Hypertension:
Children <6 years: Limited data available: Oral: Initial: 0.1 mg/kg/dose once daily; titrate based on clinical response; maximum daily dose: 0.6 mg/kg/day or 5 mg/day (Ref).
Children ≥6 years and Adolescents: Oral: Initial: 2.5 mg once daily; titrate based on clinical response; maximum daily dose: 10 mg/day (Ref).
Raynaud phenomenon, treatment: Very limited data available:
Children ≥6 years and Adolescents: Oral: Usual dosage range: 2.5 to 10 mg once daily; start dose low and increase as tolerated and based on symptom response (Ref). Note: In addition to nonpharmacologic interventions (eg, cold avoidance), dihydropyridine calcium channel blockers are recommended for management; although nifedipine has the most data and is generally used first-line, amlodipine is an acceptable alternative (Ref).
Children ≥6 years and Adolescents: No dosage adjustment necessary.
There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling; based on prolonged half-life in severe hepatic impairment and experience in adult patients, dosing adjustment and slow titration suggested.
(For additional information see "Amlodipine: Drug information")
Angina:
Chronic stable angina (alternative agent):
Note: A beta-blocker is the preferred initial therapy; if there are ongoing symptoms on beta-blocker therapy, a long acting dihydropyridine calcium channel blocker (eg, amlodipine) may be added; amlodipine may also be used as an alternative therapy if there are contraindications or unacceptable adverse effects with beta-blockade (Ref).
Oral: 5 to 10 mg once daily.
Vasospastic angina:
Note: May use alone or in combination with nitrates (Ref).
Oral: 5 to 10 mg once daily.
Hypertension, chronic:
Note: For patients who warrant combination therapy (BP >20/10 mm Hg above goal or suboptimal response to monotherapy), may use with another appropriate agent (eg, angiotensin-converting enzyme [ACE] inhibitor, angiotensin II receptor blocker [ARB], or thiazide diuretic) (Ref).
Oral: Initial: 2.5 to 5 mg once daily; evaluate response after ~2 to 4 weeks and titrate dose, as needed, up to a maximum of 10 mg once daily; if additional blood pressure control is needed, consider combination therapy (Ref); antihypertensive effect attenuates with higher doses and adverse effects may become more prominent. Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (Ref).
Raynaud phenomenon (off-label use): Oral: 5 mg once daily; if needed, increase dose gradually based on patient response and tolerability, usually once every 4 weeks, but not more frequently than once every 7 to 10 days; monitor blood pressure closely with each dose increase; maximum dose: 20 mg/day (Ref).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Poorly dialyzed: No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Note: Elimination half-life is approximately doubled and AUC increased ~1.4 times in patients with Child-Turcotte-Pugh class A (Ref). Calcium channel blockers may produce additional mesenteric vasodilation that may worsen portopulmonary hypertension especially in severe liver insufficiency (Ref).
Liver impairment prior to treatment initiation:
Initial or dose adjustment in patients with preexisting liver cirrhosis:
Child-Turcotte-Pugh class A to B: Oral: Initial: 2.5 mg once daily; if needed, may increase dose based on tolerability and response in increments of 2.5 mg/day, no more frequently than every 14 days; maximum dose: 10 mg/day (Ref).
Child-Turcotte-Pugh class C: Avoid use (Ref).
Liver impairment developing in patient already receiving amlodipine:
Chronic disease progression (eg, outpatient):
Baseline to Child-Turcotte-Pugh class A to C: No dosage adjustment necessary; if needed, adjust dose based on response (eg, blood pressure target) and tolerability (Ref).
Acute worsening of liver function (eg, requiring hospitalization):
Baseline to Child-Turcotte-Pugh class A to C: No dosage adjustment necessary; if needed, adjust dose based on response (eg, blood pressure target) and tolerability (Ref).
Peripheral edema is the most common adverse reaction with amlodipine, characterized by ankle and leg swelling independent of fluid retention (Ref). It is a bothersome adverse reaction for patients and may lead to discontinuation (Ref). Peripheral edema can be expected to subside within several days following intervention.
