Adult Dosing

Hypertension

• In patients whose blood pressure is not adequately controlled with losartan (50 mg/day ) or hydrochlorothiazide (25 mg/day ) monotherapy: Start with 12.5 mg/50 mg (hydrochlorothiazide/losartan) PO daily, allow 3 weeks for anti-hypertensive effect
• In patients whose blood pressure is not adequately controlled with losartan (100 mg) monotherapy: Start with 12.5 mg/100 mg (hydrochlorothiazide/losartan) PO daily

• If blood pressure remains uncontrolled after about 3 weeks of therapy: Increase the dose to 2 tabs of 12.5 mg/50 mg (hydrochlorothiazide/losartan) PO daily or 1 tab of 25 mg/100 mg (hydrochlorothiazide/losartan) PO daily
• Max: 25 mg/100 mg (hydrochlorothiazide/losartan) PO daily
• This combination may be substituted for the titrated components

Stroke prevention

• In patients whose blood pressure is not adequately controlled with losartan (50 mg/day ) monotherapy: Start with 12.5 mg/50 mg (hydrochlorothiazide/losartan) PO qd
• If needed increase to 12.5 mg/100 mg (hydrochlorothiazide/losartan) PO daily; then increase to 25 mg/100 mg (hydrochlorothiazide/losartan) PO daily to control blood pressure
• Max: 25 mg/100 mg (hydrochlorothiazide/losartan) PO daily

Pediatric Dosing

• Safety and effectiveness in pediatric patients has not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• For the treatment of hypertension
• Note: Not indicated for initial therapy of hypertension, unless in circumstances were hypertension is severe enough that the value of achieving prompt blood pressure control exceeds the risk of initiating combination therapy
• To reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy

• Hypersensitivity to any of the ingredients of the product
• Hypersensitivity to other sulfonamides
• Anuria
• Dofetilide
• Co-administration with aliskiren in patients with diabetes

• On detection of pregnancy, immediately discontinue therapy with this combination drug. Injury and even death have occurred in developing fetus on using this drug in pregnancy during the second and third trimesters

Renal Dose Adjustment (Based on CrCl)

• <30 mL/min: Avoid use

Hepatic Dose Adjustment

• Hepatic impairment: Avoid use

See Supplemental Patient Information

• Fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death have occurred in developing fetuses on using this drug in pregnancy during the second and third trimesters [US Black Box Warning]
• Oligohydramnios associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development has occurred. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also occurred. Apprise mothers of the potential hazards to their fetuses, and perform serial ultrasound examinations to assess the intraamniotic environment. On observation of oligohydramnios discontinue therapy unless it is considered lifesaving for the mother. As appropriate perform contraction stress testing (CST), a nonstress test (NST), or biophysical profiling (BPP) depending upon the week of pregnancy. Oligohydramnios may not be observed until after the fetus has sustained irreversible injury
• The ACE inhibitor component of this combination drug is associated with hypotension, oliguria, and hyperkalemia; closely observe infants with histories of in utero exposure to ACE inhibitors. Provide support for blood pressure and renal perfusion on occurrence of oliguria. If required, provide exchange transfusion or dialysis as means of reversing hypotension and/or substituting for impaired renal function
• Hydrochlorothiazide component is associated with fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions in adults
• Patients with intravascular volume or sodium depletion are susceptible to symptomatic hypotension. Correct such volume depletion prior to initiation of antihypertensive therapy
• Avoid using this combination drug for patients with hepatic impairment requiring titration with losartan
• Minor alterations of fluid and electrolyte balance is associated with precipitation of hepatic coma in patients with impaired hepatic function or progressive liver disease
• Hydrochlorothiazide component is associated with hypersensitivity reactions in patients with or without a history of allergy or bronchial asthma; patients having such a history are more prone
• Exacerbation or activation of systemic lupus erythematosus is associated with thiazide component of this drug
• Avoid administration of lithium with thiazides
• Dose dependent decrease in the hypokalemic response to hydrochlorothiazide has occurred as the dose of losartan was increased and dose dependent decrease in serum uric acid has also occurred with increasing doses of losartan
• At appropriate intervals, periodically determine serum electrolytes to detect possible electrolyte imbalance. Observe patients receiving thiazide therapy for clinical signs of fluid or electrolyte imbalance. Determine serum and urine electrolyte when the patient is vomiting excessively or receiving parenteral fluids. Hypokalemia with brisk diuresis has occurred in presence of severe cirrhosis or after long term therapy. Cardiac arrhythmia has occurred in association with hypokalemia resulting in sensitization or exaggeration of the response of the heart to the toxic effects of digitalis. Chloride replacement may be essential for treatment of metabolic alkalosis. Dilutional hyponatremia has occurred in edematous patients in hot weather; Impose water restriction rather than administration of salt except in rare occasions when hyponatremia is fatal. In actual salt depletion provide appropriate replacement therapy. Thiazide component is associated with hyperuricemia or precipitation of frank gout in certain patients
• Anticipate changes in renal function in susceptible individuals. A patient whose renal function is depending on the activity of the renin-angiotensin-aldosterone system treatment with ACE inhibitors is associated with oliguria and/or progressive azotemia and rarely with acute renal failure or death. Increase in serum creatinine or BUN have occurred in hypertensive patients with unilateral or bilateral renal artery stenosis. Thiazide component is associated with precipitation of azotemia in patients with renal disease. Cumulative effects have developed in patients with impaired renal function

