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Sticky Threads
The poetry section had a challenge and now it is time to challenge the writers of fiction.
Your challenge, is to write a short story which MUST begin with the line "The door creaked open slowly..."
It can be original or fan fiction with a maximum word count of 1000 words (you are permitted to...
Greetings fellow writers and readers.
As you may have noticed, when posting a new thread in this forum there is now a drop-down menu of "prefixes" which can be applied to the thread. This is a new feature which will eventually replace the thread titling system we already have in place. It will...
*Read Before Posting!* FanFiction Forum Rules
What Kind of Writing Can Be Posted?
While called the "fanfiction" forum, we accept many other forms of writing. Fanfiction, original fiction, non-fiction, essays, plays, and more are all accepted here.
Fanfiction - Fanfiction is loosely...
What's Going On?
This is to be your one stop thread to what's currently going on in the forum. Links to writing challenges, contests, and featured stories, both past and present, will all be located here. Other fun activities may find their way into being linked here as well, so make sure you...
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Normal Threads
Yayakoshii means puzzling. English can be poor since I am Dutch, English is not my first language.
Please enjoy reading and comment if you like!
It's late spring and as I walk to...
We had Innuyasha and Innuyasha: The Final Chapter, but now we have Innuyasha: One Year Later!
It has been a year since Kagome decided to stay with Innuyasha in the feudal period as his wife. But after a year, the romance has faced. Kagome and Innuyasha seek help from a marriage consular.
I'm posting this under Fan Fic, since I figure it's as good place as any.
Pick an anime. Any anime. And come up with your own sequel or spin-off. Include a synopsis of what the new series would be about.
Unnamed Blood+ Spinoff. At the end of Blood+, we are told that Mao and Akihiro go...
First, what is a "round robin?" I will start a story. Then someone else continues it. Then another person continues. I will check back in and add some more. The rules:
1. You are free to write in your own personal style.
2. You must continue where the other person left off, though you...
Story Summary:
Genre: horror, romance, and adventure.
Day by day, the demons of the underworld take more of the earth. With King Darch dead and his daughter unable to claim the throne, the earth is done for. The King's daughter made a pact with the devil, and now she must overcome the evil...
Inside an old house, Fred, Velma, Daphne, and Scooby are standing around talking. Shaggy is slumped over in a chair at a nearby table.
Fred: Lets go, gang! Its time to catch that werewolf! Scooby, go wake up Shaggy.
Scooby: (Pokes Shaggy) Raggy? Hey, rake up! Raggy? (Long silence)...
Hell Girl, as performed by the cast of Family Guy!
Ai . . . . . . . . . Meg
Wanyuudou . . . . . . . . Peter
Onna . . . . . . . . . Lois
Ren . . . . . . . . Chris
Kikuri . . . . . . . . Brian
Stewie . . . . . . . . Stewie
A chilling scene from Monty Pythons Death Note.
Ryuk walks into an apple store.
Ryuk: Excuse me, do you have any Jonathan apples?
Clerk: Sorry sir, we are fresh out.
Ryuk: OK, then . How about Braeburn?
This is not a fan-fiction, but rather, an idea concept for a manga series I've just thought about several days ago. And I think it would be interesting to share with you guys.
The idea is, each person has his/her own talent and ability. These ability can be natural born, or acquired from excessive...
Kei Nagai, the brooding anti-hero of Ajin: Demi-Human, has been making the rounds at comic and anime conventions pushing the series to American audiences. Despite limited access on streaming on-line, the show has gained a cult following a large cult following judging by the crowd which gathered...
Scene 1 -- Inuyasha and Sesshomaru are about to do battle.
Inuyasha: Hey, Sesshomaru! Liberace called! He wants his wardrobe back.
Sesshomaru: Inuyasha, I am going to slap you so silly.
Jaken: Lord Sesshomaru, you must hurry to defeat Inuyasha! Otherwise we will be late for the...
Charlie Brown: Does anyone know the true meaning of Christmas?
Linus: I know the true meaning, Charlie Brown. Christmas is an artificial creation of the corporate structure designed to pressure the working class into making purchases of items they do not need and cannot afford.
Lucy: ...
It's a little late for this, but I have been putting if off until now.
Peppermint Patty: You call this a Thanksgiving dinner? Where's the turkey? Where's the giblets? Where's the stuffing? Where's the mashed potatoes? Where's the crack cocaine?
Charlie Brown: Crack cocaine?
Sorry this is late, but I kept putting it off.
Linus: Every Halloween, the Great Pumpkin rises out of the pumpkin patch and searches the world over for bad little boys and girls. And when he finds them he rips off their arms and legs, disembowels them, and feasts on their internal organs.
This is Law & Order: Anime Victims Unit, the story of an anime girl named Yohjo, and her efforts to discover what happened to her missing twin sister.
The story of her investigation, begins with her on an island, where tips have suggested that her sister had be seen. Here she is, after having...
Towards the end of their run, things got pretty testy between Rocky and Bullwinkle.
Bullwinkle: Hey Rocky! Watch me pull a rabbit out of my hat!
Rocky: I'd like to see you try to pull one out of your a-ss.
Bullwinkle: What?
Rocky: Nothing.
Ayako: There is definitely a spirit here. Look at the signs.
Masako: There is no spirit here. That is not what I sense.
Ayako: How can you say there is no spirit? Isnt it obvious that. . . .
Kazuya: But you do sense something.
Masako: Yes. It is not a spirit though. But it is...
Vegita, Krillin and Gohan prepare to do battle with Freeza.
Freeza: (Laughing) So you puny fools think you can do battle with me? I would like to see you try.
Vegita: (Chuckles) Be careful what you wish for. Im a lot stronger now than what I used to be.
Gohan: Krillin, did you notice...
She could feel it. She could feel the piercing blade as if it were shot through her skin. She could feel the sensation of a lifeless body against her own skin, embracing her tightly as she briefly heard the last whispers of her knight.
The princess was never a fighter to begin with, just...
I want to implied these legends in some way in my story. Chinese Legendary:
Butterfly Lovers
Girl disguise herself as a man.
lie to her secret crush about him meeting her "Sister"
Her parents make arrange marriage to rich guy.
Her crush died.
The sunlight streamed through the window, burning my eyelids. I couldn't move my arms to put a hand over my eyes, and though I didn't particularly want to open my eyes I did. I was quite stunned and confused by my surroundings. When did I get into this room? It wasn't my room at home at all. The...
Death is just the end to a physical being, and nothing more. Once someone is dead youll never be able to touch them, smell them, see them, or hear them. Its not the end though- what you dont know is that theyre energy is still there. It will stay with you forever, because when someone dies, a...
I was tired. Tired of everything I knew, tired of my friends, my family, the things I was interested in at one point, I was so tired of being the same old person, always going to parties with my friends, dating a different guy almost every month. I was tired of my once fun life. Hell, even my music...
The Sugarplum Fairy
By, Clayton Overstreet
There are monsters in the world. When you think of them you usually think of big things. Giants, dragons, trolls, and the like. If you think smaller then maybe you think of vampires, werewolves, and goblins. Around Christmas you may even think of...
This seems to be a question that always comes to my mind when it comes to writing fanfiction: Will people actually read my story? I tend to be something of an attention whore and I have an overwhelming need to know that what I put out there is appreciated.
There is a story that I wrote a while...
The title can seem misleading, but it works. This story is about an alien that hitches a ride on one of the Voyager Space Probe back to Earth. There she'll meet the main protagonist Billy and his sister Beatrice.
This story was going to be a standalone but I found it works with another story...
This will be a work in progress.
I am also extremely new to writing; actually, I have never written a story before.
Comments are appreciated, constructive and critical alike.
What is Bound Souls?
Well, Chapter two will explain that.
Have Boruto series be closer to the Naruto as possible but the end pairings should be these two couples: InojiXSarada and BorutoXChocho.
But please tease Boruto and Sarada like Kishimoto did with NaruSaku fans.
I dog dare NaruHina and SasuSaku fans to this challenge. If you guys have the...
this is actually about a year old, and the only full length short story i've ever finished. i dug it up, did some major editing and now here it is.
I recoiled from the stiff uppercut to the gut and my stomach threatened an exodus of its contents. My vision doubled and my lungs evacuated,...
Author's note: except for the first couple paragraphs, this first part has been almost completely rewritten. Since I added so much, this first part doesn't get as far into the story as my first draft because of size constraints. The first draft of part two is written, and I'll post the second draft...
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The Food and Drug Administration (FDA) warns the public from purchasing and using the unauthorized cosmetic product, BATH & BODY WORKS PINK CASHMERE BODY LOTION .
