Meta Information
ID:amlodipine
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/class/cyp3a4-strong-inhibitors
Target name:
Strong CYP3A4 Inhibitors (e.g., Ketoconazole, Clarithromycin, Ritonavir)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Strong CYP3A4 inhibitors block the primary enzyme that breaks down amlodipine, leading to dangerously high drug levels, which can cause severe low blood pressure, dizziness, and swelling.
Actionable advice:
These medications should not be used together; if unavoidable, a significant dose reduction of amlodipine is required under close medical supervision.
Validation status:
validated_via_regulatory
Evidence tier:
tier_b
Evidence basis:
regulatory_advisory_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
For current labeling information, please visit https://www.fda.gov/drugsatfda Co-administration of 240 mL of grapefruit juice with a single oral dose of amlodipine 10 mg in 20 healthy volunteers had no significant effect on the pharmacokinetics of amlodipine.
Label source:
FDA label: Amlodipine
Action type:
avoid
Target id:
/intervention/simvastatin
Target name:
Simvastatin
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Amlodipine inhibits the breakdown of simvastatin, increasing its concentration in the blood and raising the risk of muscle-related side effects, including a rare but serious condition called rhabdomyolysis.
Actionable advice:
A daily dose of 20 mg of simvastatin should not be exceeded when taking amlodipine.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Co-administration of multiple 10 mg doses of NORVASC with 80 mg of atorvastatin resulted in no significant change in the steady-state pharmacokinetic parameters of atorvastatin.
Label source:
FDA label: Amlodipine
Action type:
informational_none
Target id:
/class/pde5-inhibitors
Target name:
PDE5 Inhibitors (e.g., Sildenafil, Tadalafil)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both amlodipine and PDE5 inhibitors are vasodilators; their combined use can cause an additive effect, leading to a significant and potentially dangerous drop in blood pressure.
Actionable advice:
Amlodipine and PDE5 inhibitors both lower blood pressure. Take the PDE5 dose cautiously, stand up slowly, and never combine either with nitrates. Tell your prescriber you take amlodipine.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
A single 100 mg dose of sildenafil in subjects with essential hypertension had no effect on the pharmacokinetic parameters of NORVASC.
Label source:
FDA label: Amlodipine
Action type:
avoid
Target id:
/class/immunosuppressants
Target name:
Calcineurin Inhibitors (e.g., Cyclosporine, Tacrolimus)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Amlodipine can increase the blood levels of these immunosuppressants, heightening the risk of toxicity, particularly kidney damage.
Actionable advice:
This combination requires close monitoring of immunosuppressant drug levels and kidney function by a physician.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered
Label source:
FDA label: Amlodipine (Norvasc 2017) — Drug Interactions: Immunosuppressants
Action type:
monitor
Target id:
/condition/hepatic-impairment
Target name:
Severe Liver Disease
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The liver is responsible for breaking down amlodipine; severe liver impairment dramatically slows this process, leading to high drug levels and an increased risk of side effects.
Actionable advice:
A lower starting dose and careful dose increases are necessary under medical supervision for patients with severe liver disease.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg once daily
Label source:
FDA label: Amlodipine (Norvasc 2017) — Dosing in hepatic insufficiency
Action type:
adjust_with_prescriber
Target id:
/class/cyp3a4-moderate-inhibitors
Target name:
Moderate CYP3A4 Inhibitors (e.g., Diltiazem, Verapamil, Fluconazole)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
These drugs moderately block the enzyme that metabolizes amlodipine, increasing its concentration and the risk of side effects like low blood pressure, dizziness, and fluid retention.
Actionable advice:
This is best used with caution, and it is a good idea to monitor for increased side effects; a doctor may need to lower the amlodipine dose.
Validation status:
validated_via_regulatory
Evidence tier:
tier_b
Evidence basis:
regulatory_advisory_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
For current labeling information, please visit https://www.fda.gov/drugsatfda Co-administration of 240 mL of grapefruit juice with a single oral dose of amlodipine 10 mg in 20 healthy volunteers had no significant effect on the pharmacokinetics of amlodipine.
Label source:
FDA label: Amlodipine
Action type:
monitor
Target id:
/dietary/grapefruit-pomelo
Target name:
Grapefruit and Grapefruit Juice
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Compounds in grapefruit inhibit the CYP3A4 enzyme in the gut wall, increasing the absorption and blood levels of amlodipine, which can lead to excessive blood pressure lowering.
Actionable advice:
Grapefruit or its juice is best avoided while taking amlodipine.
