Tenizide20 mg+12.5 mg

Established / FDA-Approved Use

Tenizide is indicated for the treatment of hypertension (high blood pressure), either asinitial therapy in patients likely to need multiple drugs to achieve their blood pressure goal, or assubstitution/add-on therapy in patients whose blood pressure is not adequately controlled on olmesartanmedoxomil or hydrochlorothiazide monotherapy alone.

Guideline-Supported Use

Major hypertension guidelines (e.g. ACC/AHA, ESC/ESH) support combination angiotensin II receptor blocker(ARB) plus thiazide diuretic therapy such as Tenizide for patients who do not reach target bloodpressure on a single agent, or who present with stage 2 hypertension requiring combination therapy from theoutset.

Not Indicated For

Tenizide lowers blood pressure but has not been shown to reduce cardiovascular morbidity andmortality as a fixed-dose starting therapy; it is not intended as initial single-pill therapy for mild,uncomplicated hypertension where monotherapy is appropriate, and it is not indicated for use in pregnancy.

Each film-coated tablet of Olmesartan Medoxomil + Hydrochlorothiazide contains two active ingredients:

• Olmesartan Medoxomil (an angiotensin II receptor blocker) — available combination strengths of 20 mg or 40 mg
• Hydrochlorothiazide (a thiazide diuretic) — available combination strengths of 12.5 mg or 25 mg

Common tablet strengths marketed include 20 mg/12.5 mg, 40 mg/12.5 mg and 40 mg/25 mg (olmesartanmedoxomil/hydrochlorothiazide).

Tenizide is a fixed-dose combination oral antihypertensive medicine that pairs an angiotensinII receptor blocker (ARB) with a thiazide diuretic. Combining two complementary mechanisms allows morepatients to reach blood pressure targets than either component alone, often with a lower dose of eachingredient and therefore a more favorable side-effect profile than up-titrating a single drug.

Tenizide is used long-term for chronic management of hypertension and is not intended forrapid or emergency blood pressure reduction.

Tenizide belongs to the therapeutic class of Angiotensin II Receptor Blocker (ARB) and Thiazide Diuretic fixed-dose combinations, used as antihypertensive agents.

Olmesartan Medoxomil + Hydrochlorothiazide combines two complementary antihypertensive mechanisms:

• Olmesartan medoxomil is a prodrug rapidly hydrolyzed to olmesartan, which selectivelyblocks the binding of angiotensin II to the AT1 receptor in vascular smooth muscle and the adrenal gland.This blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II, producing vasodilationand reduced sodium/water retention.
• Hydrochlorothiazide is a thiazide diuretic that inhibits sodium reabsorption in thedistal convoluted tubule of the kidney, increasing excretion of sodium, chloride and water, which reducesplasma volume and lowers blood pressure. It also causes some potassium and magnesium loss.

The two mechanisms are complementary: the diuretic-induced volume contraction activates therenin-angiotensin system, and the ARB component blunts this compensatory response, giving anadditive/synergistic antihypertensive effect.

Tenizide should be taken by mouth, once daily, at approximately the same time each day, withor without food. Tablets should be swallowed whole with a glass of water and should not be crushed orchewed unless otherwise directed. Blood pressure should be monitored regularly, and the medicine should notbe stopped abruptly without medical advice.

• Dual RAAS blockade / Aliskiren: Concomitant use of Tenizide with aliskirenis contraindicated in patients with diabetes and not recommended in patients with renal impairment, due toincreased risk of hyperkalemia, hypotension and renal impairment. Combination with ACE inhibitors isgenerally avoided for the same reasons.
• Lithium: Both ARBs and thiazides reduce lithium clearance, increasing serum lithiumlevels and risk of lithium toxicity; concurrent use requires close monitoring of lithium levels.
• NSAIDs (including selective COX-2 inhibitors): May reduce the antihypertensive effectof Tenizide and can worsen renal function, particularly in elderly, volume-depleted, orrenally-impaired patients.
• Potassium-sparing diuretics, potassium supplements, or salt substitutes containing potassium:May increase the risk of hyperkalemia when used with the olmesartan component.
• Other antihypertensives, alcohol, barbiturates, or narcotics: May potentiate theblood-pressure-lowering and orthostatic hypotensive effects of the thiazide component.
• Corticosteroids/ACTH: May intensify electrolyte depletion, particularly hypokalemia,caused by the hydrochlorothiazide component.
• Digoxin: Thiazide-induced hypokalemia or hypomagnesemia may increase the risk ofdigoxin-related cardiac arrhythmias.
• Cholestyramine and colestipol resins: May reduce absorption of the hydrochlorothiazidecomponent; separate dosing is advised.
• Antidiabetic agents (insulin, oral hypoglycemics): The thiazide component may raiseblood glucose, requiring dose adjustment of antidiabetic therapy.

The following side effects have been reported with Tenizide:

Common Side Effects

Less Common / Serious Side Effects

• Symptomatic hypotension, especially after the first dose in volume-depleted patients.
• Electrolyte disturbances — hypokalemia, hyponatremia, hypomagnesemia, hypochloremic alkalosis (seePrecautions).
• Sprue-like enteropathy — severe, chronic diarrhea with substantial weight loss (see Precautions).
• Angioedema (swelling of face, lips, tongue, throat) — rare but requires immediate discontinuation.
• Acute kidney injury or worsening renal function, particularly with volume depletion or in patients ondual RAAS blockade.
• Photosensitivity reaction of the skin.