The abovementioned product was verified by FDA through postmarketing surveillance and shows no valid Certificate of Product Notification (CPN) as of 31 January 2022. Pursuant to Book II, Article I, Section 1 (a) of the Rules and Regulations Implementing Republic Act No. 9711, otherwise known as the "Food and Drug Administration Act of 2009", the manufacture, importation, exportation, sale, offering for sale, distribution, transfer, non-consumer use, promotion, advertising, or sponsorship of any health product without the proper authorization from the FDA is prohibited.
Since the abovementioned unauthorized cosmetic product has not gone through the notification process of the FDA, the agency cannot assure their quality and safety. The use of such violative product may pose health risks to consumers.
Potential hazards may come from ingredients that are not allowed to be part of a cosmetic product or from the contamination of heavy metals. The use of substandard and possibly adulterated cosmetic products may result to adverse reactions including, but not limited to, skin irritation, itchiness, anaphylactic shock and organ failure.
In light of the foregoing, the public is advised not to purchase the aforementioned violative cosmetic product. Always check if a product is notified with the FDA by using the FDA Verification Portal feature accessible at https://verification.fda.gov.ph. which may be used by typing in the name of the product before the purchase and/or using the cosmetic products.
All concerned establishments are warned not to distribute violative cosmetic product until they have fully complied with the rules and regulation of the FDA.
All FDA Regional Field Offices and Regulatory Enforcement Units, in coordination with law enforcement agencies and Local Government Units, are requested to ensure that violative products are not sold or made available in the market or areas of their jurisdiction.
To report any sale, distribution, complaint and/or adverse event on the use of the violative cosmetic products, the online reporting facility, eReport can be accessed at [email protected], or call us at the Center for Cosmetics and Household/Urban Hazardous Substances Regulation and Research (CCHUHSRR) hotline (02) 8857-1900 loc. 8113 or 8107.
Dissemination of this advisory to all concerned is hereby requested.


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Label: COZAAR- losartan potassium tablet, film coated
Contains inactivated NDC Code(s)
NDC Code(s): 54868-2335-0, 54868-2335-1, 54868-3726-0, 54868-3726-1, view more54868-5077-0
- Packager: Physicians Total Care, Inc.
- This is a repackaged label.
- Source NDC Code(s): 0006-0951, 0006-0952, 0006-0960
- Category: HUMAN PRESCRIPTION DRUG LABEL
- DEA Schedule: None
- Marketing Status: New Drug Application
Drug Label Information
Updated October 1, 2012
If you are a consumer or patient please visit this version.
- Download DRUG LABEL INFO: PDF XML
- Official Label (Printer Friendly)
(What is this?)
When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, COZAAR® should be discontinued as soon as possible. See WARNINGS, Fetal/Neonatal Morbidity and Mortality.
COZAAR (losartan potassium) is an angiotensin II receptor (type AT1) antagonist. Losartan potassium, a non-peptide molecule, is chemically described as 2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-methanol monopotassium salt.
Its empirical formula is C22H22ClKN6O, 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.
COZAAR is available as tablets 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.
COZAAR 25 mg, 50 mg and 100 mg tablets 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. COZAAR 25 mg, COZAAR 50 mg, and COZAAR 100 mg may also contain carnauba wax.
Mechanism of Action
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 AT1 receptor found in many tissues, (e.g., vascular smooth muscle, adrenal gland). There is also an AT2 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 AT1 receptor and have much greater affinity (about 1000-fold) for the AT1 receptor than for the AT2 receptor. In vitro binding studies indicate that losartan is a reversible, competitive inhibitor of the AT1 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 AT1 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.
Losartan is an orally active agent that undergoes substantial first-pass metabolism by cytochrome P450 enzymes. It is converted, in part, to an active carboxylic acid metabolite that is responsible for most of the angiotensin II receptor antagonism that follows losartan treatment. Losartan metabolites have been identified in human plasma and urine. In addition to the active carboxylic acid metabolite, several inactive metabolites are formed. Following oral and intravenous administration of 14C-labeled losartan potassium, circulating plasma radioactivity is primarily attributed to losartan and its active metabolite. In vitro studies indicate that cytochrome P450 2C9 and 3A4 are involved in the biotransformation of losartan to its metabolites. Minimal conversion of losartan to the active metabolite (less than 1% of the dose compared to 14% of the dose in normal subjects) was seen in about one percent of individuals studied.
The terminal half-life of losartan is about 2 hours and of the metabolite is about 6-9 hours.
The pharmacokinetics of losartan and its active metabolite are linear with oral losartan doses up to 200 mg and do not change over time. Neither losartan nor its metabolite accumulate in plasma upon repeated once-daily dosing.
Following oral administration, losartan is well absorbed (based on absorption of radiolabeled losartan) and undergoes substantial first-pass metabolism; the systemic bioavailability of losartan is approximately 33%. About 14% of an orally-administered dose of losartan is converted to the active metabolite. Mean peak concentrations of losartan and its active metabolite are reached in 1 hour and in 3-4 hours, respectively. While maximum plasma concentrations of losartan and its active metabolite are approximately equal, the AUC of the metabolite is about 4 times as great as that of losartan. A meal slows absorption of losartan and decreases its Cmax but has only minor effects on losartan AUC or on the AUC of the metabolite (about 10% decreased).
The pharmacokinetics of losartan and its active metabolite were also determined after IV doses of each component separately in healthy volunteers. The volume of distribution of losartan and the active metabolite is about 34 liters and 12 liters, respectively. Total plasma clearance of losartan and the active metabolite is about 600 mL/min and 50 mL/min, respectively, with renal clearance of about 75 mL/min and 25 mL/min, respectively. After single doses of losartan administered orally, about 4% of the dose is excreted unchanged in the urine and about 6% is excreted in urine as active metabolite. Biliary excretion contributes to the elimination of losartan and its metabolites. Following oral 14C-labeled losartan, about 35% of radioactivity is recovered in the urine and about 60% in the feces. Following an intravenous dose of 14C-labeled losartan, about 45% of radioactivity is recovered in the urine and 50% in the feces.
Both losartan and its active metabolite are highly bound to plasma proteins, primarily albumin, with plasma free fractions of 1.3% and 0.2%, respectively. Plasma protein binding is constant over the concentration range achieved with recommended doses. Studies in rats indicate that losartan crosses the blood-brain barrier poorly, if at all.
Special Populations
Pediatric: Pharmacokinetic parameters after multiple doses of losartan (average dose 0.7 mg/kg, range 0.36 to 0.97 mg/kg) as a tablet to 25 hypertensive patients aged 6 to 16 years are shown in Table 1 below. Pharmacokinetics of losartan and its active metabolite were generally similar across the studied age groups and similar to historical pharmacokinetic data in adults. The principal pharmacokinetic parameters in adults and children are shown in the table below.
Table 1: Pharmacokinetic Parameters in Hypertensive Adults and Children Age 6-16 Following Multiple Dosing Adults given 50 mg once daily for 7 days
Age 6-16 given 0.7 mg/kg once daily for 7 days
- *
- Mean ± standard deviation
Parent Active Metabolite Parent Active Metabolite AUC0-24*(ng•h/mL) 442 ± 173 1685 ± 452 368 ± 169 1866 ± 1076 CMAX (ng/mL)* 224 ± 82 212 ± 73 141 ± 88 222 ± 127 T1/2 (h) 2.1 ± 0.70 7.4 ± 2.4 2.3 ± 0.8 5.6 ± 1.2 TPEAK (h) 0.9 3.5 2.0 4.1 CLREN (mL/min)* 56 ± 23 20 ± 3 53 ± 33 17 ± 8
The bioavailability of the suspension formulation was compared with losartan tablets in healthy adults. The suspension and tablet are similar in their bioavailability with respect to both losartan and the active metabolite (see DOSAGE AND ADMINISTRATION, Preparation of Suspension).
Geriatric and Gender: Losartan pharmacokinetics have been investigated in the elderly (65-75 years) and in both genders. Plasma concentrations of losartan and its active metabolite are similar in elderly and young hypertensives. Plasma concentrations of losartan were about twice as high in female hypertensives as male hypertensives, but concentrations of the active metabolite were similar in males and females. No dosage adjustment is necessary (see DOSAGE AND ADMINISTRATION).
Race: Pharmacokinetic differences due to race have not been studied (see also PRECAUTIONS, Race and CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Reduction in the Risk of Stroke, Race).
Renal Insufficiency: Following oral administration, plasma concentrations and AUCs of losartan and its active metabolite are increased by 50-90% in patients with mild (creatinine clearance of 50 to 74 mL/min) or moderate (creatinine clearance 30 to 49 mL/min) renal insufficiency. In this study, renal clearance was reduced by 55-85% for both losartan and its active metabolite in patients with mild or moderate renal insufficiency. Neither losartan nor its active metabolite can be removed by hemodialysis. No dosage adjustment is necessary for patients with renal impairment unless they are volume-depleted (see WARNINGS, Hypotension — Volume-Depleted Patients and DOSAGE AND ADMINISTRATION).
