Co-Eziday

Each tablet contains Losartan (Co-Eziday) potassium 50 or 100 mg and Hydrochlorothiazide (Co-Eziday) 12.5 mg.

Losartan (Co-Eziday) Potassium: Losartan (Co-Eziday) potassium, a nonpeptide molecule, is chemically described as 2-butyl-4-chloro-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-methanol monopotassium salt.

Its empirical formula is C₂₂H₂₂ClKN₆O.

Losartan (Co-Eziday) potassium is a white to off-white free-flowing crystalline powder with a molecular weight of 461.01. It is freely soluble in water, soluble in alcohols, and slightly soluble in common organic solvents eg, acetonitrile and methyl ethyl ketone.

Oxidation of the 5-hydroxymethyl group on the imidazole ring results in the active metabolite of Losartan (Co-Eziday).

Hydrochlorothiazide (Co-Eziday): Hydrochlorothiazide (Co-Eziday) is 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide.

Its empirical formula is C₇H₈ClN₃O₄S₂.

It is a white, or practically white, crystalline powder with a molecular weight of 297.74, which is slightly soluble in water, but freely soluble in sodium hydroxide solution.

Hypertension

Co-Eziday® is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure lowers the risk of fatal and non-fatal cardiovascular (CV) events, primarily strokes and myocardial infarction. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including Losartan (Co-Eziday) and Hydrochlorothiazide (Co-Eziday).

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 1 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.

This fixed dose combination is not indicated for initial therapy of hypertension, except when the hypertension is severe enough that the value of achieving prompt blood pressure control exceeds the risk of initiating combination therapy in these patients.

Co-Eziday may be administered with other antihypertensive agents.

Hypertensive Patients With Left Ventricular Hypertrophy

Co-Eziday is indicated to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy, but there is evidence that this benefit does not apply to Black patients.

Co-Eziday contains a combination of Co-Eziday. Hydrochlorothiazide (Co-Eziday) is a thiazide diuretic (water pill) that helps prevent your body from absorbing too much salt, which can cause fluid retention. Losartan (Co-Eziday) is an angiotensin II receptor antagonist. Losartan (Co-Eziday) keeps blood vessels from narrowing, which lowers blood pressure and improves blood flow.

Co-Eziday is used to treat high blood pressure (hypertension). It is also used to lower the risk of stroke in certain people with heart disease.

Co-Eziday may also be used for purposes not listed in this medication guide.

Hypertension

The usual starting dose of Co-Eziday is 50/12.5 (Losartan (Co-Eziday) 50 mg/Hydrochlorothiazide (Co-Eziday) 12.5 mg) once daily. The dosage can be increased after 3 weeks of therapy to a maximum of 100/25 (Losartan (Co-Eziday) 100 mg/Hydrochlorothiazide (Co-Eziday) 25 mg) once daily as needed to control blood pressure.

Initiate a patient whose blood pressure is not adequately controlled with Losartan (Co-Eziday) 50 mg monotherapy with Co-Eziday 50/12.5 once daily. If blood pressure remains uncontrolled after about 3 weeks of therapy, the dosage may be increased to two tablets of Co-Eziday 50/12.5 once daily or one tablet of Co-Eziday 100/25 once daily.

Initiate a patient whose blood pressure is not adequately controlled with Losartan (Co-Eziday) 100 mg monotherapy with Co-Eziday 100/12.5 (Losartan (Co-Eziday) 100 mg/Hydrochlorothiazide (Co-Eziday) 12.5 mg) once daily. If blood pressure remains uncontrolled after about 3 weeks of therapy, increase the dose to two tablets of Co-Eziday 50/12.5 once daily or one tablet of Co-Eziday 100/25 once daily.

Initiate a patient whose blood pressure is inadequately controlled with Hydrochlorothiazide (Co-Eziday) 25 mg once daily, or is controlled but who experiences hypokalemia with this regimen, on Co-Eziday 50/12.5 once daily, reducing the dose of Hydrochlorothiazide (Co-Eziday) without reducing the overall expected antihypertensive response. Evaluate the clinical response to Co-Eziday 50/12.5 and, if blood pressure remains uncontrolled after about 3 weeks of therapy, increase the dose to two tablets of Co-Eziday 50/12.5 once daily or one tablet of Co-Eziday 100/25 once daily.

Hypertensive Patients With Left Ventricular Hypertrophy

In patients whose blood pressure is not adequately controlled on 50 mg Losartan (Co-Eziday) potassium, initiate treatment with Co-Eziday 50/12.5. If additional blood pressure reduction is needed, increase the dose to Co-Eziday 100/12.5, followed by Co-Eziday 100/25. For further blood pressure reduction add other antihypertensives.

How supplied

Dosage Forms And Strengths

• Co-Eziday 50/12.5 are yellow, oval, film-coated tablets, with code 717 on one side.
• Co-Eziday 100/12.5 are white, oval, film-coated tablets, with code 745 on one side.
• Co-Eziday 100/25 are light yellow, oval, film-coated tablets, with code 747 on one side.

