Inzirqo

Description

Hydrochlorothiazide, USP is a diuretic and antihypertensive agent, chemically designated as 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. It is the 3,4-dihydro derivative of chlorothiazide. The compound appears as a white, or practically white, crystalline powder. Hydrochlorothiazide is slightly soluble in water and freely soluble in sodium hydroxide solution, n-butylamine, and dimethylformamide. It is sparingly soluble in methanol and insoluble in ether, chloroform, and dilute mineral acids. The molecular formula is C7H8ClN3O4S2, and it has a molecular weight of 297.74.

INZIRQO (hydrochlorothiazide) is supplied in one strength as an off-white to light-brown colored powder for oral suspension. When reconstituted with 66 mL of water, the total volume of the suspension is 80 mL, containing 10 mg/mL of hydrochlorothiazide, USP. The formulation includes inactive ingredients such as anhydrous citric acid, caramel flavor (composed of artificial flavor, caramel, maltodextrin, molasses, propylene glycol, salt, and sucrose), cellulose, peppermint flavor (derived from acacia and natural flavor), potassium sorbate, sucrose, talc, and xanthan gum.

Uses and Indications

INZIRQO™ (hydrochlorothiazide) is indicated for the treatment of hypertension in adult and pediatric patients, 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 infarction.

Additionally, INZIRQO™ is indicated for the management of edema associated with congestive heart failure, hepatic cirrhosis, and renal disease, including nephrotic syndrome, in both adult and pediatric populations.

There are no teratogenic or nonteratogenic effects associated with the use of this medication.

Dosage and Administration

For the treatment of hypertension in adults, the recommended initial dose is 25 mg administered orally once daily. Based on clinical response, the dose may be increased to 50 mg orally once daily or divided into two doses.

In the management of edema in adults, the recommended dosage ranges from 25 mg to 100 mg taken orally daily, which may be given as a single dose or divided into multiple doses. To minimize the risk of electrolyte imbalances, intermittent therapy is advised, such as administering the medication on alternate days or for 3 to 5 days each week.

For pediatric patients requiring treatment for hypertension and edema, the recommended dosage is 1 mg/kg to 2 mg/kg administered orally per day, either as a single dose or divided into two doses. It is important to note that the maximum daily dose should not exceed 37.5 mg for patients under 2 years of age or 100 mg for children aged 2 to less than 13 years. Additionally, infants less than 6 months of age may require doses of up to 3 mg/kg orally per day, administered in two divided doses.

Contraindications

Use of INZIRQO is contraindicated in patients with anuria, as the drug's mechanism may not be effective in the absence of urine output. Additionally, it is contraindicated in individuals with hypersensitivity to hydrochlorothiazide or any component of INZIRQO, as well as those with hypersensitivity to sulfonamide-derived drugs, due to the potential for severe allergic reactions.

Warnings and Precautions

Healthcare professionals are advised to implement the following warnings and precautions to ensure the safe use of the medication.

Renal Function Monitoring Periodic assessment of kidney function is essential. Healthcare providers should monitor renal parameters to detect any potential impairment that may arise during treatment (5.1).

Electrolyte Management Prior to initiating therapy, it is crucial to evaluate and correct any abnormalities in serum electrolytes. Continuous monitoring of these levels should be conducted periodically throughout the treatment course to prevent complications (5.2).

Metabolic Monitoring Regular monitoring of blood sugar, lipid levels, uric acid, and calcium levels is recommended. These parameters should be assessed periodically to identify any metabolic disturbances that may occur as a result of the medication (5.3).

Systemic Lupus Erythematosus Considerations There is a risk of exacerbation or activation of systemic lupus erythematosus in patients receiving this medication. Clinicians should remain vigilant for any signs or symptoms indicative of this condition (5.4).

Ocular Health Risks Patients may experience acute angle-closure glaucoma and acute myopia. It is important for healthcare providers to monitor patients for any ocular symptoms and to manage these conditions promptly if they arise (5.5).

Side Effects

Patients may experience a range of adverse reactions while using INZIRQO, categorized by seriousness and frequency.

Serious adverse reactions include anuria, exacerbation or activation of systemic lupus erythematosus, acute angle-closure glaucoma, and acute myopia. These events necessitate immediate medical attention and monitoring.

Commonly reported electrolyte imbalances associated with INZIRQO include hypokalemia, hyponatremia, hypomagnesemia, hyperglycemia, hyperuricemia, hyperlipidemia, and hypotension. These conditions may arise during treatment and should be regularly assessed in patients.

