Olmesartan medoxomil/Hydrochlorothiazide

Uses and Indications

Olmesartan medoxomil and hydrochlorothiazide tablet is indicated for the treatment of hypertension, aimed at lowering blood pressure. Effective management of hypertension is associated with a reduction in the risk of both fatal and nonfatal cardiovascular events, including strokes and myocardial infarctions.

This medication is not indicated for initial therapy. There are no teratogenic or nonteratogenic effects associated with the use of olmesartan medoxomil and hydrochlorothiazide tablet.

Dosage and Administration

The recommended starting dose for patients not adequately controlled with olmesartan monotherapy is 40 mg of olmesartan combined with 12.5 mg of hydrochlorothiazide. For patients not adequately controlled with hydrochlorothiazide monotherapy, the recommended starting dose is 20 mg of olmesartan combined with 12.5 mg of hydrochlorothiazide.

Dosing adjustments may be made after 2 to 4 weeks based on the patient's response to treatment. The maximum allowable dose is 40 mg of olmesartan combined with 25 mg of hydrochlorothiazide.

Healthcare professionals should ensure that the dosing regimen is tailored to the individual patient's needs, taking into account their response and tolerability to the medication.

Contraindications

Use of olmesartan medoxomil and hydrochlorothiazide tablets is contraindicated in the following situations:

Patients with hypersensitivity to any component of the formulation.

Patients with anuria, as the medication may exacerbate renal function.

Co-administration with aliskiren is contraindicated in patients with diabetes due to the potential for adverse effects.

Warnings and Precautions

When pregnancy is detected, olmesartan medoxomil and hydrochlorothiazide should be discontinued immediately. This medication can cause fetal toxicity, leading to potential injury or death to the developing fetus due to its action on the renin-angiotensin system.

General precautions must be observed when administering this medication. It is essential to correct any volume depletion prior to initiation to prevent hypotension. Healthcare professionals should monitor renal function and potassium levels in patients who are susceptible to these changes. Additionally, vigilance for signs of fluid or electrolyte imbalance is necessary.

There is a risk of acute angle-closure glaucoma associated with this medication. Furthermore, cases of sprue-like enteropathy have been reported; therefore, if no other etiology is identified, consideration should be given to discontinuing olmesartan medoxomil and hydrochlorothiazide tablets.

Regular laboratory tests to monitor renal function and potassium levels are recommended for patients at risk. This proactive approach will help ensure patient safety and mitigate potential adverse effects associated with the use of this medication.

Side Effects

Patients receiving olmesartan medoxomil and hydrochlorothiazide may experience a range of adverse reactions. The most common adverse reactions, occurring in at least 2% of participants, include nausea, hyperuricemia, dizziness, and upper respiratory infections.

Serious warnings associated with this medication include fetal toxicity. It is imperative that olmesartan medoxomil and hydrochlorothiazide be discontinued as soon as pregnancy is detected, as drugs that act directly on the renin-angiotensin system can lead to injury or death of the developing fetus.

Additional adverse reactions that may occur include hypotension, which necessitates the correction of volume depletion prior to administration. Patients should be monitored for renal function and potassium levels, particularly those who are susceptible. Signs of fluid or electrolyte imbalance should also be observed. Other reported adverse reactions include acute angle-closure glaucoma and sprue-like enteropathy, which may warrant discontinuation of the medication if no other etiology is identified. Hypersensitivity reactions to any component of olmesartan medoxomil and hydrochlorothiazide tablets have been noted, as well as anuria.

It is also important to note that co-administration of aliskiren with olmesartan medoxomil and hydrochlorothiazide is contraindicated in patients with diabetes.

Drug Interactions

Agents that increase potassium levels may result in elevated serum potassium concentrations when co-administered. This interaction necessitates monitoring of serum potassium levels to prevent hyperkalemia.

The concomitant use of lithium poses a risk of lithium toxicity. It is advisable to monitor lithium levels closely and adjust the dosage as necessary to mitigate this risk.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) can diminish the diuretic, natriuretic, and antihypertensive effects of certain medications, while also increasing the risk of renal toxicity. Patients should be monitored for renal function and blood pressure when NSAIDs are used concurrently.