Mechanism: Dose-and time-related; related to the pharmacologic action. Calcium channel blocker-mediated peripheral edema is caused by arteriolar vasodilation that subsequently leads to increased hydrostatic pressure in the precapillary circulation and fluid movement from the capillary vasculature to the interstitial space (Ref). In addition, impaired postural vasoconstriction may contribute (Ref).
Onset: Varied; has been reported between 4 weeks to >6 months after initiation (Ref).
Risk factors:
• Dose-related; doses of 2.5 to 5 mg resulted in lower rates of edema versus 10 mg (Ref); however, may develop more frequently and at lower doses in patients with impaired postural autoregulation (eg, diabetes, arterial disease) (Ref).
• Duration-related (>6 months) (Ref)
• Females
• Dihydropyridine calcium channel blockers (DHPs) versus non-DHPs (Ref)
• Lipophilic DHPs (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Cardiovascular: Peripheral edema (2% to 11%, dose related; females: 15%; males: 6%) (table 1)
Drug (Amlodipine) |
Placebo |
Population |
Dose |
Number of Patients (Amlodipine) |
Number of Patients (Placebo) |
---|---|---|---|---|---|
15% |
5% |
Females |
N/A |
512 |
336 |
6% |
1% |
Males |
N/A |
1,218 |
914 |
11% |
0.6% |
N/A |
10 mg/day |
268 |
520 |
3% |
0.6% |
N/A |
5 mg/day |
296 |
520 |
2% |
0.6% |
N/A |
2.5 mg/day |
275 |
520 |
1% to 10%:
Cardiovascular: Flushing (≤3%, dose related, more frequent in females), palpitations (≤5%, dose related, more frequent in females)
Dermatologic: Pruritus (≤2%), skin rash (≤2%)
Gastrointestinal: Abdominal pain (2%), nausea (3%)
Genitourinary: Male sexual disorder (≤2%)
Nervous system: Asthenia (≤2%), dizziness (doses ≥5 mg/day: 3%), drowsiness (1% to 2%), fatigue (5%)
Neuromuscular & skeletal: Muscle cramps (≤2%)
Respiratory: Dyspnea (≤2%)
<1%:
Cardiovascular: Peripheral ischemia, sinus tachycardia, syncope, vasculitis
Dermatologic: Diaphoresis, erythema multiforme
Endocrine & metabolic: Hot flash, hyperglycemia, weight gain, weight loss
Gastrointestinal: Anorexia, constipation, dysphagia, flatulence, gingival hyperplasia, pancreatitis, vomiting, xerostomia
Genitourinary: Difficulty in micturition, female sexual disorder, nocturia, urinary frequency
Hematologic & oncologic: Leukopenia, purpuric disease, thrombocytopenia (Ref)
Hypersensitivity: Angioedema, hypersensitivity reaction
Nervous system: Abnormal dreams, anxiety, depersonalization, depression, hypoesthesia, insomnia, malaise, pain, paresthesia, peripheral neuropathy, rigors, tremor, vertigo
Neuromuscular & skeletal: Arthralgia, back pain, myalgia, osteoarthritis
Ophthalmic: Conjunctivitis, diplopia, eye pain
Otic: Tinnitus
Respiratory: Epistaxis
Postmarketing:
Cardiovascular: Atrioventricular node dysfunction (BRASH syndrome: Bradycardia, renal failure syndrome, atrioventricular block, shock, hyperkalemia) (Ref)
Dermatologic: Dermatologic disorder (Schamberg's disease) (Ref), psoriasis (Ref), toxic epidermal necrolysis (Ref)
Endocrine & metabolic: Gynecomastia (Ref)
Gastrointestinal: Gingival hyperplasia (Ref)
Hepatic: Ascites (Ref), cholestatic hepatitis (Ref), hepatotoxicity (Ref)
Nervous system: Akathisia (Ref), parkinsonism (Ref), tardive dystonia (Ref)
Neuromuscular & skeletal: Subacute cutaneous lupus erythematosus (Ref)
Renal: Acute interstitial nephritis (Ref)
Hypersensitivity to amlodipine or any component of the formulation.