Storage And Handling

Co-Eziday is supplied as a film-coated tablet.

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). Keep container tightly closed. Protect from light.

Manufactured for: Merck Sharp & Dohme Corp., a subsidiary of MERCK & CO., INC., Whitehouse Station, NJ 08889, USA. Revised: Dec 2015

See also:
What is the most important information I should know about Co-Eziday?

Hypersensitivity to Losartan (Co-Eziday), sulphonamide-derived substances (as Hydrochlorothiazide (Co-Eziday)) or to any of the excipients of Co-Eziday.

Therapy resistant hypokalemia or hypercalcemia; severe hepatic impairment; cholestasis and biliary obstructive disorders; refractory hyponatremia; symptomatic hyperuricemia/gout; 2nd and 3rd trimester of pregnancy; lactation; severe renal impairment (ie, creatinine clearance <30 mL/min); anuria.

Excipient: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Co-Eziday.

Use in lactation: It is not known whether Losartan (Co-Eziday) is excreted in human milk. However, Losartan (Co-Eziday) is excreted in the milk of lactating rats. Because no information is available regarding the use of Losartan (Co-Eziday) during breastfeeding, Losartan (Co-Eziday) is not recommended and alternative treatments with better established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm infant.

Thiazides pass into human milk and may inhibit lactation. Because of the potential for adverse effects on the nursing infant, Losartan (Co-Eziday)/HCTZ is contraindicated during breastfeeding.

Use Co-Eziday as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Co-Eziday. Talk to your pharmacist if you have questions about this information.
• Take Co-Eziday by mouth with or without food.
• Drinking extra fluids while you are taking Co-Eziday is recommended. Check with your doctor for instructions.
• Co-Eziday may increase the amount of urine or cause you to urinate more often when you first start taking it. To keep this from disturbing your sleep, try to take your dose before 6 pm.
• If you take cholestyramine or colestipol, ask your doctor or pharmacist how to take it with Co-Eziday.
• Continue to take Co-Eziday even if you feel well. Do not miss any doses.
• If you miss a dose of Co-Eziday, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Co-Eziday.

Use: Labeled Indications

Hypertension: Management of hypertension.

Hypertension with left ventricular hypertrophy: To reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy (LVH). Evidence suggests that this benefit does not apply to black patients.

See also:
What other drugs will affect Co-Eziday?

Agents Increasing Serum Potassium

Coadministration of Losartan (Co-Eziday) with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients.

Lithium

Increases in serum lithium concentrations and lithium toxicity have been reported with concomitant use of angiotensin II receptor antagonists or thiazide diuretics. Monitor lithium levels in patients receiving Co-Eziday and lithium.

Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors

Losartan (Co-Eziday) Potassium

In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists (including Losartan (Co-Eziday)) may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving Losartan (Co-Eziday) and NSAID therapy.

The antihypertensive effect of angiotensin II receptor antagonists, including Losartan (Co-Eziday), may be attenuated by NSAIDs, including selective COX-2 inhibitors.

Hydrochlorothiazide (Co-Eziday)

The administration of a non-steroidal anti-inflammatory agent including a selective COX-2 inhibitor can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when Co-Eziday and non-steroidal anti-inflammatory agents including selective COX-2 inhibitors are used concomitantly, observe closely to determine if the desired effect of the diuretic is obtained.

In patients receiving diuretic therapy, coadministration of NSAIDs with angiotensin receptor blockers, including Losartan (Co-Eziday), may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving Hydrochlorothiazide (Co-Eziday), Losartan (Co-Eziday), and NSAID therapy.

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, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.

The Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial enrolled 1448 patients with type 2 diabetes, elevated urinary-albumin-to-creatinine ratio, and decreased estimated glomerular filtration rate (GFR 30 to 89.9 mL/min), randomized them to lisinopril or placebo on a background of Losartan (Co-Eziday) therapy and followed them for a median of 2.2 years. Patients receiving the combination of Losartan (Co-Eziday) and lisinopril did not obtain any additional benefit compared to monotherapy for the combined endpoint of decline in GFR, end-stage renal disease, or death, but experienced an increased incidence of hyperkalemia and acute kidney injury compared with the monotherapy group.

Closely monitor blood pressure, renal function, and electrolytes in patients on Co-Eziday and other agents that affect the RAS.

Do not coadminister aliskiren with Co-Eziday in patients with diabetes. Avoid use of aliskiren with Co-Eziday in patients with renal impairment (GFR < 60 mL/min).

The Use Of Hydrochlorothiazide (Co-Eziday) With Other Drugs

When administered concurrently, the following drugs may interact with thiazide diuretics :

Antidiabetic drugs (oral agents and insulin) — dosage adjustment of the antidiabetic drug may be required.