The dual inhibition of the renin-angiotensin system may lead to an increased risk of renal impairment, hypotension, and hyperkalemia. Close monitoring of renal function and blood pressure is recommended in patients receiving such combinations.

When administering olmesartan in conjunction with colesevelam hydrochloride, it is recommended to administer olmesartan at least 4 hours prior to the colesevelam hydrochloride dose to ensure optimal absorption.

Antidiabetic drugs may require dosage adjustments when used concurrently, necessitating careful monitoring of blood glucose levels to maintain glycemic control.

Cholestyramine and colestipol can reduce the absorption of thiazide diuretics. It is advisable to monitor the therapeutic effects of thiazides and consider adjusting the dosage if necessary.

Packaging & NDC

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

Pediatric Use

Safety and effectiveness of olmesartan medoxomil and hydrochlorothiazide tablets 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 needed to determine appropriate dosing and outcomes in this population.

Geriatric Use

Clinical studies of olmesartan medoxomil and hydrochlorothiazide tablets did not include a sufficient number of subjects aged 65 and over to determine whether these elderly patients respond differently compared to younger individuals. However, other reported clinical experiences have not identified significant differences in responses between geriatric patients and their younger counterparts.

In general, dose selection for elderly patients should be approached with caution. It is advisable to start at the low end of the dosing range, taking into account the increased likelihood of decreased hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies.

Both olmesartan and hydrochlorothiazide are substantially excreted by the kidneys, which raises concerns regarding the risk of toxic reactions in patients with impaired renal function. Therefore, careful monitoring of renal function is recommended when prescribing these medications to geriatric patients to mitigate potential adverse effects.

Pregnancy

Olmesartan medoxomil and hydrochlorothiazide tablets can cause fetal harm when administered to pregnant patients. The use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy is associated with reduced fetal renal function, which can lead to increased fetal and neonatal morbidity and mortality. Therefore, when pregnancy is detected, it is recommended to discontinue olmesartan medoxomil and hydrochlorothiazide tablets as soon as possible and to consider alternative antihypertensive therapy.

The estimated background risk of major birth defects and miscarriage in the general population is not well defined for this specific medication. However, it is acknowledged that all pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is approximately 2% to 4% and 15% to 20%, respectively.

Hypertension during pregnancy poses additional risks, including increased maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications such as the need for cesarean section and postpartum hemorrhage. Furthermore, hypertension can increase the fetal risk for intrauterine growth restriction and intrauterine death. Therefore, pregnant women with hypertension should be closely monitored and managed appropriately.

The use of drugs affecting the renin-angiotensin system in the second and third trimesters can lead to oligohydramnios, which may result in reduced fetal renal function, anuria, renal failure, fetal lung hypoplasia, skeletal deformations (including skull hypoplasia), hypotension, and death. Serial ultrasound examinations should be performed to assess the intra-amniotic environment, and fetal testing may be warranted based on gestational age. It is important to note that oligohydramnios may not manifest until after the fetus has sustained irreversible injury.

Infants with a history of in utero exposure to olmesartan medoxomil and hydrochlorothiazide tablets should be closely observed for signs of hypotension, oliguria, and hyperkalemia. In cases of oliguria or hypotension, measures should be taken to maintain adequate blood pressure and renal perfusion, which may include exchange transfusions or dialysis to reverse hypotension and support renal function.

Hydrochlorothiazide, a component of this medication, can cross the placenta, with concentrations in the umbilical vein approaching those in maternal plasma. It can cause placental hypoperfusion and accumulates in the amniotic fluid, with reported concentrations up to 19 times that in umbilical vein plasma. The use of thiazides during pregnancy is associated with risks of fetal or neonatal jaundice and thrombocytopenia. Since thiazides do not prevent or alter the course of preeclampsia, they should not be used to treat hypertension in pregnant women, and their use for other indications, such as heart disease, should also be avoided during pregnancy.

Lactation

There is no specific information available regarding the use of this drug in nursing mothers or its effects on lactation. Consequently, the safety and efficacy of this medication in lactating mothers and breastfed infants have not been established. Healthcare professionals should exercise caution and consider the potential risks and benefits when prescribing this medication to lactating mothers.

