How does Cozaar work to lower blood pressure. What are the recommended dosages for adults and children. What are the most common side effects of Cozaar. How should Cozaar be taken properly. Who should not take Cozaar due to contraindications.

Understanding Cozaar: An Overview of the Medication

Cozaar is the brand name for losartan, a medication that belongs to a class of drugs called angiotensin II receptor blockers (ARBs). It is primarily used to treat hypertension, or high blood pressure, in adults and children over 6 years old. Cozaar works by blocking the action of angiotensin II, a chemical in the body that causes blood vessels to constrict. By preventing this constriction, Cozaar allows blood vessels to relax and widen, which lowers blood pressure.

Beyond its primary use for hypertension, Cozaar has additional applications. It can be prescribed to adults with type 2 diabetes who have high blood pressure and protein in their urine (proteinuria). In these cases, Cozaar helps protect the kidneys from further damage caused by diabetes.

How Cozaar Works: Mechanism of Action Explained

To understand how Cozaar functions in the body, it’s important to grasp its mechanism of action. Angiotensin II is a hormone that plays a crucial role in regulating blood pressure. When released, it causes blood vessels to narrow, which increases blood pressure. Cozaar blocks the receptors that angiotensin II normally binds to, effectively preventing its action.

By inhibiting the effects of angiotensin II, Cozaar leads to several beneficial outcomes:

• Vasodilation: Blood vessels relax and widen, reducing resistance to blood flow
• Decreased aldosterone production: This helps reduce sodium and water retention
• Improved kidney function: By reducing pressure in the kidneys’ small blood vessels

The full effects of Cozaar are typically observed within 3 to 6 weeks after starting treatment. This gradual onset allows the body to adjust to the changes in blood pressure regulation.

Dosage Guidelines: Proper Administration of Cozaar

The appropriate dosage of Cozaar varies depending on several factors, including age, weight, and specific medical conditions. It’s crucial to follow your doctor’s instructions precisely when taking this medication.

Adult Dosage

For adults with hypertension, the typical recommended doses are:

• Starting dose: 50 mg once daily
• Maintenance dose: 25-100 mg once daily
• Maximum dose: 100 mg once daily

In some cases, particularly for patients with intravascular volume depletion, a lower starting dose of 25 mg may be advisable.

Pediatric Dosage

For children aged 6-16 years, the dosage is based on body weight:

• 20-49 kg: Starting dose of 25 mg once daily, may be increased to 50 mg
• 50 kg or more: Starting dose of 50 mg once daily, may be increased to 100 mg

Can Cozaar be taken with or without food? Cozaar can be taken either way, but it’s important to be consistent. If you choose to take it with food, continue to do so every day. Similarly, if you take it without food, maintain that routine.

Side Effects: What to Expect When Taking Cozaar

Like all medications, Cozaar can cause side effects, although not everyone experiences them. Understanding potential side effects can help you recognize and report any issues to your healthcare provider promptly.

Common Side Effects

The most frequently reported side effects of Cozaar include:

• Dizziness
• Headache
• Upper respiratory infections
• Fatigue
• Diarrhea
• Muscle pain

These side effects are generally mild and often subside as your body adjusts to the medication. However, if they persist or worsen, it’s important to consult your doctor.

Serious Side Effects

While less common, some side effects require immediate medical attention:

• Symptoms of high potassium levels (hyperkalemia): irregular heartbeat, muscle weakness
• Signs of kidney problems: changes in urination, swelling in feet or ankles
• Severe allergic reactions: rash, itching, swelling, severe dizziness, difficulty breathing

If you experience any of these serious side effects, seek medical help immediately.

Drug Interactions: Medications to Avoid While Taking Cozaar

Cozaar can interact with various medications, potentially altering its effectiveness or increasing the risk of side effects. It’s crucial to inform your healthcare provider about all medications, supplements, and herbal products you’re taking.

Key Drug Interactions

• NSAIDs (e.g., ibuprofen, naproxen): May reduce the blood pressure-lowering effect of Cozaar
• Potassium supplements or salt substitutes: Can increase potassium levels in the blood
• Lithium: Cozaar may increase lithium levels, potentially leading to toxicity
• Other blood pressure medications: May cause excessive blood pressure lowering

Are there any specific medications that should never be combined with Cozaar? The combination of Cozaar with aliskiren in patients with diabetes or moderate to severe kidney disease is contraindicated due to increased risk of kidney problems, high potassium levels, and low blood pressure.

