Micardis Hct

Description

MICARDIS HCT tablets are a fixed-dose combination of telmisartan, an orally active angiotensin II receptor antagonist, and hydrochlorothiazide, a thiazide diuretic. Telmisartan is a non-peptide molecule with the chemical designation 4'-[(1,4'-dimethyl-2'-propyl2,6'-bi-1H-benzimidazol-1'-yl)methyl]-1,1'-biphenyl-2-carboxylic acid, exhibiting an empirical formula of C33H30N4O2 and a molecular weight of 514.63. It appears as a white to slightly yellowish solid, is practically insoluble in water across a pH range of 3 to 9, sparingly soluble in strong acids (except hydrochloric acid), and soluble in strong bases.

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

MICARDIS HCT tablets are available for oral administration in three dosage combinations: 40 mg/12.5 mg, 80 mg/12.5 mg, and 80 mg/25 mg of telmisartan and hydrochlorothiazide, respectively. The formulation includes inactive ingredients such as sodium hydroxide, meglumine, povidone, sorbitol, magnesium stearate, lactose monohydrate, microcrystalline cellulose, maize starch, and sodium starch glycolate. The 40 mg/12.5 mg and 80 mg/12.5 mg tablets contain ferric oxide red as a coloring agent, while the 80 mg/25 mg tablets contain ferric oxide yellow. MICARDIS HCT tablets are hygroscopic and must be protected from moisture.

Uses and Indications

MICARDIS HCT is indicated for the treatment of hypertension, either as monotherapy or in combination with other antihypertensive agents, to effectively lower blood pressure. The reduction of blood pressure is associated with a decreased risk of both fatal and nonfatal cardiovascular events, including strokes and myocardial infarctions.

Limitations of Use: MICARDIS HCT is not indicated for initial therapy in the management of hypertension.

Dosage and Administration

The usual starting dose for the medication is 80 mg/12.5 mg administered once daily. Based on the patient's response and tolerability, the dose may be titrated up to a maximum of 160 mg/25 mg as needed.

For patients with biliary obstructive disorders or hepatic insufficiency, it is recommended to initiate treatment at a lower dose of 40 mg/12.5 mg once daily. Careful monitoring of the patient's condition is advised during the titration process to ensure optimal therapeutic outcomes while minimizing potential adverse effects.

Contraindications

Use of this product is contraindicated in the following situations:

Patients with hypersensitivity to telmisartan or any of its components should not use this medication due to the risk of severe allergic reactions.

The product is also contraindicated in individuals with anuria, as it may exacerbate renal function impairment.

Co-administration with aliskiren is contraindicated in patients with diabetes, as this combination may increase the risk of adverse effects.

Warnings and Precautions

Fetal toxicity is a significant concern associated with the use of MICARDIS HCT. It is imperative that the medication be discontinued as soon as pregnancy is detected, as drugs that act directly on the renin-angiotensin system may cause injury or death to the developing fetus. Healthcare professionals should ensure that patients are aware of this risk and take appropriate measures to avoid fetal or neonatal exposure.

Prior to initiating therapy with MICARDIS HCT, it is essential to correct any volume or salt depletion. Clinicians should closely monitor patients for signs and symptoms of hypotension, particularly in those who may be at increased risk. Additionally, renal function and potassium levels should be monitored in susceptible patients to prevent potential complications. It is also important to observe for clinical signs of fluid or electrolyte imbalance, as these can indicate adverse reactions to the medication.

Healthcare providers should remain vigilant for hypersensitivity reactions in patients taking MICARDIS HCT. Furthermore, there is a risk of acute myopia and secondary angle-closure glaucoma, which necessitates careful monitoring of patients for any visual disturbances or ocular symptoms.

In summary, the safe use of MICARDIS HCT requires thorough patient assessment, appropriate laboratory monitoring, and proactive management of potential risks associated with therapy.

Side Effects

Patients receiving MICARDIS HCT may experience a range of adverse reactions. Common adverse reactions, occurring in 2% or more of patients, include upper respiratory tract infection, dizziness, sinusitis, diarrhea, fatigue, influenza-like symptoms, and nausea.

Serious warnings associated with MICARDIS HCT include the potential for fetal toxicity. It is imperative to discontinue the medication as soon as pregnancy is detected, as drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. Therefore, fetal or neonatal exposure should be avoided.

Additional adverse reactions and important considerations include the need to correct volume or salt depletion prior to initiating therapy, as well as monitoring for signs and symptoms of hypotension. Renal function and potassium levels should be closely observed in susceptible patients, and clinical signs of fluid or electrolyte imbalance should be monitored. Hypersensitivity reactions, acute myopia, secondary angle-closure glaucoma, and anuria have also been reported. Caution is advised when co-administering with aliskiren in patients with diabetes.