Renal Impairment

Patients with renal impairment should have their renal function and potassium levels monitored closely. This is particularly important for those with reduced kidney function, as they may be at increased risk for complications. Dosing adjustments may be necessary based on the degree of renal impairment to ensure safety and efficacy.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

Limited data are available regarding the overdosage of olmesartan medoxomil in humans. The most likely manifestations of overdosage include hypotension and tachycardia; however, bradycardia may occur if there is parasympathetic (vagal) stimulation. In the event of symptomatic hypotension, it is recommended that supportive treatment be initiated. The dialyzability of olmesartan medoxomil remains unknown.

Acute toxicity studies conducted in mice and rats have shown no lethality with single oral doses of olmesartan medoxomil up to 2000 mg/kg. In dogs, the minimum lethal oral dose was found to be greater than 1500 mg/kg.

In contrast, the most common signs and symptoms associated with hydrochlorothiazide overdose in humans are primarily due to electrolyte depletion, which includes hypokalemia, hypochloremia, and hyponatremia, as well as dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may exacerbate cardiac arrhythmias. The extent to which hydrochlorothiazide is removed by hemodialysis has not been established. The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in both mice and rats.

Healthcare professionals should remain vigilant for these potential symptoms and manage them accordingly in cases of suspected overdosage.

Nonclinical Toxicology

No information is available regarding teratogenic effects associated with olmesartan medoxomil and hydrochlorothiazide.

Carcinogenicity studies have not been conducted for olmesartan medoxomil and hydrochlorothiazide. However, olmesartan medoxomil was not found to be carcinogenic when administered via diet to rats for up to two years. The highest dose tested, 2000 mg/kg/day, was approximately 480 times the maximum recommended human dose (MRHD) of 40 mg/day. Two carcinogenicity studies in mice also revealed no evidence of a carcinogenic effect for olmesartan medoxomil. In addition, two-year feeding studies in mice and rats indicated no carcinogenic potential for hydrochlorothiazide in female mice or in male and female rats.

In terms of mutagenicity, olmesartan medoxomil and hydrochlorothiazide, when tested in a ratio of 20:12.5, were negative in the Salmonella-Escherichia coli/mammalian microsome reverse mutation test. However, a positive response was observed for each component and combination ratio in the in vitro Chinese hamster lung chromosomal aberration assay, although no synergistic clastogenic activity was detected between the two compounds at any combination ratio. Olmesartan medoxomil and hydrochlorothiazide tested negative in the in vivo mouse bone marrow erythrocyte micronucleus assay at doses up to 3144 mg/kg. Both compounds tested negative in the in vitro Syrian hamster embryo cell transformation assay and showed no evidence of genetic toxicity in the Ames test. Nevertheless, both were found to induce chromosomal aberrations in cultured cells in vitro and tested positive for thymidine kinase mutations in the in vitro mouse lymphoma assay. Importantly, olmesartan medoxomil tested negative in vivo for mutations in the MutaMouse intestine and kidney, as well as for clastogenicity in mouse bone marrow at oral doses up to 2000 mg/kg.

No studies have been conducted to assess the impairment of fertility with olmesartan medoxomil and hydrochlorothiazide. However, fertility in rats was unaffected by olmesartan medoxomil at doses as high as 1000 mg/kg/day, which is 240 times the MRHD, when dosing began 2 weeks prior to mating for females and 9 weeks for males. Hydrochlorothiazide also demonstrated no adverse effects on the fertility of mice and rats of either sex in studies where these species were exposed to dietary doses of up to 100 mg/kg and 4 mg/kg, respectively, prior to mating and throughout gestation.

Postmarketing Experience

During post-approval use of olmesartan medoxomil and hydrochlorothiazide tablets, several adverse reactions have been reported voluntarily from a population of uncertain size. These reactions include asthenia, vomiting, hyperkalemia, rhabdomyolysis, alopecia, and pruritus. Due to the nature of voluntary reporting, it is not always possible to reliably estimate the frequency of these events or establish a causal relationship to drug exposure.

