Angina pectoris:
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).
Chronic stable angina (alternative agent); vasospastic angina: Oral: Initial: 5 mg once daily; titrate slowly in patients with severe hepatic impairment.
Hypertension, chronic: Oral: Initial: 2.5 mg once daily; titrate slowly in patients with severe hepatic impairment.
(For additional information see "Amlodipine: Pediatric drug information")
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.
Dosing should start at the lower end of dosing range and be titrated to response due to possible increased incidence of hepatic, renal, or cardiac impairment. Elderly patients also show decreased clearance of amlodipine.
Chronic stable angina (alternative agent); vasospastic angina: Oral: Initial: 5 mg once daily.
Hypertension, chronic: Oral: Initial: 2.5 mg once daily.
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
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
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.
Oral: May be administered without regard to food.
Suspension: Shake well before using.
Angina: Treatment of symptomatic chronic stable angina; treatment of confirmed or suspected vasospastic angina (previously referred to as Prinzmetal or variant angina). May be used alone or in combination with other antianginal agents.
Hypertension, chronic: Management of hypertension in adults and children ≥6 years of age.
Raynaud phenomenon
AmLODIPine may be confused with aMILoride
Norvasc may be confused with Navane, Norvir, Vascor
Norvasc [US, Canada, and multiple international markets] may be confused with Vascor brand name for imidapril [Philippines] and simvastatin [Malaysia, Singapore, and Thailand]
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 (Cvetković 2013)
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) (Gouveia 2022)
Dermatologic: Dermatologic disorder (Schamberg's disease) (Schetz 2015), psoriasis (Song 2021), toxic epidermal necrolysis (Baetz 2011)
Endocrine & metabolic: Gynecomastia (Cornes 2001)
Gastrointestinal: Gingival hyperplasia (John 2020)
Hepatic: Ascites (Arasan 2020), cholestatic hepatitis (Egbuonu 2019; Zinsser 2004), hepatotoxicity (Demirci 2013; Hammerstrom 2015)
Nervous system: Akathisia (Dressler 2014), parkinsonism (Teive 2002), tardive dystonia (Dressler 2014)
Neuromuscular & skeletal: Subacute cutaneous lupus erythematosus (Mizuta 2022)
Renal: Acute interstitial nephritis (Ejaz 2000)
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 hepatic impairment; may require lower starting dose; titrate slowly in patients with severe hepatic impairment.
• 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 2020]).
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.
Substrate of CYP3A4 (major); 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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect 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 diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Charcoal, Activated: May decrease the serum concentration of AmLODIPine. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy
CycloSPORINE (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of AmLODIPine. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of AmLODIPine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of AmLODIPine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of AmLODIPine. Risk C: Monitor therapy
Dabigatran Etexilate: AmLODIPine may diminish the therapeutic effect of Dabigatran Etexilate. Risk C: Monitor therapy
Dantrolene: May enhance the hyperkalemic effect of Calcium Channel Blockers. Dantrolene may enhance the negative inotropic effect of Calcium Channel Blockers. Risk X: Avoid combination
Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy
Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Inhalational Anesthetics: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the 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-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the 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
Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification
Loop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Lovastatin: AmLODIPine may increase the serum concentration of Lovastatin. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the adverse/toxic effect of Calcium Channel Blockers (Dihydropyridine). Specifically, the risk of hypotension or muscle weakness may be increased. Risk C: Monitor therapy
Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect 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 enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Red Yeast Rice: AmLODIPine may increase the serum concentration of Red Yeast Rice. Risk C: Monitor therapy
Simvastatin: AmLODIPine may increase the 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 diminish the therapeutic effect 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 the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the 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 the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the 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
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).
Chronic maternal hypertension may increase the risk of birth defects, low birth weight, preterm delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to duration and severity of maternal hypertension. Untreated hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, myocardial infarction, preeclampsia, stroke, and delivery complications (ACOG 203 2019).
Calcium channel blockers may be used to treat hypertension in pregnant women; however, agents other than amlodipine are more commonly used (ACOG 203 2019; ESC [Regitz-Zagrosek 2018]). Females with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]).
Amlodipine is present in breast milk.
The relative infant dose (RID) of amlodipine is 4.18% (interquartile range 3.12% to 7.25%) when calculated using a median breast milk concentration and compared to a weight adjusted maternal dose of 6.01 mg ± 2.31 mg/day.
In general, breastfeeding is considered acceptable when the RID is <10%; when an RID is >25% breastfeeding should generally be avoided (Anderson 2016; Ito 2000).
Using a median predose milk concentration (11.5 ng/mL; IQR 9.84 to 18 ng/mL), authors of a study calculated the estimated daily infant dose via breast milk to be 4.17 mcg/kg/day (IQR 3.05 to 6.32 mcg/kg/day). This milk concentration was obtained following maternal administration of amlodipine at a median daily dose of 6.01 mg ± 2.31 mg; the women (n=31) were ~3 weeks postpartum and sampling occurred prior to a dose and ~10 days after treatment initiation. The maximum RID calculated was 15.2%. Adverse events were not observed in the breastfed infants (Naito 2015a). In a second study of eight breastfeeding women and their nine breastfeeding infants, peak breast milk concentrations of amlodipine (6.5 to 19.7 ng/mL) occurred 8 hours after the maternal dose (5 mg/day n=7; 2.5 mg/day n =1). In this study, six women started therapy 1 to 2 days postpartum and two women were taking amlodipine throughout pregnancy; sampling of foremilk occurred 5 to 7 days' postpartum. Plasma concentrations of amlodipine in the infants were lower than the limit of quantification (<0.4 ng/mL). Authors of this study calculated the RID to be 1.56% to 4.32% of the weight-adjusted maternal dose (Aoki 2018).
Heart rate, BP.
BP goals: May vary depending on clinical condition, different clinical practice guidelines, and expert opinion. Refer to clinical practice guidelines for specific treatment goals.
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; increased with hepatic dysfunction.
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: AUC may increase ~40% to 60%.
Older adult: AUC may increase ~40% to 60%.
Moderate to severe heart failure: AUC may increase ~40% to 60%.
Solution (Norliqva Oral)
1 mg/mL (per mL): $4.12
Suspension (Katerzia Oral)
1 mg/mL (per mL): $4.43
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 - $2.39
Tablets (Norvasc Oral)
2.5 mg (per each): $9.05
5 mg (per each): $9.05
10 mg (per each): $12.41
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