Losartan

Losartan Uses, Dosage, Side Effects, Food Interaction and all others data.

Losartan, the first of a new class of antihypertensives, is a specific and selective antagonist of angiotensin II at the AT1 sites. Angitensin II is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. Losartan and its principal active metabolite block the vasoconstriction and aldosterone secreting effects of angiotensin II to the AT1 receptor found in many tissues. Losartan is now regarded as the first-line therapy option for treating high blood pressue.

Losartan is an angiotensin II receptor blocker used to treat hypertension, diabetic nephropathy, and to reduce the risk of stroke. Losartan has a long duration of action as it is given once daily. Patients taking losartan should be regularly monitored for hypotension, renal function, and potassium levels.

Trade Name Losartan
Availability Prescription only
Generic Losartan
Losartan Other Names Losartan
Related Drugs amlodipine, lisinopril, metoprolol, furosemide, hydrochlorothiazide, atenolol, ramipril, captopril, enalapril, irbesartan
Weight 25mg, 50mg, 100mg,
Type Tablet Medlife Pure Generics, + Hydrochlorothiazide Tablet Medlife Pure Generics, Tablet
Formula C22H23ClN6O
Weight Average: 422.911
Monoisotopic: 422.162187095
Protein binding

Losartan is 98.6-98.8% protein bound and the active metabolite (E-3174) is 99.7% protein bound in serum.

Groups Approved
Therapeutic Class Angiotensin-ll receptor blocker
Manufacturer Medlife, Tulip Lab Pvt Ltd, Albion Pharmaceuticals Ltd, Premier Pharmaceuticals Ltd, Don Valley Pharmaceuticals (pvt) Ltd, , Novell Phamaceuticals, Swiss Pharma Pvt Ltd
Available Country India, Bangladesh, Pakistan, United States, Indonesia, Portugal, Switzerland, Nigeria
Last Updated: September 19, 2023 at 7:00 am
Losartan
Losartan

Uses

Losartan is an angiotensin II receptor blocker (ARB) used for:

  • Treatment of hypertension, to lower blood pressure in adults and children greater than 6 years old. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.
  • Reduction of the risk of stroke in patients with hypertension and left ventricular hypertrophy. There is evidence that this benefit does not apply to Black patients.
  • Treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria in patients with type 2 diabetes and a history of hypertension.

Losartan is also used to associated treatment for these conditions: Diabetic Nephropathy, Heart Failure, High Blood Pressure (Hypertension), Marfan Syndrome, Stroke

How Losartan works

Losartan reversibly and competitively prevents angiotensin II binding to the AT1 receptor in tissues like vascular smooth muscle and the adrenal gland. Losartan and its active metabolite bind the AT1 receptor with 1000 times more affinity than they bind to the AT2 receptor. The active metabolite of losartan is 10-40 times more potent by weight than unmetabolized losartan as an inhibitor of AT1 and is a non-competitive inhibitor. Losartan's prevention of angiotensin II binding causes vascular smooth muscle relaxation, lowering blood pressure.

Angiotensin II would otherwise bind to the AT1 receptor and induce vasoconstriction, raising blood pressure.

Dosage

Losartan dosage

Hypertension:

  • Usual adult dose: 50 mg once daily.
  • Usual pediatric starting dose: 0.7 mg per kg once daily (up to 50 mg).

Hypertensive Patients with Left Ventricular Hypertrophy:

  • Usual starting dose: 50 mg once daily.
  • Add hydrochlorothiazide 12.5 mg and/or increase Losartan to 100 mg followed by an increase to hydrochlorothiazide 25 mg if further blood pressure response is needed.

Nephropathy in Type 2 Diabetic Patients:

  • Usual dose: 50 mg once daily.
  • Increase dose to 100 mg once daily if further blood pressure response is needed.

Use in elderly: 

  • Patients up to 75 years: No initial dosage adjustment is necessary for this group of patients.
  • Patients over 75 years: A lower starting dose of 25 mg once daily is recommended.

Side Effects

In controlled clinical trials in patients with essential hypertension, dizziness was the only side effect reported that occurred with an incidence greater than placebo in 1% or more of patients treated with Losartan. Rarely, rash was reported although the incidence in controlled clinical trials was less than placebo. Angioedema, involving swelling of the face, lips and/or tongue has been reported rarely in patients treated with Losartan. Serious hypotension (particularly on initiating treatment in salt-depleted patients) or renal failure (mainly in patients with renal artery stenosis) may be encountered during Losartan treatment.