Hepatic Insufficiency: Following oral administration in patients with mild to moderate alcoholic cirrhosis of the liver, plasma concentrations of losartan and its active metabolite were, respectively, 5-times and about 1.7-times those in young male volunteers. Compared to normal subjects the total plasma clearance of losartan in patients with hepatic insufficiency was about 50% lower and the oral bioavailability was about 2-times higher. A lower starting dose is recommended for patients with a history of hepatic impairment (see DOSAGE AND ADMINISTRATION).
Drug Interactions
Losartan, administered for 12 days, did not affect the pharmacokinetics or pharmacodynamics of a single dose of warfarin. Losartan did not affect the pharmacokinetics of oral or intravenous digoxin. There is no pharmacokinetic interaction between losartan and hydrochlorothiazide. Coadministration of losartan and cimetidine led to an increase of about 18% in AUC of losartan but did not affect the pharmacokinetics of its active metabolite. Coadministration of losartan and phenobarbital led to a reduction of about 20% in the AUC of losartan and that of its active metabolite. A somewhat greater interaction (approximately 40% reduction in the AUC of active metabolite and approximately 30% reduction in the AUC of losartan) has been reported with rifampin. Fluconazole, an inhibitor of cytochrome P450 2C9, decreased the AUC of the active metabolite by approximately 40%, but increased the AUC of losartan by approximately 70% following multiple doses. Conversion of losartan to its active metabolite after intravenous administration is not affected by ketoconazole, an inhibitor of P450 3A4. The AUC of active metabolite following oral losartan was not affected by erythromycin, another inhibitor of P450 3A4, but the AUC of losartan was increased by 30%.
Pharmacodynamics and Clinical Effects
Adult Hypertension
Losartan inhibits the pressor effect of angiotensin II (as well as angiotensin I) infusions. A dose of 100 mg inhibits the pressor effect by about 85% at peak with 25-40% inhibition persisting for 24 hours. Removal of the negative feedback of angiotensin II causes a 2- to 3-fold rise in plasma renin activity and consequent rise in angiotensin II plasma concentration in hypertensive patients. Losartan does not affect the response to bradykinin, whereas ACE inhibitors increase the response to bradykinin. Aldosterone plasma concentrations fall following losartan administration. In spite of the effect of losartan on aldosterone secretion, very little effect on serum potassium was observed.
In a single-dose study in normal volunteers, losartan had no effects on glomerular filtration rate, renal plasma flow or filtration fraction. In multiple-dose studies in hypertensive patients, there were no notable effects on systemic or renal prostaglandin concentrations, fasting triglycerides, total cholesterol or HDL-cholesterol or fasting glucose concentrations. There was a small uricosuric effect leading to a minimal decrease in serum uric acid (mean decrease <0.4 mg/dL) during chronic oral administration.
The antihypertensive effects of COZAAR were demonstrated principally in 4 placebo-controlled, 6- to 12-week trials of dosages from 10 to 150 mg per day in patients with baseline diastolic blood pressures of 95-115. The studies allowed comparisons of two doses (50-100 mg/day) as once-daily or twice-daily regimens, comparisons of peak and trough effects, and comparisons of response by gender, age, and race. Three additional studies examined the antihypertensive effects of losartan and hydrochlorothiazide in combination.
The 4 studies of losartan monotherapy included a total of 1075 patients randomized to several doses of losartan and 334 to placebo. The 10- and 25-mg doses produced some effect at peak (6 hours after dosing) but small and inconsistent trough (24 hour) responses. Doses of 50, 100 and 150 mg once daily gave statistically significant systolic/diastolic mean decreases in blood pressure, compared to placebo in the range of 5.5-10.5/3.5-7.5 mmHg, with the 150-mg dose giving no greater effect than 50-100 mg. Twice-daily dosing at 50-100 mg/day gave consistently larger trough responses than once-daily dosing at the same total dose. Peak (6 hour) effects were uniformly, but moderately, larger than trough effects, with the trough-to-peak ratio for systolic and diastolic responses 50-95% and 60-90%, respectively.
Addition of a low dose of hydrochlorothiazide (12.5 mg) to losartan 50 mg once daily resulted in placebo-adjusted blood pressure reductions of 15.5/9.2 mmHg.
Analysis of age, gender, and race subgroups of patients showed that men and women, and patients over and under 65, had generally similar responses. COZAAR was effective in reducing blood pressure regardless of race, although the effect was somewhat less in Black patients (usually a low-renin population).
The effect of losartan is substantially present within one week but in some studies the maximal effect occurred in 3-6 weeks. In long-term follow-up studies (without placebo control) the effect of losartan appeared to be maintained for up to a year. There is no apparent rebound effect after abrupt withdrawal of losartan. There was essentially no change in average heart rate in losartan-treated patients in controlled trials.
Pediatric Hypertension
The antihypertensive effect of losartan was studied in one trial enrolling 177 hypertensive pediatric patients aged 6 to 16 years old. Children who weighed <50 kg received 2.5, 25 or 50 mg of losartan daily and patients who weighed ≥50 kg received 5, 50 or 100 mg of losartan daily. Children in the lowest dose group were given losartan in a suspension formulation (see DOSAGE AND ADMINISTRATION, Preparation of Suspension). The majority of the children had hypertension associated with renal and urogenital disease. The sitting diastolic blood pressure (SiDBP) on entry into the study was higher than the 95th percentile level for the patient's age, gender, and height. At the end of three weeks, losartan reduced systolic and diastolic blood pressure, measured at trough, in a dose-dependent manner. Overall, the two higher doses (25 to 50 mg in patients <50 kg; 50 to 100 mg in patients ≥50 kg) reduced diastolic blood pressure by 5 to 6 mmHg more than the lowest dose used (2.5 mg in patients <50 kg; 5 mg in patients ≥50 kg). The lowest dose, corresponding to an average daily dose of 0.07 mg/kg, did not appear to offer consistent antihypertensive efficacy. When patients were randomized to continue losartan at the two higher doses or to placebo after 3 weeks of therapy, trough diastolic blood pressure rose in patients on placebo between 5 and 7 mmHg more than patients randomized to continuing losartan. When the low dose of losartan was randomly withdrawn, the rise in trough diastolic blood pressure was the same in patients receiving placebo and in those continuing losartan, again suggesting that the lowest dose did not have significant antihypertensive efficacy. Overall, no significant differences in the overall antihypertensive effect of losartan were detected when the patients were analyzed according to age (<, ≥12 years old) or gender. While blood pressure was reduced in all racial subgroups examined, too few non-White patients were enrolled to compare the dose-response of losartan in the non-White subgroup.
Reduction in the Risk of Stroke
The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study was a multinational, double-blind study comparing COZAAR and atenolol in 9193 hypertensive patients with ECG-documented left ventricular hypertrophy. Patients with myocardial infarction or stroke within six months prior to randomization were excluded. Patients were randomized to receive once daily COZAAR 50 mg or atenolol 50 mg. If goal blood pressure (<140/90 mmHg) was not reached, hydrochlorothiazide (12.5 mg) was added first and, if needed, the dose of COZAAR or atenolol was then increased to 100 mg once daily. If necessary, other antihypertensive treatments (e.g., increase in dose of hydrochlorothiazide therapy to 25 mg or addition of other diuretic therapy, calcium-channel blockers, alpha-blockers, or centrally acting agents, but not ACE inhibitors, angiotensin II antagonists, or beta-blockers) were added to the treatment regimen to reach the goal blood pressure.
Of the randomized patients, 4963 (54%) were female and 533 (6%) were Black. The mean age was 67 with 5704 (62%) age ≥65. At baseline, 1195 (13%) had diabetes, 1326 (14%) had isolated systolic hypertension, 1469 (16%) had coronary heart disease, and 728 (8%) had cerebrovascular disease. Baseline mean blood pressure was 174/98 mmHg in both treatment groups. The mean length of follow-up was 4.8 years. At the end of study or at the last visit before a primary endpoint, 77% of the group treated with COZAAR and 73% of the group treated with atenolol were still taking study medication. Of the patients still taking study medication, the mean doses of COZAAR and atenolol were both about 80 mg/day, and 15% were taking atenolol or losartan as monotherapy, while 77% were also receiving hydrochlorothiazide (at a mean dose of 20 mg/day in each group). Blood pressure reduction measured at trough was similar for both treatment groups but blood pressure was not measured at any other time of the day. At the end of study or at the last visit before a primary endpoint, the mean blood pressures were 144.1/81.3 mmHg for the group treated with COZAAR and 145.4/80.9 mmHg for the group treated with atenolol [the difference in systolic blood pressure (SBP) of 1.3 mmHg was significant (p<0.001), while the difference of 0.4 mmHg in diastolic blood pressure (DBP) was not significant (p=0.098)].
