Losartan potassium/Hydrochlorothiazide

Description

Losartan Potassium and Hydrochlorothiazide Tablets USP are a combination of an angiotensin II receptor (type AT1) antagonist, losartan potassium, and the diuretic hydrochlorothiazide. Losartan potassium is a non-peptide molecule with the chemical designation 2-butyl-4-chloro-1-p-(o-1H-tetrazol-5-ylphenyl)benzylimidazole-5-methanol monopotassium salt, having a molecular formula of C22H22ClKN6O and a molecular weight of 461.01. It appears as a white to off-white free-flowing crystalline powder, which is freely soluble in water, soluble in alcohols, and slightly soluble in common organic solvents such as acetonitrile and methyl ethyl ketone.

Hydrochlorothiazide is chemically identified as 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, with a molecular formula of C7H8ClN3O4S2 and a molecular weight of 297.74. This compound is a white or practically white crystalline powder, slightly soluble in water but freely soluble in sodium hydroxide solution.

These tablets are formulated for oral administration and are available in three combinations: Losartan Potassium and Hydrochlorothiazide Tablets USP 50-12.5, which contains 50 mg of losartan potassium and 12.5 mg of hydrochlorothiazide; Losartan Potassium and Hydrochlorothiazide Tablets USP 100-12.5, which contains 100 mg of losartan potassium and 12.5 mg of hydrochlorothiazide; and Losartan Potassium and Hydrochlorothiazide Tablets USP 100-25, which contains 100 mg of losartan potassium and 25 mg of hydrochlorothiazide.

Each tablet formulation contains inactive ingredients including lactose, magnesium stearate, microcrystalline cellulose, and pregelatinized starch. The 50-12.5 mg and 100-25 mg tablets also include Opadry II (Yellow), while the 100-12.5 mg tablet contains Opadry II (White). Opadry II (Yellow) consists of D&C yellow #10 aluminum lake, hypromellose, lactose monohydrate, polyethylene glycol, titanium dioxide, and triacetin, whereas Opadry II (White) contains hypromellose, polyethylene glycol, polydextrose, titanium dioxide, and triacetin. The potassium content in the tablets is as follows: 4.24 mg (0.108 mEq) in the 50-12.5 mg formulation, and 8.48 mg (0.216 mEq) in both the 100-12.5 mg and 100-25 mg formulations.

Uses and Indications

Losartan Potassium and Hydrochlorothiazide Tablets USP are indicated for the treatment of hypertension. This fixed-dose combination is not recommended for initial therapy of hypertension, except in cases where the hypertension is severe enough that the benefits of achieving prompt blood pressure control outweigh the risks associated with initiating combination therapy in these patients.

Additionally, Losartan Potassium and Hydrochlorothiazide Tablets USP are indicated to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy. However, it is important to note that the evidence supporting this benefit does not extend to Black patients.

Dosage and Administration

The usual starting dose of losartan is 50 mg administered once daily. For patients with intravascular volume depletion, a recommended starting dose of 25 mg once daily is advised. Losartan can be given once or twice daily, with total daily doses ranging from 25 mg to 100 mg. In cases where the antihypertensive effect is insufficient with once-daily dosing, a twice-daily regimen at the same total daily dose or an increase in dose may be considered.

Hydrochlorothiazide is effective at doses ranging from 12.5 mg to 50 mg once daily. It may also be administered in combination with losartan at doses of 12.5 mg to 25 mg.

For patients whose blood pressure is not adequately controlled with losartan monotherapy or hydrochlorothiazide alone, it is recommended to switch to losartan potassium and hydrochlorothiazide 50-12.5 (losartan 50 mg/hydrochlorothiazide 12.5 mg) once daily. If blood pressure remains uncontrolled after approximately 3 weeks, the dose may be increased to two tablets of losartan potassium and hydrochlorothiazide 50-12.5 once daily or one tablet of losartan potassium and hydrochlorothiazide 100-25 (losartan 100 mg/hydrochlorothiazide 25 mg) once daily. The usual dose for losartan potassium and hydrochlorothiazide is one tablet of losartan potassium and hydrochlorothiazide 50-12.5 once daily. Doses exceeding two tablets of losartan potassium and hydrochlorothiazide 50-12.5 once daily or one tablet of losartan potassium and hydrochlorothiazide 100-25 once daily are not recommended.

