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Amlodipine And Olmesartan Medoxomil

FDA Drug Information • Also known as: Amlodipine And Olmesartan Medoxomil

Brand Names
Amlodipine And Olmesartan Medoxomil
Route
ORAL
Dosage Form
TABLET, FILM COATED
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: FETAL TOXICITY

  • When pregnancy is detected, discontinue amlodipine and olmesartan medoxomil tablets as soon as possible ( 5.1, 8.1).
  • Drugs that act directly on the renin-angiotensin system (RAS) can cause injury and death to the developing fetus (5.1, 8.1). WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning.
  • When pregnancy is detected, discontinue amlodipine and olmesartan medoxomil tablets as soon as possible ( 5.1 , 8.1 ).
  • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus ( 5.1 , 8.1 ).

    • Description

    11 DESCRIPTION Amlodipine and olmesartan medoxomil USP provided as a tablet for oral administration, is a combination of the calcium channel blocker (CCB) amlodipine besylate and the angiotensin II receptor blocker (ARB) olmesartan medoxomil. The amlodipine besylate component of amlodipine and olmesartan medoxomil tablet is chemically described as 3,5-pyridine dicarboxylic acid, 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl,3-ethyl 5-methyl ester, (±)-monobenzene sulfonate. Its molecular formula is C 26 H 31 ClN 2 O 8 S. Olmesartan medoxomil, a prodrug, is hydrolyzed to olmesartan during absorption from the gastrointestinal tract. The olmesartan medoxomil component of amlodipine and olmesartan medoxomil tablet is chemically described as 1H-Imadazole-5-carboxylic acid, 4-(1-hydroxy-1-methyl-ethyl)- 2-Propyl-1-[[2’-(1H tetrazole-5-yl) [1,1’-biphenyl]-4-yl]methyl-, (5- methyl-2-oxo-1, 3-dioxol-4-yl) methyl ester. Its molecular formula is C 29 H 30 N 6 O 6 . The structural formula for amlodipine besylate is: The structural formula for olmesartan medoxomil is: Amlodipine and olmesartan medoxomil tablet USP contains amlodipine besylate USP, a white or almost white powder, and olmesartan medoxomil USP, a white to off white crystalline powder. The molecular weights of amlodipine besylate and olmesartan medoxomil are 567.1 and 558.6, respectively. Amlodipine besylate USP is freely soluble in methanol, sparingly soluble in ethanol, slightly soluble in 2-propanol and in water. Olmesartan medoxomil USP is practically insoluble in water and in heptane, slightly soluble in ethanol (96%), sparingly soluble in methanol. Each tablet of amlodipine and olmesartan medoxomil also contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose and pregelatinized starch. The color coating contains polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide. In addition, the 5 mg/40 mg, 10...

    What Is Amlodipine And Olmesartan Medoxomil Used For?

    1 INDICATIONS AND USAGE Amlodipine and olmesartan medoxomil tablet is indicated for the treatment of hypertension, alone or with other antihypertensive agents, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular (CV) events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with amlodipine and olmesartan medoxomil tablet. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Amlodipine and olmesartan medoxomil tablet may also be used as initial therapy in patients who are likely to need multiple antihypertensive agents to achieve their blood pressure goals. Patients with moderate or severe hypertension are at relatively high risk for cardiovascular events (such as strokes, heart...

    Dosage and Administration

    2 DOSAGE AND ADMINISTRATION The usual starting dose of amlodipine and olmesartan medoxomil tablet is 5 mg/20 mg once daily. The dosage can be increased after 1 to 2 weeks of therapy to a maximum dose of one 10 mg/40 mg tablet once daily as needed to control blood pressure [see Clinical Studies (14.1)] .

  • Recommended starting dose: 5 mg/20 mg once daily (2).
  • Titrate as needed in two week intervals up to a maximum of 10 mg/40 mg once daily ( 2 ).