Toxicity

The oral TDLO in mice is 1000mg/kg and in rats is 2000mg/kg. In humans the TDLO for men is 10mg/kg/2W and for women is 1mg/kg/1D.

Symptoms of overdose are likely to include hypotension, tachycardia, or bradycardia due to vagal stimulation. Supportive treatment should be instituted for symptomatic hypotension. Hemodialysis will not remove losartan or its active metabolite due to their high rates of protein binding.

Precaution

A lower dose should be considered for patients with a history of hepatic and renal impairment. Losartan should not be used with potassium-sparing diuretic

Interaction

No drug interaction of clinical significance has been identified. Compounds which have been studied in clinical pharmacokinetic trials include hydrochlorothiazide, digoxin, warfarin, cimetidine, ketoconazole and phenobarbital.

Food Interaction

  • Take at the same time every day.
  • Take with or without food. Food delays absorption, but does not affect the extent of absorption.

[Moderate] GENERALLY AVOID: Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs).

ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion.

Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician.

If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended.

Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs.

MONITOR: Grapefruit juice may modestly decrease and delay the conversion of losartan to its active metabolite, E3174.

The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

The clinical significance is unknown.

Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.



MANAGEMENT: Patients who regularly consume grapefruits and grapefruit juice should be monitored for altered efficacy of losartan.

Grapefruits and grapefruit juice should be avoided if an interaction is suspected.

Orange juice is not expected to interact.

Volume of Distribution

The volume of distribution of losartan is 34.4±17.9L and 10.3±1.1L for the active metabolite (E-3174).

Elimination Route

Losartan is approximately 33% orally bioavailable. Losartan has a Tmax of 1 hour and the active metabolite has a Tmax of 3-4 hours. Taking losartan with food decreases the Cmax but does only results in a 10% decrease in the AUC of losartan and its active metabolite. A 50-80mg oral dose of losartan leads to a Cmax of 200-250ng/mL.

Half Life

The terminal elimination half life of losartan is 1.5-2.5 hours while the active metabolite has a half life of 6-9 hours.

Clearance

Losartan has a total plasma clearance of 600mL/min and a renal clearance of 75mL/min. E-3174, the active metabolite, has a total plasma clearance of 50mL/min and a renal clearance of 25mL/min.

Elimination Route

A single oral dose of losartan leads to 4% recovery in the urine as unchanged losartan, 6% in the urine as the active metabolite. Oral radiolabelled losartan is 35% recovered in urine and 60% in feces. Intravenous radiolabelled losartan is 45% recovered in urine and 50% in feces.

Pregnancy & Breastfeeding use

Although there is no experience with the use of Losartan in pregnant women, animal studies with Losartan potassium have demonstrated fetal and neonatal injury and death, the mechanism of which is believed to be pharmacologically mediated through effects on the renin angiotensinaldosterone system. Losartan should not be used in pregnancy and if pregnancy is detected Losartan should be discontinued as soon as possible.

It is not known whether Losartan is excreted in human breast milk. However, significant level of Losartan found in rat milk which suggests that the drug should not be used in lactating mother.

Contraindication

It is also contraindicated to patients who are hypersensitive to any component of this product. In patients who are intravenously volume depleted (e.g. those treated with high dose diuretics), symptomatic hypotension may occur. These conditions Losartan potassium should be corrected prior to administer Losartan or a lower starting dose (usually 25 mg) should be used.

Special Warning

No initial dosage adjustment is necessary in patients with mild renal impairment (CrCl 20-50 ml/min). For patients with moderate to severe renal impairment (CrCl <20 ml/min) or patients on dialysis, a lower starting dose of 25 mg is recommended.

Acute Overdose

Limited data are available regarding overdose in humans. The most likely manifestation of overdose would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. Supportive treatment should include repletion of the intravascular volume. Neither Losartan nor the active metabolite can be removed by hemodialysis.

Storage Condition

Store between 15-30°C

Innovators Monograph

You find simplified version here Losartan

Losartan contains Losartan see full prescribing information from innovator Losartan Monograph, Losartan MSDS, Losartan FDA label

FAQ

What is Losartan used for?

