olmesartan (Rx)

1-10%

Dizziness

Headache

Fatigue

Diarrhea

Hyperglycemia

Hypertriglyceridemia

Back pain

Bronchitis

Inflicted injury

Flulike symptoms

Pharyngitis

Rhinitis

Sinusitis

Upper respiratory tract infection (URTI)

Frequency Not Defined (selected)

Anaphylactic reaction

Angioedema

Facial edema

Rhabdomyolysis

Hyperkalemia

Tachycardia

Hypercholesterolemia

Gastroenteritis

Hyperlipidemia

Contraindications

Hypersensitivity

Do not coadminister with aliskiren in patients with diabetes mellitus or with renal impairment (ie, GFR <60 mL/min/1.73 m²)

Cautions

Use caution in congestive heart failure (CHF), surgery or anesthesia, volume depletion (consider lower dosage)

Angioedema reported; may occur at any time during treatment, especially after first dose; risk increases in patients with idiopathic or hereditary angioedema or experiencing angioedema following ACE-inhibitor therapy; prolonged monitoring of air pathways may be necessary as reactions are associated with airway obstruction; not for administration to patients with prior history of angioedema following therapy with ARBs; discontinue therapy immediately if angioedema occurs; intramuscular administration of epinephrine may be necessary to manage angioedema

Coadministration with mTOR inhibitors (eg, temsirolimus) may increase risk for angioedema

Risk of hypotension, especially in patients with volume or salt depletion secondary to salt restriction or prolonged diuretic treatment; initiate treatment in such patients under close medical supervision and consider starting at a lower dose

Risk of hyperkalemia; monitor serum electrolytes periodically; use with caution, if at all and monitor potassium closely in patients with risk factors, including diabetes mellitus, renal dysfunction, potassium supplements and/or potassium containing salts

Use with caution in patients with unstented unilateral/bilateral renal artery stenosis; avoid therapy when unstented bilateral renal artery stenosis is present due to elevated risk of deterioration in renal function unless possible benefits outweigh risks

Renal impairment reported; may occur in patients with low renal blood flow (eg, heart failure, renal artery stenosis), whose glomerular filtration rate is dependent on efferent arteriolar vasoconstriction by angiotensin II, which may result in acute renal failure, oliguria, and progressive azotemia; discontinue therapy only in patients with progressive and/or significant deterioration in renal function

Use caution in patients with pre-existing renal insufficiency

Avoid use in patients with ascites resulting from cirrhosis or refractory ascites; monitor blood pressure and renal function closely if use cannot be avoided

Intestinal problems (ie, sprue-like enteropathy) reported; symptoms may include severe, chronic diarrhea with substantial weight loss; discontinue treatment and consider other antihypertensive therapy

Dual blockade of the renin-angiotensin system with angiotensin-receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, or aliskiren is associated with increased risk of hypotension, hyperkalemia, and altered renal function (including acute renal failure) in comparison with monotherapy; closely monitor blood pressure

Children <1 year of age must not receive olmesartan for hypertension; drugs that act directly on the renin-angiotensin-aldosterone system can have adverse effects on the development of immature kidneys

Pregnancy

Can cause fetal harm when administered to a pregnant woman; use of drugs that act on renin-angiotensin system during second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death

Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents

Hypertension in pregnancy increases maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and post-partum hemorrhage)

Hypertension increases fetal risk for intrauterine growth restriction and intrauterine death

Pregnant women with hypertension should be carefully monitored and managed accordingly

Fetal adverse reactions

• Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in
• Reduced fetal renal function leading to anuria and renal failure
• Fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death
• In patients taking drug during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment
• Fetal testing may be appropriate, based on the week of gestation
• Patients and physicians should be aware, that oligohydramnios may not appear until after the fetus has sustained irreversible injury
• Closely observe infants with histories of in utero exposure to drug for hypotension, oliguria, and hyperkalemia
• In neonates with a history of in utero exposure to drug, if oliguria or hypotension occurs, utilize measures to maintain adequate blood pressure and renal perfusion
• Exchange transfusions or dialysis may be required as a means of reversing hypotension and supporting renal function

Animal data

• In animal reproduction studies, treatment during organogenesis resulted in increased embryofetal toxicity in rats at doses lower than maternally toxic doses
• Discontinue therapy as soon as possible when pregnancy detected; consider alternative antihypertensive therapy during pregnancy

Lactation

There is no information regarding presence of drug in human milk, effects on breastfed infant, or on milk production; drug is secreted at low concentration in milk of lactating rats; because of potential for adverse effects on nursing infant, a decision should be made whether to discontinue nursing or discontinue drug, considering importance of drug to mother

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Blocks binding of angiotensin II to type 1 angiotensin II receptors; blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II

Absorption

Bioavailability: 26%

Onset: <2 weeks

Peak response: 4-6 weeks

Duration: 24 hr

Peak plasma time: 1-2 hr

Distribution

Protein bound: 99%

Vd: 17 L; does not cross blood-brain barrier

Metabolism

Rapidly and completely deesterified to active olmesartan in intestinal wall; no further metabolism occurs

Metabolites: RNH-6270 (deesterified olmesartan; active)

Elimination

Half-life: 13 hr

Renal clearance: 0.5-0.8 L/hr

Total body clearance: 1.3 L/hr

Excretion: Bile (50-65%), urine (35-50%)