In cases of overdosage, the most likely manifestations include hypotension, dizziness, and tachycardia, with bradycardia potentially occurring due to parasympathetic (vagal) stimulation. For hydrochlorothiazide overdose, the most common signs and symptoms are those resulting from electrolyte depletion, such as hypokalemia, hypochloremia, and hyponatremia, along with dehydration due to excessive diuresis. If digitalis has been administered concurrently, hypokalemia may exacerbate cardiac arrhythmias.

Drug Interactions

The use of certain medications in conjunction with this drug may lead to significant interactions that require careful consideration and management.

Pharmacodynamic Interactions

• Lithium: Co-administration may increase the risk of lithium toxicity. Monitoring of lithium levels is recommended to avoid adverse effects.

• Non-steroidal Anti-inflammatory Drugs (NSAIDs): The concurrent use of NSAIDs may diminish the diuretic, natriuretic, and antihypertensive effects of this drug. Additionally, there is an increased risk of renal impairment. It is advisable to monitor renal function and adjust therapy as necessary.

• Dual Blockade of the Renin-Angiotensin System: The combination of this drug with other agents that block the renin-angiotensin system may elevate the risk of renal impairment, hypotension, and hyperkalemia. Close monitoring of blood pressure, renal function, and potassium levels is recommended.

Pharmacokinetic Interactions

• Antidiabetic Drugs: When used in conjunction with antidiabetic medications, dosage adjustments may be necessary to maintain glycemic control. Regular monitoring of blood glucose levels is advised.

• Cholestyramine and Colestipol: These agents may reduce the absorption of thiazides, potentially leading to decreased therapeutic efficacy. It is recommended to separate the administration of these medications to minimize interaction effects.

Packaging & NDC

The table below lists all NDC Code configurations of Micardis Hct (telmisartan and hydrochlorothiazide), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Safety and effectiveness of MICARDIS HCT in pediatric patients have not been established.

In neonates with a history of in utero exposure to MICARDIS HCT, if oliguria or hypotension occurs, it is essential to support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required to reverse hypotension and/or substitute for disordered renal function.

Geriatric Use

In controlled clinical trials involving 1,017 patients, approximately 20% of those treated with telmisartan/hydrochlorothiazide were aged 65 years or older, with 5% being 75 years of age or older. The data indicate that there were no overall differences in the effectiveness and safety of telmisartan/hydrochlorothiazide in these elderly patients compared to their younger counterparts.

However, while clinical experience has not consistently identified differences in responses between elderly and younger patients, it is important to note that greater sensitivity to the medication in some older individuals cannot be excluded. Therefore, when prescribing telmisartan/hydrochlorothiazide to geriatric patients, careful consideration should be given to dose selection. It is generally recommended to initiate treatment at the lower end of the dosing range. This approach accounts for the increased likelihood of diminished hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies that may affect the patient's response to treatment.

Healthcare providers should remain vigilant in monitoring elderly patients for any potential adverse effects or changes in therapeutic response, adjusting the dosage as necessary to ensure optimal safety and efficacy.

Pregnancy

MICARDIS HCT can cause fetal harm when administered to a pregnant woman. The use of drugs that act on the renin-angiotensin system (RAS) during the second and third trimesters of pregnancy is associated with reduced fetal renal function, leading to oligohydramnios, fetal lung hypoplasia, skeletal deformations, hypotension, and increased fetal and neonatal morbidity and mortality. When pregnancy is detected, MICARDIS HCT should be discontinued as soon as possible.

Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive agents in the first trimester have not specifically distinguished drugs affecting the RAS from other antihypertensive medications. Animal studies with telmisartan have shown fetotoxicity only at maternally toxic doses. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown; however, 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 2% to 4% and 15% to 20%, respectively.

Hypertension in pregnancy poses increased maternal risks, including pre-eclampsia, gestational diabetes, premature delivery, and delivery complications. It also increases fetal risks such as intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be closely monitored and managed accordingly.

In the unusual case where there is no appropriate alternative to therapy with RAS-affecting drugs, the mother should be informed of the potential risks to the fetus. For patients taking MICARDIS HCT during pregnancy, serial ultrasound examinations should be performed to assess the intra-amniotic environment, and fetal testing may be warranted based on gestational age. If oligohydramnios is observed, MICARDIS HCT should be discontinued unless it is deemed lifesaving for the mother. 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 MICARDIS HCT should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occurs, supportive measures for blood pressure and renal perfusion may be necessary, and exchange transfusions or dialysis may be required to address hypotension and restore renal function.

Thiazides, including hydrochlorothiazide, cross the placenta and are associated with risks of fetal or neonatal jaundice, thrombocytopenia, and other adverse reactions. Hydrochlorothiazide can also cause placental hypoperfusion and accumulates in the amniotic fluid, with concentrations reported to be up to 19 times that in umbilical vein plasma. Due to their ineffectiveness in preventing or altering the course of edema, proteinuria, and hypertension gestosis (pre-eclampsia), thiazides should not be used to treat hypertension in pregnant women, and their use for other indications during pregnancy should be avoided.

