Hydrochlorothiazide / Losartan

Hydrochlorothiazide/losartan is a combination medicine approved for two related uses:

• Treatment of high blood pressure (hypertension) — to lower blood pressure and reduce the risk of heart attack and stroke. Both Hyzaar and Losartan Potassium and Hydrochlorothiazide tablets are approved for this use.
• Reducing the risk of stroke in patients who have high blood pressure and left ventricular hypertrophy (an enlarged left pumping chamber of the heart). Both Hyzaar and Losartan Potassium and Hydrochlorothiazide tablets carry this indication. Important: Clinical evidence shows this stroke-reduction benefit does not apply to Black patients.

This tablet pairs two complementary blood pressure medicines. Losartan is an angiotensin II receptor blocker (ARB): it blocks the action of angiotensin II, a hormone that normally constricts (tightens) blood vessels and triggers the release of another hormone, aldosterone, that causes the body to retain sodium and water. By blocking this hormone, losartan helps blood vessels relax and blood pressure fall. Hydrochlorothiazide is a thiazide diuretic (water pill) that makes the kidneys excrete more sodium and water in the urine, which reduces blood volume and lowers pressure. Because losartan blocks the aldosterone pathway, it also tends to counteract the potassium loss that hydrochlorothiazide can cause.

These tablets are taken once daily by mouth and can be taken with or without food. Your prescriber will typically start at a lower strength and may increase the dose after about three weeks if blood pressure is not yet controlled. This fixed combination is generally not the first medicine used for high blood pressure — it is usually started after a single blood pressure medicine alone has not been effective enough.

• Take it at the same time each day to keep blood pressure steady.
• Do not stop taking it without talking to your prescriber first.
• Follow your prescriber's instructions exactly — do not adjust the dose on your own.

Most people tolerate this medication well. Common side effects include:

• Dizziness
• Upper respiratory infection
• Back pain
• Cough
• Palpitations (awareness of heartbeat)
• Rash
• Sinusitis
• Abdominal pain

Serious reactions to act on immediately include: sudden eye pain or vision loss (possible angle-closure glaucoma), swelling of the face, lips, tongue, or throat (angioedema), signs of very low blood pressure (severe dizziness or fainting), or significant changes in urination that may signal kidney problems. Stop the medication and seek medical help right away if any of these occur.

• Pregnancy: This is the most critical warning. Hydrochlorothiazide/losartan can cause severe fetal harm or death, especially in the second and third trimesters. Stop taking it as soon as you learn you are pregnant and call your doctor immediately.
• Low blood pressure: If you are dehydrated or on high-dose diuretics, you may experience symptomatic hypotension (dizziness or fainting) when starting this medication. Dehydration should be corrected before starting.
• Kidney function: This combination can affect kidney function, especially in people with pre-existing kidney disease, renal artery narrowing, or severe heart failure. Kidney function should be monitored regularly.
• Electrolyte imbalances: Hydrochlorothiazide can lower potassium, sodium, and magnesium; losartan can raise potassium. Both directions can be clinically significant and require monitoring.
• Acute angle-closure glaucoma: Hydrochlorothiazide can rarely trigger sudden eye pressure buildup. Seek immediate care for sudden eye pain or vision changes.
• Lupus: Thiazide diuretics may worsen systemic lupus erythematosus (SLE).
• Liver disease: This combination is not recommended as initial therapy for patients with hepatic impairment because a sufficiently low starting dose is not available in this fixed combination form.

Several medications and substances can interact with hydrochlorothiazide/losartan in clinically important ways:

• Potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes — can raise blood potassium to dangerous levels when combined with losartan.
• Lithium — this combination can increase lithium levels and raise the risk of lithium toxicity; blood lithium levels should be monitored closely.
• NSAIDs (e.g., ibuprofen, naproxen) and COX-2 inhibitors — can reduce the blood pressure-lowering effect and may worsen kidney function, especially in older adults or those who are dehydrated.
• Aliskiren — must not be combined with this medication in patients with diabetes; should be avoided in patients with significantly reduced kidney function.
• Cholestyramine or colestipol (cholesterol-lowering resins) — can significantly reduce absorption of hydrochlorothiazide; take the tablet at least 1–2 hours before these agents.
• Rifampin — an antibiotic that can lower losartan levels in the body, potentially reducing its effectiveness.
• Fluconazole — an antifungal that can alter losartan metabolism and change drug levels.
• Alcohol, sedatives, or narcotic pain medicines — can add to the blood pressure-lowering effect and increase the risk of dizziness when standing up.

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Pregnancy: Do not take this medication if you are pregnant. It can seriously harm or kill an unborn baby.
• Breastfeeding: Hydrochlorothiazide passes into breast milk; it is unknown whether losartan does. Discuss with your doctor whether to stop nursing or stop the medication.
• Children: Safety and effectiveness in pediatric patients have not been established.
• Older adults: Side effects may be somewhat more common in older adults; no dose adjustment is specifically required, but monitoring is important.
• Kidney disease: This combination requires caution in people with reduced kidney function and is not recommended in patients with severe renal impairment (very low kidney filtration rates).
• Liver disease: Not recommended as initial therapy in patients with hepatic impairment because the appropriate lower starting dose of losartan is not available in this combination form.
• Diabetes: Do not use with aliskiren if you have diabetes.
• Allergy to sulfonamides or penicillin: This may increase the risk of the rare eye reaction (angle-closure glaucoma) associated with hydrochlorothiazide.
• Anuria (inability to produce urine): This medication is contraindicated if you cannot produce urine.
• Allergy to any component: Do not take if you are allergic to losartan, hydrochlorothiazide, or any other ingredient in the tablet.

Taking too much of this medication is most likely to cause very low blood pressure (hypotension) and a fast heart rate; a slow heart rate is also possible. Hydrochlorothiazide overdose can cause electrolyte imbalances — particularly low potassium — and dehydration. If you suspect an overdose, seek emergency medical care immediately. Neither losartan nor its active metabolite can be removed by hemodialysis.

Losartan blocks the blood vessel-tightening effect of angiotensin II, helping blood vessels relax and blood pressure fall; this effect begins within one week, with maximum benefit typically seen within 3 to 6 weeks of starting. Hydrochlorothiazide begins producing a diuretic (urine-increasing) effect within about 2 hours of a dose, peaks around 4 hours, and lasts approximately 6 to 12 hours. By combining an ARB with a diuretic, the two drugs lower blood pressure through separate but complementary mechanisms, and losartan's effect on the aldosterone pathway tends to reduce the potassium loss caused by hydrochlorothiazide.

After you take losartan by mouth, it is absorbed and converted partly by liver enzymes (CYP2C9 and CYP3A4) into an active metabolite that is 10 to 40 times more potent and does most of the blood pressure-lowering work; losartan itself has a half-life of about 2 hours, while the active metabolite lasts 6 to 9 hours. Eating a meal slightly slows losartan absorption but does not meaningfully affect its overall blood pressure-lowering action. Hydrochlorothiazide is not broken down by the body — it is eliminated unchanged by the kidneys, with a half-life ranging from roughly 6 to 15 hours. In patients with reduced kidney function, both drugs build up to higher levels in the body, so close monitoring is needed; neither losartan nor its active metabolite can be cleared by dialysis.

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