Meta Information
ID:angiotensin-receptor-blockers
Name:Angiotensin Receptor Blockers
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6 + wave9_class_population
Interactions
Target id:
/class/potassium-elevators
Target name:
Potassium-Sparing Diuretics, Potassium Supplements, or Salt Substitutes
Severity:
major
Interaction type:
adverse
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
ARBs reduce the body's ability to excrete potassium. Combining them with other agents that raise potassium, such as potassium-sparing diuretics (e.g., spironolactone) or potassium supplements/salt substitutes, can lead to dangerously high potassium levels (hyperkalemia).
Actionable advice:
Avoid this combination unless under strict medical supervision with frequent potassium monitoring.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Coadministration of losartan with other drugs that raise serum potassium levels may result in hyperkalemia
Label source:
FDA label: Losartan (Cozaar)
Action type:
avoid
Target id:
/class/ace-inhibitors
Target name:
ACE Inhibitors
Severity:
major
Interaction type:
adverse
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining an ARB with an ACE inhibitor provides dual blockade of the same hormonal pathway (RAAS), which significantly increases risks of low blood pressure, high potassium, and kidney damage without proven additional benefit.
Actionable advice:
Avoid using an ARB and an ACE inhibitor together; this combination is generally contraindicated.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy
Label source:
FDA label: Losartan (Cozaar)
Action type:
avoid
Target id:
/intervention/aliskiren
Target name:
Aliskiren
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining an ARB with aliskiren (a direct renin inhibitor) results in dual blockade of the renin-angiotensin system, increasing the risk of hypotension, hyperkalemia, and acute kidney injury, especially in patients with diabetes or kidney disease.
Actionable advice:
This combination is contraindicated and must be avoided, particularly in patients with diabetes.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Do not coadminister aliskiren with losartan potassium in patients with diabetes
Label source:
FDA label: Losartan (Cozaar)
Action type:
avoid
Target id:
/class/nsaids
Target name:
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Severity:
major
Interaction type:
adverse
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
NSAIDs (e.g., ibuprofen, naproxen) can constrict blood vessels supplying the kidneys, while ARBs relax them. This opposing action can impair kidney function, reduce the blood pressure-lowering effect of the ARB, and increase the risk of acute kidney injury, especially in the elderly or dehydrated.
Actionable advice:
Avoid regular, long-term use of NSAIDs; consult a doctor for safer pain relief alternatives.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
coadministration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists (including losartan) may result in deterioration of renal function, including possible acute renal failure
Label source:
FDA label: Losartan (Cozaar)
Action type:
avoid
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
ARBs are contraindicated in pregnancy as they can cause significant harm or death to the developing fetus, particularly affecting the kidneys and skull development (black box warning).
Actionable advice:
Stop taking ARBs immediately if you become pregnant and consult your doctor for an alternative.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
When pregnancy is detected, discontinue losartan potassium tablets as soon as possible
Label source:
FDA label: Losartan (Cozaar)
Action type:
informational_none
Target id:
/condition/renal-impairment
Target name:
Renal Impairment or Renal Artery Stenosis
Severity:
major
Interaction type:
monitoring
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
In individuals with pre-existing kidney disease or narrowed kidney arteries, ARBs can sometimes acutely worsen kidney function and significantly increase potassium levels.
Actionable advice:
Use requires careful dose selection and close monitoring of kidney function and potassium 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:
Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on losartan potassium
Label source:
FDA label: Losartan (Cozaar)
Action type:
monitor
Target id:
/condition/dehydration
Target name:
Dehydration or Volume Depletion
Severity:
major
Interaction type:
adverse
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
When you are dehydrated (e.g., from vomiting, diarrhea), your body relies on the renin-angiotensin system to maintain blood pressure. Taking an ARB in this state can cause a sudden and severe drop in blood pressure.
Actionable advice:
Correct any dehydration before starting an ARB, and be cautious during illnesses that cause fluid loss.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with losartan potassium tablets
Label source:
FDA label: Losartan (Cozaar)
Action type:
informational_none
Target id:
/intervention/lithium
Target name:
Lithium
Severity:
major
Interaction type:
adverse
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
ARBs can decrease the kidneys' ability to excrete lithium, causing it to build up in the body to toxic levels.
Actionable advice:
If this combination is necessary, lithium levels must be monitored frequently, and the dose may need to be reduced.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists
Label source:
FDA label: Losartan (Cozaar)
Action type:
adjust_with_prescriber
Target id:
/class/antihypertensives
Target name:
Other Antihypertensive Medications
Severity:
moderate
Interaction type:
adverse
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Taking ARBs with other blood pressure-lowering medications has an additive effect. While often intentional, this can sometimes cause blood pressure to drop too low (hypotension), leading to dizziness.