The primary endpoint was the first occurrence of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. Patients with nonfatal events remained in the trial, so that there was also an examination of the first event of each type even if it was not the first event (e.g., a stroke following an initial myocardial infarction would be counted in the analysis of stroke). Treatment with COZAAR resulted in a 13% reduction (p=0.021) in risk of the primary endpoint compared to the atenolol group (see Figure 1 and Table 2); this difference was primarily the result of an effect on fatal and nonfatal stroke. Treatment with COZAAR reduced the risk of stroke by 25% relative to atenolol (p=0.001) (see Figure 2 and Table 2).
Figure 1. Kaplan-Meier estimates of the primary endpoint of time to cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction in the groups treated with COZAAR and atenolol. The Risk Reduction is adjusted for baseline Framingham risk score and level of electrocardiographic left ventricular hypertrophy.
Figure 2. Kaplan-Meier estimates of the time to fatal/nonfatal stroke in the groups treated with COZAAR and atenolol. The Risk Reduction is adjusted for baseline Framingham risk score and level of electrocardiographic left ventricular hypertrophy.
Table 2 shows the results for the primary composite endpoint and the individual endpoints. The primary endpoint was the first occurrence of stroke, myocardial infarction or cardiovascular death, analyzed using an intention-to-treat (ITT) approach. The table shows the number of events for each component in two different ways. The Components of Primary Endpoint (as a first event) counts only the events that define the primary endpoint, while the Secondary Endpoints count all first events of a particular type, whether or not they were preceded by a different type of event.
Table 2: Incidence of Primary Endpoint Events
COZAAR Atenolol Risk
N (%) Rate* N (%) Rate*
Primary Composite Endpoint
508 (11)
588 (13)
2% to 23%
Components of Primary Composite Endpoint (as a first event)
Stroke (nonfatal†) 209 (5)
286 (6)
Myocardial infarction (nonfatal†) 174 (4)
168 (4)
Cardiovascular mortality 125 (3)
134 (3)
Secondary Endpoints (any time in study)
Stroke (fatal/nonfatal) 232 (5) 10.8 309 (7) 14.5 25% 11% to 37% 0.001 Myocardial infarction (fatal/nonfatal) 198 (4) 9.2 188 (4) 8.7 -7% -13% to 12% 0.491 Cardiovascular mortality 204 (4) 9.2 234 (5) 10.6 11% -7% to 27% 0.206 Due to CHD 125 (3) 5.6 124 (3) 5.6 -3% -32% to 20% 0.839 Due to Stroke 40 (1) 1.8 62 (1) 2.8 35% 4% to 67% 0.032 Other 39 (1) 1.8 48 (1) 2.2 16% -28% to 45% 0.411
Although the LIFE study favored COZAAR over atenolol with respect to the primary endpoint (p=0.021), this result is from a single study and, therefore, is less compelling than the difference between COZAAR and placebo. Although not measured directly, the difference between COZAAR and placebo is compelling because there is evidence that atenolol is itself effective (vs. placebo) in reducing cardiovascular events, including stroke, in hypertensive patients.
Other clinical endpoints of the LIFE study were: total mortality, hospitalization for heart failure or angina pectoris, coronary or peripheral revascularization procedures, and resuscitated cardiac arrest. There were no significant differences in the rates of these endpoints between the COZAAR and atenolol groups.
For the primary endpoint and stroke, the effects of COZAAR in patient subgroups defined by age, gender, race and presence or absence of isolated systolic hypertension (ISH), diabetes, and history of cardiovascular disease (CVD) are shown in Figure 3 below. Subgroup analyses can be difficult to interpret and it is not known whether these represent true differences or chance effects.
Figure 3. Primary Endpoint Events† within Demographic Subgroups
In the LIFE study, Black patients treated with atenolol were at lower risk of experiencing the primary composite endpoint compared with Black patients treated with COZAAR. In the subgroup of Black patients (n=533; 6% of the LIFE study patients), there were 29 primary endpoints among 263 patients on atenolol (11%, 26 per 1000 patient-years) and 46 primary endpoints among 270 patients (17%, 42 per 1000 patient-years) on COZAAR. This finding could not be explained on the basis of differences in the populations other than race or on any imbalances between treatment groups. In addition, blood pressure reductions in both treatment groups were consistent between Black and non-Black patients. 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 provides no evidence that the benefits of COZAAR on reducing the risk of cardiovascular events in hypertensive patients with left ventricular hypertrophy apply to Black patients.
Nephropathy in Type 2 Diabetic Patients
The Reduction of Endpoints in NIDDM with the Angiotensin II Receptor Antagonist Losartan (RENAAL) study was a randomized, placebo-controlled, double-blind, multicenter study conducted worldwide in 1513 patients with type 2 diabetes with nephropathy (defined as serum creatinine 1.3 to 3.0 mg/dl in females or males ≤60 kg and 1.5 to 3.0 mg/dl in males >60 kg and proteinuria [urinary albumin to creatinine ratio ≥300 mg/g]).
Patients were randomized to receive COZAAR 50 mg once daily or placebo on a background of conventional antihypertensive therapy excluding ACE inhibitors and angiotensin II antagonists. After one month, investigators were instructed to titrate study drug to 100 mg once daily if the trough blood pressure goal (140/90 mmHg) was not achieved. Overall, 72% of patients received the 100-mg daily dose more than 50% of the time they were on study drug. Because the study was designed to achieve equal blood pressure control in both groups, other antihypertensive agents (diuretics, calcium-channel blockers, alpha- or beta-blockers, and centrally acting agents) could be added as needed in both groups. Patients were followed for a mean duration of 3.4 years.
The study population was diverse with regard to race (Asian 16.7%, Black 15.2%, Hispanic 18.3%, White 48.6%). Overall, 63.2% of the patients were men, and 66.4% were under the age of 65 years. Almost all of the patients (96.6%) had a history of hypertension, and the patients entered the trial with a mean serum creatinine of 1.9 mg/dl and mean proteinuria (urinary albumin/creatinine) of 1808 mg/g at baseline.
The primary endpoint of the study was the time to first occurrence of any one of the following events: doubling of serum creatinine, end-stage renal disease (ESRD) (need for dialysis or transplantation), or death. Treatment with COZAAR resulted in a 16% risk reduction in this endpoint (see Figure 4 and Table 3). Treatment with COZAAR also reduced the occurrence of sustained doubling of serum creatinine by 25% and ESRD by 29% as separate endpoints, but had no effect on overall mortality (see Table 3).
The mean baseline blood pressures were 152/82 mmHg for COZAAR plus conventional antihypertensive therapy and 153/82 mmHg for placebo plus conventional antihypertensive therapy. At the end of the study, the mean blood pressures were 143/76 mmHg for the group treated with COZAAR and 146/77 mmHg for the group treated with placebo.
Figure 4. Kaplan-Meier curve for the primary composite endpoint of doubling of serum creatinine, end stage renal disease (need for dialysis or transplantation) or death.
Table 3: Incidence of Primary Endpoint Events Incidence Risk Reduction 95% C.I. p-Value
Losartan Placebo
Primary Composite Endpoint
2.3% to 27.9%
Doubling of Serum Creatinine, ESRD and Death Occurring as a First Event
Doubling of Serum Creatinine 21.6% 26.0%
Death 13.4% 12.6%
Overall Incidence of Doubling of Serum Creatinine, ESRD and Death
Doubling of Serum Creatinine 21.6% 26.0% 25.3% 7.8% to 39.4% 0.006 ESRD 19.6% 25.5% 28.6% 11.5% to 42.4% 0.002 Death 21.0% 20.3% -1.7% -26.9% to 18.6% 0.884
The secondary endpoints of the study were change in proteinuria, change in the rate of progression of renal disease, and the composite of morbidity and mortality from cardiovascular causes (hospitalization for heart failure, myocardial infarction, revascularization, stroke, hospitalization for unstable angina, or cardiovascular death). Compared with placebo, COZAAR significantly reduced proteinuria by an average of 34%, an effect that was evident within 3 months of starting therapy, and significantly reduced the rate of decline in glomerular filtration rate during the study by 13%, as measured by the reciprocal of the serum creatinine concentration. There was no significant difference in the incidence of the composite endpoint of cardiovascular morbidity and mortality.
The favorable effects of COZAAR were seen in patients also taking other anti-hypertensive medications (angiotensin II receptor antagonists and angiotensin converting enzyme inhibitors were not allowed), oral hypoglycemic agents and lipid-lowering agents.
