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Losartan Potassium

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Overview

What is Losartan Potassium?

Losartan potassium is an angiotensin II receptor (type AT) antagonist. Losartan potassium, a non-peptide molecule, is chemically described as 2-butyl-4-chloro-1-[-(-1-tetrazol-5-ylphenyl)benzyl]imidazole-5-methanol monopotassium salt.

Its empirical formula is CHClKNO, and its structural formula is:

Losartan potassium is a white to off-white free-flowing crystalline powder with a molecular weight of 461.01. It is freely soluble in water, soluble in alcohols, and slightly soluble in common organic solvents, such as acetonitrile and methyl ethyl ketone. Oxidation of the 5-hydroxymethyl group on the imidazole ring results in the active metabolite of losartan.

Losartan potassium tablets are available for oral administration containing either 25 mg, 50 mg or 100 mg of losartan potassium and the following inactive ingredients: microcrystalline cellulose, lactose hydrous, pregelatinized starch, magnesium stearate, hydroxypropyl cellulose, hypromellose, and titanium dioxide.

Losartan potassium tablets 25 mg, 50 mg and 100 mg contain potassium in the following amounts: 2.12 mg (0.054 mEq), 4.24 mg (0.108 mEq) and 8.48 mg (0.216 mEq), respectively. Losartan potassium tablets 25 mg, losartan potassium tablets 50 mg, and losartan potassium tablets 100 mg may also contain carnauba wax.



What does Losartan Potassium look like?



What are the available doses of Losartan Potassium?

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What should I talk to my health care provider before I take Losartan Potassium?

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How should I use Losartan Potassium?

Losartan potassium tablets are indicated for the treatment of hypertension. They may be used alone or in combination with other antihypertensive agents, including diuretics.

Losartan potassium tablets may be administered with other antihypertensive agents, and with or without food.

Dosing must be individualized. The usual starting dose of losartan potassium tablets is 50 mg once daily, with 25 mg used in patients with possible depletion of intravascular volume (e.g., patients treated with diuretics) (see ) and patients with a history of hepatic impairment (see ). Losartan potassium tablets can be administered once or twice daily with total daily doses ranging from 25 mg to 100 mg.

If the antihypertensive effect measured at trough using once-a-day dosing is inadequate, a twice-a-day regimen at the same total daily dose or an increase in dose may give a more satisfactory response. The effect of losartan is substantially present within one week but in some studies the maximal effect occurred in 3-6 weeks (see ).

If blood pressure is not controlled by losartan potassium tablets alone, a low dose of a diuretic may be added. Hydrochlorothiazide has been shown to have an additive effect (see ).

No initial dosage adjustment is necessary for elderly patients or for patients with renal impairment, including patients on dialysis.


What interacts with Losartan Potassium?

Losartan potassium tablets are contraindicated in patients who are hypersensitive to any component of this product.



What are the warnings of Losartan Potassium?

Fetal/Neonatal Morbidity and Mortality

Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature in patients who were taking angiotensin converting enzyme inhibitors. When pregnancy is detected, losartan potassium tablets should be discontinued as soon as possible.

The use of drugs that act directly on the renin-angiotensin system during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to exposure to the drug.

These adverse effects do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester.

Mothers whose embryos and fetuses are exposed to an angiotensin II receptor antagonist only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should have the patient discontinue the use of losartan potassium tablets as soon as possible.

Rarely (probably less often than once in every thousand pregnancies), no alternative to an angiotensin II receptor antagonist will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intra-amniotic environment.

If oligohydramnios is observed, losartan potassium tablets should be discontinued unless they are considered life-saving for the mother. Contraction stress testing (CST), a non-stress test (NST), or biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.

Infants with histories of exposure to an angiotensin II receptor antagonist should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function.

Losartan potassium tablets have been shown to produce adverse effects in rat fetuses and neonates, including decreased body weight, delayed physical and behavioral development, mortality and renal toxicity. With the exception of neonatal weight gain (which was affected at doses as low as 10 mg/kg/day), doses associated with these effects exceeded 25 mg/kg/day (approximately three times the maximum recommended human dose of 100 mg on a mg/mbasis). These findings are attributed to drug exposure in late gestation and during lactation. Significant levels of losartan and its active metabolite were shown to be present in rat fetal plasma during late gestation and in rat milk.

Hypotension — Volume-Depleted Patients

In patients who are intravascularly volume-depleted (e.g., those treated with diuretics), symptomatic hypotension may occur after initiation of therapy with losartan potassium tablets. These conditions should be corrected prior to administration of losartan potassium tablets, or a lower starting dose should be used (see ).


