Amlodipine-Olmesartan (amlodipine besylate/olmesartan medoxomil)

Olmesartan is available as olmesartan medoxomil; dosages are expressed in terms of the salt. Dosage of olmesartan medoxomil must be individualized.

Dosage of amlodipine besylate and amlodipine benzoate is expressed in terms of amlodipine.

Olmesartan medoxomil is administered orally without regard to meals. Twice-daily dosing offers no therapeutic advantage over the same total dose given once daily.

Olmesartan medoxomil is commercially available as a film-coated tablet. It is also commercially available in fixed-combination tablets containing olmesartan medoxomil with hydrochlorothiazide, olmesartan medoxomil with amlodipine and hydrochlorothiazide, and olmesartan medoxomil with amlodipine; see the full prescribing information of these products for administration information.

Store olmesartan tablets at 20-25degreesC.

For pediatric patients unable to swallow tablets, olmesartan may be administered orally as an extemporaneously prepared suspension. An extemporaneous suspension containing olmesartan medoxomil 2 mg/mL can be prepared in the following manner. First, 50 mL of purified water is added to an amber polyethylene terephthalate (PET) bottle containing twenty 20-mg tablets of olmesartan medoxomil, and the contents allowed to stand for a minimum of 5 minutes. The container should then be shaken for at least 1 minute and allowed to stand for at least 1 minute; this step of alternating shaking and standing should be repeated 4 additional times. The concentrated suspension should then be diluted with 100 mL of syrup (Ora-Sweet(R)) and 50 mL of a suspending vehicle (Ora-Plus(R)) and the container shaken well for at least 1 minute to disperse the ingredients. The suspension should be shaken well before dispensing each dose. The extemporaneous suspension is stable for up to 4 weeks when stored at 2-8degreesC. Olmesartan medoxomil tablets and the extemporaneously prepared oral suspension of the drug are bioequivalent.

Amlodipine is administered orally (as tablets, solution, or suspension) without regard to meals, preferably at the same time each day. Amlodipine is also commercially available in fixed combination with benazepril (e.g., Lotrel(R)), olmesartan medoxomil (e.g., Azor(R)), olmesartan medoxomil and hydrochlorothiazide (e.g., Tribenzor(R)), telmisartan, valsartan (e.g., Exforge(R)), valsartan and hydrochlorothiazide (e.g., Exforge(R) HCT), and atorvastatin (e.g., Caduet(R)). See the full prescribing information for additional administration instructions for each specific combination product.

If a dose of amlodipine is missed, the missed dose may be administered as soon as possible. If the dose is missed for more than 12 hours, do not take the dose and resume treatment with the next scheduled dose.

Amlodipine besylate tablets: Store the tablets at 15-30degreesC; dispense in a tight, light-resistant container.

Amlodipine besylate oral solution (Norliqva(R)): Store the oral solution at 20-25degreesC (excursions permitted to 15-30degreesC). Store and dispense in the original packaging (amber glass bottle).

Amlodipine benzoate oral suspension (Katerzia(R)): Shake the suspension well and measure each dose with a calibrated measuring device; do not use a household teaspoon or tablespoon. Store the oral suspension at 2-8degreesC and protect from light. Avoid freezing and excessive heat.

No dosing information is available for this tab.

No dosing information is available for this tab.

Amlodipine is a weak inhibitor of cytochrome P-450 (CYP) 3A isoenzymes.

When amlodipine is used in fixed combination with other drugs, interactions associated with the concomitant agent(s) must be considered in addition to those associated with amlodipine.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Concomitant therapy with aliskiren in patients with diabetes mellitus.

Amlodipine is contraindicated in patients with known hypersensitivity to the drug.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

In placebo-controlled studies, the only adverse effect that occurred in more than 3% of adults receiving olmesartan, and at an incidence greater than with placebo, was dizziness. The incidence of adverse effects was not affected by age, gender, or race.

Adverse effects reported in 1% or more of patients receiving amlodipine include dose-related edema, dizziness, flushing, and palpitations; fatigue, nausea, abdominal pain, and somnolence also reported. Adverse effects reported in the clinical trial in pediatric patients with hypertension were similar to those that have been reported in adults.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

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Safety and efficacy of olmesartan have been established in a randomized, double-blind, placebo-controlled trial in pediatric patients 6-16 years of age with hypertension. Similar to adults, smaller blood pressure reductions have been observed in Black pediatric patients compared with non-Black pediatric patients. Adverse effects generally were similar to those observed in adults.

Olmesartan has also been studied in 59 patients who were 1-5 years of age; treatment with olmesartan medoxomil (0.3 mg/kg once daily) in this age group did not result in a statistically significant reduction in blood pressure compared with placebo. The manufacturer states that olmesartan has not been shown to be effective for hypertension in patients <6 years of age. Olmesartan has not been evaluated in infants <1 year of age; because of the possibility of abnormal kidney development, the drug must not be used in this age group.