For the primary endpoint and ESRD, the effects of COZAAR in patient subgroups defined by age, gender and race are shown in Table 4 below. Subgroup analyses can be difficult to interpret and it is not known whether these represent true differences or chance effects.
Table 4: Efficacy Outcomes within Demographic Subgroups Primary Composite Endpoint ESRD No. of Patients COZAAR
Event Rate
Event Rate
Hazard Ratio
Event Rate
Event Rate
Hazard Ratio
Overall Results 1513 43.5 47.1 0.839 (0.721, 0.977) 19.6 25.5 0.714 (0.576, 0.885) Age <65 years 1005 44.1 49.0 0.784 (0.653, 0.941) 21.1 28.5 0.670 (0.521, 0.863) ≥65 years 508 42.3 43.5 0.978 (0.749, 1.277) 16.5 19.6 0.847 (0.560, 1.281) Gender Female 557 47.8 54.1 0.762 (0.603, 0.962) 22.8 32.8 0.601 (0.436, 0.828) Male 956 40.9 43.3 0.892 (0.733, 1.085) 17.5 21.5 0.809 (0.605, 1.081) Race Asian 252 41.9 54.8 0.655 (0.453, 0.947) 18.8 27.4 0.625 (0.367, 1.066) Black 230 40.0 39.0 0.983 (0.647, 1.495) 17.6 21.0 0.831 (0.456, 1.516) Hispanic 277 55.0 54.0 1.003 (0.728, 1.380) 30.0 28.5 1.024 (0.661, 1.586) White 735 40.5 43.2 0.809 (0.645, 1.013) 16.2 23.9 0.596 (0.427, 0.831)
COZAAR is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents, including diuretics.
Hypertensive Patients with Left Ventricular Hypertrophy
COZAAR is indicated to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy, but there is evidence that this benefit does not apply to Black patients. (See PRECAUTIONS, Race and CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Reduction in the Risk of Stroke, Race.)
Nephropathy in Type 2 Diabetic Patients
COZAAR is indicated for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g) in patients with type 2 diabetes and a history of hypertension. In this population, COZAAR reduces the rate of progression of nephropathy as measured by the occurrence of doubling of serum creatinine or end stage renal disease (need for dialysis or renal transplantation) (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects).
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, COZAAR 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 COZAAR 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, COZAAR should be discontinued unless it is 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 in utero 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 has 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/m2 basis). 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 COZAAR. These conditions should be corrected prior to administration of COZAAR, or a lower starting dose should be used (see DOSAGE AND ADMINISTRATION).
Hypersensitivity: Angioedema. See ADVERSE REACTIONS, Post-Marketing Experience.
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 DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY, Pharmacokinetics).
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 COZAAR; 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 COZAAR.
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 COZAAR; 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 COZAAR as compared to the placebo group; however, few patients discontinued therapy due to hyperkalemia (see ADVERSE REACTIONS).
Information for Patients
Pregnancy: Female patients of childbearing age should be told about the consequences of second- and third-trimester exposure to drugs that act on the renin-angiotensin system, and they should also be told that these consequences do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester. These patients should be asked to report pregnancies to their physicians as soon as possible.
Potassium Supplements: A patient receiving COZAAR should be told not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician (see PRECAUTIONS, Drug Interactions).
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 CLINICAL PHARMACOLOGY, Drug Interactions.) 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: As with other drugs which affect the excretion of sodium, lithium excretion may be reduced. Therefore, serum lithium levels should be monitored carefully if lithium salts are to be co-administered with angiotensin II receptor antagonists.
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors): In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists (including losartan) may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving losartan and NSAID therapy.
The antihypertensive effect of angiotensin II receptor antagonists, including losartan, may be attenuated by NSAIDs, including selective COX-2 inhibitors.
Dual blockade of the renin-angiotensin-aldosterone system: Dual blockade of the renin-angiotensin-aldosterone system is associated with increased risk of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure). Closely monitor blood pressure, renal function, and electrolytes in patients on COZAAR and ACE 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 in vitro alkaline elution and in vitro and in vivo chromosomal aberration assays. In addition, the active metabolite showed no evidence of genotoxicity in the microbial mutagenesis, in vitro alkaline elution, and in vitro 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<0.05) decrease in the number of corpora lutea/female, implants/female, and live fetuses/female at C-section. At 100 mg/kg/day only a decrease in the number of corpora lutea/female was observed. The relationship of these findings to drug-treatment is uncertain since there was no effect at these dosage levels on implants/pregnant female, percent post-implantation loss, or live animals/litter at parturition. In nonpregnant rats dosed at 135 mg/kg/day for 7 days, systemic exposure (AUCs) for losartan and its active metabolite were approximately 66 and 26 times the exposure achieved in man at the maximum recommended human daily dosage (100 mg).
Pregnancy Categories C (first trimester) and D (second and third trimesters). See WARNINGS, Fetal/Neonatal Morbidity and Mortality.
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 COZAAR have been established in hypertensive pediatric patients aged 6 to 16 years. There are no data on the effect of COZAAR on blood pressure in pediatric patients under the age of 6 or in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m2 (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Pharmacodynamics and Clinical Effects, and DOSAGE AND ADMINISTRATION).
Geriatric Use
Of the total number of patients receiving COZAAR 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.
In the LIFE study, Black patients with hypertension and left ventricular hypertrophy had a lower risk of stroke on atenolol than on COZAAR. 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 COZAAR on reducing the risk of cardiovascular events in hypertensive patients with left ventricular hypertrophy apply to Black patients. (See CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects; Reduction in the Risk of Stroke.)
COZAAR has 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 COZAAR was well-tolerated. The overall incidence of adverse experiences reported with COZAAR 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 COZAAR 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 COZAAR and more commonly than placebo are shown in the table below.
Cramp, muscle
Pain, back
Pain, leg
Nervous System/Psychiatric
Congestion, nasal
Infection, upper respiratory
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 COZAAR, 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 <1% of patients in clinical studies are listed below. It cannot be determined whether these events were causally related to losartan: Body as a Whole: facial edema, fever, orthostatic effects, syncope; Cardiovascular: angina pectoris, second degree AV block, CVA, hypotension, myocardial infarction, arrhythmias including atrial fibrillation, palpitation, sinus bradycardia, tachycardia, ventricular tachycardia, ventricular fibrillation; Digestive: anorexia, constipation, dental pain, dry mouth, flatulence, gastritis, vomiting; Hematologic: anemia; Metabolic: gout; Musculoskeletal: arm pain, hip pain, joint swelling, knee pain, musculoskeletal pain, shoulder pain, stiffness, arthralgia, arthritis, fibromyalgia, muscle weakness; Nervous System/Psychiatric: anxiety, anxiety disorder, ataxia, confusion, depression, dream abnormality, hypesthesia, decreased libido, memory impairment, migraine, nervousness, paresthesia, peripheral neuropathy, panic disorder, sleep disorder, somnolence, tremor, vertigo; Respiratory: dyspnea, bronchitis, pharyngeal discomfort, epistaxis, rhinitis, respiratory congestion; Skin: alopecia, dermatitis, dry skin, ecchymosis, erythema, flushing, photosensitivity, pruritus, rash, sweating, urticaria; Special Senses: blurred vision, burning/stinging in the eye, conjunctivitis, taste perversion, tinnitus, decrease in visual acuity; Urogenital: impotence, nocturia, urinary frequency, urinary tract infection.
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.
Study 1 HCTZ Losartan Lisinopril Cough 25% 17% 69% Study 2 Placebo Losartan Lisinopril Cough 35% 29% 62%
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: No relevant differences between the adverse experience profile for pediatric patients and that previously reported for adult patients were identified.
Hypertensive Patients with Left Ventricular Hypertrophy
In the LIFE study, adverse events with COZAAR 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 COZAAR or placebo, the overall incidences of reported adverse experiences were similar for the two groups. COZAAR was generally well tolerated as evidenced by a similar incidence of discontinuations due to side effects compared to placebo (19% for COZAAR, 24% for placebo). The adverse experiences, regardless of drug relationship, reported with an incidence of ≥4% of patients treated with COZAAR and occurring more commonly than placebo, on a background of conventional antihypertensive therapy, are shown in the table below.
and Conventional
and Conventional
Body as a Whole
Chest Pain
Influenza-like disease
Orthostatic hypotension
Diabetic neuropathy
Diabetic vascular disease
Eyes, Ears, Nose and Throat
Metabolic and Nutrition
Weight gain
Back pain
Leg pain
Knee pain
Muscular weakness
Nervous System
Urinary tract infection
Post-Marketing Experience
The following additional adverse reactions have been reported in post-marketing experience:
Digestive: Hepatitis (reported rarely).