What are the precautions of Losartan Potassium?

General

Hypersensitivity:

Impaired Hepatic Function

Based on pharmacokinetic data which demonstrate significantly increased plasma concentrations of losartan in cirrhotic patients, a lower dose should be considered for patients with impaired liver function (see and ).

Impaired Renal Function

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function have been reported in susceptible individuals treated with losartan potassium tablets; in some patients, these changes in renal function were reversible upon discontinuation of therapy.

In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure), treatment with angiotensin converting enzyme inhibitors has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. Similar outcomes have been reported with losartan potassium tablets.

In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen (BUN) have been reported. Similar effects have been reported with losartan potassium tablets; in some patients, these effects were reversible upon discontinuation of therapy.

Electrolyte Imbalance

Electrolyte imbalances are common in patients with renal impairment, with or without diabetes, and should be addressed. In a clinical study conducted in type 2 diabetic patients with proteinuria, the incidence of hyperkalemia was higher in the group treated with losartan potassium tablets as compared to the placebo group; however, few patients discontinued therapy due to hyperkalemia (see ).

Information for Patients

Pregnancy:

Potassium Supplements:

Drug Interactions

No significant drug-drug pharmacokinetic interactions have been found in interaction studies with hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital. Rifampin, an inducer of drug metabolism, decreased the concentrations of losartan and its active metabolite. (See .) In humans, two inhibitors of P450 3A4 have been studied. Ketoconazole did not affect the conversion of losartan to the active metabolite after intravenous administration of losartan, and erythromycin had no clinically significant effect after oral administration. Fluconazole, an inhibitor of P450 2C9, decreased active metabolite concentration and increased losartan concentration. The pharmacodynamic consequences of concomitant use of losartan and inhibitors of P450 2C9 have not been examined. Subjects who do not metabolize losartan to active metabolite have been shown to have a specific, rare defect in cytochrome P450 2C9. These data suggest that the conversion of losartan to its active metabolite is mediated primarily by P450 2C9 and not P450 3A4.

As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium.

Lithium:

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors):

The antihypertensive effect of angiotensin II receptor antagonists, including losartan, may be attenuated by NSAIDs, including selective COX-2 inhibitors.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Losartan potassium was not carcinogenic when administered at maximally tolerated dosages to rats and mice for 105 and 92 weeks, respectively. Female rats given the highest dose (270 mg/kg/day) had a slightly higher incidence of pancreatic acinar adenoma. The maximally tolerated dosages (270 mg/kg/day in rats, 200 mg/kg/day in mice) provided systemic exposures for losartan and its pharmacologically active metabolite that were approximately 160- and 90-times (rats) and 30- and 15-times (mice) the exposure of a 50 kg human given 100 mg per day.

Losartan potassium was negative in the microbial mutagenesis and V-79 mammalian cell mutagenesis assays and in the alkaline elution and and chromosomal aberration assays. In addition, the active metabolite showed no evidence of genotoxicity in the microbial mutagenesis, alkaline elution, and chromosomal aberration assays.

Fertility and reproductive performance were not affected in studies with male rats given oral doses of losartan potassium up to approximately 150 mg/kg/day. The administration of toxic dosage levels in females (300/200 mg/kg/day) was associated with a significant (p
Pregnancy

Pregnancy Categories C (first trimester) and D (second and third trimesters). See .

Nursing Mothers

It is not known whether losartan is excreted in human milk, but significant levels of losartan and its active metabolite were shown to be present in rat milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Antihypertensive effects of losartan potassium tablets have been established in hypertensive pediatric patients aged 6 to 16 years. There are no data on the effect of losartan potassium tablets on blood pressure in pediatric patients under the age of 6 or in pediatric patients with glomerular filtration rate
Geriatric Use

Of the total number of patients receiving losartan potassium tablets in controlled clinical studies for hypertension, 391 patients (19%) were 65 years and over, while 37 patients (2%) were 75 years and over. In a controlled clinical study for renal protection in type 2 diabetic patients with proteinuria, 248 patients (33%) were 65 years and over. In a controlled clinical study for the reduction in the combined risk of cardiovascular death, stroke and myocardial infarction in hypertensive patients with left ventricular hypertrophy, 2857 patients (62%) were 65 years and over, while 808 patients (18%) were 75 years and over. No overall differences in effectiveness or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Race

In the LIFE study, Black patients with hypertension and left ventricular hypertrophy had a lower risk of stroke on atenolol than on losartan potassium tablets. Given the difficulty in interpreting subset differences in large trials, it cannot be known whether the observed difference is the result of chance. However, the LIFE study does not provide evidence that the benefits of losartan potassium tablets on reducing the risk of cardiovascular events in hypertensive patients with left ventricular hypertrophy apply to Black patients. (See .)