Validation status:
validated_via_regulatory
Evidence tier:
tier_b
Evidence basis:
regulatory_advisory_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
For current labeling information, please visit https://www.fda.gov/drugsatfda Co-administration of 240 mL of grapefruit juice with a single oral dose of amlodipine 10 mg in 20 healthy volunteers had no significant effect on the pharmacokinetics of amlodipine.
Label source:
FDA label: Amlodipine
Action type:
avoid
Target id:
/class/broad-spectrum-inducers
Target name:
CYP3A4 Inducers (e.g., Rifampin, Carbamazepine, Phenytoin)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
These medications speed up the enzyme that breaks down amlodipine, significantly lowering its blood levels and reducing its effectiveness at controlling blood pressure.
Actionable advice:
This combination is best avoided if possible; a doctor may need to increase the amlodipine dose if co-administration is necessary.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Blood pressure should be closely monitored when Amlodipine is co-administered with CYP3A4 inducers. 7.12 Drug/Laboratory Test Interactions None known.
Label source:
FDA label: Amlodipine
Action type:
avoid
Target id:
/intervention/saint-johns-wort
Target name:
St. John's Wort
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
St. John's Wort induces the CYP3A4 enzyme, which accelerates the metabolism of amlodipine, potentially making it less effective for blood pressure control.
Actionable advice:
St. John's Wort is best avoided with amlodipine due to the risk of reduced efficacy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
No information is available on the quantitative effects of CYP3A4 inducers on amlodipine
Label source:
FDA label: Amlodipine (Norvasc) — Drug Interactions (7.11) CYP3A4 Inducers
Action type:
avoid
Target id:
/class/antihypertensives
Target name:
Other Blood Pressure Lowering Medications
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining amlodipine with other antihypertensives has an additive effect, which is often intentional but can sometimes lead to excessive blood pressure drops (hypotension).
Actionable advice:
It is worth watching out for dizziness or lightheadedness, especially when starting or changing doses of any blood pressure medication.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
NORVASC is a calcium channel blocker and may be used alone or in
Label source:
FDA label: Amlodipine (Norvasc) — Indications: combination antihypertensive use
Action type:
monitor
Target id:
/class/statins
Target name:
Certain Statins (especially Atorvastatin, Lovastatin)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Amlodipine can modestly increase the levels of statins that are metabolized by CYP3A4, potentially increasing the risk of muscle pain or weakness.
Actionable advice:
It is worth watching out for muscle-related side effects, and a doctor may consider a lower statin dose or a different statin.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Co-administration of multiple 10 mg doses of NORVASC with 80 mg of atorvastatin resulted in no significant change in the steady-state pharmacokinetic parameters of atorvastatin.
Label source:
FDA label: Amlodipine
Action type:
monitor
Target id:
/condition/geriatric
Target name:
Older Adults (Geriatric)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Older adults may have slower clearance of amlodipine and be more sensitive to its blood pressure-lowering effects, increasing the risk of falls from dizziness or hypotension.
Actionable advice:
A lower starting dose is recommended for older adults, with gradual increases as needed under medical supervision.
Validation status:
validated_via_regulatory
Evidence tier:
tier_b
Evidence basis:
regulatory_advisory_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
For current labeling information, please visit https://www.fda.gov/drugsatfda at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Label source:
FDA label: Amlodipine
Action type:
adjust_with_prescriber
Target id:
/circadian/sleep
Target name:
Going to Sleep
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
null
Description:
Some evidence suggests that taking blood pressure medication in the evening may improve control of nighttime blood pressure, and amlodipine's long half-life makes it suitable for this strategy.
Actionable advice:
Consider taking amlodipine in the evening, but maintaining a consistent time each day is the most important factor.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
informational_none
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
minor
Interaction type:
informational
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Amlodipine's absorption is not significantly affected by food, allowing for flexible dosing. Taking it with a meal can aid in establishing a consistent daily routine and minimize potential stomach upset.
Actionable advice:
You can take amlodipine with or without food at the same time each day.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
bioavailability of NORVASC is not altered by the presence of food
Label source:
FDA label: Amlodipine (Norvasc) — Pharmacokinetics: food effect
Action type:
informational_none
Target id:
/intervention/calcium-citrate
Target name:
High-Dose Calcium Supplements
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Theoretically, large supplemental doses of calcium could counteract the mechanism of a calcium channel blocker, potentially reducing its effectiveness, though this is not well-established clinically.
Actionable advice:
Standard calcium supplementation is generally safe, but avoid very high doses without consulting your doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect.
Label source:
FDA label: Amlodipine
Action type:
avoid