Losartan used to treat high blood pressure. It is also used for diabetic kidney disease, heart failure, and left ventricular enlargement. Losartan protect your kidneys if you have both kidney disease and diabetes.

How safe is Losartan?

Losartan is generally safe to take for a long time. In fact, Losartan works best when you take it for a long time. Taking Losartan for a long time can sometimes cause your kidneys not to work as well as they should. Your doctor will check how well your kidneys are working with regular blood tests.

How does Losartan work?

Losartan relaxes and widens your blood vessels. This lowers your blood pressure and makes it easier for your heart to pump blood around your body.

What are the common side effects of Losartan?

Common side effects of Losartan are include:

  • Blurred vision.
  • difficult breathing.
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position.
  • fast or irregular heartbeat.
  • nausea or vomiting.
  • numbness or tingling in the hands, feet, or lips.
  • stomach pain.
  • weakness or heaviness of the legs.

Is Losartan safe during pregnancy?

Do not take Losartan if you are pregnant. If you become pregnant while you are taking Losartan, stop taking Losartan and call your doctor immediately. Losartan may cause death or serious injury to the fetus when taken in the last 6 months of pregnancy.

Is Losartan safe during breastfeeding?

Losartan is not known if Losartan passes into breast milk. It is not recommended for women who are breastfeeding because other medicines with a more established safety profile are available.

Can I drink alcohol with Losartan?

Losartan may cause low blood pressure, resulting in dizziness, lightheadedness, and fainting. Moderate alcohol consumption while taking Losartan is generally considered safe, but alcohol may make the side effects of Losartan worse.

Can I drive after taking Losartan?

Avoid driving or using heavy machinery while dizzy. See a doctor if dizziness or lightheadedness persists or gets worse.

When should be taken of Losartan?

Take Losartan tablets once a day. Your doctor may suggest that you take your first dose before bedtime, because it can make you dizzy. After the very first dose, you can take Losartan at any time of day. Try to take it at the same time every day.

Can I take Losartan on an empty stomach?

You can take Losartan tablets with or without food. Swallow the tablets with a drink of water.

Is it better to take Losartan in the morning or in the evening?

For once daily dosing, there are no absolute recommendations about taking it in the morning vs. night. For high blood pressure, some research suggests taking medicines at night reduces the risk of cardiovascular events in the morning.

How long does Losartan take to work?

Losartan starts to reduce high blood pressure after about 6 hours but it may take 3 to 6 weeks to fully take effect. If you have high blood pressure, you may not have any symptoms.

How long does Losartan stay in my system?

The Losartan half-life is about 2 hours and the metabolite half-life is 6 to 9 hours. This means it can take a couple of days to clear Losartan and its metabolite from your system.

Can I take Losartan for a long time?

Losartan  is generally safe to take for a long time. In fact, it works best when you take it for a long time. However taking Losartan for a long time can sometimes cause your kidneys not to work as well as they should. Your doctor will check how well your kidneys are working with regular blood tests.

Is Losartan bad for my kidney?

There is a risk of acute kidney failure developing in people taking Losartan.

Can I take Losartan every other day?

Your doctor may suggest that you take your first dose before bedtime, because it can make you dizzy. After the very first dose, you can take losartan at any time of day. Try to take it at the same time every day. You can take Losartan tablets with or without food.

How many hours does Losartan last?

Losartan taken once daily, does not last the full 24 hours at lower doses like 25 or 50 mg. At 100 mg daily Losartan does last the full 24 hours. If you take Losartan 50 mg in the morning, you may notice your blood pressure rises at night, because it's not covering you for a full 24 hours.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happen If I overdose on Losartan?

An overdose of Losartan can cause dizziness, sleepiness and a pounding heartbeat.

What happen If I stop taking Losartan?

Stopping it suddenly can cause your blood pressure to increase quickly. This raises your risk of a heart attack or stroke. If you want to stop taking Losartan, talk with your doctor. They will slowly taper your dosage so that you can stop using the drug safely.

Can Losartan cause heart problems?

An irregular heartbeat  has been reported with Losartan but is rare.

Can Losartan affects my liver?

Losartan is associated with a low rate of transient serum aminotransferase elevations and has been linked to rare instances of acute liver injury.

Will Losartan affect my fertility?

One experimental animal study did not find effects on fertility.

*** Taking medicines without doctor's advice can cause long-term problems.
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