In cases of severe hypertension, the starting dose is one tablet of losartan potassium and hydrochlorothiazide 50-12.5 once daily. If there is an inadequate response after 2 to 4 weeks, the dose may be increased to one tablet of losartan potassium and hydrochlorothiazide 100-25 once daily, with a maximum dose of one tablet of losartan potassium and hydrochlorothiazide 100-25 once daily.

For hypertensive patients with left ventricular hypertrophy, treatment should be initiated with losartan potassium 50 mg once daily. If blood pressure reduction is inadequate, hydrochlorothiazide 12.5 mg may be added, or losartan potassium and hydrochlorothiazide 50-12.5 may be substituted. For further reduction, losartan potassium 100 mg and hydrochlorothiazide 12.5 mg or losartan potassium and hydrochlorothiazide 100-12.5 may be used, followed by losartan potassium 100 mg and hydrochlorothiazide 25 mg or losartan potassium and hydrochlorothiazide 100-25.

Losartan potassium and hydrochlorothiazide may be administered with or without food.

Contraindications

Losartan Potassium and Hydrochlorothiazide Tablets USP are contraindicated in patients with a known hypersensitivity to any component of the formulation.

Additionally, the use of this product is contraindicated in patients with anuria or those who have a hypersensitivity to other sulfonamide-derived drugs, attributable to the hydrochlorothiazide component.

Co-administration of aliskiren with Losartan Potassium and Hydrochlorothiazide Tablets USP is contraindicated in patients with diabetes due to potential adverse effects.

Warnings and Precautions

Drugs that act directly on the renin-angiotensin system, including losartan potassium and hydrochlorothiazide, pose significant risks when administered to pregnant women. These medications can lead to fetal and neonatal morbidity and mortality. Therefore, upon detection of pregnancy, it is imperative to discontinue these agents as soon as possible. The use of such drugs during the second and third trimesters has been linked to serious fetal injuries, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and even death.

Oligohydramnios has been reported in association with decreased fetal renal function, which can result in fetal limb contractures, craniofacial deformation, and hypoplastic lung development. In rare instances where no alternative to an angiotensin II receptor antagonist is available, healthcare providers must inform mothers of the potential risks to their fetuses. In these cases, serial ultrasound examinations should be conducted to monitor the intra-amniotic environment. If oligohydramnios is detected, losartan potassium and hydrochlorothiazide should be discontinued unless their use is deemed life-saving for the mother. Infants exposed in utero to an angiotensin II receptor antagonist should be closely monitored for signs of hypotension, oliguria, and hyperkalemia.

General precautions should be observed when prescribing losartan potassium and hydrochlorothiazide. This combination is not recommended for patients with hepatic impairment requiring titration with losartan. Caution is advised when using thiazides in patients with impaired hepatic function or progressive liver disease, as even minor fluid and electrolyte imbalances may precipitate hepatic coma. Hypersensitivity reactions to hydrochlorothiazide can occur in patients with or without a history of allergy or bronchial asthma, although the risk is heightened in those with such a history. Additionally, thiazide diuretics may exacerbate or activate systemic lupus erythematosus. Lithium should generally be avoided in conjunction with thiazides.

Monitoring parameters may include contraction stress testing (CST), non-stress testing (NST), or biophysical profiling (BPP), depending on the gestational age of the pregnancy.

In the event of oliguria, immediate attention should focus on supporting blood pressure and renal perfusion, with exchange transfusion or dialysis potentially required to address hypotension and/or substitute for impaired renal function. For cases of acute angle-closure glaucoma, prompt medical or surgical intervention may be necessary if intraocular pressure remains uncontrolled. The primary treatment for acute angle-closure glaucoma involves the rapid discontinuation of hydrochlorothiazide.

Side Effects

Patients receiving treatment may experience a range of adverse reactions, which can be categorized by frequency and seriousness.

Common adverse reactions occurring in 1% or more of patients include:

• Nervous/Psychiatric: Dizziness (5.7%).

• Respiratory: Upper respiratory infection (6.1%), cough (2.6%), and sinusitis (1.2%).

• Musculoskeletal: Back pain (2.1%).

• Cardiovascular: Palpitations (1.4%).