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to other dihydropyridines; severe hypotension (systolic BP <90 mm Hg); breastfeeding; shock (including cardiogenic shock); obstruction of the outflow tract of the left ventricle (eg, high-grade aortic stenosis); hemodynamically unstable heart failure after acute myocardial infarction; hereditary fructose intolerance (oral solution); hyperglycerolemia or glycerol kinase deficiency (oral solution).
Concerns related to adverse effects:
• Hypotension: Symptomatic hypotension can occur; acute hypotension upon initiation is unlikely due to the gradual onset of action. Blood pressure must be lowered at a rate appropriate for the patient's clinical condition.
Disease-related concerns:
• Aortic stenosis: Use amlodipine with extreme caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia.
• Heart failure: With the exception of amlodipine, calcium channel blockers should be avoided whenever possible in patients with heart failure with reduced ejection fraction (HFrEF). Amlodipine may be used for the treatment of hypertension or ischemic heart disease in patients with HFrEF, but has no effect on functional status or mortality (AHA/ACC/HFSA [Heidenreich 2022]).
• Hepatic impairment: Use with caution in patients with mild to moderate hepatic impairment; may require lower starting dose; avoid use in patients with severe hepatic impairment. Also, may worsen portopulmonary hypertension especially in severe liver insufficiency (Bozbas 2016).
• Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction: Use amlodipine with caution in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (AHA/ACC [Ommen 2024]).
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP 1997; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Ethanol: Oral solution contains 4% v/v ethyl alcohol.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Special populations:
• Older adult: Initiate at a lower dose in the elderly.
Other warnings/precautions:
• Titration: Peak antihypertensive effect is delayed; dosage titration should occur after 7 to 14 days on a given dose.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral, as besylate [strength expressed as base]:
Norliqva: 1 mg/mL (150 mL) [contains alcohol, usp]
Suspension, Oral, as benzoate [strength expressed as base]:
Katerzia: 1 mg/mL (150 mL) [contains polysorbate 80, sodium benzoate]
Tablet, Oral, as besylate [strength expressed as base]:
Norvasc: 2.5 mg, 5 mg, 10 mg
Generic: 2.5 mg, 5 mg, 10 mg
May be product dependent
Solution (Norliqva Oral)
1 mg/mL (per mL): $4.12
Suspension (Katerzia Oral)
1 mg/mL (per mL): $5.12
Tablets (amLODIPine Besylate Oral)
2.5 mg (per each): $0.06 - $1.92
5 mg (per each): $0.06 - $1.93
10 mg (per each): $0.07 - $2.38
Tablets (Norvasc Oral)
2.5 mg (per each): $10.37
5 mg (per each): $10.37
10 mg (per each): $14.22
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral, as besylate [strength expressed as base]:
Generic: 1 mg/mL (150 mL)
Tablet, Oral, as besylate [strength expressed as base]:
Norvasc: 5 mg, 10 mg
Generic: 2.5 mg, 5 mg, 10 mg
Note: Commercial oral liquid preparations are available (1 mg/mL).
1 mg/mL Oral Suspension
A 1 mg/mL oral suspension may be made with tablets and either a 1:1 mixture of simple syrup and 1% methylcellulose or a 1:1 mixture of Ora-Plus and Ora-Sweet. Crush fifty 5 mg tablets in a mortar and reduce to a fine powder. Add small portions of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 250 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 250 mL. Label "shake well" and "refrigerate". Stable for 56 days at room temperature or 91 days refrigerated.
The following feeding tube recommendations are based upon the best available evidence and clinical expertise. Senior editor panel: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter, PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang, MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN.
Note: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties that may vary among products from different manufacturers.
Oral: May be administered without regard to food.
Oral solution (commercially available): Administer with an accurate measuring device (calibrated oral syringe or measuring cup); do not use a household teaspoon or tablespoon to measure dose (overdosage may occur).