Pharmacokinetics of olmesartan have been evaluated in pediatric patients 1-16 years of age; clearance of the drug (adjusted for body weight) in these pediatric patients was similar to that observed in adults.

Safety and efficacy of amlodipine in children younger than 6 years of age have not been established. Safety and effectiveness of amlodipine (2.5-5 mg daily) for the treatment of pediatric patients 6-17 years of age with hypertension have been established in a trial of 8 weeks' duration.

Safety and efficacy of amlodipine in fixed combination with atorvastatin, benazepril, olmesartan (with or without hydrochlorothiazide), telmisartan, or valsartan (with or without hydrochlorothiazide) have not been established in pediatric patients.

Olmesartan may cause fetal and neonatal morbidity and mortality when administered to a pregnant woman. Olmesartan should be discontinued as soon as possible when pregnancy is detected. Alternative antihypertensive agents should be considered during pregnancy.

Untreated hypertension during pregnancy is associated with an increased risk of maternal preeclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and risk of post-partum hemorrhage). Hypertension also increases the risk of fetal growth restriction in utero, and intrauterine death.

In pregnant women who receive olmesartan during pregnancy, serial ultrasound examinations should be performed along with fetal testing, based on gestational age. Oligohydramnios may not appear, however, until the fetus has sustained irreversible injury.

In infants with exposure to olmesartan in utero, carefully observe for hypotension, oliguria, and hyperkalemia, and use appropriate measures to maintain adequate blood pressure and renal perfusion. Exchange transfusions or dialysis may be required.

The manufacturers state that there are limited data on use of amlodipine in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. There is some data indicating that amlodipine crosses the placenta in measurable quantities in the third trimester of pregnancy.

Hypertension in pregnancy is a major cause of maternal, fetal or neonatal morbidity and mortality. Maternal risks include pre-eclampsia, gestational diabetes, premature delivery, placental abruption, delivery complications (e.g., need for cesarean section, postpartum hemorrhage), stroke, pulmonary edema, thromboembolic events, multiple organ failure (liver, kidney) and disseminated intravascular coagulation. Fetal risks include intrauterine growth restriction, prematurity, and intrauterine death. Neonates may require prolonged high-level care and experience morbidity. Pregnant women with hypertension should be carefully monitored and managed accordingly.

Teratogenicity or other embryo-fetal toxicity was not observed when pregnant rats and rabbits were treated orally with a different salt form of amlodipine (amlodipine maleate) at doses up to 10 mg/kg per day (approximately 10 and 20 times the maximum recommended human dose (MRHD) based on body surface area, respectively) during their respective periods of major organogenesis. However, when amlodipine maleate at doses up to 10 mg amlodipine/kg per day was administered to rats for 14 days prior to mating and throughout gestation, litter size decreased approximately 50%, and a 5-fold increase in the number of intrauterine deaths was observed at this dose equivalent to 10 times the MDRD. Amlodipine maleate has also been shown to prolong both the gestation period and the duration of labor in rats at this dose.

Olmesartan is distributed into milk in rats; it is not known whether the drug is distributed into milk in humans. The effects of olmesartan on the breast-fed child or on milk production are not known. Because of the potential for serious adverse reactions to olmesartan in breast-feeding infants, a decision should be made whether to discontinue breast-feeding or the drug, taking into account the importance of the drug to the woman.

The manufacturer states limited available data from a published clinical lactation study reported that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. No adverse effects of amlodipine on the breastfed infant have been observed; there is no available information on the effects of amlodipine on milk production.

The manufacturer states that no adjustment in initial olmesartan medoxomil dosage is necessary in geriatric patients.

The elimination of amlodipine may be impaired substantially in geriatric patients, resulting in increased exposure to the drug (AUC increases of 40-60%). For management of hypertension, some manufacturers recommend an initial amlodipine dosage of 2.5 mg once daily for geriatric patients. For management of vasospastic (Prinzmetal variant) angina or chronic stable angina in geriatric patients, an amlodipine dosage of 5 mg daily is recommended; adequate control of angina usually requires a maintenance dosage of 10 mg once daily.

No overall differences in safety and efficacy of olmesartan have been observed in geriatric patients >=65 years of age relative to younger adults, but increased sensitivity to the drug cannot be ruled out.

Modest accumulation of olmesartan has been observed in geriatric patients following repeated doses.

In geriatric patients, amlodipine clearance is decreased and AUC is increased by about 40-60%. Therefore, amlodipine dosage should be selected carefully, usually initiating therapy with dosages at the lower end of the recommended range (i.e., 2.5 mg daily). The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly also should be considered.

Clinical studies of amlodipine did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients; however, other clinical experience has not revealed age-related differences in response or tolerance.