Benicar

Angiotensin-II Receptor Blockers/ARBs

Oral Administration

May administer without regard to food.

Oral Liquid Formulations

Extemporaneous Preparation of 2 mg/ml Oral Suspension:
Add 20 olmesartan 20 mg tablets to an amber polyethylene terephthalate (PET) bottle.
Add 50 ml of purified water to the PET bottle containing the olmesartan tablets and allow to stand for a minimum of 5 minutes.
Shake the container for at least 1 minute and allow the suspension to stand for at least 1 minute.
Repeat 1-minute shaking and 1-minute standing four additional times.
Add 100 ml of Ora-Sweet and 50 ml of Ora-Plus to the suspension and shake well for at least 1 minute.
This preparation makes 200 ml of a 2 mg/ml suspension.
Shake the suspension well before each use.
Store the suspension under refrigeration at 2 to 8 degrees C (36 to 45 degrees F); the extemporaneously prepared suspension may be stored for up to 4 weeks.

Severe

anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
hyperkalemia / Delayed / Incidence not known
oliguria / Early / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
azotemia / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
teratogenesis / Delayed / Incidence not known

Moderate

elevated hepatic enzymes / Delayed / 0.1-0.1
hypertriglyceridemia / Delayed / 1.0
hyperglycemia / Delayed / 1.0
hematuria / Delayed / 1.0
sinus tachycardia / Rapid / 0.5
peripheral edema / Delayed / 0.5
hyperlipidemia / Delayed / 0.5
chest pain (unspecified) / Early / 0.5
hypercholesterolemia / Delayed / 0.5
hyperuricemia / Delayed / 0.5
hypotension / Rapid / Incidence not known
orthostatic hypotension / Delayed / Incidence not known

Mild

dizziness / Early / 3.0-3.0
cough / Delayed / 0.9-0.9
sinusitis / Delayed / 1.0
headache / Early / 1.0
pharyngitis / Delayed / 1.0
back pain / Delayed / 1.0
rhinitis / Early / 1.0
rash / Early / 0.5
nausea / Early / 0.5
abdominal pain / Early / 0.5
diarrhea / Early / 1.0
dyspepsia / Early / 0.5
vertigo / Early / 0.5
arthralgia / Delayed / 0.5
myalgia / Early / 0.5
syncope / Early / Incidence not known
urticaria / Rapid / Incidence not known
pruritus / Rapid / Incidence not known
asthenia / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
vomiting / Early / Incidence not known
weight loss / Delayed / Incidence not known

Pregnancy

When pregnancy is detected, every effort should be made to discontinue olmesartan therapy. Women of child-bearing age should be made aware of the potential risk, and olmesartan should only be given after careful counseling and consideration of individual risks and benefits. When used during the second and third trimesters, medications that affect the renin-angiotensin system (e.g., ACE inhibitors, angiotensin II receptor antagonists) have been associated with reduced fetal renal function and increased fetal and neonatal morbidity and death. Use of drugs that affect the renin-angiotensin system during pregnancy can cause fetal death or injury such as hypotension, neonatal skull hypoplasia, reversible or irreversible renal failure and death. Anhydramnios and oligohydramnios have also been reported. Development of oligohydramnios may be associated with decreased fetal renal function leading to anuria and renal failure and results in fetal limb contractures, craniofacial deformation, hypotension, hypoplastic lung development, and death. Retrospective data indicate that first trimester use of ACE inhibitors has been associated with a potential risk of birth defects. However, a much larger observational study (n = 465,754) found that the risk of birth defects was similar in infants exposed to ACE inhibitors during the first trimester, in infants exposed to other antihypertensives during the first trimester, and in those whose mothers were hypertensive but were not treated. Infants born to mothers with hypertension, either treated or untreated, had a higher risk of birth defects than those born to mothers without hypertension. The authors concluded that the presence of hypertension likely contributed to the development of birth defects rather than the use of medications. An observational cohort study evaluating the outcomes of angiotensin receptor blockers (ARBs) use during the first trimester of pregnancy found an increased rate of major birth defects compared to non-hypertensive pregnancies, 5.4% and 3%, respectively; the difference did not reach statistical significance. The authors noted that there was a higher risk of major birth defects with ARB therapy beyond 6 weeks of gestation compared to discontinuation of ARBs before week 6, 7.3% and 2.8%, respectively. The rates of prematurity and reduced birth weight were also increased in the ARB group. There were no statistically significant differences in the rates of major birth defects, spontaneous abortions, or preterm births between women with chronic hypertension treated with an ARB versus methyldopa. In rare cases when another antihypertensive agent cannot be used to treat a pregnant patient, serial ultrasound examinations should be performed to assess the intraamniotic environment. If oligohydramnios is observed, discontinue olmesartan unless it is considered life-saving for the mother. It should be noted that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe newborns with histories of in utero exposure to olmesartan for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occurs, blood pressure and renal perfusion support may be required, as well as exchange transfusion or dialysis to reverse hypotension and/or support decreased renal function.

