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Losartan

 
Drug Info: Losartan

Brand names: Cozaar®



Losartan tablets

What are losartan tablets?

LOSARTAN (Cozaar®) helps lower blood pressure to normal levels. It controls high blood pressure, but it is not a cure. High blood pressure can damage your kidneys, and may lead to a stroke or heart failure. Losartan helps prevent these things from happening. Losartan is also used to improve symptoms in patients with heart failure. Generic losartan tablets are not yet available.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
• previous swelling of the tongue, face, or lips with difficulty breathing, difficulty swallowing, hoarseness, or tightening of the throat
• heart failure
• kidney disease
• liver disease
• electrolyte imbalance (e.g. low or high levels of potassium in the blood)
• if you are on a special diet, such as a low-salt diet (e.g. using potassium substitutes)
• an unusual or allergic reaction to losartan, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I take this medicine?

Take losartan tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Losartan can be taken with or without food. Take your doses at regular intervals. Do not take your medicine more often than directed.

What if I miss a dose?

If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What drug(s) may interact with losartan?

• antiinflammatory pain medicines such as ibuprofen (Motrin®)
• blood pressure medications
bosentan
cimetidine
delavirdine
fluconazole
• hawthorn
lithium
• monoamine oxidase inhibitors (Azilect®, Eldepryl®, Emsam®, Marplan®, Nardil®, Parnate®, Zelapar™)
phenobarbital
• potassium salts or potassium supplements
rifampin
voriconazole
• water pills (especially potassium-sparing diuretics such as triamterene or amiloride)

Tell your prescriber or health care professional about all other medicines you are taking, including nonprescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What should I watch for while taking losartan?

Check your blood pressure regularly while you are taking losartan. Ask your prescriber or health care professional what your blood pressure should be and when you should contact him or her. When you check your blood pressure, write down the measurements to show your prescriber or health care professional. If you are taking this medicine for a long time you must visit your prescriber or health care professional for regular checks on your progress. Make sure you schedule appointments on a regular basis.

You may experience dizziness. Do not drive, use machinery, or do anything that requires mental alertness until you know how losartan affects you. To avoid dizziness, do not stand or sit up quickly.

Avoid salt substitutes unless you are told otherwise by your prescriber or health care professional.

If you are going to have surgery tell your prescriber or health care professional that you are taking losartan.

Women should inform their doctor if they wish to become pregnant or think they might be pregnant. There is a potential for serious side effects to an unborn child, particularly in the second or third trimester. Talk to your health care professional or pharmacist for more information.

What side effects may I notice from taking losartan?

Side effects that you should report to your prescriber or health care professional as soon as possible:
Rare or uncommon:
• difficulty breathing or swallowing, hoarseness, or tightening of the throat
• swelling of your face, lips, tongue, hands, or feet
• unusual rash
Other:
• confusion, dizziness, lightheadedness or fainting spells
• decreased amount of urine passed
• decreased sexual function
• fast or uneven heart beat, palpitations, or chest pain

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
• cough
• diarrhea
• fatigue or tiredness
• headache
• inability to sleep
• nausea or stomach pain
• nasal congestion or stuffiness
• sore or cramping muscles
• upset stomach

Where can I keep my medicine?

Keep out of the reach of children in a container that small children cannot open.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Protect from light. Keep container tightly closed. Throw away any unused medicine after the expiration date.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

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Wikipedia: Losartan
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Losartan
Systematic (IUPAC) name
(2-butyl-4-chloro-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazol-5-yl)methanol
Identifiers
CAS number 114798-26-4
ATC code C09CA01
PubChem 3961
DrugBank APRD00052
Chemical data
Formula C22H23ClN6O 
Mol. mass 422.91
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 25–35%
Metabolism Hepatic (CYP2C9, CYP3A4)
Half life 1.5–2 hours
Excretion Renal 13–25%, biliary 50–60%
Therapeutic considerations
Pregnancy cat.

D(AU) D(US)

Legal status

Prescription only

Routes Oral
 Yes check.svgY(what is this?)  (verify)

Losartan (rINN) (pronounced /loʊˈsɑrtən/) is an angiotensin II receptor antagonist drug used mainly to treat high blood pressure (hypertension). Losartan was the first angiotensin II receptor antagonist to be marketed. It is currently marketed by Merck & Co. under the trade name Cozaar.

