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Losartan and Hydrochlorothiazide


Pronunciation

 (loe SAR tan & hye droe klor oh THYE a zide)


U.S. Brand Names

 Hyzaar®


Synonyms

 Hydrochlorothiazide and Losartan


Generic Available

 No


Canadian Brand Names

 Hyzaar®; Hyzaar® DS


Use

 Treatment of hypertension


Pregnancy Risk Factor

 C/D (2nd and 3rd trimesters)


Pregnancy Implications

 See individual agents.


Lactation

 Enters breast milk/contraindicated


Contraindications

Based on losartan component: Hypersensitivity to losartan or any component of the formulation; hypersensitivity to other A-II receptor antagonists; bilateral renal artery stenosis; pregnancy (2nd and 3rd trimesters)

Based on hydrochlorothiazide component: Hypersensitivity to hydrochlorothiazide, thiazides, sulfonamide-derived drugs, or any component of the formulation; anuria; renal decompensation; pregnancy (2nd and 3rd trimesters)


Warnings/Precautions

Based on losartan component: Avoid use or use a smaller dose in patients who are volume depleted; correct depletion first. Deterioration in renal function can occur with initiation. Use with caution in unilateral renal artery stenosis and pre-existing renal insufficiency; significant aortic/mitral stenosis.

Based on hydrochlorothiazide component: Avoid in severe renal disease (ineffective). Electrolyte disturbances (hypokalemia, hypochloremic alkalosis, hyponatremia) can occur. Use with caution in severe hepatic dysfunction; hepatic encephalopathy can be caused by electrolyte disturbances. Gout can be precipitate in certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure. Cautious use in diabetics; may see a change in glucose control. Hypersensitivity reactions can occur. Can cause SLE exacerbation or activation. Use with caution in patients with moderate or high cholesterol concentrations. Photosensitization may occur. Correct hypokalemia before initiating therapy.

Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.


Adverse Reactions

 See individual agents.


Drug Interactions

 Losartan: Substrate (major) of CYP2C8/9, 3A4; Inhibits CYP1A2 (weak), 2C8/9 (moderate), 2C19 (weak), 3A4 (weak)

Also see individual agents.


Pharmacodynamics/Kinetics

 See individual agents.


Dosage

 Oral (dosage must be individualized): Adults: 1 tablet daily


Patient Education

 See individual agents. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Do not breast-feed.


Cardiovascular Considerations

 Combination therapy for the treatment of hypertension should be individualized for each patient. Potential advantages for losartan and hydrochlorothiazide combination therapy may include improved compliance and synergistic reductions in blood pressure with an accompanied reduction in side effects. See Special Cardiovascular Considerations for individual agents.


Dental Health: Effects on Dental Treatment

 No significant effects or complications reported


Dental Health: Vasoconstrictor/Local Anesthetic Precautions

 No information available to require special precautions


Mental Health: Effects on Mental Status

 May cause dizziness or insomnia; may rarely cause anxiety, confusion, depression, and sleep disorders


Mental Health: Effects on Psychiatric Treatment

 Barbiturates may decrease the effects of losartan; may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels


Dosage Forms

 Tablet [film coated]:

50-12.5: Losartan potassium 50 mg and hydrochlorothiazide 12.5 mg

100-25: Losartan potassium 100 mg and hydrochlorothiazide 25 mg


References

Chobanian AV, Bakris GL, Black HR, et al, "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report," JAMA , 2003, 289(19):2560-71.

"Consensus Recommendations for the Management of Chronic Heart Failure. On Behalf of the Membership of the Advisory Council to Improve Outcomes Nationwide in Heart Failure," Am J Cardiol , 1999, 83(2A):1A-38A.

Kaplan NM and Sever PS, "Combination Therapy: A Key to Comprehensive Patient Care," Am J Hypertens , 1997, 10(7 Pt 2):127S.

Moser M and Black HR, "The Role of Combination Therapy in the Treatment of Hypertension," Am J Hypertens , 1998, 11(6 Pt 2):73S-8S, 95S-100S.


International Brand Names

 Hyzaar® (CA); Hyzaar® DS (CA)


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