Olmesartan Medoxomil, Amlodipine Besylate And Hydrochlorothiazide
FDA Drug Information • Also known as: Olmesartan Medoxomil, Amlodipine And Hydrochlorothiazide
- Brand Names
- Olmesartan Medoxomil, Amlodipine And Hydrochlorothiazide
- Drug Class
- Thiazide Diuretic [EPC]
- Route
- ORAL
- Dosage Form
- TABLET, FILM COATED
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: FETAL TOXICITY When pregnancy is detected, discontinue olmesartan medoxomil, amlodipine and hydrochlorothiazide 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 olmesartan medoxomil, amlodipine and hydrochlorothiazide 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 Olmesartan medoxomil, amlodipine and hydrochlorothiazide provided as a tablet for oral administration, is a fixed combination of olmesartan medoxomil (ARB), amlodipine (CCB), and hydrochlorothiazide (thiazide diuretic). Olmesartan medoxomil USP, a prodrug, is hydrolyzed to olmesartan during absorption from the gastrointestinal tract. The olmesartan medoxomil USP component of olmesartan medoxomil, amlodipine, hydrochlorothiazide tablet is chemically described as 2,3-dihydroxy-2-butenyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[ p -( o -1 H -tetrazol-5ylphenyl)benzyl]imidazole-5-carboxylate, cyclic 2,3-carbonate. Its molecular formula is C 29 H 30 N 6 O 6 . The amlodipine besylate USP component of olmesartan medoxomil, amlodipine, hydrochlorothiazide tablet is chemically described as 3-ethyl-5methyl (±)-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5pyridinedicarboxylate, monobenzenesulphonate. Its molecular formula is C 20 H 25 CIN 2 O 5
What Is Olmesartan Medoxomil, Amlodipine Besylate And Hydrochlorothiazide Used For?
1 INDICATIONS AND USAGE Olmesartan medoxomil, amlodipine and hydrochlorothiazide 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 olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets. 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. Limitations of Use This fixed combination drug is not indicated for the initial therapy of hypertension. Olmesartan medoxomil, amlodipine and hydrochlorothiazide tablet is a combination of olmesartan medoxomil, an angiotensin II receptor blocker, amlodipine, a...
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Dose once daily. Dosage may be increased in 2-week intervals, as needed. The maximum recommended dose of olmesartan medoxomil, amlodipine and hydrochlorothiazide is 40/10/25 mg. Dose selection should be individualized based on previous therapy. Dose once daily. Dosage may be increased after 2 weeks to a maximum dose of 40 /10 /25 mg once daily ( 2 ). Dose selection should be individualized based on previous therapy ( 2 ).
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS Most common adverse reactions (incidence ≥2%) are dizziness, peripheral edema, headache, fatigue, nasopharyngitis, muscle spasms, nausea, upper respiratory tract infection, diarrhea, urinary tract infection, and joint swelling ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Micro Labs USA, Inc. at 1-855-839-8195 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. Olmesartan medoxomil, amlodipine and hydrochlorothiazide In the controlled trial of olmesartan medoxomil, amlodipine and hydrochlorothiazide, patients were randomized to olmesartan medoxomil, amlodipine and hydrochlorothiazide 40/10/25 mg, olmesartan medoxomil/amlodipine 40/10 mg, olmesartan medoxomil/hydrochlorothiazide 40/25 mg, or amlodipine/hydrochlorothiazide 10/25 mg. Subjects who received triple combination therapy were treated between two and four weeks with one of the three dual combination therapies. Safety data from this study were obtained in 574 patients with hypertension who received olmesartan medoxomil, amlodipine and hydrochlorothiazide for 8 weeks. The frequency of adverse reactions was similar between men and women, patients <65 years of age and patients ≥65 years of age, patients with and without diabetes, and Black and non-Black patients. Discontinuations because of adverse events occurred in 4% of patients treated with olmesartan medoxomil, amlodipine and hydrochlorothiazide 40/10/25 mg compared to 1% of patients treated with olmesartan medoxomil/amlodipine 40/10 mg, 2% of patients treated with olmesartan medoxomil/hydrochlorothiazide 40/25 mg, and 2% of patients treated with amlodipine/hydrochlorothiazide 10/25 mg. The most common reason for discontinuation with olmesartan medoxomil, amlodipine and hydrochlorothiazide was dizziness (1%). Dizziness was one of the most frequently reported adverse reactions with incidence of 1.4% to 3.6% in subjects continuing on dual combination therapy compared to 5.8% to 8.9% in subjects who switched to olmesartan medoxomil, amlodipine and hydrochlorothiazide. The other most frequent adverse reactions that occurred in at least 2% of subjects are presented in the table below: Table 1 Adverse Reaction OM40/ AML10/ HCTZ 25 mg (N = 574) n (%) OM40/ AML10 mg (N = 596) n (%) OM40/ HCTZ 25 mg (N = 580) n (%) AML10/ HCTZ 25 mg (N = 552) n (%) Edema peripheral 44 (7.7) 42 (7) 6 (1) 46 (8.3) Headache 37 (6.4) 42 (7) 38 (6.6) 33 (6) Fatigue 24 (4.2) 34 (5.7) 31 (5.3) 36 (6.5) Nasopharyngitis 20 (3.5) 11 (1.8) 20 (3.4) 16 (2.9) Muscle spasms 18 (3.1) 12 (2) 14 (2.4) 13 (2.4) Nausea 17 (3) 12 (2) 22 (3.8) 12 (2.2) Upper respiratory tract infection 16 (2.8) 26 (4.4) 18 (3.1) 14 (2.5) Diarrhea 15 (2.6) 14 (2.3) 12 (2.1) 9 (1.6) Urinary tract infection 14 (2.4) 8 (1.3) 6 (1) 7 (1.3) Joint swelling 12 (2.1) 17 (2.9) 2 (0.3) 16 (2.9) Syncope was reported by 1% of olmesartan medoxomil, amlodipine and hydrochlorothiazide subjects compared to 0.5% or less for the other treatment groups. Olmesartan medoxomil Olmesartan medoxomil has been evaluated for safety in more than 3825 patients/subjects, including more than 3275 patients treated for hypertension in controlled trials. This experience included about 900 patients treated for at least 6 months and more than 525 treated for at least 1 year. Treatment with olmesartan medoxomil was well tolerated, with an incidence of adverse reactions similar to that seen with placebo. Adverse reactions were generally mild, transient, and without relationship to the dose of olmesartan medoxomil. Amlodipine Amlodipine has been evaluated for safety in more than 11,000 patients in U.S. and foreign clinical trials. 6.2 Post-marketing Experience The following adverse reactions have...