Pregnancy: Tenizide is contraindicated in pregnancy. Drugs that actdirectly on the renin-angiotensin system, such as the olmesartan component, can cause fetal and neonatalinjury and death, including oligohydramnios, fetal renal failure, skull hypoplasia and death, when used inthe second and third trimesters. Tenizide should be discontinued as soon as possible oncepregnancy is detected, and a physician should be consulted immediately for alternative therapy.

Lactation: It is not known whether olmesartan or hydrochlorothiazide passes into humanbreast milk in clinically significant amounts. Because thiazides are known to appear in breast milk and cansuppress lactation, and because of the potential for adverse effects in a nursing infant, a decision shouldbe made whether to discontinue breastfeeding or discontinue Tenizide, taking into account theimportance of the medicine to the mother; use only if clearly needed and only under medical supervision.

Fetal Toxicity

Tenizide can cause fetal harm when used in pregnancy; discontinue as soon as pregnancy isdetected (see Pregnancy and Lactation).

Sprue-Like Enteropathy

The olmesartan component of Tenizide has been associated with a distinct, well-documentedsprue-like enteropathy: severe, chronic diarrhea with substantial weight loss, sometimes accompanied bymalabsorption, that can develop months to years after starting therapy. It may be mistaken for celiacdisease, but intestinal biopsy findings resolve and symptoms improve after discontinuingTenizide. Report unexplained chronic diarrhea and weight loss to a physician promptly; if noother cause is found, discontinuation should be considered.

Electrolyte and Fluid Balance

The hydrochlorothiazide component can cause hypokalemia, hyponatremia, hypomagnesemia and hypochloremicalkalosis, while the olmesartan component can cause hyperkalemia, particularly in patients with renalimpairment, diabetes, or those taking potassium-sparing agents. Periodic monitoring of serum electrolytes isrecommended.

Renal Function

Changes in renal function, including acute renal failure, can occur, particularly in patients whose renalfunction depends on the renin-angiotensin-aldosterone system (e.g. severe heart failure, volume depletion,bilateral renal artery stenosis). Monitor renal function periodically.

Hyperuricemia and Gout

The thiazide component may raise serum uric acid and precipitate gout flares in susceptible patients.

Hypotension in Volume/Salt-Depleted Patients

Symptomatic hypotension may occur, especially the first dose, in patients who are volume- orsalt-depleted (e.g. from prior diuretic use, dietary salt restriction, vomiting, or diarrhea); correctvolume depletion before starting therapy.

Photosensitivity

Photosensitivity reactions have been reported with thiazide diuretics; minimize sun/UV exposure and usesun protection.

Metabolic Effects

The thiazide component may worsen glucose tolerance and lipid profile; monitor patients with diabetes ordyslipidemia.

Sulfonamide Allergy

Hydrochlorothiazide is a sulfonamide derivative; use caution in patients with a history of allergy tosulfonamide-derived drugs.

Overdose with Tenizide is most likely to present as symptomatic hypotension (dizziness,weakness, fainting), along with possible electrolyte disturbances (hypokalemia, hyponatremia), dehydrationand reduced kidney function due to the diuretic component. There is no specific antidote.

If overdose is suspected, seek immediate medical attention or contact emergency services / a poisoncontrol center right away. Treatment is supportive and may include intravenous fluids and monitoring ofvital signs, renal function, and serum electrolytes in a medical facility; do not attempt home treatment.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Renal Impairment

Use with caution and monitor renal function and electrolytes; not recommended in severe renal impairment(see Dosage and Administration and Precautions).

Hepatic Impairment

Use cautiously; thiazides can precipitate hepatic coma in patients with impaired hepatic function orprogressive liver disease.

Elderly

No specific dose adjustment is generally required in elderly patients, but they may be more sensitive toblood-pressure-lowering and electrolyte effects; monitor closely, particularly at treatment initiation.

Pediatric Patients

Safety and efficacy of Tenizide have not been established in pediatric patients (seePediatric Use).

Pregnancy and Lactation

See Pregnancy and Lactation section — contraindicated in pregnancy; use in lactation only if clearlyneeded.

Tenizide is intended for long-term, ongoing management of chronic hypertension rather thanshort-course treatment. Blood pressure and clinical response should be reassessed periodically, and therapyis generally continued indefinitely as long as it remains effective and well tolerated; it should not bestopped abruptly without consulting a physician.

Olmesartan Medoxomil + Hydrochlorothiazide belongs to the Angiotensin II Receptor Blocker (ARB) + Thiazide Diuretic fixed-dose combination class of antihypertensive drugs.

Olmesartan Medoxomil + Hydrochlorothiazide lowers blood pressure through two complementary actions: the olmesartan componentblocks AT1 angiotensin II receptors to prevent vasoconstriction and aldosterone release, while thehydrochlorothiazide component inhibits renal sodium reabsorption to reduce circulating volume. Together theyproduce a greater antihypertensive effect than either agent alone (see Pharmacology for full mechanism).

D (legacy FDA pregnancy category; contraindicated in pregnancy — see Pregnancy and Lactation)

The safety and effectiveness of Tenizide have not been established in pediatric patients.Use of this fixed-dose combination is therefore not recommended in children, and individual componentsshould only be considered under specialist pediatric guidance where age-appropriate data exist.