Benicar

Rx

Angiotensin II antagonist; used once daily for HTN; does not inhibit ACE and accumulate bradykinin; less likely to cause cough or angioedema than ACE inhibitors; not metabolized by the liver; lacks interactions with cytochrome P-450 inhibitors or inducers.

For the treatment of hypertension. Oral dosage Adults

20 mg PO once daily is the recommended starting dose for monotherapy in patients who are not volume-depleted. Increase the dose to 40 mg PO once daily if further blood pressure reduction is needed after 2 weeks of therapy. For patients who may be volume depleted, initiate therapy under close medical supervision and consider a lower starting dose. Doses greater than 40 mg/day do not appear to have a greater effect, and twice-daily dosing offers no advantage over the same total dose given once daily. If blood pressure is not controlled with olmesartan alone, a diuretic (e.g., hydrochlorothiazide) may be added.

Adolescents 17 years

20 mg PO once daily is the recommended starting dose for monotherapy in patients who are not volume-depleted. Increase the dose to 40 mg PO once daily if further blood pressure reduction is needed after 2 weeks of therapy. For patients who may be volume depleted, initiate therapy under close medical supervision and consider a lower starting dose. Doses greater than 40 mg/day do not appear to have a greater effect, and twice-daily dosing offers no advantage over the same total dose given once daily. If blood pressure is not controlled with olmesartan alone, a diuretic (e.g., hydrochlorothiazide) may be added.

Children and Adolescents 6 to 16 years weighing 35 kg or more

20 mg PO once daily initially. Increase the dose to 40 mg PO once daily if further blood pressure reduction is needed after 2 weeks of therapy. Max: 40 mg/day.

Children and Adolescents 6 to 16 years weighing 20 to 34 kg

10 mg PO once daily initially. Increase the dose to 20 mg PO once daily if further blood pressure reduction is needed after 2 weeks of therapy. Max: 20 mg/day.

Hepatic Impairment

No initial dosage adjustment is recommended. Although the manufacturer recommends no initial dosage adjustment for hepatic disease, patients with moderate hepatic impairment have a 60% higher olmesartan AUC compared to normal controls. Severe hepatic impairment has not been studied. Adjust dosage cautiously based on therapeutic response.

Renal Impairment

No dosage adjustment is needed.