General Disorders and Administration Site Conditions: Malaise.
Hemic: Thrombocytopenia (reported rarely).
Hypersensitivity: Angioedema, including swelling of the larynx and glottis, causing airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue has been reported rarely in patients treated with losartan; some of these patients previously experienced angioedema with other drugs including ACE inhibitors. Vasculitis, including Henoch-Schönlein purpura, has been reported. Anaphylactic reactions have been reported.
Metabolic and Nutrition: Hyperkalemia, hyponatremia have been reported with losartan.
Musculoskeletal: Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers.
Nervous system disorders: Dysgeusia
Respiratory: Dry cough (see above).
Skin: Erythroderma
Laboratory Test Findings
In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of COZAAR.
Creatinine, Blood Urea Nitrogen: Minor increases in blood urea nitrogen (BUN) or serum creatinine were observed in less than 0.1 percent of patients with essential hypertension treated with COZAAR alone (see PRECAUTIONS, Impaired Renal Function).
Hemoglobin and Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.11 grams percent and 0.09 volume percent, respectively) occurred frequently in patients treated with COZAAR alone, but were rarely of clinical importance. No patients were discontinued due to anemia.
Liver Function Tests: Occasional elevations of liver enzymes and/or serum bilirubin have occurred. In patients with essential hypertension treated with COZAAR alone, one patient (<0.1%) was discontinued due to these laboratory adverse experiences.
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/m2 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.
Adult Hypertensive Patients
COZAAR may be administered with other antihypertensive agents, and with or without food.
Dosing must be individualized. The usual starting dose of COZAAR is 50 mg once daily, with 25 mg used in patients with possible depletion of intravascular volume (e.g., patients treated with diuretics) (see WARNINGS, Hypotension — Volume-Depleted Patients) and patients with a history of hepatic impairment (see PRECAUTIONS, General). COZAAR 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 CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Hypertension).
If blood pressure is not controlled by COZAAR alone, a low dose of a diuretic may be added. Hydrochlorothiazide has been shown to have an additive effect (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Hypertension).
No initial dosage adjustment is necessary for elderly patients or for patients with renal impairment, including patients on dialysis.
Pediatric Hypertensive Patients ≥6 years of age
The usual recommended starting dose is 0.7 mg/kg once daily (up to 50 mg total) administered as a tablet or a suspension (see Preparation of Suspension). Dosage should be adjusted according to blood pressure response. Doses above 1.4 mg/kg (or in excess of 100 mg) daily have not been studied in pediatric patients. (See CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Pharmacodynamics and Clinical Effects, and WARNINGS, Hypotension — Volume-Depleted Patients.)
COZAAR is not recommended in pediatric patients <6 years of age or in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m2 (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations, Pharmacodynamics and Clinical Effects, and PRECAUTIONS).
Preparation of Suspension (for 200 mL of a 2.5 mg/mL suspension)
Add 10 mL of Purified Water USP to an 8 ounce (240 mL) amber polyethylene terephthalate (PET) bottle containing ten 50 mg COZAAR tablets. Immediately shake for at least 2 minutes. Let the concentrate stand for 1 hour and then shake for 1 minute to disperse the tablet contents. Separately prepare a 50/50 volumetric mixture of Ora-Plus™1 and Ora-Sweet SF™1. Add 190 mL of the 50/50 Ora-Plus™/Ora-Sweet SF™ mixture to the tablet and water slurry in the PET bottle and shake for 1 minute to disperse the ingredients. The suspension should be refrigerated at 2-8°C (36-46°F) and can be stored for up to 4 weeks. Shake the suspension prior to each use and return promptly to the refrigerator.
- 1
Trademark of Paddock Laboratories, Inc.
Hypertensive Patients with Left Ventricular Hypertrophy
The usual starting dose is 50 mg of COZAAR once daily. Hydrochlorothiazide 12.5 mg daily should be added and/or the dose of COZAAR should be increased to 100 mg once daily followed by an increase in hydrochlorothiazide to 25 mg once daily based on blood pressure response (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Reduction in the Risk of Stroke).
Nephropathy in Type 2 Diabetic Patients
The usual starting dose is 50 mg once daily. The dose should be increased to 100 mg once daily based on blood pressure response (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Nephropathy in Type 2 Diabetic Patients). COZAAR may be administered with insulin and other commonly used hypoglycemic agents (e.g., sulfonylureas, glitazones and glucosidase inhibitors).
No. 8441 — Tablets COZAAR, 25 mg, are white, oval, film-coated tablets with code 951 on one side and plain on the other. They are supplied as follows:
Bottles of 30
No. 8442 — Tablets COZAAR, 50 mg, are white, oval, film-coated tablets with code 952 on one side and scored on the other. They are supplied as follows:
Bottles of 30
Bottles of 90
No. 3849 — Tablets COZAAR, 100 mg, are white, teardrop-shaped, film-coated tablets with code 960 on one side and plain on the other. They are supplied as follows:
Bottles of 30
Bottles of 90
Manuf. for: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA
Copyright © 2003, 2011 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
All rights reserved.
Revised: 11/2011
Patient Information
COZAAR® (CO-zar)
(losartan potassium tablets)
25 mg, 50 mg, 100 mg
Rx only
Read the Patient Information that comes with COZAAR® before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your condition and treatment.
What is the most important information I should know about COZAAR?
Do not take COZAAR if you are pregnant or plan to become pregnant. COZAAR can harm your unborn baby causing injury and even death. Stop taking COZAAR if you become pregnant and call your doctor right away. If you plan to become pregnant, talk to your doctor about other treatment options before taking COZAAR.
What is COZAAR?
COZAAR is a prescription medicine called an angiotensin receptor blocker (ARB). It is used:
- alone or with other blood pressure medicines to lower high blood pressure (hypertension).
- to lower the chance of stroke in patients with high blood pressure and a heart problem called left ventricular hypertrophy. COZAAR may not help Black patients with this problem.
- to slow the worsening of diabetic kidney disease (nephropathy) in patients with type 2 diabetes who have or had high blood pressure.
COZAAR has not been studied in children less than 6 years old or in children with certain kidney problems.
High Blood Pressure (hypertension). Blood pressure is the force in your blood vessels when your heart beats and when your heart rests. You have high blood pressure when the force is too much. COZAAR can help your blood vessels relax so your blood pressure is lower.
Left Ventricular Hypertrophy (LVH) is an enlargement of the walls of the left chamber of the heart (the heart's main pumping chamber). LVH can happen from several things. High blood pressure is the most common cause of LVH.
Type 2 Diabetes with Nephropathy. Type 2 diabetes is a type of diabetes that happens mainly in adults. If you have diabetic nephropathy it means that your kidneys do not work properly because of damage from the diabetes.
Who should not take COZAAR?
- Do not take COZAAR if you are allergic to any of the ingredients in COZAAR. See the end of this leaflet for a complete list of ingredients in COZAAR.
What should I tell my doctor before taking COZAAR?
Tell your doctor about all of your medical conditions including if you:
- are pregnant or planning to become pregnant. See "What is the most important information I should know about COZAAR?"
- are breast-feeding. It is not known if COZAAR passes into your breast milk. You should choose either to take COZAAR or breast-feed, but not both.
- are vomiting a lot or having a lot of diarrhea
- have liver problems
- have kidney problems
Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. COZAAR and certain other medicines may interact with each other. Especially tell your doctor if you are taking:
- potassium supplements
- salt substitutes containing potassium
- water pills (diuretics)
- medicines used to treat pain and arthritis, called non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors
- other medicines to reduce blood pressure
How should I take COZAAR?
- Take COZAAR exactly as prescribed by your doctor. Your doctor may change your dose if needed.
- COZAAR can be taken with or without food.
- If you miss a dose, take it as soon as you remember. If it is close to your next dose, do not take the missed dose. Just take the next dose at your regular time.
- If you take too much COZAAR, call your doctor or Poison Control Center, or go to the nearest hospital emergency room right away.
What are the possible side effects of COZAAR?
COZAAR may cause the following side effects that may be serious:
- Injury or death of unborn babies. See "What is the most important information I should know about COZAAR?"
- Allergic reaction. Symptoms of an allergic reaction are swelling of the face, lips, throat or tongue. Get emergency medical help right away and stop taking COZAAR.
- Low blood pressure (hypotension). Low blood pressure may cause you to feel faint or dizzy. Lie down if you feel faint or dizzy. Call your doctor right away.
- For people who already have kidney problems, you may see a worsening in how well your kidneys work. Call your doctor if you get swelling in your feet, ankles, or hands, or unexplained weight gain.