Precautions and Warnings: Important Considerations Before Taking Cozaar

Before starting Cozaar, it’s essential to discuss your complete medical history with your healthcare provider. Certain conditions and factors may affect the safety and efficacy of this medication.

Medical Conditions to Consider

• Kidney disease: Cozaar may affect kidney function
• Liver disease: The liver processes Cozaar, so liver impairment may affect its metabolism
• Heart conditions: Including congestive heart failure or aortic/mitral valve stenosis
• Dehydration: Can increase the risk of low blood pressure
• Pregnancy: Cozaar can cause harm to an unborn baby, especially in the second and third trimesters

How does pregnancy affect the use of Cozaar? Cozaar is contraindicated during pregnancy, particularly in the second and third trimesters, as it can cause injury and even death to the developing fetus. Women who become pregnant while taking Cozaar should discontinue use immediately and consult their healthcare provider.

Long-Term Use of Cozaar: Benefits and Considerations

For many patients, Cozaar is a long-term medication used to manage chronic hypertension or protect kidney function in diabetic patients. Understanding the long-term implications of Cozaar use is crucial for patients and healthcare providers alike.

Long-Term Benefits

• Sustained blood pressure control
• Reduced risk of cardiovascular events
• Kidney protection in diabetic patients with proteinuria
• Potential reduction in the risk of stroke in patients with left ventricular hypertrophy

While these benefits are significant, long-term use of any medication requires ongoing monitoring and evaluation.

Considerations for Long-Term Use

Patients on long-term Cozaar therapy should be aware of the following:

• Regular blood pressure checks and kidney function tests
• Potential need for dosage adjustments over time
• Importance of maintaining a healthy lifestyle alongside medication
• Vigilance for any new side effects that may develop with prolonged use

What should patients on long-term Cozaar therapy discuss with their healthcare providers? Regular check-ups should include discussions about the continued appropriateness of the medication, any new health changes or concerns, and potential interactions with other medications or supplements.

Cozaar in Special Populations: Considerations for Specific Groups

While Cozaar is widely used, its use in certain populations requires special consideration and, in some cases, dosage adjustments or alternative treatments.

Elderly Patients

Older adults may be more sensitive to the effects of Cozaar, particularly in terms of blood pressure lowering. While no initial dosage adjustment is typically necessary, closer monitoring may be required.

Pediatric Patients

Cozaar is approved for use in children 6 years and older for the treatment of hypertension. Dosing is based on weight, and the safety and efficacy in children under 6 years have not been established.

Patients with Renal Impairment

For patients with decreased kidney function, lower initial doses may be recommended. Regular monitoring of kidney function and potassium levels is crucial.

Patients with Hepatic Impairment

Lower initial doses should be considered in patients with a history of hepatic impairment, as the liver plays a role in metabolizing Cozaar.

How does liver function affect the dosing of Cozaar? In patients with mild to moderate hepatic impairment, a lower starting dose of 25 mg once daily should be considered. Cozaar has not been studied in patients with severe hepatic impairment.

Understanding these special considerations ensures that Cozaar can be used safely and effectively across diverse patient populations, maximizing its benefits while minimizing potential risks. As with any medication, individualized treatment plans and close monitoring by healthcare professionals are key to optimal outcomes.

Cozaar – Uses, Side Effects, Interactions

How does this medication work? What will it do for me?

Losartan belongs to a family of medications known as angiotensin II receptor blockers. These medications are used in adults and children over the age of six to lower mild-to-moderate hypertension (high blood pressure).

Angiotensin II is a chemical that the body releases to cause the constriction of blood vessels. Losartan blocks the action of angiotensin II, resulting in the relaxation of the blood vessels. This relaxation causes the blood pressure to drop. The full effects of losartan are usually seen within 3 to 6 weeks after treatment has started. Losartan may be used alone or in combination with a diuretic (water pill).

Losartan may also be taken by adults who have type 2 diabetes along with hypertension and protein in the urine (proteinuria). In these cases, losartan is used to protect the kidneys from further damage due to diabetes.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

What form(s) does this medication come in?

25 mg
Each white, oval-shaped, unscored, film-coated tablet, with code “951” on one side and plain on the other, contains losartan potassium 25 mg. Nonmedicinal ingredients: carnauba wax, corn starch, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose, magnesium stearate, microcrystalline cellulose, and titanium dioxide.