• Skin: Rash (1.4%).

• Body as a Whole: Edema/swelling (1.3%) and abdominal pain (1.2%).

In addition to these common reactions, other adverse experiences have been reported with losartan, regardless of causality. These include:

• Body as a Whole: Chest pain, facial edema, fever, orthostatic effects, and syncope.

• Cardiovascular: Angina pectoris, various arrhythmias (including atrial fibrillation, sinus bradycardia, tachycardia, ventricular tachycardia, and ventricular fibrillation), cerebrovascular accident (CVA), hypotension, myocardial infarction, and second-degree AV block.

• Digestive: Anorexia, constipation, dental pain, dry mouth, dyspepsia, flatulence, gastritis, and vomiting.

• General Disorders: Malaise.

• Hematologic: Anemia.

• Metabolic: Gout.

• Musculoskeletal: Arm pain, arthralgia, arthritis, fibromyalgia, hip pain, joint swelling, knee pain, leg pain, muscle cramps, muscle weakness, musculoskeletal pain, myalgia, shoulder pain, and stiffness.

• Nervous System/Psychiatric: Anxiety, anxiety disorder, ataxia, confusion, depression, dream abnormality, hypesthesia, insomnia, decreased libido, memory impairment, migraine, nervousness, panic disorder, paresthesia, peripheral neuropathy, sleep disorder, somnolence, tremor, and vertigo.

• Respiratory: Dyspnea, epistaxis, nasal congestion, pharyngeal discomfort, respiratory congestion, rhinitis, and sinus disorder.

• Skin: Alopecia, dermatitis, dry skin, ecchymosis, erythema, flushing, photosensitivity, pruritus, sweating, and urticaria.

• Special Senses: Blurred vision, burning/stinging in the eye, conjunctivitis, decreased visual acuity, taste perversion, and tinnitus.

• Urogenital: Impotence, nocturia, urinary infrequency, and urinary tract infection.

Specific adverse reactions associated with hydrochlorothiazide include:

• Body as a Whole: Weakness.

• Digestive: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, and gastric irritation.

• Hematologic: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, and thrombocytopenia.

• Hypersensitivity: Purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, and respiratory distress (including pneumonitis and pulmonary edema).

• Metabolic: Hyperglycemia, glycosuria, and hyperuricemia.

• Musculoskeletal: Muscle spasm.

• Nervous System/Psychiatric: Restlessness.

• Renal: Renal failure, renal dysfunction, and interstitial nephritis.

• Skin: Erythema multiforme (including Stevens-Johnson syndrome) and exfoliative dermatitis (including toxic epidermal necrolysis).

• Special Senses: Transient blurred vision and xanthopsia.

Post-marketing experience has revealed additional adverse reactions, including rare cases of hepatitis, thrombocytopenia, angioedema (which may involve swelling of the larynx and glottis, potentially causing airway obstruction), vasculitis (including Henoch-Schönlein purpura), anaphylactic reactions, hyperkalemia, hyponatremia, rare instances of rhabdomyolysis, dry cough, and erythroderma.

Warnings regarding fetal and neonatal morbidity and mortality are significant, as drugs acting on the renin-angiotensin system can lead to serious adverse effects when administered to pregnant women, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development.

Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, although they are more likely in those with such a history. Additionally, thiazide diuretics have been associated with exacerbation or activation of systemic lupus erythematosus.

Hydrochlorothiazide may also cause an idiosyncratic reaction leading to acute transient myopia and acute angle-closure glaucoma, with symptoms including acute onset of decreased visual acuity or ocular pain.

Drug Interactions

Concomitant use of losartan with other medications may lead to significant drug interactions, categorized into pharmacokinetic and pharmacodynamic interactions.

Pharmacokinetic Interactions:

• Rifampin: This drug is known to induce drug metabolism, resulting in decreased concentrations of losartan and its active metabolite. Monitoring of losartan levels may be warranted when co-administered with rifampin.

• Fluconazole: As an inhibitor of P450 2C9, fluconazole decreases the concentration of the active metabolite of losartan while increasing the concentration of losartan itself. The clinical implications of this interaction should be considered, although the pharmacodynamic consequences have not been specifically examined.