Contents

Clinical use

As with all angiotensin I receptor antagonists, losartan is indicated for the treatment of hypertension. Losartan may also delay progression of diabetic nephropathy and is also indicated for the reduction of renal disease progression in patients with type 2 diabetes, hypertension and microalbuminuria (>30 mg/24 hours) or proteinuria (>900 mg/24 hours).[1]

Although angiotensin I receptor antagonists are not usually considered first-line, because of the proven efficacy and lower costs of thiazide diuretics and beta blockers, losartan may be used first-line in patients with increased cardiovascular risk. The LIFE study demonstrated that losartan was significantly superior to atenolol in the primary prevention of adverse cardiovascular events (myocardial infarction or stroke), with a significant reduction in cardiovascular morbidity and mortality for a comparable reduction in blood pressure.[2]

Combination with diuretic

Losartan is available in a combination formulation with a low dose thiazide diuretic to achieve an additive antihypertensive effect. The losartan/hydrochlorothiazide combination preparation is marketed by Merck under the trade name Hyzaar and by Xeno Pharmaceuticals under the name, Anzaplus. A Philippine-based drug company, Chira Pharmaceuticals, markets the combination formulation under the trade name "2Zaris" in the country. Merck, Sharp & Dohme market it as Ocsaar Plus in Israel.

Pharmacokinetics

Losartan is well absorbed following oral administration and undergoes significant first-pass metabolism to produce 5-carboxylic acid metabolite, designated as EXP3174. This metabolite is long-acting (6 to 8 hr), noncompetitive antagonist at the AT1 receptor and contribute to the pharmacological effects of Losartan. This metabolite is 10-40 times more potent in blocking AT1 receptors than the original Losartan. Its bioavailability is about 32%.

Research

Losartan has been found to downregulate the expression of transforming growth factor beta (TGF-β) types I and II receptors in the kidney of diabetic rats, which may partially account for its nephroprotective effects.[3] Effects on TGF-β expression may also account for its potential efficacy in Marfan syndrome and Duchenne muscular dystrophy (DMD) – losartan has been shown to prevent aortic aneurysm and certain pulmonary complications in a mouse model of the disease.[4]

Losartan is being studied for use in the treatment the 20% of breast cancer tumors positive for AGTR1. The University of Michigan Comprehensive Cancer Center has announced the result of an animal study which found losartan to "block" - reverse neoplastic changes - caused by this gene. [5][6]

Mechanism of action & pharmacological actions

Losartan is a selective, competitive Angiotensin II receptor type 1 (AT1) receptor antagonist, reducing the end organ responses to angiotensin II. Losartan administration results in a decrease in total peripheral resistance (afterload) and cardiac venous return (preload) All of the physiological effects of angiotensin II, including stimulation of release of aldosterone, are antagonized in the presence of losartan. Reduction in blood pressure occurs independently of the status of the renin-angiotensin system. As a result of losartan dosing, plasma renin activity increases due to removal of the angiotensin II feedback.

Other uses

Losartan is an uricosuric. Because losartan can cause hyperkalemia, potassium supplements or salt substitutes containing potassium should not be used without consulting the prescribing physician.

Losartan is being researched as a possible drug for marked slowing of aortic enlargement in Marfan and related syndromes.

References

  1. ^ Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
  2. ^ Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H (March 2002). "Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol". Lancet 359 (9311): 995–1003. doi:10.1016/S0140-6736(02)08089-3. PMID 11937178. 
  3. ^ Guo ZX, Qiu MC. [Losartan downregulates the expression of transforming growth factor beta type I and type II receptors in kidney of diabetic rat] Zhonghua Nei Ke Za Zhi 2003;42(6):403-8. PMID 12895325
  4. ^ Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome, and preserves muscle tissue architecture in DMD mouse models. Science 2006;312(5770):117-21. PMID 16601194
  5. ^ University of Michigan Health System (06-07-2009). "Breast Cancer Gene Can Be Blocked By Blood Pressure Drug" (in Eng). ScienceDaily. http://www.sciencedaily.com/releases/2009/06/090601182651.htm. Retrieved 06-08-2009. 
  6. ^ Rhodes DR, Ateeq B, Cao Q, Tomlins SA, Mehra R, Laxman B, Kalyana-Sundaram S, Lonigro RJ, Helgeson BE, Bhojani MS, Rehemtulla A, Kleer CG, Hayes DF,Lucas PC, Varambally S, Chinnaiyan AM. AGTR1 overexpression defines a subset of breast cancer and confers sensitivity to losartan, an AGTR1 antagonist. PNAS 2009; www.pnas.org/cgi/doi/10.1073/pnas.0900351106

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