losartan and hydrochlorothiazide

Hyzaar is a combination of losartan (Cozaar) and hydrochlorothiazide and is used for treating high blood pressure. Losartan is an oral medication that belongs to a class of drugs called angiotensin receptor blockers (ARBs). Other ARBs include irbesartan (Avapro), valsartan (Diovan), and candesartan (Atacand).

Angiotensin, formed in the blood by the action of angiotensin converting enzyme (ACE), is a powerful chemical that attaches to angiotensin receptors found in many tissues but primarily on smooth muscle cells surrounding blood vessels. Angiotensin's attachment to the receptors causes the muscles to contract and the blood vessels to narrow (vasoconstrict) which leads to an increase in blood pressure (hypertension). Losartan (more specifically, the chemical formed when the liver converts the inactive losartan into an active chemical) blocks the angiotensin receptor. By blocking the action of angiotensin, losartan relaxes the muscles, dilates blood vessels and thereby reduces blood pressure.

Hydrochlorothiazide (HCTZ) is a diuretic (water pill) used for treating high blood pressure (hypertension) and accumulation of fluid. It works by blocking salt and fluid reabsorption in the kidneys, causing an increased amount of urine containing salt (diuresis). The mechanism of its action in lowering high blood pressure is not well understood. The combination of losartan and HCTZ reduces blood pressure better than either drug alone. Losartan increases potassium levels while HCTZ reduces potassium levels; the combination of both drugs has less effect on potassium levels. The FDA approved Hyzaar in April 1995.

Common side effects of losartan/hydrochlorothiazide are:

• nausea,
• vomiting,
• back pain,
• stomach upset,
• dizziness, and
• upper respiratory infection.

Other important side effects that may be caused by losartan/hydrochlorothiazide include:

• persistent cough,
• severe hypotension,
• changes in electrolyte concentrations,
• impotence, and
• angioedema.

Losartan/hydrochlorothiazide may reduce kidney function in some patients and should not be used by patients who have bilateral renal artery stenosis (narrowing of both arteries going to the kidneys). Rare cases of rhabdomyolysis (muscle breakdown), hepatitis, reduced number of platelets, and pancreatitis have been reported.

• The usual starting dose is 12.5/50 mg of losartan/hydrochlorothiazide once daily for patients not controlled on losartan or HCTZ treatment alone.
• The dose may be increased after 3 weeks to 2 tablets of 12.5/50 mg or one tablet of 25/100 mg daily.
• Patients who have not been controlled on losartan 100 mg alone should be switched to Hyzaar 12.5/100 mg.

• Losartan may increase levels of blood potassium which can lead to serious heart problems (arrhythmias). Therefore, concomitant use of other substances that increase blood potassium-such as potassium-sparing diuretics (for example, spironolactone (Aldactone), triamterene, and amiloride), potassium supplements, or salt substitutes containing potassium may lead to dangerous increases in serum potassium.
• Combining losartan or other ARBs with nonsteroidal anti-Inflammatory drugs (NSAIDs) in patients who are elderly, volume-depleted (including those on diuretic therapy), or with poor kidney function may result in reduced kidney function, including kidney failure. These effects usually are reversible. The antihypertensive effect of losartan may be reduced by aspirin and other NSAIDs such as ibuprofen (Advil, Children's Advil/Motrin, Medipren, Motrin, Nuprin, PediaCare Fever, etc.), indomethacin (Indocin, Indocin-SR), and naproxen (Anaprox, Naprelan, Naprosyn, Aleve). HCTZ reduces the elimination of lithium (Lithobid, Eskalith) by the kidneys and can lead to lithium toxicity. NSAIDs, for example, ibuprofen, may reduce the blood pressure effects of hydrochlorothiazide.
• Blood sugar levels can be elevated by HCTZ, necessitating adjustment in the doses of medications that are used for treating diabetes.
• Combining HCTZ with corticosteroids may increase the risk for low levels of blood potassium and other electrolytes. Low blood potassium (hypokalemia) can increase the toxicity of digoxin (Lanoxin). Cholestyramine (Questran, Questran Light) and colestipol (Colestid) bind to hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by 43%-85%.

• When used in the second or third trimester of pregnancy ACE inhibitors and ARBs can cause injury and even death to the fetus. Losartan/hydrochlorothiazide should not be used during pregnancy.
• It is not known whether losartan is excreted in breast milk , but losartan and its active metabolite are excreted in rat milk. Due to the possibility of harm to the nursing infant, if possible, losartan should be discontinued by women who are breastfeeding. HCTZ is excreted in breast milk.

What preparations of losartan/hydrochlorothiazide are available?

Tablets (HCTZ/losartan): 12.5/50 mg, 12.5/100 mg, and 25/100 mg

How should I keep losartan/hydrochlorothiazide stored?

Tablets should be stored at room temperature, between 15 C - 30 C (59 F - 86 F) and protected from excessive light and humidity. They should be kept in a tightly-closed, light-resistant container.