enzyme in the cardiopulmonary system and the receptor for nitric oxide. When taken with nitrates, severe hypotension may occur
- Tissue plasminogen activator (t-PA, Activase®, Alteplase®) - IV nitroglycerin has been shown to decrease the effectiveness and blood levels of t-PA. [23, 24]
- Metabolism and clearance
- Hydralazine (Apresoline®)
- CYP2D6 - weak inhibitor
- Isosorbide dinitrate (Isordil®)
- CYP3A4 - substrate
- Isosorbide mononitrate (ISMO®)
- CYP3A4 - substrate
- Minoxidil (Loniten®)
- Primarily metabolized by glucuronidation
- Nitroglycerin (Nitrostat®, etc.)
- Nitroglycerin is metabolized by a reductase enzyme in the liver
- Nitroglycerin also undergoes extrahepatic metabolism in red blood cells and vascular walls
- PRICE ($) INFO
Pricing legend
- $ = 0 - $50
- $$ = $51 - $100
- $$$ = $101 - $150
- $$$$ = > $150
- Pricing based on one month of therapy at standard dosing in an adult
- Pricing based on information from GoodRX.com®
- Pricing may vary by region and availability
- BIBLIOGRAPHY
- 1 - Manufacturer's Package Insert for each drug listed
- 2 - PMID 1706804
- 3 - PMID 1780961
- 4 - PMID 21444888
- 5 - PMID 7572574
- 6 - PMID 7942523
- 7 - PMID 2112878
- 8 - PMID 2121114