Acarbose: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Isometheptene has sympathomimetic properties. Patients taking antihypertensive agents may need to have their therapy modified. Careful blood pressure monitoring is recommended.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Acrivastine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Aldesleukin, IL-2: (Moderate) Angiotensin II receptor antagonists may potentiate the hypotension seen with aldesleukin, IL 2.
Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
Aliskiren: (Major) Aliskiren-containing products are contraindicated in combination with angiotensin II receptor antagonists (ARBs) in patients with diabetes mellitus. In general, avoid combined use of two renin-angiotensin-aldosterone system (RAAS) inhibitors, particularly in patients with CrCl less than 60 mL/minute. Combination therapy increases the risk for hyperkalemia, renal impairment, hypotension, and other side effects. Most patients receiving a comination of two RAAS inhibitors, such as ARBs and aliskiren, do not obtain any additional benefit compared to monotherapy. Closely monitor blood pressure, renal function, and electrolytes if aliskiren must be combined with another RAAS inhibitor. In the ALTITUDE trial, patients with type 2 diabetes and renal impairment, a population at high risk for cardiovascular and renal events, were given aliskiren in addition to ACE inhibitors or ARBs. The trial was stopped early because aliskiren was associated with an increased risk of non-fatal stroke, renal complications, hyperkalemia, and hypotension. In the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial, no additional benefit over monotherapy was seen in patients receiving the combination of losartan and lisinopril compared to monotherapy; however, there was an increased incidence of hyperkalemia and acute renal injury.
Aliskiren; Hydrochlorothiazide, HCTZ: (Major) Aliskiren-containing products are contraindicated in combination with angiotensin II receptor antagonists (ARBs) in patients with diabetes mellitus. In general, avoid combined use of two renin-angiotensin-aldosterone system (RAAS) inhibitors, particularly in patients with CrCl less than 60 mL/minute. Combination therapy increases the risk for hyperkalemia, renal impairment, hypotension, and other side effects. Most patients receiving a comination of two RAAS inhibitors, such as ARBs and aliskiren, do not obtain any additional benefit compared to monotherapy. Closely monitor blood pressure, renal function, and electrolytes if aliskiren must be combined with another RAAS inhibitor. In the ALTITUDE trial, patients with type 2 diabetes and renal impairment, a population at high risk for cardiovascular and renal events, were given aliskiren in addition to ACE inhibitors or ARBs. The trial was stopped early because aliskiren was associated with an increased risk of non-fatal stroke, renal complications, hyperkalemia, and hypotension. In the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial, no additional benefit over monotherapy was seen in patients receiving the combination of losartan and lisinopril compared to monotherapy; however, there was an increased incidence of hyperkalemia and acute renal injury.
Alogliptin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Alpha-glucosidase Inhibitors: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as angiotensin II receptor antagonists (angiotensin receptor blockers, or ARBs), may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
Amifostine: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Amiloride: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Amiloride; Hydrochlorothiazide, HCTZ: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Amobarbital: (Moderate) Concurrent use of amobarbital with antihypertensive agents may lead to hypotension. Monitor for decreases in blood pressure during times of coadministration.
Amphetamine; Dextroamphetamine Salts: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
Angiotensin II: (Moderate) Angiotensin II receptor antagonists (angiotensin receptor blockers, or ARBs) may decrease the response to angiotensin II. Angiotensin II is a naturally occurring peptide hormone of the renin-angiotensin-aldosterone system (RAAS) that causes vasoconstriction and an increase in blood pressure. ARBs block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the angiotensin receptor in many tissues.
Angiotensin-converting enzyme inhibitors: (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Apomorphine: (Moderate) Use of angiotensin II receptor antagonists and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Apraclonidine: (Minor) Alpha blockers as a class may reduce heart rate and blood pressure. While no specific drug interactions have been identified with systemic agents and apraclonidine during clinical trials, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Patients using cardiovascular drugs concomitantly with apraclonidine should have their pulse and blood pressure monitored periodically.
Aripiprazole: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Articaine; Epinephrine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of asenapine and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
Benzphetamine: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
Brexpiprazole: (Moderate) Due to brexpiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Brompheniramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Brompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Bupivacaine; Epinephrine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including angiotensin II receptor antagonists. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure.
Calcium Phosphate, Supersaturated: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as angiotensin II receptor antagonists, may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
Canagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Carbidopa; Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Carbidopa; Levodopa; Entacapone: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
Cetirizine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Chlorpheniramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Clozapine: (Moderate) Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug.
Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Codeine; Phenylephrine; Promethazine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Co-Enzyme Q10, Ubiquinone: (Moderate) Co-enzyme Q10, ubiquinone (CoQ10) may lower blood pressure. CoQ10 use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients who choose to take CoQ10 concurrently with antihypertensive medications should receive periodic blood pressure monitoring. Patients should be advised to inform their prescriber of their use of CoQ10.
Colesevelam: (Moderate) Colesevelam decreases the Cmax and AUC of olmesartan by approximately 28% and 39%, respectively. Administer olmesartan at least 4 hours before colesevelam.