50 mg
Each white, oval-shaped, film-coated tablet, with code “952” on one side and scored on the other, contains losartan potassium 50 mg. Do not split COZAAR 50 mg tablets. Nonmedicinal ingredients: carnauba wax, corn starch, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose, magnesium stearate, microcrystalline cellulose, and titanium dioxide.

100 mg
Each white, teardrop-shaped, unscored, film-coated tablet, with code “960” on one side and plain on the other, contains losartan potassium 100 mg. Nonmedicinal ingredients: carnauba wax, corn starch, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose, magnesium stearate, microcrystalline cellulose, and titanium dioxide.

How should I use this medication?

The usual recommended dose of losartan for adults is 50 mg or 100 mg once daily.  The usual starting dose is 50 mg once daily. In some cases, a lower starting dose of 25 mg once daily may be advisable. Do not take more than 100 mg once daily. Your doctor will adjust the dosage according to individual needs.

The usual recommended dose of losartan for children, aged 6 – 16 years, is based on body weight. The dose is 25 mg once daily for children weighing between 20 kg and 49 kg. This dose may be increased to 50 mg once daily. In children weighing more than 50 kg, the starting dose is 50 mg taken once daily. This dose may be increased to 100 mg once daily.

Losartan may be taken with or without food, but should be taken the same way each day.

Many things can affect the dose of a medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

It is important that this medication be taken exactly as prescribed by your doctor. If you miss a dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Who should NOT take this medication?

Do not use this medication if you:

• are allergic to losartan or any ingredients of the medication
• have diabetes or moderate-to-severe kidney disease and are taking the medication aliskiren

What side effects are possible with this medication?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent. The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• back or leg pain
• changed sense of taste
• diarrhea
• dizziness
• fatigue
• headache
• muscle cramps
• vomiting

Although most of these side effects listed below don’t happen very often, they could lead to serious problems if you do not check with your doctor or seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• fainting or dizziness when rising from a sitting or lying position
• signs of clotting problems (e.g., unusual nosebleeds, bruising, blood in urine, coughing blood, bleeding gums, cuts that don’t stop bleeding)
• signs of kidney problems (e.g., change in the amount or colour of urine, increased urination at night, blood in the urine, swelling in the feet or legs)
• signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
• signs of too much potassium in the body (e.g., irregular heartbeat, muscle weakness, generally feeling unwell)
• unexplained muscle pain, weakness, or dark brown urine

Stop taking the medication and seek immediate medical attention if any of the following occur:

• signs of a serious allergic reaction (e. g., swelling of face or throat, hives, or difficulty breathing)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for this medication?

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Blood pressure: Occasionally, a larger-than-expected drop in blood pressure occurs after taking losartan, in some cases after the first dose. It is more likely to occur if you take diuretics (water pills) or the medication aliskiren, have reduced salt intake, are on dialysis, or are experiencing diarrhea or vomiting. Blood pressure should be checked more often in these situations. If you have low blood pressure or are just starting to take this medication, you should move slowly when you are rising from a reclining to an upright position to reduce the risk of dizziness.

Dizziness: Losartan may cause dizziness, affecting your ability to drive or operate machinery. Avoid these and other hazardous tasks until you have determined how this medication affects you.

Kidney problems: The use of losartan may affect the function of the kidneys, especially for those who already have kidney problems. Certain people have experienced changes in kidney function (e.g., people with narrowed blood vessels in their kidneys, or those with severe congestive heart failure). The use of diuretics (water pills), nonsteroidal anti-inflammatory drugs (NSAIDs) or aliskiren may further increase risk of kidney problems for people already at risk for this problem. If you have kidney function problems, your doctor will likely closely monitor your condition while you are taking this medication.

Liver function: Losartan is removed from the body by the liver. Liver disease or reduced liver function may cause this medication to build up in the body, causing side effects. If you have liver problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Your doctor may want to test your liver function regularly with blood tests while you are taking this medication.

Potassium: Increases in blood levels of potassium can occur with use of this medication. This rarely causes problems, but your doctor may want to monitor your potassium levels through blood tests.

Pregnancy: Losartan should not be taken by pregnant women as it can cause severe harm or death to an unborn child. If you are planning to become pregnant, discuss alternative medications for blood pressure control with your doctor.

If you become pregnant while taking this medication, stop taking it and tell your doctor at once.

Breast-feeding: It is not known if losartan passes into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of using this medication have not been established for children less than 6 years of age.

