Olmesartan/amlodipine/hydrochlorothiazide

What is Olmesartan/amlodipine/hydrochlorothiazide?

Olmesartan/amlodipine/hydrochlorothiazide (Tribenzor) is a combination of olmesartan medoxomil, an angiotensin II receptor blocker, amlodipine, a dihydropyridine calcium channel blocker, and hydrochlorothiazide, a thiazide diuretic used to treat high blood pressure.

Olmesartan medoxomil metabolism

Amlodipine

Hydrochlorothiazide

What are the uses of this medicine?

• Tribenzor 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 events, primarily strokes and myocardial infarctions.

Limitations of use:

• This fixed combination drug is not indicated for the initial therapy of hypertension.

How does this medicine work?

• The active ingredients of Tribenzor target three separate mechanisms involved in blood pressure regulation.

Olmesartan medoxomil:

• Olmesartan blocks the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in vascular smooth muscle.
• Its action is, therefore, independent of the pathways for angiotensin II synthesis.
• Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is a mechanism of many drugs used to treat hypertension.
• Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and circulating angiotensin II levels do not overcome the effect of olmesartan on blood pressure.

Amlodipine:

• Amlodipine is a dihydropyridine calcium channel blocker that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle.
• Experimental data suggests that amlodipine binds to both dihydropyridine and nonhydropyridine binding sites.
• Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.

Hydrochlorothiazide:

• Hydrochlorothiazide is a thiazide diuretic.
• Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts.
• Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium.

Who Should Not Use this medicine ?

This medicine cannot be used in patients:

• with anuria
• with hypersensitivity to any component, or hypersensitivity to other sulfonamide-derived drugs
• with diabetes who use aliskiren

What drug interactions can this medicine cause?

Drug Interactions with Olmesartan Medoxomil:

• 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.
• Do not co-administer aliskiren with Tribenzor in patients with diabetes. Avoid use of aliskiren with Tribenzor in patients with renal impairment (GFR <60 ml/min).
• 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.
• Consider administering olmesartan at least 4 hours before the colesevelam hydrochloride dose.
• Monitor lithium levels in patients receiving Tribenzor and lithium.

Drug Interactions with Amlodipine:

• 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.
• Frequent monitoring of trough blood levels of cyclosporine and tacrolimus is recommended and adjust the dose when appropriate.
• Monitor for symptoms of hypotension and edema when amlodipine is co-administered with CYP3A inhibitors to determine the need for dose adjustment.
• Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers.

Drug Interactions with Hydrochlorothiazide:

• When administered concurrently the following drugs may interact with thiazide diuretics:
• Antidiabetic Drugs (oral agents and insulin)
• Cholestyramine and Colestipol Resins
• Corticosteroids, ACTH
• Non-steroidal Anti-inflammatory Drugs

Is this medicine FDA approved?

• Initial U.S. Approval: 2010

How should this medicine be used?

Recommended dosage:

• Dose once daily.
• Dosage may be increased in 2-week intervals, as needed.
• The maximum recommended dose of Tribenzor is 40/10/25 mg.
• Dose selection should be individualized based on previous therapy.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: (olmesartan medoxomil/amlodipine/hydrochlorothiazide) 20 /5 /12.5 mg, 40 /5 /12.5 mg, 40 /5 /25 mg, 40 /10 /12.5 mg, 40 /10 /25 mg

This medicine is available in fallowing brand namesː

• Tribenzor

What side effects can this medication cause?

The most common side effects of this medicine include:

• dizziness, peripheral edema, headache, fatigue, nasopharyngitis, muscle spasms, nausea, upper respiratory tract infection, diarrhea, urinary tract infection, and joint swelling.

What special precautions should I follow?

• In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients (e.g., those being treated with high doses of diuretics) symptomatic hypotension may be anticipated after initiation of treatment with olmesartan medoxomil. Correct volume or salt depletion prior to administration.
• Impaired renal function was reported in Tribenzor. Monitor renal function and potassium in susceptible patients.
• Patients, particularly those with severe obstructive coronary artery disease, may develop increased frequency, duration, or severity of angina or acute myocardial infarction upon starting calcium channel blocker therapy or at the time of dosage increase.
• Tribenzor contains hydrochlorothiazide which can cause hypokalemia, hyponatremia and hypomagnesemia. Observe for signs of fluid or electrolyte imbalance.
• The antihypertensive effects of the drug may be enhanced in the post-sympathectomy patient.
• Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.
• Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.
• Severe, chronic diarrhea with substantial weight loss has been reported in patients taking olmesartan months to years after drug initiation. Consider discontinuation of Tribenzor in cases where no other etiology is identified.
• Tribenzor can cause fetal harm when administered to a pregnant woman. When pregnancy is detected, discontinue Tribenzor as soon as possible.
• Thiazides cross the placental barrier and appear in cord blood. Adverse reactions include fetal or neonatal jaundice and thrombocytopenia.

What to do in case of emergency/overdose?

Symptoms of overdosage may include: Olmesartan medoxomil overdose:

• hypotension
• tachycardia
• bradycardia

Management:

• If symptomatic hypotension should occur, supportive treatment should be initiated. The dialyzability of olmesartan is unknown.

Amlodipine overdose:

• peripheral vasodilation
• hypotension
• reflex tachycardia

Management:

• Frequent blood pressure measurements are essential.
• If 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 overdose:

• electrolyte depletion (hypokalemia, hypochloremia, hyponatremia)
• dehydration
• cardiac arrhythmias

Management:

• The degree to which hydrochlorothiazide is removed by hemodialysis has not been established.

Can this medicine be used in pregnancy?

• Tribenzor 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.
• When pregnancy is detected, discontinue Tribenzor as soon as possible.
• Consider alternative antihypertensive therapy during pregnancy.

Can this medicine be used in children?

• The safety and effectiveness of Tribenzor in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

• Active Ingredients:
• OLMESARTAN MEDOXOMIL
• AMLODIPINE BESYLATE
• HYDROCHLOROTHIAZIDE

• Inactive ingredients:
• STARCH, CORN
• MICROCRYSTALLINE CELLULOSE
• CROSCARMELLOSE SODIUM
• MAGNESIUM STEARATE
• SILICON DIOXIDE

Who manufactures and distributes this medicine?

• Manufactured for Daiichi Sankyo, Inc., Basking Ridge, NJ
• Manufactured by Daiichi Sankyo Europe GmbH, Germany

What should I know about storage and disposal of this medication?

• Store at 25ºC (77ºF); excursions permitted to 15ºC-30ºC (59ºF-86ºF).

• Dailymed label info on Olmesartan/amlodipine/hydrochlorothiazide
• FDA Olmesartan/amlodipine/hydrochlorothiazide

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