    • Side Effects (Adverse Reactions)

    6 ADVERSE REACTIONS Most common adverse reaction (incidence ≥3%) is edema ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Hetero Labs Limited at 1-866-495-1995 or FDA at 1-800-332-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Amlodipine and olmesartan medoxomil The data described below reflect exposure to amlodipine and olmesartan medoxomil in more than 1600 patients including more than 1000 exposed for at least 6 months and more than 700 exposed for 1 year. Amlodipine and olmesartan medoxomil was studied in one placebo-controlled factorial trial [see Clinical Trials ( 14.1 )]. The population had a mean age of 54 years and included approximately 55% males. Seventy-one percent were Caucasian and 25% were Black. Patients received doses ranging from 5 mg/20 mg to 10 mg/40 mg orally once daily. The overall incidence of adverse reactions on therapy with amlodipine and olmesartan medoxomil was similar to that seen with corresponding doses of the individual components of amlodipine and olmesartan medoxomil, and to placebo. The reported adverse reactions were generally mild and seldom led to discontinuation of treatment (2.6% for amlodipine and olmesartan medoxomil and 6.8% for placebo). Edema Edema is a known, dose-dependent adverse effect of amlodipine but not of olmesartan medoxomil. The placebo-subtracted incidence of edema during the 8-week, randomized, double-blind treatment period was highest with amlodipine 10 mg monotherapy. The incidence was significantly reduced when 20 mg or 40 mg of olmesartan medoxomil was added to the 10 mg amlodipine dose. Placebo-Subtracted Incidence of Edema During the Double-Blind Treatment Period Olmesartan Medoxomil Placebo 20 mg 40 mg Amlodipine Placebo － * -2.4% 6.2% 5 mg 0.7% 5.7% 6.2% 10 mg 24.5% 13.3% 11.2% *12.3% = actual placebo incidence Across all treatment groups, the frequency of edema was generally higher in women than men, as has been observed in previous studies of amlodipine. There was a greater decrease in hemoglobin and hematocrit in patients treated with amlodipine and olmesartan medoxomil as compared to patients receiving either component. Adverse reactions seen at lower rates during the double-blind period also occurred in the patients treated with amlodipine and olmesartan medoxomil at about the same or greater incidence as in patients receiving placebo. These included hypotension, orthostatic hypotension, rash, pruritus, palpitation, urinary frequency, and nocturia. The adverse event profile obtained from 44 weeks of open-label combination therapy with amlodipine plus olmesartan medoxomil was similar to that observed during the 8-week, double-blind, placebo-controlled period. Initial Therapy Analyzing the data described above specifically for initial therapy, it was observed that higher doses of amlodipine and olmesartan medoxomil caused slightly more hypotension and orthostatic symptoms, but not at the recommended starting dose of amlodipine and olmesartan medoxomil 5 mg/20 mg. No increase in the incidence of syncope or near syncope was observed. The incidences of discontinuation because of any treatment emergent adverse events in the double-blind phase are summarized in the table below. Discontinuation for any Treatment Emergent Adverse Event 1 Olmesartan Medoxomil Placebo 10 mg 20 mg 40 mg Amlodipine Placebo 4.9% 4.3% 5.6% 3.1% 5 mg 3.7% 0% 1.2% 3.7% 10 mg 5.5% 6.8% 2.5% 5.6% 1 Hypertension is counted as treatment failure and not as treatment emergent adverse event. N=160 to 163 subjects per treatment group. Amlodipine Amlodipine has been evaluated for safety in more than 11,000 patients in U.S. and foreign clinical trials. Most adverse reactions reported during therapy with amlodipine...

    Drug Interactions

    7 DRUG INTERACTIONS Amlodipine ( 7.1 ):

  • If simvastatin is co-administered with amlodipine, do not exceed 20 mg daily of simvastatin.
  • Increased exposure of cyclosporine and tacrolimus.
  • Increased exposure of amlodipine when coadministered with CYP3A inhibitors. Olmesartan medoxomil ( 7.2 ):
  • Nonsteroidal anti-inflammatory drugs (NSAIDS) may lead to increased risk of renal impairment and loss of antihypertensive effect.
  • Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia.
  • Colesevelam hydrochloride: Consider administering olmesartan at least 4 hours before colesevelam hydrochloride dose.
  • Lithium: Increases in serum lithium concentrations and lithium toxicity. 7.1 Drug Interactions with Amlodipine Simvastatin: Co-administration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily [see Clinical Pharmacology ( 12.3) ]. Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. Frequent monitoring of trough blood levels of cyclosporine and tacrolimus is recommended and adjust the dose when appropriate [see Clinical Pharmacology ( 12.3) ]. CYP3A Inhibitors: Co-administration of amlodipine with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is co-administered with CYP3A inhibitors to determine the need for dose adjustment. CYP3A Inducers: No information is available on the quantitative effects of CYP3A inducers on amlodipine. Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers. 7.2 Drug Interactions with Olmesartan Medoxomil Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors): In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including olmesartan medoxomil, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving olmesartan medoxomil and NSAID therapy. The antihypertensive effect of angiotensin II receptor antagonists, including olmesartan medoxomil may be attenuated by NSAIDs including selective COX-2 inhibitors. Dual Blockade of the Renin-Angiotensin System (RAS): Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional...