Cholestyramine and colestipol resins — Absorption of Hydrochlorothiazide (Co-Eziday) is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the Hydrochlorothiazide (Co-Eziday) and reduce its absorption from the gastrointestinal tract by up to 85 and 43 percent, respectively. Stagger the dosage of Hydrochlorothiazide (Co-Eziday) and the resin such that Hydrochlorothiazide (Co-Eziday) is administered at least 4 hours before or 4 to 6 hours after the administration of the resin.

See also:
What are the possible side effects of Co-Eziday?

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Losartan (Co-Eziday) potassium-Hydrochlorothiazide (Co-Eziday) has been evaluated for safety in 858 patients treated for essential hypertension and 3889 patients treated for hypertension and left ventricular hypertrophy. Most adverse reactions have been mild and transient in nature and have not required discontinuation of therapy. In controlled clinical trials, discontinuation of therapy due to clinical adverse events was required in only 2.8% and 2.3% of patients treated with the combination and placebo, respectively.

In these double-blind controlled clinical trials, adverse reactions occurring in greater than 2% of subjects treated with Losartan (Co-Eziday)-Hydrochlorothiazide (Co-Eziday) and at a greater rate than placebo were: back pain (2.1% vs 0.6%), dizziness (5.7% vs 2.9%), and upper respiratory infection (6.1% vs 4.6%).

The following additional adverse reactions have been reported in clinical trials with Co-Eziday and/or the individual components:

Blood and the lymphatic system disorders: Anemia, aplastic anemia, hemolytic anemia, leukopenia, agranulocytosis.

Metabolism and nutrition disorders: Anorexia, hyperglycemia, hyperuricemia, electrolyte imbalance including hyponatremia and hypokalemia.

Psychiatric disorders: Insomnia, restlessness.

Nervous system disorders: Dysgeusia, headache, migraine, paraesthesias.

Eye disorders: Xanthopsia, transient blurred vision.

Cardiac disorders: Palpitation, tachycardia.

Vascular disorders: Dose-related orthostatic effects, necrotizing angiitis (vasculitis, cutaneous vasculitis).

Respiratory, thoracic and mediastinal disorders: Nasal congestion, pharyngitis, sinus disorder, respiratory distress (including pneumonitis and pulmonary edema).

Gastrointestinal disorders: Dyspepsia, abdominal pain, gastric irritation, cramping, diarrhea, constipation, nausea, vomiting, pancreatitis, sialoadenitis.

Hepato-biliary disorders: Jaundice (intrahepatic cholestatic jaundice).

Skin and subcutaneous tissue disorders: Rash, pruritus, purpura, toxic epidermal necrolysis, urticaria, photosensitivity, cutaneous lupus erythematosus.

Musculoskeletal and connective tissue disorders: Muscle cramps, muscle spasm, myalgia, arthralgia.

Renal and urinary disorders: Glycosuria, renal dysfunction, interstitial nephritis, renal failure.

Reproductive system and breast disorders: Erectile dysfunction/impotence.

General disorders and administration site conditions: Chest pain, edema/swelling, malaise, fever, weakness.

Investigations: Liver function abnormalities.

Cough

Persistent dry cough has been associated with ACE-inhibitor use and in practice can be a cause of discontinuation of ACE-inhibitor therapy. Two prospective, parallel-group, double-blind, randomized, controlled trials were conducted to assess the effects of Losartan (Co-Eziday) on the incidence of cough in hypertensive patients who had experienced cough while receiving ACE-inhibitor therapy. Patients who had typical ACE-inhibitor cough when challenged with lisinopril, whose cough disappeared on placebo, were randomized to Losartan (Co-Eziday) 50 mg, lisinopril 20 mg, or either placebo (one study, n=97) or 25 mg Hydrochlorothiazide (Co-Eziday) (n=135). The double-blind treatment period lasted up to 8 weeks. The incidence of cough is shown in Table 1 below.

These studies demonstrate that the incidence of cough associated with Losartan (Co-Eziday) therapy, in a population that all had cough associated with ACE-inhibitor therapy, is similar to that associated with Hydrochlorothiazide (Co-Eziday) or placebo therapy.

Cases of cough, including positive re-challenges, have been reported with the use of Losartan (Co-Eziday) in postmarketing experience.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Co-Eziday. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.

Digestive: Hepatitis has been reported rarely in patients treated with Losartan (Co-Eziday).

Hematologic: Thrombocytopenia.

Hypersensitivity: Angioedema, including swelling of the larynx and glottis, causing airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue has been reported rarely in patients treated with Losartan (Co-Eziday); some of these patients previously experienced angioedema with other drugs including ACE inhibitors. Vasculitis, including Henoch-Schönlein purpura, has been reported with Losartan (Co-Eziday). Anaphylactic reactions have been reported.

Musculoskeletal: rhabdomyolysis

Skin: Erythroderma