What other drugs could interact with this medication?

There may be an interaction between losartan and any of the following:

• aldesleukin
• aldosterone antagonists (e.g., eplerenone, finerenone, spironolactone)
• aliskiren
• alpha-agonists (e.g., clonidine, methyldopa)
• alpha-blockers (e.g., alfuzosin, tamsulosin)
• amiodarone
• amphetamines (e.g., dextroamphetamine)
• angiotensin converting enzyme inhibitors (ACEIs; e. g., captopril, lisinopril, ramipril)
• other angiotensin receptor blockers (ARBs; e.g., candesartan, irbesartan)
• antipsychotics (e.g., cariprazine, chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
• apomorphine
• barbiturates (e.g., butalbital, phenobarbital)
• bortezomib
• brimonidine
• bromocriptine
• calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
• celecoxib
• CF transmembrane regulators (e.g., ivacaftor, lumacaftor)
• conivaptan
• diuretics (water pills; e.g., bumetanide, furosemide)
• drospirenone
• duloxetine
• fluconazole
• flunarizine
• general anesthetics (medications used to put people to sleep before surgery)
• heparin and low-molecular weight heparins (e.g., dalteparin, tinzaparin)
• iron sucrose
• levodopa
• lithium
• methylphenidate
• mifepristone
• monoamine oxidase inhibitors (MAOIs; e. g., phenelzine, rasagiline, selegiline, tranylcypromine)
• medications that increase the level of potassium in the blood (e.g., spironolactone, amiloride, triamterene, or salt substitutes that contain potassium)
• mifepristone
• minoxidil
• morphine
• nabilone
• nitrates (e.g., nitroglycerin, isosorbide dinitrate, isosorbide mononitrate)
• non-steroidal anti-inflammatory medications (NSAIDs; e.g., diclofenac, ibuprofen, ketorolac, naproxen)
• obinutuzumab
• pentoxifylline
• phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
• pramipexole
• primidone
• certain protein kinase inhibitors (e.g., asciminib, brigatinib)
• ranolazine
• riociguat
• ropinirole
• rotigotine
• sacubitril
• sodium phosphates
• sotalol
• tacrolimus
• tizanidine
• tolvaptan
• tretinoin
• tricyclic antidepressants (e. g., clomipramine, imipramine)
• trimethoprim
• yohimbine

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

All material copyright MediResource Inc. 1996 – 2023. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/drug/getdrug/Cozaar

Side effects of losartan – NHS

Like all medicines, losartan can cause side effects, although not everyone gets them. Side effects often improve as your body gets used to the medicine.

Common side effects

These common side effects of losartan happen in more than 1 in 100 people. There are things you can do to help cope with them:

Feeling dizzy

If losartan makes you feel dizzy when you stand up, try getting up very slowly or stay sitting down until you feel better. If you begin to feel dizzy, lie down so that you do not faint, then sit until you feel better. Do not drive, ride a bike or use tools or machinery if you feel dizzy.

Headaches

Make sure you rest, and drink plenty of fluids. It’s best not to drink too much alcohol. Ask your pharmacist to recommend a painkiller.

Headaches should usually go away after the first week of taking losartan. Talk to your doctor if they last longer than a week or are severe.

Feeling sick (nausea)

Try taking your tablets with or after a meal or snack. It may also help if you do not eat rich or spicy food.

Being sick (vomiting)

Stick to simple meals and do not eat rich or spicy food. It might help to take your losartan after you have eaten.

Try drinking small, frequent sips of water to avoid dehydration. Signs of dehydration include peeing less than usual or having dark, strong-smelling pee.

Do not take any other medicines to treat vomiting without speaking to a pharmacist or doctor.

If you take contraceptive pills and you’re being sick, your contraception may not protect you from pregnancy. Check the pill packet for advice.

Diarrhoea

Drink plenty of fluids, such as water or squash, to prevent dehydration. Signs of dehydration include peeing less than usual or having dark, strong-smelling pee.

If you get severe diarrhoea from a stomach bug or illness, tell your doctor. You may need to stop taking losartan for a while until you feel better. Do not take any medicines to treat diarrhoea without talking to a pharmacist or doctor.

If you take contraceptive pills and you have severe diarrhoea, your contraception may not protect you from pregnancy. Check the pill packet for advice.

Pain in your joints or muscles

If you get unusual muscle pain, weakness or tiredness which is not from exercise or physical hard work, talk to your doctor. You may need a blood test to check what might be causing it.