    • Contraindications

    4 CONTRAINDICATIONS Do not co-administer aliskiren with amlodipine and olmesartan medoxomil tablet in patients with diabetes [see Drug Interactions ( 7.2) ].

  • Do not co-administer aliskiren with amlodipine and olmesartan medoxomil tablet in patients with diabetes ( 4 ).

    • Pregnancy and Breastfeeding

    8.1 Pregnancy Risk Summary Amlodipine and olmesartan medoxomil can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death [see Clinical Considerations] . 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. When pregnancy is detected, discontinue amlodipine and olmesartan medoxomil as soon as possible. Consider alternative antihypertensive therapy during pregnancy. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly. Fetal/Neonatal Adverse Reactions Olmesartan medoxomil Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. Perform serial ultrasound examinations to assess...

    Overdosage

    10 OVERDOSAGE There is no information on overdosage with amlodipine and olmesartan medoxomil in humans. Amlodipine . Single oral doses of amlodipine maleate equivalent to 40 mg amlodipine/kg and 100 mg amlodipine/kg in mice and rats, respectively, caused deaths. Single oral amlodipine maleate doses equivalent to 4 or more mg amlodipine/kg or higher in dogs (11 or more times the maximum recommended human dose on a mg/m2 basis) caused a marked peripheral vasodilation and hypotension. Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional overdosage of amlodipine is limited. If massive overdose should occur, active cardiac and respiratory monitoring should be instituted. Frequent blood pressure measurements are essential. Should hypotension occur, cardiovascular support including elevation of the extremities and the judicious administration of fluids should be initiated. If hypotension remains unresponsive to these conservative measures, administration of vasopressors (such as phenylephrine) should be considered with attention to circulating volume and urine output. Intravenous calcium gluconate may help to reverse the effects of calcium entry blockade. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit. Olmesartan medoxomil. Limited data are available related to overdosage in humans. The most likely manifestations of overdosage would be hypotension and tachycardia; bradycardia could be encountered if parasympathetic (vagal) stimulation occurs. If symptomatic hypotension should occur, supportive treatment should be initiated. The dialyzability of olmesartan is unknown.

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING Amlodipine and olmesartan medoxomil tablets USP contain amlodipine besylate at a dose equivalent to 5 mg or 10 mg amlodipine and olmesartan medoxomil in the strengths described below. Amlodipine and olmesartan medoxomil tablets USP are supplied for oral administration in the following strength and package configurations: Amlodipine and olmesartan medoxomil tablets USP, 5 mg/20 mg are white to off-white, round, biconvex film coated tablets debossed with ‘H’ on one side and ‘A 9’ on the other side. They are supplied as follows: Bottle of 30 tablets NDC 31722-445-30 Bottle of 90 tablets NDC 31722-445-90 Amlodipine and olmesartan medoxomil tablets USP, 5 mg/40 mg are cream, round, biconvex film coated tablets debossed with ‘H’ on one side and ‘A 11’ on the other side. They are supplied as follows: Bottle of 30 tablets NDC 31722-446-30 Bottle of 90 tablets NDC 31722-446-90 Amlodipine and olmesartan medoxomil tablets USP, 10 mg/20 mg are grayish orange, round, biconvex film coated tablets debossed with ‘H’ on one side and ‘A 10’ on the other side. They are supplied as follows: Bottle of 30 tablets NDC 31722-447-30 Bottle of 90 tablets NDC 31722-447-90 Amlodipine and olmesartan medoxomil tablets USP, 10 mg/40 mg are brownish-red, round, biconvex film coated tablets debossed with ‘H’ on one side and ‘A 12’ on the other side. They are supplied as follows: Bottle of 30 tablets NDC 31722-448-30 Bottle of 90 tablets NDC 31722-448-90 Store at 20° to 25°C (68°F to 77°F) [see USP Controlled Room Temperature] .

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.