Drug Interactions
7 DRUG INTERACTIONS Olmesartan medoxomil ( 7.1 ): 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. Amlodipine ( 7.2 ): Limit simvastatin to 20 mg daily when coadministered. Increased exposure to cyclosporin and tacrolimus. Increased amlodipine exposure when coadministered with CYP3A inhibitors Hydrochlorothiazide ( 7.3 ): Antidiabetic drugs: Dosage adjustment of antidiabetic may be required. Cholestyramine and colestipol: Reduced absorption of thiazides. NSAIDs: Can reduce the diuretic, natriuretic, and antihypertensive effects of diuretics. 7.1 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 benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on olmesartan medoxomil, amlodipine and hydrochlorothiazide and other agents that affect the RAS. Do not co-administer aliskiren with olmesartan medoxomil, amlodipine and hydrochlorothiazide in patients with diabetes [See Contraindications (4) ]. Avoid use of aliskiren with olmesartan medoxomil, amlodipine and hydrochlorothiazide in patients with renal impairment (GFR <60 ml/min). Use with Colesevelam Hydrochloride: Concurrent administration of bile acid sequestering agent colesevelam hydrochloride reduces the systemic exposure and peak plasma concentration of olmesartan. Administration of olmesartan at least 4 hours prior to colesevelam hydrochloride decreased the drug interaction effect. Consider...
Contraindications
4 CONTRAINDICATIONS Because of the hydrochlorothiazide component, olmesartan medoxomil, amlodipine and hydrochlorothiazide tablet is contraindicated in patients with anuria, hypersensitivity to any component, or hypersensitivity to other sulfonamide-derived drugs. Do not co-administer aliskiren with olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets in patients with diabetes [See Drug Interactions (7.2) ]. Anuria: Hypersensitivity to sulfonamide-derived drugs ( 4 ). Do not co-administer aliskiren with olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets in patients with diabetes ( 4 ).
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Olmesartan medoxomil, amlodipine and hydrochlorothiazide 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 olmesartan medoxomil, amlodipine and hydrochlorothiazide 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% to 4% and 15% to 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....
Overdosage
10 OVERDOSAGE There is no information on overdosage with olmesartan medoxomil, amlodipine and hydrochlorothiazide in humans. 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. 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/m 2 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. Hydrochlorothiazide . The most common signs and symptoms of overdose observed in humans are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets contain olmesartan medoxomil, amlodipine besylate at a dose equivalent to 5 or 10 mg amlodipine and hydrochlorothiazide in the strengths described below. Olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets are differentiated by tablet color/size and are debossed with an individual product tablet code on one side. Olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets are supplied for oral administration in the following strength and package configurations: 20 /5 /12.5 mg Olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets are Orange white, round, biconvex, film coated tablet debossed with “85” on one side and “I” on other side. Bottles of 30 NDC 42571-245-30 Bottles of 90 NDC 42571-245-90 Bottles of 500 NDC 42571-245-05 Bottles of 1000 NDC 42571-245-10 40 /5 /12.5 mg Olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets are Light yellow, round, biconvex, film coated tablet debossed with “86” on one side and “I” on other side. Bottles of 30 NDC 42571-246-30 Bottles of 90 NDC 42571-246-90 Bottles of 500 NDC 42571-246-05 Bottles of 1000 NDC 42571-246-10 40 /5 /25 mg Olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets are Light yellow, oval, film coated tablet debossed with “87” on one side and “I” on other side. Bottles of 30 NDC 42571-247-30 Bottles of 90 NDC 42571-247-90 Bottles of 500 NDC 42571-247-05 Bottles of 1000 NDC 42571-247-10 40 /10 /12.5 mg Olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets are grayish-red, round, biconvex, film coated tablet debossed with “88” on one side and “I” on other side. Bottles of 30 NDC 42571-248-30 Bottles of 90 NDC 42571-248-90 Bottles of 500 NDC 42571-248-05 Bottles of 1000 NDC 42571-248-10 40 /10 /25 mg Olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets are grayish-red, oval, film coated tablet debossed with “89” on one side and “I” on...
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.