Cyclosporine: (Moderate) Coadministration of cyclosporine and an angiotensin II receptor antagonist, like olmesartan, may increase the risk of hyperkalemia and reduced renal function. In response to cyclosporine-induced renal afferent vasoconstriction and glomerular hypoperfusion, angiotensin II is required to maintain an adequate glomerular filtration rate. Inhibition of angiotensin-converting enzyme (ACE) could reduce renal function acutely. Several cases of acute renal failure have been associated with the addition of enalapril to cyclosporine therapy in renal transplant patients. Also, cyclosporine can cause hyperkalemia, and inhibition of angiotensin II leads to reduced aldosterone concentrations, which can increase the serum potassium concentration. Closely monitor renal function and serum potassium concentrations in patients receiving cyclosporine concurrently with olmesartan.
Dapagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Desloratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Dexbrompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Dextromethorphan; Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agents. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving beta-blockers, hydralazine, methyldopa, minoxidil, nitrites, prazosin, reserpine, or other antihypertensive agents.
Diethylpropion: (Moderate) Diethylpropion has vasopressor effects and may limit the benefit of angiotensin II receptor antagonists. Although leading drug interaction texts differ in the potential for an interaction between diethylpropion and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications.
Digoxin: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Drospirenone: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of angiotensin II receptor antagonists (ARBs) may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if ARBs are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function.
Drospirenone; Estetrol: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of angiotensin II receptor antagonists (ARBs) may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if ARBs are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function.
Drospirenone; Estradiol: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of angiotensin II receptor antagonists (ARBs) may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if ARBs are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function.
Drospirenone; Ethinyl Estradiol: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of angiotensin II receptor antagonists (ARBs) may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if ARBs are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of angiotensin II receptor antagonists (ARBs) may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if ARBs are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function.
Duloxetine: (Moderate) Orthostatic hypotension and syncope have been reported during duloxetine administration. The concurrent administration of antihypertensive agents and duloxetine may increase the risk of hypotension. Monitor blood pressure if the combination is necessary.
Eltrombopag: (Moderate) Use caution and monitor blood pressure closely if eltrombopag and olmesartan are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as olmesartan, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ephedrine: (Moderate) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Ephedrine; Guaifenesin: (Moderate) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Epinephrine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
Eplerenone: (Major) Monitor serum potassium and serum creatinine concentrations within 3 to 7 days of initiating coadministration of eplerenone and angiotensin II receptor antagonists (ARBs). Hyperkalemia risk is increased when eplerenone is used with ARBs. Patients who develop hyperkalemia may continue eplerenone with proper dose adjustment; eplerenone dose reduction decreases potassium concentrations.
Epoprostenol: (Moderate) Angiotensin II receptor antagonists can enhance the hypotensive effects of antihypertensive agents if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly.
Ertugliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Estradiol: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormonal contraceptives should be monitored for antihypertensive effectiveness.
Etomidate: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Fexofenadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Finerenone: (Moderate) Monitor serum potassium concentrations closely if finerenone and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Gemfibrozil: (Moderate) Coadministration may result in an increase in olmesartan exposure. A dose reduction of olmesartan may be required if used concomitantly with gemfibrozil. Use olmesartan and gemfibrozil together with caution. Olmesartan is a substrate of the OATP1B1 transporter. Gemfibrozil inhibits OATP1B1.
General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Glipizide; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glyburide; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Haloperidol: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Hydrocodone; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Ibritumomab Tiuxetan: (Major) Avoid coadministration of potassium phosphate and angiotensin II receptor antagonists as concurrent use may increase the risk of severe and potentially fatal hyperkalemia, particularly in high-risk patients (renal impairment, cardiac disease, adrenal insufficiency). If concomitant use is necessary, closely monitor serum potassium concentrations.
Ibuprofen; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Iloprost: (Moderate) Angiotensin II receptor antagonists can enhance the hypotensive effects of antihypertensive agents if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly.
Incretin Mimetics: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Indapamide: (Moderate) The effects of indapamide may be additive when administered with other antihypertensive agents or diuretics. In some patients, this may be desirable, but orthostatic hypotension may occur. Angiotensin II receptor antagonists tend to reverse the potassium loss, but not the serum uric acid rise associated with thiazide diuretic monotherapy.
Insulins: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin II receptor blocker use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Intravenous Lipid Emulsions: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when isocarboxazid is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of isocarboxazid with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of isocarboxazid and an angiotensin II receptor antagonist.
Isoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Isoproterenol: (Moderate) The pharmacologic effects of isoproterenol may cause an increase in blood pressure. If isoproterenol is used concomitantly with antihypertensives, the blood pressure should be monitored as the administration of isoproterenol can compromise the effectiveness of antihypertensive agents.
Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Isosorbide Mononitrate: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Ketamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Lidocaine; Epinephrine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Lisdexamfetamine: (Minor) Lisdexamfetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
Lithium: (Moderate) Monitor serum lithium concentrations during concomitant angiotensin II receptor blocker use; reduce the lithium dose based on serum lithium concentration and clinical response. Concomitant use may increase steady-state lithium concentrations.
Loop diuretics: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
Loratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as angiotensin II receptor antagonists.
Meglitinides: (Moderate) Angiotensin II receptor antagonists (ARB) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Repaglinide: (Moderate) Angiotensin II receptor antagonists (ARB) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Rosiglitazone: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Methamphetamine: (Minor) Methamphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
Methohexital: (Moderate) Concurrent use of methohexital and antihypertensive agents increases the risk of developing hypotension.
Methylphenidate Derivatives: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Miglitol: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Naproxen; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Nateglinide: (Moderate) Angiotensin II receptor antagonists (ARB) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
Nefazodone: (Minor) Although relatively infrequent, nefazodone may cause orthostatic hypotension in some patients; this effect may be additive with antihypertensive agents. Blood pressure monitoring is recommended. Dependent upon clinical response, dosage adjustments of either drug may be necessary.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Nitrates: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Nitroglycerin: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Fluoxetine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Samidorphan: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. If these drugs are used together, closely monitor for changes in blood pressure.
Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and angiotensin II receptor antagonists who are susceptible to hypotension.
Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced.
Phenelzine: (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Pioglitazone; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Polyethylene Glycol; Electrolytes: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as angiotensin II receptor antagonists.
Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as angiotensin II receptor antagonists.
Potassium Phosphate: (Major) Avoid coadministration of potassium phosphate and angiotensin II receptor antagonists as concurrent use may increase the risk of severe and potentially fatal hyperkalemia, particularly in high-risk patients (renal impairment, cardiac disease, adrenal insufficiency). If concomitant use is necessary, closely monitor serum potassium concentrations.
Potassium Phosphate; Sodium Phosphate: (Major) Avoid coadministration of potassium phosphate and angiotensin II receptor antagonists as concurrent use may increase the risk of severe and potentially fatal hyperkalemia, particularly in high-risk patients (renal impairment, cardiac disease, adrenal insufficiency). If concomitant use is necessary, closely monitor serum potassium concentrations.
Potassium: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Pramlintide: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of pramlintide by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with pramlintide should be monitored for changes in glycemic control.
Prazosin: (Moderate) Monitor blood pressure during concomitant use of prazosin and angiotensin II receptor blockers (ARBs). Concomitant use may produce additive hypotension and increase the risk for syncope. The risk for significant hypotension and syncope is greatest when adding an antihypertensive to a regimen that includes high dose prazosin and following a rapid dosage increase. To minimize the risk for adverse effects, consider reducing the prazosin dose to 1 to 2 mg three times a day during initiation of a new antihypertensive and then retitrating prazosin based on clinical response.
Prilocaine; Epinephrine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
Procainamide: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
Promethazine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Pseudoephedrine; Triprolidine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Rasagiline: (Moderate) Additive hypotensive effects may be seen when rasagiline is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during coadministration. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Repaglinide: (Moderate) Angiotensin II receptor antagonists (ARB) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
Risperidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of angiotensin II receptor antagonists. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving angiotensin II receptor antagonists concomitantly.
Sevoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
SGLT2 Inhibitors: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Silodosin: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as angiotensin II receptor antagonists, may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Moderate) Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that may affect renal function such as angiotensin II receptor antagonists. In addition, use caution in patients receiving drugs where hypokalemia is a particular risk.
Sparsentan: (Contraindicated) Concomitant use of sparsentan and angiotensin receptor blockers (ARBs) is contraindicated due to the additive risk for serious adverse effects such as hypotension, syncope, hyperkalemia, and renal dysfunction.
Spironolactone: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Sulfonylureas: (Moderate) Monitor blood glucose during concomitant sulfonylurea and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents.
Thiazolidinediones: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Tizanidine: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Tolvaptan: (Moderate) Monitor serum potassium concentrations closely if tolvaptan and angiotensin II receptor blockers are used together. In clinical studies, hyperkalemia was reported at a rate 1% to 2% higher when tolvaptan was administered with angiotensin II receptor blockers compared to administration of these medications with placebo.
Tranylcypromine: (Contraindicated) The use of hypotensive agents and tranylcypromine is contraindicated by the manufacturer of tranylcypromine because the effects of hypotensiv