What are the side effects of Losartan Potassium?

Hypertension

Losartan potassium tablets have been evaluated for safety in more than 3300 adult patients treated for essential hypertension and 4058 patients/subjects overall. Over 1200 patients were treated for over 6 months and more than 800 for over one year. In general, treatment with losartan potassium tablets was well-tolerated. The overall incidence of adverse experiences reported with losartan potassium tablets was similar to placebo.

In controlled clinical trials, discontinuation of therapy due to clinical adverse experiences was required in 2.3 percent of patients treated with losartan potassium tablets and 3.7 percent of patients given placebo.

The following table of adverse events is based on four 6- to 12-week, placebo-controlled trials involving over 1000 patients on various doses (10-150 mg) of losartan and over 300 patients given placebo. All doses of losartan are grouped because none of the adverse events appeared to have a dose-related frequency. The adverse experiences reported in ≥1% of patients treated with losartan potassium tablets and more commonly than placebo are shown in the table below.

The following adverse events were also reported at a rate of 1% or greater in patients treated with losartan, but were as, or more frequent, in the placebo group: asthenia/fatigue, edema/swelling, abdominal pain, chest pain, nausea, headache, pharyngitis, diarrhea, dyspepsia, myalgia, insomnia, cough, sinus disorder.

Adverse events occurred at about the same rates in men and women, older and younger patients, and Black and non-Black patients.

A patient with known hypersensitivity to aspirin and penicillin, when treated with losartan potassium tablets, was withdrawn from study due to swelling of the lips and eyelids and facial rash, reported as angioedema, which returned to normal 5 days after therapy was discontinued.

Superficial peeling of palms and hemolysis were reported in one subject.

In addition to the adverse events above, potentially important events that occurred in at least two patients/subjects exposed to losartan or other adverse events that occurred in
Persistent dry cough (with an incidence of a few percent) has been associated with ACE-inhibitor use and in practice can be a cause of discontinuation of ACE-inhibitor therapy. Two prospective, parallel-group, double-blind, randomized, controlled trials were conducted to assess the effects of losartan on the incidence of cough in hypertensive patients who had experienced cough while receiving ACE-inhibitor therapy. Patients who had typical ACE-inhibitor cough when challenged with lisinopril, whose cough disappeared on placebo, were randomized to losartan 50 mg, lisinopril 20 mg, or either placebo (one study, n=97) or 25 mg hydrochlorothiazide (n=135). The double-blind treatment period lasted up to 8 weeks. The incidence of cough is shown below.

These studies demonstrate that the incidence of cough associated with losartan therapy, in a population that all had cough associated with ACE-inhibitor therapy, is similar to that associated with hydrochlorothiazide or placebo therapy.

Cases of cough, including positive re-challenges, have been reported with the use of losartan in post-marketing experience.

Pediatric Patients:

 Losartan(n=1075)Incidence%Placebo(n=334)Incidence%
Musculoskeletal
Nervous System/Psychiatric
Respiratory
Study 1 HCTZLosartanLisinopril
Cough25%17%69%
    
Study 2 PlaceboLosartanLisinopril
Cough35%29%62%


Hypertensive Patients with Left Ventricular Hypertrophy

In the LIFE study, adverse events with losartan potassium tablets were similar to those reported previously for patients with hypertension.

Nephropathy in Type 2 Diabetic Patients

In the RENAAL study involving 1513 patients treated with losartan potassium tablets or placebo, the overall incidences of reported adverse experiences were similar for the two groups. Losartan potassium tablets were generally well tolerated as evidenced by a similar incidence of discontinuations due to side effects compared to placebo (19% for losartan potassium tablets, 24% for placebo). The adverse experiences, regardless of drug relationship, reported with an incidence of ≥4% of patients treated with losartan potassium tablets and occurring more commonly than placebo, on a background of conventional antihypertensive therapy, are shown in the table below.

Losartanand ConventionalAntihypertensiveTherapyIncidence%(n=751)Placeboand Conventional Antihypertensive TherapyIncidence%(n=762)
Body as a Whole
Cardiovascular
Digestive
Endocrine
Eyes, Ears, Nose and Throat
Hemic
Metabolic and Nutrition
Musculoskeletal
Nervous System
Respiratory
Skin
Urogenital


Post-Marketing Experience

The following additional adverse reactions have been reported in post-marketing experience:

Digestive:

General Disorders and Administration Site Conditions:

Hemic:

Hypersensitivity:

Metabolic and Nutrition:

Musculoskeletal:

Nervous system disorders:

Respiratory:

Skin:

Laboratory Test Findings

In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of losartan potassium tablets.