• Ketoconazole and Erythromycin: These agents do not significantly affect the pharmacokinetics of losartan. Ketoconazole does not alter the conversion of losartan to its active metabolite, and erythromycin has no clinically significant effect on losartan after oral administration.

• Lithium: Co-administration of lithium salts with angiotensin II receptor antagonists, including losartan, necessitates careful monitoring of serum lithium levels due to the potential for increased lithium toxicity.

Pharmacodynamic Interactions:

• Potassium-Sparing Diuretics and Potassium Supplements: The use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increased serum potassium levels. Monitoring of serum potassium is recommended.

• NSAIDs: The co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists may result in renal function deterioration, including the risk of acute renal failure. Additionally, the antihypertensive effect of losartan may be diminished by NSAIDs. Caution is advised when using these medications together.

• Dual Blockade of the Renin-Angiotensin System (RAS): The combination of angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, syncope, hyperkalemia, and renal function changes compared to monotherapy. It is contraindicated to co-administer aliskiren with losartan potassium and hydrochlorothiazide in patients with diabetes or renal impairment (GFR <60 ml/min).

• Thiazide Diuretics: The concurrent use of thiazide diuretics with alcohol, barbiturates, or narcotics may enhance the risk of orthostatic hypotension. Additionally, dosage adjustments of antidiabetic drugs may be necessary when thiazide diuretics are used. The absorption of hydrochlorothiazide can be impaired by cholestyramine and colestipol resins.

• Electrolyte Depletion: Corticosteroids, ACTH, or Glycyrrhizin may exacerbate electrolyte depletion, particularly hypokalemia, when used with thiazide diuretics.

• Pressor Amines and Muscle Relaxants: There may be a decreased response to pressor amines (e.g., norepinephrine) and increased responsiveness to nondepolarizing skeletal muscle relaxants (e.g., tubocurarine) when thiazide diuretics are administered.

In summary, careful consideration and monitoring are advised when losartan and hydrochlorothiazide are used in conjunction with other medications, particularly those affecting potassium levels, renal function, and blood pressure.

Packaging & NDC

The table below lists all NDC Code configurations of Losartan Potassium and Hydrochlorothiazide, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Safety and effectiveness of losartan potassium and hydrochlorothiazide in pediatric patients have not been established. Therefore, caution is advised when considering the use of this medication in children and adolescents. Further studies are necessary to determine appropriate dosing and outcomes in this population.

Geriatric Use

In a controlled clinical study aimed at reducing the combined risk of cardiovascular death, stroke, and myocardial infarction in hypertensive patients with left ventricular hypertrophy, a significant proportion of participants were elderly. Specifically, 62% of the 2857 patients enrolled were aged 65 years and older, and 18% were aged 75 years and older.

The findings indicated that there were no overall differences in effectiveness between elderly patients and their younger counterparts. However, it is important to note that adverse events occurred somewhat more frequently in the elderly population compared to non-elderly patients across both the losartan and hydrochlorothiazide treatment groups as well as the control groups.

Given these observations, healthcare providers should exercise caution when prescribing this medication to geriatric patients. Monitoring for adverse events may be warranted, and consideration should be given to potential dose adjustments based on individual patient factors, including age and overall health status.

Pregnancy

Losartan potassium and hydrochlorothiazide have been evaluated for their effects on fertility and fetal outcomes in animal studies. In female rats, coadministration of losartan at doses as low as 10 mg/kg/day and hydrochlorothiazide at 2.5 mg/kg/day resulted in slight but statistically significant decreases in fecundity and fertility indices. At higher toxic dosage levels (300/200 mg/kg/day), there was a significant decrease in the number of corpora lutea, implants, and live fetuses observed at cesarean section (p<0.05). At a dose of 100 mg/kg/day, only a decrease in the number of corpora lutea was noted, while no effects were observed on the number of implants, post-implantation loss, or live animals per litter at parturition.

The relationship of these findings to drug treatment remains uncertain, as the effects were not consistently observed across all dosage levels. Additionally, hydrochlorothiazide did not demonstrate adverse effects on fertility in studies involving mice and rats, where doses of up to 100 mg/kg and 4 mg/kg, respectively, were administered prior to mating and throughout gestation.