e agents may be markedly potentiated.
Trazodone: (Minor) Due to additive hypotensive effects, patients receiving antihypertensive agents concurrently with trazodone may have excessive hypotension. Decreased dosage of the antihypertensive agent may be required when given with trazodone.
Triamterene: (Moderate) Monitor serum potassium concentrations in patients receiving angiotensin II receptor antagonists concomitantly with triamterene. Concomitant use may result in hyperkalemia.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations in patients receiving angiotensin II receptor antagonists concomitantly with triamterene. Concomitant use may result in hyperkalemia.
Trimethoprim: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Ziprasidone: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.

Benicar/Olmesartan Medoxomil Oral Tab: 5mg, 20mg, 40mg

Adults

40 mg/day PO.

Geriatric

40 mg/day PO.

Adolescents

17 years: 40 mg/day PO.
13 to 16 years weighing 35 kg or more: 40 mg/day PO.
13 to 16 years weighing 20 to 34 kg: 20 mg/day PO.

Children

6 to 12 years weighing 35 kg or more: 40 mg/day PO.
6 to 12 years weighing 20 to 34 kg: 20 mg/day PO.
6 to 12 years weighing less than 20 kg: Safety and efficacy have not been established.
1 to 5 years: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Mechanism of Action: Olmesartan antagonizes angiotensin II at the AT1 receptor subtype in vascular smooth muscle. Two angiotensin II receptors, AT1 and AT2, have been identified; olmesartan exhibits more than 12,500-fold greater affinity for the AT1 receptor than the AT2 receptor. The AT2 subtype is not known to mediate cardiovascular homeostasis. Angiotensin II is the primary vasoactive hormone of the renin-angiotensin system and plays an important role in the pathophysiology of hypertension and congestive heart failure. Besides being a potent vasoconstrictor, the effects of angiotensin II include stimulation of the synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. By blocking the effects of angiotensin II, olmesartan decreases systemic vascular resistance without a marked change in heart rate. Circulating levels of both renin and angiotensin II rise in response to blockade of AT1 receptors; however, the increases in renin and angiotensin II do not overcome the effect of olmesartan on blood pressure. Because olmesartan does not inhibit angiotensin-converting enzyme (ACE), it does not affect the breakdown of bradykinin. Similar to ACE inhibitors, angiotensin II antagonists reduce LVH, do not worsen insulin resistance or serum lipid profiles, and generally do not cause sexual dysfunction.