Administration via feeding tube:
Gastric (eg, NG, G-tube) or post-pyloric tubes (eg, J-tube): Dilute dose with at least an equivalent volume of purified water to reduce osmolality and viscosity; some experts recommend diluting in a volume of purified water that is twice the amlodipine solution volume (eg, 10 mL amlodipine solution diluted in 20 mL purified water) immediately prior to administering. Draw up diluted solution into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Undiluted Norliqva has a reported osmolality of ~1,476 mOsm/kg (per the manufacturer); oral solutions with an osmolality >600 mOsm/kg may increase the probability of adverse GI effects (eg, diarrhea, cramping, abdominal distention, slowed gastric emptying), particularly if administered post-pylorically, inadequately diluted, and/or used in at-risk patients (eg, neonates and infants, patients with short bowel syndrome) (Ref).
General guidance: Hold enteral nutrition during amlodipine administration (Ref). Flush feeding tube with the lowest volume of purified water necessary to clear the tube prior to administration based on size of patient and/or feeding tube (eg, neonates: 1 to 3 mL; infants and children: 2 to 5 mL; adolescents: 15 mL); refer to institutional policies and procedures (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (Ref).
Oral suspension (commercially available): Shake well before using. Administer with an accurate measuring device (calibrated oral syringe or measuring cup); do not use a household teaspoon or tablespoon to measure dose (overdosage may occur).
Administration via feeding tube:
Gastric (eg, NG, G-tube) or post-pyloric tubes (eg, J-tube): Shake suspension well prior to drawing up dose for dilution. Dilute dose in volume of purified water that is twice the amlodipine suspension volume (eg, 10 mL amlodipine suspension diluted in 20 mL purified water) immediately prior to administration. Draw up diluted suspension into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Although there is no information available on the osmolality of amlodipine oral suspension, this product may have elevated osmolality which could impact tolerance; consider the potential risks versus benefits prior to use (Ref).
General guidance: Hold enteral nutrition during amlodipine administration (Ref). Flush feeding tube with the lowest volume of purified water necessary to clear the tube prior to administration based on size of patient and/or feeding tube (eg, neonates: 1 to 3 mL; infants and children: 2 to 5 mL; adolescents: 15 mL); refer to institutional policies and procedures (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (Ref).
Tablets :
Administration via feeding tube:
Gastric tubes (eg, NG, G-tube) or post-pyloric tubes (eg, J-tube) (≥8 French): Crush and disperse tablet in 10 mL purified water; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
General guidance: Hold enteral nutrition during amlodipine administration (Ref). Flush feeding tube with the lowest volume of purified water necessary to clear the tube prior to administration based on size of patient and/or feeding tube (eg, neonates: 1 to 3 mL; infants and children: 2 to 5 mL; adolescents: 15 mL); refer to institutional policies and procedures (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (Ref).
Oral: Administer without regard to meals. Shake suspension well before using. Administer with an accurate measuring device (calibrated oral syringe or measuring cup); do not use a household teaspoon to measure dose.
Enteral feeding tube:
The following recommendations are based upon the best available evidence and clinical expertise. Senior editorial team: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter, PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang, MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN.
Oral solution (commercially available):
Gastric (eg, NG, G-tube ) or post-pyloric (eg, J-tube) tubes: Dilute dose with at least an equivalent volume of purified water prior to administering to reduce osmolality and viscosity; some experts recommend diluting in a volume of purified water that is twice the amlodipine solution volume (eg, 10 mL amlodipine solution diluted in 20 mL purified water) immediately prior to administration. Draw up diluted solution into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: One undiluted oral solution has been reported to have an osmolality of ~1,500 mOsm/kg (per the manufacturer); oral solutions with an osmolality >600 mOsm/kg may increase the probability of adverse GI effects (eg, diarrhea, cramping, abdominal distention, slowed gastric emptying), particularly if administered post-pylorically, inadequately diluted, and/or used in at-risk patients (eg, neonates and infants, patients with short bowel syndrome) (Ref).
General guidance: Hold enteral nutrition during amlodipine administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) and restart enteral nutrition (Ref).
Oral suspension (commercially available):
Gastric (eg, NG, G-tube) or post-pyloric (eg, J-tube) tubes: Shake suspension well prior to drawing up dose for dilution. Dilute dose in volume of purified water that is twice the amlodipine suspension volume (eg, 10 mL amlodipine suspension diluted in 20 mL purified water) immediately prior to administration. Draw up diluted suspension into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Although there is no information available on the osmolality of amlodipine oral suspension, this product may have elevated osmolality which could impact tolerance; consider the potential risks versus benefits prior to use (Ref).