Hypersensitivity reactions have been noted, particularly in individuals with a known hypersensitivity to hydrochlorothiazide or any ingredient in INZIRQO, as well as those with hypersensitivity to sulfonamide-derived drugs.

In cases of overdosage, patients may exhibit signs and symptoms related to electrolyte depletion, such as hypokalemia, hypochloremia, and hyponatremia, along with dehydration resulting from excessive diuresis.

Additionally, there have been rare reports of jaundice, thrombocytopenia, and electrolyte imbalances in infants exposed to thiazide medications during pregnancy, highlighting the importance of careful consideration in pregnant patients. Regular monitoring and appropriate management strategies are recommended to mitigate these risks.

Drug Interactions

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in conjunction with this medication may result in an increased risk of renal impairment. Additionally, the antihypertensive and diuretic effects of this medication may be diminished when NSAIDs are co-administered.

Cholestyramine and colestipol can significantly reduce the absorption of thiazide diuretics, potentially leading to decreased therapeutic efficacy.

When used alongside lithium, this medication may elevate lithium concentrations, thereby increasing the risk of lithium toxicity. Monitoring of lithium levels is advised to prevent adverse effects.

For patients taking antidiabetic drugs, it may be necessary to adjust the dosage of these medications to maintain optimal glycemic control while using this medication. Regular monitoring of blood glucose levels is recommended to ensure appropriate management.

Packaging & NDC

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

Pediatric Use

Pediatric patients may be treated with INZIRQO for hypertension to effectively lower blood pressure. Additionally, INZIRQO is indicated for the management of edema associated with congestive heart failure, hepatic cirrhosis, and renal disease, including nephrotic syndrome.

Healthcare professionals should consider the specific age ranges and dosing adjustments necessary for pediatric patients, as these may differ from adult populations. Careful monitoring is advised to ensure safety and efficacy in this demographic.

Geriatric Use

Elderly patients may exhibit increased sensitivity to the effects of hydrochlorothiazide. Due to the potential for reduced kidney function in this population, dosage adjustments may be necessary. It is essential to monitor kidney function periodically in geriatric patients, as they are at a higher risk for acute kidney injury.

Additionally, healthcare providers should consider the risk of electrolyte imbalances, particularly hypokalemia, in elderly patients. This condition can be symptomatic and may require careful monitoring and correction.

Furthermore, elderly patients may have a higher likelihood of experiencing adverse reactions, including hypotension. This risk may be exacerbated by the concurrent use of other medications, such as alcohol, barbiturates, or narcotics. Therefore, close monitoring and appropriate management strategies are recommended to ensure the safety and efficacy of treatment in this population.

Pregnancy

Untreated hypertension during pregnancy can lead to adverse outcomes for both the mother and the fetus. Available data from published observational studies have not demonstrated a drug-associated risk of major birth defects, miscarriage, or adverse maternal outcomes with the use of hydrochlorothiazide during pregnancy. However, there have been rare reports of jaundice, thrombocytopenia, and electrolyte imbalances in infants exposed to thiazide medications during pregnancy.

The background risk of major birth defects and miscarriage for the indicated population is unknown. 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. It is important to note that hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications, such as the need for cesarean section and post-partum hemorrhage. Additionally, hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death; therefore, pregnant women with hypertension should be closely monitored.

Studies in which hydrochlorothiazide was orally administered to pregnant mice and rats during their respective periods of major organogenesis at doses up to 3000 and 1000 mg hydrochlorothiazide/kg (approximately 146-fold and 97-fold the maximum recommended human dose based on body surface area) provided no evidence of harm to the fetus.

Lactation

Available data from published literature indicate that hydrochlorothiazide is present in human milk. A single study involving one lactating mother demonstrated a peak concentration of 275 mcg/L in breast milk at 3 hours following a 50 mg dose. However, no drug was detected in the infant’s plasma (<20 mcg/L) at 2 and 11 hours after the mother’s dose.

There are no reports of adverse effects on breastfed infants exposed to hydrochlorothiazide during lactation. It is important to note that doses of hydrochlorothiazide associated with clinically significant diuresis may impair milk production.

Healthcare professionals should consider the developmental and health benefits of breastfeeding alongside the mother’s clinical need for INZIRQO and any potential adverse effects on the breastfed infant from INZIRQO or from the underlying maternal condition.

Renal Impairment

Patients with renal impairment should have their kidney function monitored periodically to assess any changes in renal status. Additionally, it is important to monitor and correct serum electrolytes prior to initiating treatment and to continue monitoring them periodically throughout the course of therapy. These precautions are essential to ensure the safe and effective use of the medication in this patient population.