Lactation

There is no information regarding the presence of MICARDIS HCT or telmisartan in human milk, nor are there data on the effects on breastfed infants or on milk production. Limited published studies indicate that hydrochlorothiazide is present in human milk; however, there is insufficient information to determine its effects on breastfed infants or on milk production.

In animal studies, telmisartan has been shown to be present in the milk of lactating rats at concentrations 1.5 to 2 times those found in plasma from 4 to 8 hours after administration. Due to the potential for serious adverse reactions in breastfed infants, including hypotension, hyperkalemia, and renal impairment, it is advised that nursing women refrain from breastfeeding during treatment with MICARDIS HCT.

Renal Impairment

In patients with severe renal impairment (creatinine clearance CrCl ≤30 mL/min), the safety and effectiveness of MICARDIS HCT have not been established, and the use of MICARDIS HCT tablets is not recommended. For patients with mild (CrCl 60 to 90 mL/min) or moderate (CrCl 30 to 60 mL/min) renal impairment, no dose adjustment is required. It is advisable to monitor renal function and potassium levels in susceptible patients.

Hepatic Impairment

Patients with biliary obstructive disorders or hepatic insufficiency should initiate treatment with the 40 mg/12.5 mg combination under close medical supervision. Due to the fact that the majority of telmisartan is eliminated through biliary excretion, these patients can be expected to experience reduced clearance and elevated blood levels of the medication.

Furthermore, it is important to note that minor alterations in fluid and electrolyte balance may precipitate hepatic coma in patients with impaired hepatic function or progressive liver disease. Therefore, careful monitoring of these parameters is essential in this patient population to mitigate potential risks associated with treatment.

Overdosage

Limited data are available regarding the overdosage of telmisartan in humans. However, the most likely manifestations of telmisartan overdosage include hypotension, dizziness, and tachycardia. In some cases, bradycardia may occur as a result of parasympathetic (vagal) stimulation.

In the event of symptomatic hypotension, it is essential to initiate supportive treatment to manage the patient's condition effectively. It is important to note that telmisartan is not removed by hemofiltration and is not dialyzable, which should be taken into consideration when planning management strategies for overdosage.

Nonclinical Toxicology

No information is available regarding teratogenic effects associated with the combination of telmisartan and hydrochlorothiazide.

The combination has not been evaluated for carcinogenicity, mutagenicity, or fertility. However, studies on telmisartan alone demonstrated no evidence of carcinogenicity when administered in the diet to mice and rats for up to two years. The highest doses given to mice (1000 mg/kg/day) and rats (100 mg/kg/day) correspond to approximately 59 and 13 times, respectively, the maximum recommended human dose (MRHD) of telmisartan. These doses resulted in average systemic exposures to telmisartan that were over 100 times and over 25 times, respectively, the systemic exposure observed in humans receiving the MRHD of telmisartan (80 mg/day).

Genotoxicity assessments did not indicate any telmisartan-related effects at either the gene or chromosome level. These assessments included bacterial mutagenicity tests with Salmonella and E. coli (Ames), a gene mutation test with Chinese hamster V79 cells, a cytogenetic test with human lymphocytes, and a mouse micronucleus test.

In terms of reproductive performance, no drug-related effects were observed in male and female rats at a dose of 100 mg/kg/day, which is approximately 13 times the MRHD of telmisartan on a mg/m² basis. This dose resulted in an average systemic exposure (telmisartan AUC as determined on day 6 of pregnancy) that was at least 50 times the average systemic exposure in humans at the MRHD.

Two-year feeding studies conducted under 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). However, the NTP did find equivocal evidence for hepatocarcinogenicity in male mice.

Hydrochlorothiazide was not found to be genotoxic in vitro in the Ames mutagenicity assay using various strains of Salmonella typhimurium and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations. In vivo assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene also showed no genotoxicity. Positive results were noted in the in vitro CHO Sister Chromatid Exchange (clastogenicity) assay, the Mouse Lymphoma Cell (mutagenicity) assay, and the Aspergillus nidulans non-disjunction assay.

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.

Postmarketing Experience

No postmarketing experience details are available in the provided data.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling (Patient Information) thoroughly. This document contains essential information regarding the medication, including its indications, usage, potential side effects, and important safety information. Emphasizing the importance of understanding this material can help patients make informed decisions about their treatment and manage their health effectively.

Storage and Handling

The product is supplied in blister packaging, ensuring the integrity and stability of the tablets until administration. It is essential to store the product at a temperature range of 20°C to 25°C (68°F to 77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F) in accordance with USP Controlled Room Temperature guidelines.

To maintain optimal quality, tablets should remain in their blister packaging and should not be removed until immediately prior to administration. This practice helps to protect the tablets from environmental factors that may affect their efficacy.

Additional Clinical Information

Clinicians are advised to monitor renal function periodically in patients whose renal function may be influenced by the activity of the renin-angiotensin system. Additionally, it is important to periodically assess serum electrolytes to ensure patient safety and optimal therapeutic outcomes.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Micardis Hct as submitted by Boehringer Ingelheim Pharmaceuticals, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)