General guidance: Hold enteral nutrition during amlodipine administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) and restart enteral nutrition (Ref).
Oral tablets:
Gastric (eg, NG, G-tube) or post-pyloric (eg, J-tube) tubes (≥8 French): Crush and disperse tablet in 10 mL purified water; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
General guidance: Hold enteral nutrition during amlodipine administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) and restart enteral nutrition (Ref).
No te: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties among manufacturers.
Solution: Store at 20°C to 25°C (68°F to 77°F); excursion permitted to 15°C to 30°C (59°F to 86°F). Store and dispense in original container.
Suspension: Store at 2°C to 8°C (36°F to 46°F); avoid freezing and excessive heat. Protect from light.
Tablets: Store at 15°C to 30°C (59°F to 86°F).
Treatment of hypertension (FDA approved in ages ≥6 years and adults); chronic stable angina (FDA approved in adults); vasospastic (Prinzmetal) angina (FDA approved in adults); angiographically documented coronary artery disease (to decrease risk of hospitalization [due to angina] and coronary revascularization procedure) (FDA approved in adults); has also been used in the treatment of Raynaud phenomenon.
AmLODIPine may be confused with aMILoride
Norvasc may be confused with Navane, Norvir, Vascor
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (pediatric liquid medications requiring measurement) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
Norvasc [US, Canada, and multiple international markets] may be confused with Vascor brand name for imidapril [Philippines] and simvastatin [Malaysia, Singapore, and Thailand]
Amlodipine is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) with symptomatic aortic stenosis (O’Mahony 2023).
Substrate of CYP3A4 (Major with inhibitors), CYP3A4 (Minor with inducers); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (Weak);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of ALPRAZolam. Risk C: Monitor
Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification
Amphetamines: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Atosiban: Calcium Channel Blockers may increase adverse/toxic effects of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Risk C: Monitor
Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Brigatinib: May decrease antihypertensive effects of Antihypertensive Agents. Brigatinib may increase bradycardic effects of Antihypertensive Agents. Risk C: Monitor
Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
Calcium Salts: May decrease therapeutic effects of Calcium Channel Blockers. Risk C: Monitor
CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase serum concentration of CarBAMazepine. Risk C: Monitor
Charcoal, Activated: May decrease serum concentration of AmLODIPine. Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CycloSPORINE (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of AmLODIPine. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of AmLODIPine. Risk C: Monitor
CYP3A4 Inhibitors (Moderate): May increase serum concentration of AmLODIPine. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of AmLODIPine. Risk C: Monitor
Dantrolene: May increase hyperkalemic effects of Calcium Channel Blockers. Dantrolene may increase negative inotropic effects of Calcium Channel Blockers. Risk X: Avoid
Dapoxetine: May increase orthostatic hypotensive effects of Calcium Channel Blockers. Risk C: Monitor
Dexmethylphenidate: May decrease therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor
Finerenone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Finerenone. Risk C: Monitor
Flibanserin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Flibanserin. Risk C: Monitor
Flunarizine: May increase therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Herbal Products with Blood Pressure Increasing Effects: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Indoramin: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Inhalational Anesthetics: May increase hypotensive effects of Calcium Channel Blockers. Risk C: Monitor
Isocarboxazid: May increase antihypertensive effects of Antihypertensive Agents. Risk X: Avoid
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ixabepilone. Risk C: Monitor
Lemborexant: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Lomitapide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider Therapy Modification
Loop Diuretics: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Lovastatin: AmLODIPine may increase serum concentration of Lovastatin. Risk C: Monitor
Magnesium Sulfate: May increase adverse/toxic effects of Calcium Channel Blockers (Dihydropyridine). Specifically, the risk of hypotension or muscle weakness may be increased. Risk C: Monitor
Melatonin: May decrease antihypertensive effects of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor
Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor
Methylphenidate: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Midazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Midazolam. Risk C: Monitor
Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may increase neuromuscular-blocking effects of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
NiMODipine: CYP3A4 Inhibitors (Weak) may increase serum concentration of NiMODipine. Risk C: Monitor
Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor
Obinutuzumab: May increase hypotensive effects of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider Therapy Modification
Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Perazine: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor
Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Pimozide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Pimozide. Risk X: Avoid
Prazosin: Antihypertensive Agents may increase hypotensive effects of Prazosin. Risk C: Monitor
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Red Yeast Rice: AmLODIPine may increase serum concentration of Red Yeast Rice. Risk C: Monitor
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Simvastatin: AmLODIPine may increase serum concentration of Simvastatin. Management: Dose of simvastatin should not exceed 20 mg daily if coadministering with amlodipine. If coadministering with simvastatin and amlodipine, close laboratory and clinical monitoring for signs and symptoms of rhabdomyolysis is warranted. Risk D: Consider Therapy Modification
Sincalide: Drugs that Affect Gallbladder Function may decrease therapeutic effects of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider Therapy Modification
Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase serum concentration of Sirolimus (Conventional). Risk C: Monitor
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Terazosin: Antihypertensive Agents may increase hypotensive effects of Terazosin. Risk C: Monitor
Triazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Triazolam. Risk C: Monitor
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider Therapy Modification
Urapidil: Antihypertensive Agents may increase hypotensive effects of Urapidil. Risk C: Monitor
Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be used in patients trying to conceive. Amlodipine is not considered a preferred agent for use in pregnant patients; consider transitioning to a preferred agent in patients planning to become pregnant (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019).
Amlodipine crosses the placenta. Cord blood concentrations were ~40% of maternal serum at delivery, and concentrations in the newborn were below the limit of quantification (<0.1 ng/mL) when measured in eight infants within 48 hours of delivery (Morgan 2017; Morgan 2018).
Due to pregnancy-induced pharmacologic changes, amlodipine pharmacokinetics may be altered immediately postpartum (Morgan 2018; Naito 2015b; Taguchi 2019).
Chronic maternal hypertension is associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 2019).
Patients with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]). When treatment of hypertension is initiated during pregnancy, agents other than amlodipine may be preferred (ACOG 2019; ESC [Cífková 2020]; ESC [Regitz-Zagrosek 2018]; SOGC [Magee 2022]).
Blood pressure, heart rate, liver enzymes.
Inhibits calcium ion from entering the “slow channels” or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization, producing a relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina. Amlodipine directly acts on vascular smooth muscle to produce peripheral arterial vasodilation reducing peripheral vascular resistance and blood pressure.
Onset of action: Antihypertensive effect: Significant reductions in blood pressure at 24 to 48 hours after first dose; slight increase in heart rate within 10 hours of administration may reflect some vasodilating activity (Donnelly 1993).
Duration: Antihypertensive effect: At least 24 hours (Donnelly 1993); has been shown to extend to at least 72 hours when discontinued after 6 to 7 weeks of therapy (Biston 1999).
Absorption: Well absorbed (Meredith 1992).
Distribution: Mean Vd:
Children >6 years: Similar to adults on a mg per kg basis; Note: Weight-adjusted Vd in younger children (<6 years of age) may be greater than in older children (Flynn 2006).
Adults: 21 L/kg (Scholz 1997).
Protein binding: ~93%.
Metabolism: Hepatic (~90%) to inactive metabolites.
Bioavailability: 64% to 90%.
Half-life elimination: Terminal (biphasic): 30 to 52 hours.
Time to peak, plasma: 6 to 12 hours.
Excretion: Urine (10% of total dose as unchanged drug, 60% of total dose as metabolites).
Clearance: May be decreased in patients with hepatic insufficiency or moderate to severe heart failure; weight-adjusted clearance in children >6 years of age is similar to adults; Note: Weight-adjusted clearance in younger children (<6 years of age) may be greater than in older children (Flynn 2006).
Hepatic function impairment: Following a single dose of amlodipine 5 mg in patients with Child-Turcotte-Pugh class A, the elimination half-life approximately doubled and AUC increased ~1.4 times (Abernathy 1989; Darnis 1993).
Older adult: AUC may increase ~40% to 60%.
Moderate to severe heart failure: AUC may increase ~40% to 60%.