Losartan (losartan potassium)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Losartan potassium, a nonpeptide tetrazole derivative, is an angiotensin II type 1 (AT1) receptor antagonist (also referred to as an angiotensin II receptor blocker (ARB)).
Losartan, a nonpeptide tetrazole derivative, is a reversible, non-competitive inhibitor of the angiotensin II receptor (type AT1). Through selective blockade of angiotensin II binding at the AT1 receptor, losartan blocks the physiologic actions of angiotensin II, including vasoconstrictor and aldosterone-secreting effects. Neither losartan nor its metabolite inhibits angiotensin converting enzyme (ACE), the enzyme involved in the conversion of angiotensin I to angiotensin II and degradation of bradykinin.
Losartan and its metabolite also do not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.
Losartan is a prodrug and requires activation in the liver to exert its pharmacologic activity. Losartan's active carboxylic acid metabolite is 10-40 times more potent by weight than losartan and appears to be a reversible, noncompetitive inhibitor of the AT1 receptor.
A dose of losartan 100 mg inhibits angiotensin II pressor effects by about 85% at peak, with 25-40% inhibition persisting for 24 hours. Effects of losartan can be observed as early as 1 week; however, maximal effects may not be observed for 3-6 weeks. Long-term follow-up studies demonstrate that the effect of losartan is maintained for up to a year.
There is no apparent rebound effect after abrupt withdrawal of losartan. No change in average heart rate was observed in controlled trials.
Losartan is well absorbed after oral administration and undergoes substantial first-pass metabolism. Its bioavailability is approximately 33%. Mean peak concentrations occur at 1 hour for losartan and 3-4 hours for the active metabolite.
Administration with a meal slows absorption but does not significantly impact the AUC of losartan or its active metabolite. The pharmacokinetics of losartan and its active metabolite are linear with doses up to 200 mg. Both the parent drug and metabolite are highly protein bound, primarily to albumin, with plasma free fractions of 1.3 and 0.2%, respectively.
Distribution across the blood-brain barrier is poor, according to animal studies. Substantial first-pass metabolism occurs via cytochrome P-450 (CYP) enzymes. Approximately 14% of an orally administered dose of losartan is converted to the active metabolite, which is responsible for most of the antagonism at the angiotensin II receptor.
In vitro studies indicate that CYP2C9 and 3A4 are involved in the metabolism of losartan. The terminal half-lives of losartan and its active metabolite are 2 hours and 6-9 hours, respectively. After a single oral dose, about 4% of unchanged drug and 6% of the active metabolite appear in urine.
Elimination occurs primarily via biliary excretion, with 35% present in urine and 60% in feces.
USES: This medication is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. It is also used to help protect the kidneys from damage due to diabetes.
It is also used to lower the risk of strokes in patients with high blood pressure and an enlarged heart. Losartan belongs to a class of drugs known as angiotensin receptor blockers (ARBs). It works by relaxing blood vessels so blood can flow more easily.
Generic name: losartan potassium
Pronunciation: (low-SAR-tan)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
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Indications
The following indications are listed for Losartan:
- Diabetic Nephropathy
- Hypertension
- Hypertension With Left Ventricular Hypertrophy
Also known as: Arterial Hypertension With Left Ventricular Hypertrophy, Elevated Blood Pressure, Essential Hypertension, Hyperpiesia, Hyperpiesia With Left Ventricular Hypertrophy, Hyperpiesis, Hyperpiesis With Left Ventricular Hypertrophy, Hypertensive Disorder, Systemic Arterial Hypertension.
Dosing
Available as losartan potassium; dosage is expressed in terms of the salt.
Losartan potassium is administered orally without regard to meals. It is available as oral tablets. It is also commercially available in fixed-combination tablets containing losartan potassium and hydrochlorothiazide; see the full prescribing information for administration of this combination product.
Losartan potassium tablets should be stored at 25degreesC (excursions permitted between 15-30degreesC) and protected from light.
For pediatric patients or patients unable to swallow tablets, losartan may be administered orally as an extemporaneously prepared suspension. An extemporaneous suspension containing losartan potassium 2.5 mg/mL can be prepared in the following manner. First, add 10 mL of purified water to a 240 mL amber polyethylene terephthalate (PET) bottle containing ten 50-mg tablets of losartan potassium. Shake the contents for at least 2 minutes. Allow the concentrated suspension to stand for 1 hour and then shake for 1 minute to disperse the contents. Separately, prepare a mixture containing equal parts (by volume) of syrup (Ora-Sweet SF(R)) and suspending vehicle (Ora-Plus(R)). To the concentrated suspension of losartan, add 190 mL of the Ora-Sweet SF(R) and Ora-Plus(R)mixture, and shake for 1 minute to disperse the ingredients. Refrigerate the suspension at 2-8degreesC. Shake the suspension before dispensing each dose and return promptly to refrigeration. The extemporaneous suspension is stable for up to 4 weeks when stored at 2-8degreesC.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
In vitro studies indicate that cytochrome P-450 (CYP) 2C9 and 3A4 are involved in the biotransformation of losartan to active and inactive metabolites.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known hypersensitivity to losartan or any ingredient in the formulation.
*Concomitant therapy with aliskiren in patients with diabetes mellitus.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects occurring in at least 2% of patients with hypertension receiving losartan, and at a higher incidence than with placebo, include dizziness, upper respiratory infection, nasal congestion, and back pain.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Antihypertensive effects of losartan have been established in hypertensive pediatric patients 6-16 years of age.
Safety and efficacy of losartan in pediatric patients <6 years of age and pediatric patients with glomerular filtration rate <30 mL/minute per 1.73 m2 have not been established.
Losartan can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the RAS during the second or third trimester of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Oligohydramnios in pregnant women who use drugs affecting the RAS in the second or third trimester of pregnancy can result in reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations (including skull hypoplasia), hypotension, and death.
Discontinue losartan immediately when pregnancy is detected. In the rare case that there is no appropriate alternative therapy, apprise the mother of the potential risk to the fetus. If losartan is taken during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment; if oligohydramnios is observed, discontinue losartan, unless it is considered life-saving for the mother. Oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe neonates who have been exposed to losartan in utero for signs of hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required.
Losartan is distributed into milk in rats; it is not known whether the drug is distributed into human breast milk. A decision should be made whether to discontinue breastfeeding or discontinue the drug, taking into account the potential risk in breastfeeding infants and the importance of the drug to the mother.
The manufacturer makes no specific dosage recommendations for geriatric patients.
In controlled clinical trials evaluating losartan for hypertension, 19% of patients were >=65 years of age and 2% were >=75 years of age. In controlled clinical trials evaluating losartan for renal protection in type 2 diabetes, 33% of patients were >=65 years of age. In controlled clinical trials evaluating losartan for the reduction of cardiovascular death, stroke, and myocardial infarction in hypertensive patients with left ventricular hypertrophy, 62% of patients were >=65 years of age and 18% were >=75 years of age. No overall differences in pharmacokinetics, safety, or efficacy of losartan have been observed between geriatric patients and younger adults, but increased sensitivity in some older individuals cannot be ruled out.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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