Given the potential for decreased fertility and the uncertain implications for fetal outcomes, healthcare professionals should exercise caution when prescribing losartan potassium and hydrochlorothiazide to pregnant patients or women of childbearing potential. It is advisable to weigh the benefits against potential risks when considering treatment in this population.

Lactation

It is not known whether losartan is excreted in human milk; however, significant levels of losartan and its active metabolite have been detected in rat milk. Thiazides are known to appear in human milk.

Due to the potential for adverse effects on the nursing infant, healthcare professionals should consider the importance of the drug to the lactating mother when making a decision to either discontinue nursing or discontinue the medication.

Renal Impairment

Patients with renal impairment should be closely monitored when considering the use of losartan potassium and hydrochlorothiazide. The combination is not recommended for patients with hepatic impairment who require titration with losartan, as the lower starting dose of losartan suitable for these patients cannot be administered in this combination formulation. Additionally, thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, as even minor alterations in fluid and electrolyte balance may precipitate hepatic coma. It is essential for healthcare professionals to assess renal function and adjust dosing accordingly to ensure patient safety.

Hepatic Impairment

Patients with hepatic impairment should be approached with caution when considering the use of losartan potassium and hydrochlorothiazide. This combination is not recommended for individuals who require titration with losartan due to the inability to administer the lower starting dose of losartan that is advised for patients with compromised liver function.

Additionally, thiazide diuretics, such as hydrochlorothiazide, should be used judiciously in patients with impaired hepatic function or those with progressive liver disease. This caution is warranted because even minor alterations in fluid and electrolyte balance can potentially precipitate hepatic coma in these patients. Regular monitoring of liver function and electrolyte levels is advisable to mitigate risks associated with treatment in this population.

Overdosage

Significant lethality has been observed in animal studies, with mice and rats exhibiting fatal outcomes following oral administration of 1000 mg/kg and 2000 mg/kg, respectively. These doses correspond to approximately 44 and 170 times the maximum recommended human dose when adjusted for body surface area (mg/m²).

In humans, data regarding overdosage are limited. The most likely clinical manifestations of an overdose include hypotension and tachycardia. Additionally, bradycardia may occur due to parasympathetic (vagal) stimulation. In the event of symptomatic hypotension, it is imperative that supportive treatment be initiated promptly to manage the patient's condition effectively.

It is important to note that neither losartan nor its active metabolite can be eliminated from the body through hemodialysis, which should be taken into consideration when managing cases of overdosage.

Nonclinical Toxicology

Teratogenic effects have been observed with losartan potassium and hydrochlorothiazide, classified as Pregnancy Categories C during the first trimester and D during the second and third trimesters.

Non-teratogenic effects were noted in various studies. Losartan potassium and hydrochlorothiazide, when tested at a weight ratio of 4:1, yielded negative results in both the Ames microbial mutagenesis assay and the V­79 Chinese hamster lung cell mutagenesis assay. Additionally, there was no evidence of direct genotoxicity in the in vitro alkaline elution assay conducted in rat hepatocytes, nor in the in vitro chromosomal aberration assay in Chinese hamster ovary cells at noncytotoxic concentrations.

In terms of fertility, the coadministration of losartan potassium with hydrochlorothiazide did not affect the fertility or mating behavior of male rats at dosages up to 135 mg/kg/day of losartan and 33.75 mg/kg/day of hydrochlorothiazide. However, in female rats, doses as low as 10 mg/kg/day of losartan and 2.5 mg/kg/day of hydrochlorothiazide were associated with slight but statistically significant decreases in fecundity and fertility indices. Studies involving male rats receiving oral doses of losartan potassium up to approximately 150 mg/kg/day indicated no adverse effects on fertility and reproductive performance. Conversely, the administration of higher toxic dosage levels in females (300/200 mg/kg/day) resulted in a significant decrease in the number of corpora lutea, implants, and live fetuses at cesarean section, while a dose of 100 mg/kg/day only showed a decrease in the number of corpora lutea. Hydrochlorothiazide did not adversely affect the fertility of mice and rats of either sex in studies where these species were exposed to doses of up to 100 mg/kg and 4 mg/kg, respectively, prior to mating and throughout gestation.