The most common side effects of COZAAR in people with high blood pressure are:
- "colds" (upper respiratory infection)
- dizziness
- stuffy nose
- back pain
The most common side effects of COZAAR in people with type 2 diabetes with diabetic kidney disease are:
- diarrhea
- tiredness
- low blood sugar
- chest pain
- high blood potassium
- low blood pressure
Tell your doctor if you get any side effect that bothers you or that won't go away.
This is not a complete list of side effects. For a complete list, ask your doctor or pharmacist.
How do I store COZAAR?
- Store COZAAR tablets at 59°F to 86°F (15°C to 30°C).
- Keep COZAAR in a tightly closed container that protects the medicine from light.
- Keep COZAAR and all medicines out of the reach of children.
General information about COZAAR
Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use COZAAR for a condition for which it was not prescribed. Do not give COZAAR to other people, even if they have the same symptoms that you have. It may harm them.
This leaflet summarizes the most important information about COZAAR. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about COZAAR that is written for health professionals.
What are the ingredients in COZAAR?
Active ingredients: losartan potassium
Inactive ingredients: microcrystalline cellulose, lactose hydrous, pregelatinized starch, magnesium stearate, hydroxypropyl cellulose, hypromellose, and titanium dioxide. COZAAR 25 mg, COZAAR 50 mg, and COZAAR 100 mg may also contain carnauba wax.
- PRINCIPAL DISPLAY PANEL - 25 mg Bottle Label
- PRINCIPAL DISPLAY PANEL - 50 mg Bottle Label
- PRINCIPAL DISPLAY PANEL - 100 mg Bottle Label
losartan potassium tablet, film coated
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:54868-5077(NDC:0006-0951) Route of Administration ORAL Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength losartan potassium (UNII: 3ST302B24A) (losartan - UNII:JMS50MPO89) losartan potassium 25 mg Inactive Ingredients Ingredient Name Strength CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U) LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X) STARCH, CORN (UNII: O8232NY3SJ) magnesium stearate (UNII: 70097M6I30) hydroxypropyl cellulose (UNII: RFW2ET671P) HYPROMELLOSES (UNII: 3NXW29V3WO) titanium dioxide (UNII: 15FIX9V2JP) CARNAUBA WAX (UNII: R12CBM0EIZ) Product Characteristics Color WHITE Score no score Shape OVAL Size 8mm Flavor Imprint Code 951 Contains Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:54868-5077-0 30 in 1 BOTTLE, PLASTIC Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020386 06/02/2004 COZAAR
losartan potassium tablet, film coated
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:54868-3726(NDC:0006-0952) Route of Administration ORAL Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength losartan potassium (UNII: 3ST302B24A) (losartan - UNII:JMS50MPO89) losartan potassium 50 mg Inactive Ingredients Ingredient Name Strength CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U) LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X) STARCH, CORN (UNII: O8232NY3SJ) magnesium stearate (UNII: 70097M6I30) hydroxypropyl cellulose (UNII: RFW2ET671P) HYPROMELLOSES (UNII: 3NXW29V3WO) titanium dioxide (UNII: 15FIX9V2JP) CARNAUBA WAX (UNII: R12CBM0EIZ) Product Characteristics Color WHITE Score 2 pieces Shape OVAL Size 10mm Flavor Imprint Code 952 Contains Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:54868-3726-0 30 in 1 BOTTLE, PLASTIC 2 NDC:54868-3726-1 90 in 1 BOTTLE, PLASTIC Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020386 04/01/1996 COZAAR
losartan potassium tablet, film coated
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:54868-2335(NDC:0006-0960) Route of Administration ORAL Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength losartan potassium (UNII: 3ST302B24A) (losartan - UNII:JMS50MPO89) losartan potassium 100 mg Inactive Ingredients Ingredient Name Strength CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U) LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X) STARCH, CORN (UNII: O8232NY3SJ) magnesium stearate (UNII: 70097M6I30) hydroxypropyl cellulose (UNII: RFW2ET671P) HYPROMELLOSES (UNII: 3NXW29V3WO) titanium dioxide (UNII: 15FIX9V2JP) CARNAUBA WAX (UNII: R12CBM0EIZ) Product Characteristics Color WHITE Score no score Shape TEAR (teardrop-shaped) Size 12mm Flavor Imprint Code 960 Contains Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:54868-2335-0 30 in 1 BOTTLE, PLASTIC 2 NDC:54868-2335-1 90 in 1 BOTTLE, PLASTIC Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020386 08/06/2003 Labeler - Physicians Total Care, Inc. (194123980) Establishment Name Address ID/FEI Business Operations Physicians Total Care, Inc. 194123980 relabel(54868-3726, 54868-5077, 54868-2335) , repack(54868-3726, 54868-5077, 54868-2335)


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One young man whose life was transformed by a Church-run drug rehabilitation center is now working with the organization to help others in the same predicament.
Residents of the rehabilitation center undergoing group therapy
As 2020 unfolds, we are asking readers like you to help us keep Union of Catholic Asian News (UCA News) free so it can be accessed from anywhere in the world at no cost.
That has been our policy for years and was made possible by donations from European Catholic funding agencies. However, like the Church in Europe, these agencies are in decline and the immediate and urgent claims on their funds for humanitarian emergencies in Africa and parts of Asia mean there is much less to distribute than there was even a decade ago.
Forty years ago, when UCA News was founded, Asia was a very different place - many poor and underdeveloped countries with large populations to feed, political instability and economies too often poised on the edge of collapse. Today, Asia is the economic engine room of the world and funding agencies quite rightly look to UCA News to do more to fund itself.
UCA News has a unique product developed from a view of the world and the Church through informed Catholic eyes. Our journalistic standards are as high as any in the quality press; our focus is particularly on a fast-growing part of the world - Asia - where, in some countries the Church is growing faster than pastoral resources can respond to - South Korea, Vietnam and India to name just three.
And UCA News has the advantage of having in its ranks local reporters that cover 22 countries and experienced native English-speaking editors to render stories that are informative, informed and perceptive.
We report from the ground where other news services simply can't or won't go. We report the stories of local people and their experiences in a way that Western news outlets simply don't have the resources to reach. And we report on the emerging life of new Churches in old lands where being a Catholic can at times be very dangerous.
With dwindling support from funding partners in Europe and the USA, we need to call on the support of those who benefit from our work.Click here to find out the ways you can support UCA News. You can make a difference for as little as US$5...


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Could your sneezing, sniffling dog have a cold?Read more
Could your sneezing, sniffling dog have a cold?Read more
Do you know how to keep your pet safe this winter?Read more
Keep Thanksgiving day safe for your pet by following these tips.Read more
Do you know the symptoms that can occur if your pet has cancer?Read more
Would you know what to do if your dog was injured?Read more
Do you know how to keep your pet safe when wearing a costume?Read more
Anemia doesn't just affect people. Your dog can become anemic too.Read more
Have you noticed a change in your dog's paws? One of these paw problems may be to blame.Read more
Is a new pet in your family's future? These tips will help your child learn pet care essentials.Read more
A lost pet is every pet owner's worst nightmare. These tips can help you keep your furry friend safe.Read more
Don't let heatstroke or sore paws keep your pet from enjoying the summer.Read more
Does your cat enjoy midnight sprints through your home? These tips can help curb the behavior.Read more
Wondering why your pet is scratching? A skin condition may be to blame.Read more
Would you like to keep your pet free of ticks and fleas? Try a few of these tips.Read more
Do you have anything planned for National Dog Party Day?Read more
Every week, every month or every year? How often should you bathe and groom your dog?Read more
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Light Green Floral Hanbok Tulle Dress (In-Stock)
CNYG040Regular price RM65.00
- Cheongsam dress made of soft cotton fabric
- Featuring floral bloom print details
- Layered tulle dress
- Back ribbon
Size 90 | Length (52cm) Bust (60cm)
Size 100 | Length (55cm) Bust (63cm)
Size 110 | Length (58cm) Bust (66cm)
Size 120 | Length (61cm) Bust (69cm)
Size 130 | Length (64cm) Bust (72cm)
**short cutting design
Light Green
Model Reference:
|Height (cm)
|Bust (cm)
|Waist (cm)
|Wears (size)
|Pre-Order Date
|16 - 22 Oct 2023
|23 - 25 Nov 2023
|23 - 29 Oct 2023
|30 Nov - 2 Dec 2023
|30 Oct - 5 Nov 2023
|7 - 9 Dec 2023
|6 - 12 Nov 2023
|14 - 16 Dec 2023
|13 - 19 Nov 2023
|28 - 30 Dec 2023
|20 - 26 Nov 2023
|4 - 6 Jan 2024
|27 Nov - 3 Dec 2023
|11 - 13 Jan 2024
1. Pre-Order Date is the date when your order is placed. Please check your order confirmation email or invoice for the date.