Cautions: Use cautiously in:

• Renal impairment
• Renal artery stenosis
• Hepatic impairment
• Progressive hepatic disease
• Diabetes mellitus
• Arrhythmias
• CHF
• Seizure disorder
• Electrolyte abnormalities
• Volume depletion
• Hyponatremia
• Post-sympathectomy
• History of gout
• History of pancreatitis
• Major surgery
• SLE
• Geriatrics

Supplemental Patient Information

• Apprise female patients of childbearing potential that use this combination drug during the second or third trimesters of pregnancy is associated with serious problems in the fetus and infant including low blood pressure, poor development of skull bones, kidney failure, and death
• Advise patients to inform their physician if they feel lightheaded or faintness; advise them to stop using this therapy and contact the prescribing doctor
• Advise patients to take adequate amount of fluids

Pregnancy Category:C (first trimester) and D (second and third trimesters)

Breastfeeding: Hydrochlorothiazide doses of 50 mg/day are acceptable during lactation. Intense diuresis with higher doses may decrease breastmilk production. Prefer an alternative drug during breastfeeding a newborn or preterm infant as appropriate literature on the use of losartan is unavailable. This information is (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 23 February 2011). This combination drug exhibits potential for adverse events on the nursing infant, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.

• CV: Severe hypotension
• METABOLIC: Electrolyte imbalance, hyperuricemia
• HEMA: Thrombocytopenia
• DERM: Erythema multiforme, exfoliative dermatitis, photosensitivity
• CNS: Dizziness
• RESP: Cough
• GU: Renal impairment, oligohydramnios, fetal/neonatal harm or death, abnormal urination, elevated BUN, elevated liver transaminases
• MUSC: Musculoskeletal pain, back pain, rhabdomyolysis
• GI: Nausea, vomiting, abdominal pain, dyspepsia
• HYPERSENSITIVITY: Angioedema, anaphylactic reactions

Hydrochlorothiazide

• Thiazide diuretic; precise mechanism of the antihypertensive effect is unknown, affects the renal tubular mechanisms of electrolyte reabsorption, thereby directly increasing excretion of sodium and chloride and blocking the reabsorption of sodium in the distal tubule
• Not metabolized
• Excreted in urine (61% unchanged)
• Half-life: 5.6-14.8 hrs

Losartan

• Angiotensin II receptor antagonist; blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in vascular smooth muscle and the adrenal gland
• Bioavailability: 33%
• Metabolized by liver; CYP450: CYP2C9, CYP3A4
• Excreted in feces (60%), urine 35% (4% unchanged)
• Half-life: 2 hr (losartan), 6-9 hr (metabolite)

US Trade Name(s)

• Hyzaar

US Availability

hydrochlorothiazide/losartan (generic)

• TABS:
• 12.5 mg/50 mg
• 12.5 mg/100 mg
• 25 mg/100 mg

Hyzaar (hydrochlorothiazide/losartan)

• TABS:
• 12.5 mg/50 mg
• 12.5 mg/100 mg
• 25 mg/100 mg

Canadian Trade Name(s)

• Hyzaar
• Hyzaar DS

Canadian Availability

Hyzaar (hydrochlorothiazide/losartan)

• TABS:
• 12.5 mg/50 mg
• 12.5 mg/100 mg

Hyzaar DS (hydrochlorothiazide/losartan)

• TABS: 25 mg/100 mg

UK Trade Name(s)

• Cozaar comp

UK Availability

Cozaar comp (hydrochlorothiazide/losartan)

• TABS:
• 12.5 mg/50 mg
• 12.5 mg/100 mg
• 25 mg/100 mg

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Cardiovascular

Antihypertensive Combinations

Pricing data from www.DrugStore.com in U.S.A.

• Hyzaar 100-25 MG TABS [Bottle] (MERCK SHARP & DOHME)
  30 mg = $130
  90 mg = $385.98
• Hyzaar 50-12.5 MG TABS [Bottle] (MERCK SHARP & DOHME)
  90 mg = $279.99
  180 mg = $536
• Hyzaar 100-12.5 MG TABS [Bottle] (MERCK SHARP & DOHME)
  30 mg = $130.66
  90 mg = $373.29

Warning: This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit drugstore.com.

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