Speak to a doctor or pharmacist if the advice on how to cope does not help and a side effect is still bothering you or lasts more than a few days.

Serious side effects

It happens rarely, but some people have serious side effects after taking losartan.

Call a doctor or call 111 straight away if:

• the whites of your eyes turn yellow, or your skin turns yellow although this may be less obvious on brown or black skin – this can be a sign of liver problems
• you get severe stomach pain – this can be a sign of an inflamed pancreas
• your skin becomes more pale than usual, you feel tired, faint or dizzy, get purple spots (that come from superficial bleeding into the skin), show any sign of bleeding, or have a sore throat and high temperature – these can be signs of a blood or bone marrow disorder
• you feel weak, have an irregular heartbeat, pins and needles and muscle cramps – these can be signs of changes in the potassium levels in your blood

Serious allergic reaction

In rare cases, it’s possible to have a serious allergic reaction (anaphylaxis) to losartan.

Immediate action required: Call 999 now if:

• your lips, mouth, throat or tongue suddenly become swollen
• you’re breathing very fast or struggling to breathe (you may become very wheezy or feel like you’re choking or gasping for air)
• your throat feels tight or you’re struggling to swallow
• your skin, tongue or lips turn blue, grey or pale (if you have black or brown skin, this may be easier to see on the palms of your hands or soles of your feet)
• you suddenly become very confused, drowsy or dizzy
• someone faints and cannot be woken up
• a child is limp, floppy or not responding like they normally do (their head may fall to the side, backwards or forwards, or they may find it difficult to lift their head or focus on your face)

You or the person who’s unwell may also have a rash that’s swollen, raised, itchy, blistered or peeling.

These can be signs of a serious allergic reaction and may need immediate treatment in hospital.

Long-term side effects

Sometimes, taking losartan for a long time can 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.

Other side effects

These are not all the side effects of losartan. For a full list, see the leaflet inside your medicine packet.

Information:

You can report any suspected side effect using the Yellow Card safety scheme.

Visit Yellow Card for further information.

Page last reviewed: 24 February 2022

Next review due: 24 February 2025

Cozaar instructions for use: indications, contraindications, side effects – description Cozaar tab.

, cover. film coated, 100 mg: 7, 14 or 28 pcs. (20650)

Kozaar film-coated tablets 50mg №14 at a low price in Omsk, instructions for use, composition, analogues

Kozaar is a specific angiotensin II receptor antagonist (type AT1) for oral administration. Angiotensin II binds selectively to AT1 receptors found in many tissues (vascular smooth muscle, adrenal glands, kidneys, and heart) and performs several important biological functions, including vasoconstriction and aldosterone release. Angiotensin II also stimulates the proliferation of smooth muscle cells.

Losartan and its pharmacologically active metabolite (E 3174), both in vitro and in vivo, block all physiological effects of angiotensin II, regardless of the source or route of synthesis. Unlike some peptide angiotensin II antagonists, losartan does not have agonist effects.

Losartan selectively binds to AT1 receptors and does not bind to or block receptors for other hormones and ion channels that play an important role in the regulation of cardiovascular function. In addition, losartan does not inhibit ACE, which is responsible for the destruction of bradykinin. Therefore, effects not directly related to the blockade of AT1 receptors, in particular, increased effects associated with exposure to bradykinin or the development of edema (losartan – 1.7%, placebo – 1.9%), are not related to the action of losartan.

Long-term (6-week) treatment of patients with arterial hypertension with losartan at a dose of 100 mg/day. there was a 2-3-fold increase in the level of angiotensin II at the time of reaching Cmax of the drug in plasma. in some patients, an even greater increase in the concentration of losartan was observed, especially with a short duration of treatment (2 weeks). During treatment, antihypertensive activity and a decrease in plasma aldosterone concentration appeared after 2 and 6 weeks of therapy, indicating an effective blockade of angiotensin II receptors. However, after the discontinuation of losartan, plasma renin activity and the level of angiotensin II after 3 days decreased to the initial values ​​observed before the start of the drug.

Since losartan is a specific angiotensin II AT1 receptor antagonist, it does not inhibit ACE, kinase II, an enzyme that inactivates bradykinin. A study comparing the effects of losartan 20 mg and 100 mg with the effects of an ACE inhibitor on response to angiotensin I, angiotensin II and bradykinin showed that losartan blocked the effects of angiotensin I and angiotensin II without affecting the effects of bradykinin, due to the specific the mechanism of action of losartan. In contrast, ACE inhibitors block the angiotensin I response and increase the response to bradykinin without affecting the response to angiotensin II, which demonstrates the pharmacodynamic difference between losartan and ACE inhibitors.