Olmesartan is administered orally. It is highly bound to plasma proteins (99%). Following conversion of olmesartan medoxomil to the active drug olmesartan, there is virtually no further metabolism. Olmesartan appears to be eliminated in a biphasic manner with a terminal elimination half-life of approximately 13 hours. Steady state levels are achieved in 3—5 days and no accumulation in plasma occurs with once-daily dosing. Almost half of the administered dose (35—50%) is eliminated in urine, while the remainder is eliminated in the feces via biliary excretion.
 
Affected cytochrome P450 isoenzymes and drug transporters: none
Olmesartan is not metabolized by the hepatic cytochrome P450 enzyme system and has no effects in vitro on CYP450 enzymes.

Oral Route

Olmesartan medoxomil is rapidly and completely converted (de-esterified) to olmesartan during absorption from the gastrointestinal tract. The absolute bioavailability of olmesartan is approximately 26%. Peak concentrations are reached about 1—2 hours after dosing. Food does not affect the bioavailability of the drug.

Pregnancy

When pregnancy is detected, every effort should be made to discontinue olmesartan therapy. Women of child-bearing age should be made aware of the potential risk, and olmesartan should only be given after careful counseling and consideration of individual risks and benefits. When used during the second and third trimesters, medications that affect the renin-angiotensin system (e.g., ACE inhibitors, angiotensin II receptor antagonists) have been associated with reduced fetal renal function and increased fetal and neonatal morbidity and death. Use of drugs that affect the renin-angiotensin system during pregnancy can cause fetal death or injury such as hypotension, neonatal skull hypoplasia, reversible or irreversible renal failure and death. Anhydramnios and oligohydramnios have also been reported. Development of oligohydramnios may be associated with decreased fetal renal function leading to anuria and renal failure and results in fetal limb contractures, craniofacial deformation, hypotension, hypoplastic lung development, and death. Retrospective data indicate that first trimester use of ACE inhibitors has been associated with a potential risk of birth defects. However, a much larger observational study (n = 465,754) found that the risk of birth defects was similar in infants exposed to ACE inhibitors during the first trimester, in infants exposed to other antihypertensives during the first trimester, and in those whose mothers were hypertensive but were not treated. Infants born to mothers with hypertension, either treated or untreated, had a higher risk of birth defects than those born to mothers without hypertension. The authors concluded that the presence of hypertension likely contributed to the development of birth defects rather than the use of medications. An observational cohort study evaluating the outcomes of angiotensin receptor blockers (ARBs) use during the first trimester of pregnancy found an increased rate of major birth defects compared to non-hypertensive pregnancies, 5.4% and 3%, respectively; the difference did not reach statistical significance. The authors noted that there was a higher risk of major birth defects with ARB therapy beyond 6 weeks of gestation compared to discontinuation of ARBs before week 6, 7.3% and 2.8%, respectively. The rates of prematurity and reduced birth weight were also increased in the ARB group. There were no statistically significant differences in the rates of major birth defects, spontaneous abortions, or preterm births between women with chronic hypertension treated with an ARB versus methyldopa. In rare cases when another antihypertensive agent cannot be used to treat a pregnant patient, serial ultrasound examinations should be performed to assess the intraamniotic environment. If oligohydramnios is observed, discontinue olmesartan unless it is considered life-saving for the mother. It should be noted that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe newborns with histories of in utero exposure to olmesartan for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occurs, blood pressure and renal perfusion support may be required, as well as exchange transfusion or dialysis to reverse hypotension and/or support decreased renal function.

Breast-feeding is not recommended during olmesartan treatment. According to the manufacturer, it is not known whether olmesartan is excreted into human milk. Because of the potential for adverse effects on the nursing infant, a decision should be made to discontinue breast-feeding or discontinue olmesartan therapy. Alternative therapies may be considered. Due to low levels in breast milk, guidelines generally consider the ACE inhibitors captopril and enalapril to be compatible with breast-feeding unless high doses are required. In addition, benazepril and quinapril are excreted in low quantities into breast milk and have been suggested as options during breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.