2. ETD is the estimated delivery date for orders to be shipped from our local warehouse.
Please note that:
A shipping confirmation email together with your shipment details will only be updated to you when your order is ready to ship from our local warehouse.
Please also note that preorders are not in-stock items. Estimated time of arrival will be vary due to the shipping service and condition. Orders delayed will be displayed on the status. Our team will try our best to send out your orders on/before the ETD.
Single order consists of pre-order and in-stock products
In this case, your order will be delivered together in one parcel based on the lead time stated in "Preorder Status". In-stock items will be reserved for the next customer. Split shipment is strictly not allowed.
Currently, we only provide shipping to Malaysia and Singapore.
What is the postage fee?
1. West Malaysia: RM10 per order.
2. East Malaysia: RM15 per order.
1. RM30 per order*.
Free Delivery
1.Malaysia- Free delivery service for purchase over RM150*
2.Singapore- Free delivery service for purchase over SGD150*
*Discounted total cart value.
What is the delivery lead time?
We try our best to prepare your orders and send them out as soon as we can!
Ready Stock
Ready stock items usually ship out within 1-3 working days.
Malaysia: Additional 2-7 working days to reach your address.
Singapore: Additional 7-10 working days to reach your address.
Pre-orders (Malaysia & Singapore)
The delivery lead time for Pre-Order collection, please check the order batch status at HERE before placing any other with us.
Cancellation and refund are strictly not allowed once payment has been made.
What if my order consists of pre-order and ready stock items?
In this case, your order will be delivered together in one parcel with pre-order batch's lead time. Your in-stock item(s) will be reserved for the next customer. Split shipment is strictly not allowed.
Can I request split packaging for my order?
Sorry to inform that we do not provide any split packaging service. Please split your order for different packaging.
**For more information on our shipping policy, please refer to HERE.
Thank you for shopping at Hemito!
Your satisfaction is our top priority, we want you to be fully satisfied with every product that you purchase from Hemito. We understand that it may be tricky when it comes to choosing a perfect fit apparel when purchasing online.
Mail your item to the following address:
Address: 51, Jalan Pucung 2, Taman Perling, 81200, Johor, Johor Bahru.
Phone Number: 016-968 7300
For all requests, please notify us with an email at firstname.lastname@example.com or FB inbox. Our team will attend to your request within 1-2 business days.


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A Safe Buy!
10 strong reasons to choose LOGOSOL
- Feel safe with a market leading company with over 25 years experience.
- You get 2 year warranty - we know that our machines are of the highest quality.
- You receive 2 months money back guarantee - test the machine before you decide.
- LOGOSOL has everything you need for small-scale wood processing.
- Our products are effective, safe and well-known for their high quality.
- Our products have big update opportunities and a high resale value.
- You get the customer magazine Woodworking Project - filled with inspiration and news!
- You get your order quickly delivered and at a low price!
- We offer several different payment options.
- You get unlimited telephone support when it comes to product know-how and product use.
Products with high quality and many opportunities
We offer you a complete range of equipment and accessories for small-scale wood processing. We also offer different courses for inspiration and valuable knowledge. From log to cabin, from board to moulded product or from board to ornate woodwork material, at LOGOSOL you can find machines to take your wood processing one step further.
Our products are effective, safe and are known for their high quality.
LOGOSOL products have been examined in minute detail to exceed your expectations. Innovative solutions and high quality has become our hallmark. All our machines are CE marked and we attach great importance to your security.
Machines with the ability to upgrade and a high resale value.
It's easy to buy from LOGOSOL, tell us about your project and we will help you find the right machine for you. Your machine from LOGOSOL then gives you plenty of options. All our machines are based on the fact that you can start with one machine in its basic version and then upgrade it to your needs. That way you always have a machine that is tailored to the demands and opportunities that you have right now. The machines also have a high resale value. If you want to exchange a product, you can either replace it with us, or sell it privately for a high price.
Feel safe with a market leading company with extensive experience. LOGOSOL was founded in 1989 by Bengt-Olov Bystrom and the company is still owned by the Bystrom family in Harnosand, Sweden. We have sold over 25,000 sawmills and more than 10,000 planers. We have over 25 years experience in small-scale wood processing and have daily contact with customers worldwide who fulfill their dreams of wood!
2-year warranty
Applies to all of our machines. The warranty covers manufacturing defects and problems that have occurred during normal use of the products. Exceptions to the warranty are consumable items such as belts, guide bars and saw chains.
We always try to be really helpful if an accident has happened. We are sure that it is best for everyone if you continue to be totally satisfied with your LOGOSOL machine.
2-month money back guarantee (Return policy)
Applies to all of our machines. This means that you can try the machine before deciding. Saw, plane or mould a good deal of timber, we are not afraid of taking back a machine with a little sawdust on it.
As a main rule the customer may within the 60 days iron-clad money back guaranteee, return the product if he is not satisfied with it. The only thing the end customer pays for is the return freight. Always suggest that the customer insure the return for protection. Consumable items, such as moulding knives, belts, guide bars and chains, are not covered by the money-back guarantee.
After 60 days the customer may still return the product, but this is something that has to be decided from case to case. This means that we do not insistently stick to the 60 days sale or return policy. When the customer knows that he has the possibility to return the product if he likes, it is much easier for him to accept other solutions as well. Despite this generous policy, our experience is that returned products are a relatively uncommon feature.
You pay for the used cutting tools and the costs of return shipping, but that's all.
Service and support
As a LOGOSOL customer you get unlimited phone support. Skilled technicians answer your questions by phone every weekday from 8.00 am to 4.00 pm. You can also receive support via email.
The LOGOSOL Concept – our promise to you
We know that our products are good, and we want you to be happy with your purchase for the rest of your life. Therefore, each product is covered by our own concept consisting of peace-of-mind package, quick delivery, unlimited support and personal service.
Whatever your aspiration, you can be assured that when you invest in the LOGOSOL Concept, you will own the highest quality equipment, that has been specifically designed for the task at hand.
We strive to provide systems that are flexible and offer easy expandability. The benefit of the LOGOSOL Concept is that you can start out with a basic system, and as your dreams or business grows, you can easily add on to your system – never losing the value of your original investment.
Peace of mind
Logosol's peace-of-mind package provides you with a 2 year warranty and the right to return products within 2 months from date of delivery if they fail to live up to your expectations.
Quick delivery
Very speedy delivery of accessories and spare parts.
Unlimited support
Unlimited support when it comes to product know-how and product use.
Personal service
Get access to over 25 years' experience of small-scale timber processing. Skilled technicians answer your questions by phone every weekday from 8.00 am to 4.00 pm. You can also receive support via email or the chat service on our website.
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Map Marketing
Leinster Historical Map 1000 Piece Jigsaw Puzzle (1610)
Leinster Historical Map 1000 Piece Jigsaw Puzzle (1610)
Sale Sold out
Regular price $25.00 USD
Regular priceUnit price per
Sale price
This is a superb jigsaw puzzle featuring the county of Leinster in approximately 1610.
Originally sourced by renowned English cartographer John Speed (1552-1629) who published an atlas called 'The Theatre of the Empire of Great Britaine'. His maps themselves were of high quality and gained a great reputation for being among the best county maps. The finished jigsaw measures 66 x 50cm and comes with a Free colour guide print.
Dimensions: 66 X 50cm
Number of Pieces: 1000


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We carry Factory Original, OEM hubcaps and wheel covers for most Scion vehicles (cars, trucks, suvs, and vans). Browse through our user friendly online catalog of Scion hubcaps and wheel covers.
If you need assistance or if you are unable to locate what you are looking for, please contact us by inquiring below or giving us a call at 800-301-5814 and one of our friendly staffers, will be happy to help you!
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With our car rental comparator in Alicante Airport you can choose among the main Rent A Car companies the best car for your work or vacation trip in Alicante Airport with the cheapest prices.
Car rental in Alicante Airport with all included prices; unlimited mileage, insurance and taxes (in most of the destinations). Request your car hire in Alicante Airport and in only three simple steps enjoy your in Alicante Airport vehicle rental with the best quality and service guarantee.
Spain-car-rentals.com offers you a in Alicante Airport car hire service of great quality and with very economic prices. Thanks to our providers, we put at your disposal an extensive and modern fleet of rental cars in Alicante Airport continuously renewed, being on average six to twelve months old, so that you can always enjoy the best vehicles with the best prices and the most profitable conditions. with spain-car-rentals.com you will be able to reserve in Alicante Airport car rental practically all over Spain, most of Europe and in the United States.
We work with the main local, national and international car rental companies to offer you a quality service with cheap prices both in Spain and in the rest of the more than 170 countries where we offer rental cars.