Data from a controlled trial and an epidemiologic study have suggested a potential increase in cardiovascular (CV) risk associated with high-dose olmesartan in diabetic patients, although the overall data remain inconclusive. The ROADMAP trial, a randomized, placebo-controlled, double-blind study involving 4,447 patients with type 2 diabetes mellitus, demonstrated that while olmesartan delayed the onset of microalbuminuria, it did not show a beneficial effect on the decline in glomerular filtration rate (GFR). Notably, there was an observed increase in CV mortality in the olmesartan group compared to placebo (15 vs. 3), with a hazard ratio (HR) of 4.9 (95% confidence interval CI 1.4, 17). Conversely, the risk of non-fatal myocardial infarction was lower in the olmesartan group (HR 0.64, 95% CI 0.35, 1.18).

In an epidemiologic study involving patients aged 65 years and older, with an overall exposure of over 300,000 patient-years, high-dose olmesartan (40 mg/d) for more than six months was associated with an increased risk of death in diabetic patients (HR 2, 95% CI 1.1, 3.8) compared to those taking other angiotensin receptor blockers. In contrast, non-diabetic patients receiving high-dose olmesartan appeared to have a decreased risk of death (HR 0.46, 95% CI 0.24, 0.86). No significant differences were noted between groups receiving lower doses of olmesartan or those treated for less than six months.

These findings raise concerns regarding a possible increased CV risk associated with high-dose olmesartan in diabetic patients. However, the credibility of these findings is tempered by the observation of a survival benefit in non-diabetic patients that is similar in magnitude to the adverse findings in diabetic patients.

Additionally, hydrochlorothiazide has been associated with an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma (SCC), as indicated by a study conducted in the Sentinel System. The increased risk was predominantly observed in white patients receiving large cumulative doses, with an approximate increase of one additional case of SCC per 16,000 patients per year in the overall population. For white patients taking a cumulative dose of ≥50,000 mg, the risk increase was approximately one additional SCC case for every 6,700 patients per year.

Patient Counseling

Healthcare providers should advise patients that if pregnancy is detected, olmesartan medoxomil and hydrochlorothiazide should be discontinued as soon as possible. It is important to communicate that medications acting directly on the renin-angiotensin system can pose significant risks, including injury and death to the developing fetus.

Patients should be informed that the use of olmesartan medoxomil and hydrochlorothiazide during pregnancy can lead to fetal harm, particularly when administered during the second and third trimesters. This class of drugs may reduce fetal renal function, increasing the risk of morbidity and mortality for both the fetus and neonate. Providers should explain that oligohydramnios, a potential consequence of such medication use, can be associated with serious complications such as fetal lung hypoplasia and skeletal deformations.

Healthcare providers should also make patients aware of the potential neonatal adverse effects, which may include skull hypoplasia, anuria, hypotension, renal failure, and even death. It is crucial to inform patients that thiazides can cross the placental barrier and may appear in cord blood, leading to adverse reactions such as fetal or neonatal jaundice and thrombocytopenia.

Providers should emphasize the importance of closely monitoring infants who have been exposed in utero to olmesartan medoxomil and hydrochlorothiazide for signs of hypotension, oliguria, and hyperkalemia. In cases where oliguria or hypotension is observed, healthcare providers should be prepared to implement measures to maintain adequate blood pressure and renal perfusion, which may include exchange transfusions or dialysis to reverse hypotension and support renal function.

Finally, healthcare providers should advise nursing women that breastfeeding is not recommended during treatment with olmesartan medoxomil and hydrochlorothiazide tablets, ensuring that patients are fully informed of the risks associated with this medication during lactation.

Storage and Handling

The product is supplied in a plastic bottle containing 90 units. It should be stored at a temperature range of 20 to 25°C (68 to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the integrity of the product.

Additional Clinical Information

Clinicians should periodically monitor renal function in patients whose renal status may be influenced by the renin-angiotensin system, including those with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion. Additionally, serum electrolytes and potassium levels should be monitored, particularly in patients receiving concomitant medications that elevate serum potassium. Serum lithium levels should also be assessed during concurrent use with lithium.

Patient counseling should include advising nursing women against breastfeeding while on olmesartan medoxomil and hydrochlorothiazide tablets. If pregnancy occurs, these tablets should be discontinued promptly. Postmarketing experience has reported adverse events such as asthenia, vomiting, hyperkalemia, rhabdomyolysis, alopecia, pruritus, and an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma, in white patients receiving large cumulative doses.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Olmesartan Medoxomil and Hydrochlorothiazide as submitted by REMEDYREPACK INC.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)