Hepatic Impairment

There is no information available regarding the use of this medication in patients with hepatic impairment. Consequently, there are no dosage adjustments, special monitoring requirements, or precautions specified for individuals with compromised liver function. Healthcare professionals should exercise caution and consider the overall clinical context when prescribing this medication to patients with liver problems, as the absence of specific guidance necessitates careful evaluation of potential risks and benefits.

Overdosage

In cases of overdosage, the most frequently observed signs and symptoms are primarily attributed to electrolyte depletion and dehydration. Healthcare professionals should be vigilant for indications of hypokalemia, hypochloremia, and hyponatremia, which may arise due to excessive diuresis associated with hydrochlorothiazide.

Management of overdosage should focus on the correction of electrolyte imbalances and rehydration. It is essential to monitor the patient's electrolyte levels closely and provide appropriate interventions as necessary.

Currently, the extent to which hydrochlorothiazide can be removed from the body through hemodialysis remains undetermined. Therefore, reliance on hemodialysis as a treatment option for hydrochlorothiazide overdosage may not be effective.

Healthcare professionals are advised to implement supportive care and symptomatic treatment as the primary approach in managing patients who have experienced an overdose.

Nonclinical Toxicology

Two-year feeding studies conducted in mice and rats under the auspices of the National Toxicology Program (NTP) revealed no evidence of carcinogenic potential for hydrochlorothiazide in female mice at doses of up to approximately 600 mg/kg/day, or in male and female rats at doses of 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 Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538, nor in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations. Additionally, it did not exhibit genotoxicity in vivo in assays involving mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene.

Positive test results were observed only in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and Mouse Lymphoma Cell (mutagenicity) assays, where hydrochlorothiazide was tested at concentrations ranging from 43 to 1300 mcg/mL. Furthermore, positive results were also noted in the Aspergillus nidulans nondisjunction assay at an unspecified concentration.

Postmarketing Experience

Patients taking hydrochlorothiazide are advised to protect their skin from sun exposure and to undergo regular skin cancer screenings. This recommendation is based on postmarketing experience and reflects the importance of monitoring for potential skin-related adverse events associated with the medication.

Patient Counseling

Healthcare providers should advise patients to discontinue INZIRQO and seek immediate medical attention if they experience symptoms indicative of Acute Myopia or Secondary Angle-Closure Glaucoma. It is important for patients taking hydrochlorothiazide to be instructed on the necessity of protecting their skin from sun exposure and to undergo regular skin cancer screenings.

Patients should be informed to always shake the bottle well before each use and to measure the dose using a calibrated oral dosing syringe to ensure accurate dosing. Healthcare providers should also inform patients that a bottle adapter and oral dosing syringes can be obtained from their pharmacy.

It is crucial to advise patients never to use household teaspoons or tablespoons for measuring INZIRQO, as this may lead to inaccurate dosing. Additionally, patients should be made aware that the oral suspension should be stored at room temperature, specifically between 20°C to 25°C (68°F to 77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F).

Patients may take INZIRQO with or without meals, and they should be instructed to discard any unused suspension 30 days after reconstitution to ensure safety and efficacy.

Storage and Handling

The product is supplied in accordance with the following specifications. It should be stored 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) as defined by USP Controlled Room Temperature guidelines. It is imperative that the product is not frozen.

Additionally, reconstituted solutions of INZIRQO must also be maintained at a temperature of 20°C to 25°C (68°F to 77°F), with the same allowable excursions. All medications, including this product, should be kept out of the reach of children to ensure safety.

Additional Clinical Information

Patients receiving INZIRQO should have their kidney function monitored periodically, along with serum electrolytes, blood sugar, and lipid levels. For those with hypercalcemia, calcium levels should also be monitored. Clinicians are advised to discontinue INZIRQO if patients experience hypokalemia with clinical symptoms such as ECG changes or muscular weakness, or if symptoms of acute angle-closure glaucoma arise. In cases of uncontrolled intraocular pressure, prompt medical or surgical intervention may be necessary.

Postmarketing experience indicates that thiazide diuretics, including hydrochlorothiazide, may exacerbate or activate systemic lupus erythematosus. Additionally, hydrochlorothiazide has been associated with idiosyncratic reactions leading to acute angle-closure glaucoma and elevated intraocular pressure, which can manifest as decreased visual acuity or ocular pain shortly after initiation of treatment. Risk factors for this condition include a history of sulfonamide or penicillin allergy, and untreated cases may result in permanent vision loss.

FDA Insert (PDF)

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

View full prescribing information (PDF)