Actionable advice:
Monitor blood pressure regularly, especially when starting or adjusting doses of concurrent antihypertensive drugs.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Add hydrochlorothiazide 12.5 mg and/or increase losartan potassium tablets to 100 mg followed by an increase to hydrochlorothiazide 25 mg if further blood pressure response is needed
Label source:
FDA label: Losartan (Cozaar)
Action type:
monitor
Target id:
/dietary/alcohol-acute
Target name:
Alcohol
Severity:
moderate
Interaction type:
adverse
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Acute alcohol consumption can potentiate the hypotensive effect of ARBs. The valsartan label explicitly warns of symptomatic hypotension in patients with activated renin-angiotensin systems (volume- or salt-depleted states, which acute alcohol use can produce via diuresis). [class-derived from: class_pharmacology]
Actionable advice:
Limit acute alcohol intake while on ARBs. Be cautious of dizziness or fainting, especially with postural changes after drinking. Avoid combining heavy alcohol use with the first dose or recent dose adjustments.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Exact phrase from label:
symptomatic hypotension may occur
Label source:
Class inference: acute alcohol diuresis + FDA volume-depletion hypotension warning
Action type:
separate
Target id:
/condition/hepatic-impairment
Target name:
Hepatic Impairment
Severity:
moderate
Interaction type:
monitoring
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The liver metabolizes many ARBs (e.g., losartan, valsartan). Impaired liver function can lead to higher concentrations of the drug in the body, increasing the risk of side effects.
Actionable advice:
Lower starting doses and careful titration are recommended for patients with 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:
The recommended starting dose of losartan potassium tablets is 25 mg in patients with mild-to-moderate hepatic impairment
Label source:
FDA label: Losartan (Cozaar)
Action type:
adjust_with_prescriber
Target id:
/class/cyp2c9-inhibitors
Target name:
Strong CYP2C9 Inhibitors (e.g., Fluconazole)
Severity:
moderate
Interaction type:
pharmacokinetic
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Certain ARBs, particularly losartan, are activated by the CYP2C9 enzyme. Strong inhibitors of this enzyme can block this activation, reducing the drug's blood pressure-lowering effectiveness.
Actionable advice:
If taking losartan, avoid strong CYP2C9 inhibitors or discuss alternative medications with 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:
Fluconazole, an inhibitor of cytochrome P450 2C9, decreased the AUC of the active metabolite by approximately 40%, but increased the AUC of losartan by approximately 70% following multiple doses
Label source:
FDA label: Losartan (Cozaar)
Action type:
avoid
Target id:
/dietary/potassium-rich-foods
Target name:
High-Potassium Foods
Severity:
moderate
Interaction type:
adverse
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
While ARBs reduce potassium excretion, excessive consumption of potassium-rich foods (like bananas, spinach, potatoes) can contribute to elevated potassium levels, especially in those with kidney issues.
Actionable advice:
Be mindful of your intake of high-potassium foods; do not consume them in excessive amounts.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Advise patients receiving losartan potassium tablets not to use potassium supplements or salt substitutes containing potassium without consulting their healthcare provider
Label source:
FDA label: Losartan (Cozaar)
Action type:
monitor
Target id:
/intervention/licorice-root
Target name:
Licorice Root
Severity:
moderate
Interaction type:
adverse
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Licorice root contains glycyrrhizin, which induces an apparent mineralocorticoid excess by inhibiting 11β-hydroxysteroid dehydrogenase type 2. This causes sodium retention, potassium depletion, and hypertension - directly opposing ARB therapy and complicating the potassium balance ARBs maintain. [class-derived from: class_pharmacology]
Actionable advice:
Avoid licorice root supplements and large amounts of black licorice while on ARBs. They reduce antihypertensive efficacy and complicate electrolyte management.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Exact phrase from label:
Label source:
Class inference: glycyrrhizin / mineralocorticoid mechanism vs ARB potassium and BP effects
Action type:
avoid
Target id:
/circadian/sleep
Target name:
Going to Sleep
Severity:
moderate
Interaction type:
monitoring
Nature:
informational
Temporal spacing:
Hours before target:
0.5
Hours after target:
null
Description:
Going to sleep coincides with the body's natural blood-pressure dip (nocturnal dipping). Taking an ARB at bedtime may potentiate this dip in some patients. Evening dosing of ARBs has been investigated for improved chronotherapy in hypertension but is not labeled. [class-derived from: class_pharmacology]
Actionable advice:
Either morning or evening dosing of ARBs is acceptable; the FDA label does not mandate timing. Be aware of nocturnal hypotension if you experience dizziness on waking.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Exact phrase from label:
Label source:
Class inference: ARB chronotherapy + nocturnal BP dipping mechanism
Action type:
informational_none
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
minor
Interaction type:
pharmacokinetic
Nature:
informational
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Food can slightly decrease the absorption of some ARBs (e.g., valsartan), potentially leading to minor variations in drug levels. The key is consistency.