Creatinine, Blood Urea Nitrogen:

Hemoglobin and Hematocrit:

Liver Function Tests:


What should I look out for while using Losartan Potassium?

Losartan potassium tablets are contraindicated in patients who are hypersensitive to any component of this product.


What might happen if I take too much Losartan Potassium?

Significant lethality was observed in mice and rats after oral administration of 1000 mg/kg and 2000 mg/kg,respectively, about 44 and 170 times the maximum recommended human dose on a mg/m basis.

Limited data are available in regard to overdosage in humans. The most likely manifestation of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted.

Neither losartan nor its active metabolite can be removed by hemodialysis.


How should I store and handle Losartan Potassium?

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].Keep out of reach of children.Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].Keep out of reach of children.No. 8441 — Losartan Potassium 25 mg Tablets are white, oval, film-coated tablets with code 951 on one side and plain on the other. They are supplied as follows:NDCNDCNo. 8442 — Losartan Potassium 50 mg Tablets are white, oval, film-coated tablets with code 952 on one side and scored on the other. They are supplied as follows:NDCNDC NDC No. 3849 — Losartan Potassium 100 mg Tablets are white, teardrop-shaped, film-coated tablets with code 960 on one side and plain on the other. They are supplied as follows:NDCNDC NDCNo. 8441 — Losartan Potassium 25 mg Tablets are white, oval, film-coated tablets with code 951 on one side and plain on the other. They are supplied as follows:NDCNDCNo. 8442 — Losartan Potassium 50 mg Tablets are white, oval, film-coated tablets with code 952 on one side and scored on the other. They are supplied as follows:NDCNDC NDC No. 3849 — Losartan Potassium 100 mg Tablets are white, teardrop-shaped, film-coated tablets with code 960 on one side and plain on the other. They are supplied as follows:NDCNDC NDCNo. 8441 — Losartan Potassium 25 mg Tablets are white, oval, film-coated tablets with code 951 on one side and plain on the other. They are supplied as follows:NDCNDCNo. 8442 — Losartan Potassium 50 mg Tablets are white, oval, film-coated tablets with code 952 on one side and scored on the other. They are supplied as follows:NDCNDC NDC No. 3849 — Losartan Potassium 100 mg Tablets are white, teardrop-shaped, film-coated tablets with code 960 on one side and plain on the other. They are supplied as follows:NDCNDC NDCNo. 8441 — Losartan Potassium 25 mg Tablets are white, oval, film-coated tablets with code 951 on one side and plain on the other. They are supplied as follows:NDCNDCNo. 8442 — Losartan Potassium 50 mg Tablets are white, oval, film-coated tablets with code 952 on one side and scored on the other. They are supplied as follows:NDCNDC NDC No. 3849 — Losartan Potassium 100 mg Tablets are white, teardrop-shaped, film-coated tablets with code 960 on one side and plain on the other. They are supplied as follows:NDCNDC NDCNo. 8441 — Losartan Potassium 25 mg Tablets are white, oval, film-coated tablets with code 951 on one side and plain on the other. They are supplied as follows:NDCNDCNo. 8442 — Losartan Potassium 50 mg Tablets are white, oval, film-coated tablets with code 952 on one side and scored on the other. They are supplied as follows:NDCNDC NDC No. 3849 — Losartan Potassium 100 mg Tablets are white, teardrop-shaped, film-coated tablets with code 960 on one side and plain on the other. They are supplied as follows:NDCNDC NDCNo. 8441 — Losartan Potassium 25 mg Tablets are white, oval, film-coated tablets with code 951 on one side and plain on the other. They are supplied as follows:NDCNDCNo. 8442 — Losartan Potassium 50 mg Tablets are white, oval, film-coated tablets with code 952 on one side and scored on the other. They are supplied as follows:NDCNDC NDC No. 3849 — Losartan Potassium 100 mg Tablets are white, teardrop-shaped, film-coated tablets with code 960 on one side and plain on the other. They are supplied as follows:NDCNDC NDCNo. 8441 — Losartan Potassium 25 mg Tablets are white, oval, film-coated tablets with code 951 on one side and plain on the other. They are supplied as follows:NDCNDCNo. 8442 — Losartan Potassium 50 mg Tablets are white, oval, film-coated tablets with code 952 on one side and scored on the other. They are supplied as follows:NDCNDC NDC No. 3849 — Losartan Potassium 100 mg Tablets are white, teardrop-shaped, film-coated tablets with code 960 on one side and plain on the other. They are supplied as follows:NDCNDC NDCNo. 8441 — Losartan Potassium 25 mg Tablets are white, oval, film-coated tablets with code 951 on one side and plain on the other. They are supplied as follows:NDCNDCNo. 8442 — Losartan Potassium 50 mg Tablets are white, oval, film-coated tablets with code 952 on one side and scored on the other. They are supplied as follows:NDCNDC NDC No. 3849 — Losartan Potassium 100 mg Tablets are white, teardrop-shaped, film-coated tablets with code 960 on one side and plain on the other. They are supplied as follows:NDCNDC NDCNo. 8441 — Losartan Potassium 25 mg Tablets are white, oval, film-coated tablets with code 951 on one side and plain on the other. They are supplied as follows:NDCNDCNo. 8442 — Losartan Potassium 50 mg Tablets are white, oval, film-coated tablets with code 952 on one side and scored on the other. They are supplied as follows:NDCNDC NDC No. 3849 — Losartan Potassium 100 mg Tablets are white, teardrop-shaped, film-coated tablets with code 960 on one side and plain on the other. They are supplied as follows:NDCNDC NDCNo. 8441 — Losartan Potassium 25 mg Tablets are white, oval, film-coated tablets with code 951 on one side and plain on the other. They are supplied as follows:NDCNDCNo. 8442 — Losartan Potassium 50 mg Tablets are white, oval, film-coated tablets with code 952 on one side and scored on the other. They are supplied as follows:NDCNDC NDC No. 3849 — Losartan Potassium 100 mg Tablets are white, teardrop-shaped, film-coated tablets with code 960 on one side and plain on the other. They are supplied as follows:NDCNDC NDCNo. 8441 — Losartan Potassium 25 mg Tablets are white, oval, film-coated tablets with code 951 on one side and plain on the other. They are supplied as follows:NDCNDCNo. 8442 — Losartan Potassium 50 mg Tablets are white, oval, film-coated tablets with code 952 on one side and scored on the other. They are supplied as follows:NDCNDC NDC No. 3849 — Losartan Potassium 100 mg Tablets are white, teardrop-shaped, film-coated tablets with code 960 on one side and plain on the other. They are supplied as follows:NDCNDC NDC