Plasma concentrations of losartan and its active metabolite, as well as the antihypertensive effect of losartan, increase with increasing dose of the drug. Because losartan and its active metabolite are angiotensin II receptor antagonists, both of which cause an antihypertensive effect.

In a study with a single dose of 100 mg of losartan in healthy volunteers (males), the use of the drug, both in patients on a diet with a limited content of table salt, and in patients consuming a lot of table salt, did not affect the glomerular filtration rate, effective renal plasma flow and filtration fraction . Losartan has a natriuretic effect, which was more pronounced with a low-salt diet and, apparently, was not associated with the suppression of early sodium reabsorption in the proximal renal tubules. Losartan also caused a transient increase in renal excretion of uric acid.

In patients with arterial hypertension, proteinuria (more than 2 g/24 h), not suffering from diabetes mellitus and taking losartan for 8 weeks at a dose of 50 mg to 100 mg, there was a significant decrease in proteinuria by 42%, fractional excretion of albumin and IgG. In these patients, losartan stabilized the glomerular filtration rate and reduced the filtration fraction.

In postmenopausal women with arterial hypertension treated with losartan potassium at a dose of 50 mg/day. within 4 weeks, there was no effect of therapy on renal and systemic prostaglandin levels.

Losartan does not affect autonomic reflexes and has no long-term effect on plasma norepinephrine levels.

In patients with arterial hypertension losartan at doses up to 150 mg/day. does not cause clinically significant changes in the level of fasting triglycerides, total cholesterol (Xc) and HDL-C. At the same doses, losartan has no effect on fasting blood glucose levels.

In general, losartan caused a decrease in serum uric acid levels (usually less than 0.4 mg/dL), which was maintained during long-term therapy. In controlled clinical trials, which included patients with arterial hypertension, there were no cases of discontinuation of the drug due to an increase in serum creatinine or potassium levels.

P a pharmacokinetics it is absorbed from the gastrointestinal tract and undergoes a first pass effect through the liver, resulting in the formation of an active carboxylated metabolite and inactive metabolites. The systemic bioavailability of losartan is approximately 33%. The average Cmax of losartan and its active metabolite are reached after 1 hour and after 3-4 hours, respectively. When taking losartan during a normal meal, there was no clinically significant effect on the plasma concentration profile of losartan.

Distribution

Losartan and its active metabolite are more than 99% bound to plasma proteins (mainly albumin). Vd losartan is 34 liters. Studies in rats have shown that losartan practically does not penetrate the BBB.

M metabolism

Approximately 14% of the dose of losartan (when administered orally and intravenously) is converted into its active metabolite. After oral or intravenous administration of 14C-labeled losartan, the radioactivity of circulating blood plasma is primarily associated with the presence of losartan and its active metabolite in it. Biologically inactive metabolites are also formed, incl. two main ones, formed as a result of hydroxylation of the butyl side chain, and one minor – N-2-tetrazole-glucuronide.

Elimination

Plasma clearance of losartan and its active metabolite is approximately 600 ml/min and 50 ml/min, respectively. The renal clearance of losartan and its active metabolite is approximately 74 ml/min and 26 ml/min, respectively. When losartan is taken orally, about 4% of the dose is excreted unchanged in the urine and about 6% of the dose is excreted in the urine as the active metabolite. Losartan and its active metabolite have linear pharmacokinetics with oral administration of losartan potassium at doses up to 200 mg.

After oral administration, plasma concentrations of losartan and its active metabolite decrease polyexponentially with a final T1 / 2 of approximately 2 and 6-9 hours, respectively. When taking the drug at a dose of 100 mg 1 time / day. there is no significant accumulation in the blood plasma of either losartan or its active metabolite.

Losartan and its metabolites are excreted in bile and urine. After ingestion of losartan labeled with 14C, about 35% of the radioactive label is found in the urine and 58% in the feces. After intravenous administration of losartan labeled with 14C, approximately 43% of the radioactive label is detected in the urine and 50% in the feces.

Pharmacokinetics in special groups of patients

Plasma concentrations of losartan and its active metabolite in elderly patients with arterial hypertension do not significantly differ from those in younger patients with arterial hypertension.