Actionable advice:
Take your ARB at the same time each day, consistently either with or without food, to ensure a stable effect.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
A meal slows absorption of losartan and decreases its C max but has only minor effects on losartan AUC or on the AUC of the metabolite (~10% decrease)
Label source:
FDA label: Losartan (Cozaar)
Action type:
informational_none
Target id:
/biomarker/serum-potassium
Target name:
Serum Potassium
Severity:
major
Interaction type:
monitoring
Nature:
informational
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
ARBs directly affect kidney function in a way that can cause potassium levels to rise (hyperkalemia). This is a critical safety parameter to track.
Actionable advice:
Regular monitoring of serum potassium is essential, especially at initiation, after dose changes, and in at-risk patients.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Monitor serum potassium periodically and treat appropriately. Dosage reduction or discontinuation of losartan potassium tablets may be required
Label source:
FDA label: Losartan (Cozaar)
Action type:
monitor
Target id:
/biomarker/egfr
Target name:
eGFR (Kidney Function)
Severity:
major
Interaction type:
monitoring
Nature:
informational
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
ARBs can cause a small, expected decrease in eGFR upon initiation by changing blood flow within the kidneys; however, a significant or progressive drop can signal kidney injury.
Actionable advice:
Kidney function should be monitored before starting, within 1-2 weeks of initiation, and periodically thereafter.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on losartan potassium
Label source:
FDA label: Losartan (Cozaar)
Action type:
monitor
Target id:
/class/diuretics
Target name:
Diuretics (Water Pills)
Severity:
moderate
Interaction type:
adverse
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Co-administration with diuretics can lead to an excessive drop in blood pressure (hypotension), especially with the first dose, and can increase the risk of kidney dysfunction.
Actionable advice:
Use this common combination only under medical supervision, often starting with lower doses and monitoring blood pressure and kidney function.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Correct volume or salt depletion prior to administration of losartan potassium tablets
Label source:
FDA label: Losartan (Cozaar)
Action type:
monitor
Target id:
/intervention/alcohol
Target name:
Alcohol
Severity:
moderate
Interaction type:
adverse
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Alcohol can potentiate the hypotensive effect of ARBs, especially with acute consumption or in volume-depleted patients. The valsartan label explicitly warns about symptomatic hypotension in patients with activated renin-angiotensin systems (which alcohol use can mimic). [class-derived from: class_pharmacology]
Actionable advice:
Limit alcohol consumption while on ARBs. Be cautious about postural changes (lying to standing) after drinking - dizziness or fainting can occur.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Exact phrase from label:
symptomatic hypotension may occur
Label source:
Class inference: hypotensive synergy + FDA volume-depletion warning
Action type:
informational_none
Target id:
/class/cyp2c9-inducers
Target name:
CYP2C9 Inducers
Severity:
moderate
Interaction type:
pharmacokinetic
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Inducers of the CYP2C9 enzyme (e.g., rifampin, carbamazepine) can increase the metabolism of certain ARBs like losartan, potentially reducing their blood pressure-lowering effects.
Actionable advice:
Blood pressure should be monitored closely if a CYP2C9 inducer is started or stopped.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
rifampin has been shown to decrease the AUC of losartan and its active metabolite by 30% and 40%, respectively
Label source:
FDA label: Losartan (Cozaar)
Action type:
monitor
Target id:
/intervention/sacubitril-valsartan
Target name:
Sacubitril/Valsartan Combination
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Sacubitril/valsartan is a combination product already containing an ARB (valsartan). Adding another ARB would constitute dual ARB therapy, which the FDA label explicitly identifies as a risk for hypotension, hyperkalemia, and renal failure (dual RAS blockade). Effective doses would also be additive at the AT1 receptor. [class-derived from: valsartan_label, class_pharmacology]
Actionable advice:
Do not combine a separate ARB with sacubitril/valsartan. Use one or the other, not both.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Exact phrase from label:
Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy
Label source:
FDA label: Valsartan (Diovan) (class-inference: dual ARB exposure)
Action type:
separate
Target id:
/intervention/digoxin
Target name:
Digoxin
Severity:
moderate
Interaction type:
pharmacokinetic
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Co-administration of telmisartan with digoxin increases digoxin peak plasma concentration by 49% and trough concentration by 20%, raising the risk of digoxin toxicity. The losartan label states no clinically significant interaction with digoxin. Effect is ARB-specific (notably telmisartan).
Actionable advice:
If taking digoxin with an ARB, monitor digoxin levels when starting, adjusting, or discontinuing telmisartan. No routine dose adjustment is required for losartan + digoxin combination.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed
Label source:
FDA label: Telmisartan (Micardis)
Action type:
adjust_with_prescriber
Derived From
arbs
Provenance Note
Interactions duplicated from 'arbs'. Class synonym (ARB).