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Clinical Information

Chemical Structure

No Image found
Clinical Pharmacology

Angiotensin II [formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE, kininase II)], is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT receptor found in many tissues, (e.g., vascular smooth muscle, adrenal gland). There is also an AT receptor found in many tissues but it is not known to be associated with cardiovascular homeostasis. Both losartan and its principal active metabolite do not exhibit any partial agonist activity at the AT receptor and have much greater affinity (about 1000-fold) for the AT receptor than for the AT receptor. binding studies indicate that losartan is a reversible, competitive inhibitor of the AT receptor. The active metabolite is 10 to 40 times more potent by weight than losartan and appears to be a reversible, non-competitive inhibitor of the AT receptor.

Neither losartan nor its active metabolite inhibits ACE (kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin); nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

Non-Clinical Toxicology
Losartan potassium tablets are contraindicated in patients who are hypersensitive to any component of this product.

No significant drug-drug pharmacokinetic interactions have been found in interaction studies with hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital. Rifampin, an inducer of drug metabolism, decreased the concentrations of losartan and its active metabolite. (See .) In humans, two inhibitors of P450 3A4 have been studied. Ketoconazole did not affect the conversion of losartan to the active metabolite after intravenous administration of losartan, and erythromycin had no clinically significant effect after oral administration. Fluconazole, an inhibitor of P450 2C9, decreased active metabolite concentration and increased losartan concentration. The pharmacodynamic consequences of concomitant use of losartan and inhibitors of P450 2C9 have not been examined. Subjects who do not metabolize losartan to active metabolite have been shown to have a specific, rare defect in cytochrome P450 2C9. These data suggest that the conversion of losartan to its active metabolite is mediated primarily by P450 2C9 and not P450 3A4.

As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium.

Lithium:

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors):

The antihypertensive effect of angiotensin II receptor antagonists, including losartan, may be attenuated by NSAIDs, including selective COX-2 inhibitors.

Hypersensitivity:

ADVERSE REACTIONS, Post-Marketing Experience

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Reference

This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"

While we update our database periodically, we cannot guarantee it is always updated to the latest version.

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Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72
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Interactions

Interactions

A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).