No carcinogenicity studies have been conducted specifically on the combination of losartan potassium and hydrochlorothiazide. However, two-year feeding studies conducted by the National Toxicology Program (NTP) revealed no evidence of carcinogenic potential for hydrochlorothiazide in female mice at doses up to approximately 600 mg/kg/day or in male and female rats at doses up to approximately 100 mg/kg/day. The NTP did find equivocal evidence for hepatocarcinogenicity in male mice.

In terms of animal pharmacology and toxicology, losartan potassium was negative in the microbial mutagenesis and V­79 mammalian cell mutagenesis assays, as well as in the in vitro alkaline elution and chromosomal aberration assays. The active metabolite also showed no evidence of genotoxicity in the microbial mutagenesis, in vitro alkaline elution, and in vitro chromosomal aberration assays.

Postmarketing Experience

Postmarketing experience has identified several adverse events reported voluntarily or through surveillance programs in patients treated with losartan.

Rare cases of hepatitis have been documented. Hematological events include reports of thrombocytopenia. Hypersensitivity reactions have been noted, including angioedema, which may involve swelling of the larynx and glottis, leading to airway obstruction, as well as swelling of the face, lips, pharynx, and tongue. Some patients experiencing angioedema had a history of similar reactions to other medications, including ACE inhibitors. Additionally, vasculitis, such as Henoch-Schönlein purpura, and anaphylactic reactions have been reported.

Metabolic and nutritional disturbances include instances of hyperkalemia and hyponatremia. Musculoskeletal events have involved rare cases of rhabdomyolysis in patients receiving angiotensin II receptor blockers. Respiratory issues, specifically dry cough, have also been reported. Lastly, skin reactions such as erythroderma have been associated with losartan use.

Patient Counseling

Healthcare providers should advise patients that upon detection of pregnancy, losartan potassium and hydrochlorothiazide should be discontinued as soon as possible. It is important to inform female patients of childbearing age about the potential consequences of exposure to medications that act on the renin-angiotensin system during the second and third trimesters of pregnancy.

Patients should be cautioned that lightheadedness may occur, particularly during the initial days of therapy, and they should report this symptom to their prescribing physician. In the event of syncope, patients must be instructed to discontinue losartan potassium and hydrochlorothiazide and consult their physician before resuming treatment.

All patients should be made aware that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to a significant drop in blood pressure, which may result in lightheadedness or syncope. Additionally, patients receiving losartan potassium and hydrochlorothiazide should be advised against using potassium supplements or salt substitutes containing potassium without prior consultation with their prescribing physician.

Patients must be informed about the potential for serious side effects, which may include injury or death of unborn babies, allergic reactions, low blood pressure, and worsening kidney or liver function. It is essential for patients to report any side effects that are bothersome or do not resolve.

Storage and Handling

The product is supplied in a container that must be kept tightly closed to maintain its integrity. It should be stored at a temperature range of 20º to 25ºC (68º to 77ºF), in accordance with USP controlled room temperature guidelines. Additionally, it is essential to protect the product from light to ensure its stability and efficacy.

Additional Clinical Information

Minor increases in blood urea nitrogen (BUN) and serum creatinine were observed in 0.6% and 0.8% of patients, respectively, treated with losartan potassium and hydrochlorothiazide for essential hypertension. No patients discontinued treatment due to increased BUN, while one patient did so due to a minor increase in serum creatinine. Small decreases in hemoglobin and hematocrit were noted, but these were rarely clinically significant, and no patients were discontinued due to anemia. Occasional elevations in liver enzymes and/or serum bilirubin were reported, yet no patients discontinued treatment for these reasons.

Clinicians should counsel female patients of childbearing age about the risks associated with renin-angiotensin system drugs during the second and third trimesters, while noting that first-trimester exposure does not appear to have adverse effects. Patients should be advised to report any lightheadedness, especially during the initial days of therapy, and to discontinue the medication if syncope occurs until consulting their physician. Additionally, patients should be warned that inadequate fluid intake or excessive perspiration, diarrhea, or vomiting may lead to significant drops in blood pressure. The use of potassium supplements or salt substitutes containing potassium should only be done after consulting a physician. Post-marketing experience has revealed rare adverse reactions, including hepatitis, thrombocytopenia, angioedema, hyperkalemia, hyponatremia, rhabdomyolysis, dry cough, and erythroderma.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Losartan Potassium and Hydrochlorothiazide as submitted by Aidarex Pharmaceuticals LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)