Accuretic

Description

ACCURETIC is a fixed-combination tablet that contains an angiotensin-converting enzyme (ACE) inhibitor, quinapril hydrochloride, and a thiazide diuretic, hydrochlorothiazide. Quinapril hydrochloride is chemically defined as [3S-[2R*(R*), 3R*]]-2-[2-[1-(ethoxycarbonyl)-3-phenylpropylamino]-1-oxopropyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid, monohydrochloride, with an empirical formula of C25H30N2O5·HCl. It appears as a white to off-white amorphous powder that is freely soluble in aqueous solvents. Hydrochlorothiazide is chemically described as 6-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, with an empirical formula of C7H8ClN3O4S2. This compound is a white to off-white crystalline powder, slightly soluble in water but freely soluble in sodium hydroxide solution.

ACCURETIC is formulated for oral administration and is available in three strengths: 10 mg of quinapril (equivalent to 10.832 mg of quinapril hydrochloride) combined with 12.5 mg of hydrochlorothiazide (ACCURETIC 10/12.5), 20 mg of quinapril (equivalent to 21.664 mg of quinapril hydrochloride) with 12.5 mg of hydrochlorothiazide (ACCURETIC 20/12.5), and 20 mg of quinapril (equivalent to 21.664 mg of quinapril hydrochloride) with 25 mg of hydrochlorothiazide (ACCURETIC 20/25). The inactive ingredients include candelilla wax, crospovidone, hydroxypropyl cellulose, hypromellose, iron oxide red, iron oxide yellow, lactose, magnesium carbonate, magnesium stearate, polyethylene glycol, povidone, and titanium dioxide.

Uses and Indications

This drug is indicated for the treatment of hypertension to lower blood pressure. Effective management of high blood pressure is essential for reducing the risk of both fatal and nonfatal cardiovascular events, particularly strokes and myocardial infarctions.

Control of hypertension should be integrated into a comprehensive cardiovascular risk management strategy, which includes lipid control, diabetes management, antithrombotic therapy, smoking cessation, regular exercise, and limited sodium intake. It is important to note that many patients may require a combination of antihypertensive medications to achieve their blood pressure goals.

Numerous antihypertensive agents have demonstrated efficacy in randomized controlled trials, showing a reduction in cardiovascular morbidity and mortality. The most significant cardiovascular outcome benefit observed is a decrease in the risk of stroke, along with reductions in myocardial infarction and overall cardiovascular mortality. Elevated systolic or diastolic blood pressure is associated with increased cardiovascular risk, and even modest reductions in severe hypertension can yield substantial health benefits.

The relative risk reduction associated with blood pressure lowering is consistent across various populations with differing absolute risk levels, with patients at higher risk experiencing greater absolute benefits, regardless of their hypertension status. It is also noted that some antihypertensive medications may exhibit diminished blood pressure-lowering effects in black patients, and many of these agents have additional approved indications and therapeutic effects.

Dosage and Administration

Quinapril may be administered as monotherapy at a dosage range of 10 to 80 mg once daily. Hydrochlorothiazide can be prescribed as monotherapy at a dosage range of 12.5 to 50 mg.

For patients requiring combination therapy, quinapril should be dosed between 2.5 to 40 mg, while hydrochlorothiazide should be dosed between 6.25 to 25 mg. It is recommended to initiate combination therapy only after the patient has not achieved the desired therapeutic effect with monotherapy.

In cases where blood pressure is not adequately controlled with quinapril monotherapy, healthcare professionals may consider the use of ACCURETIC 10/12.5 or 20/12.5. It is important to note that the hydrochlorothiazide dosage should generally not be increased until a period of 2 to 3 weeks has elapsed to assess the patient's response.

For patients who are adequately managed on a regimen of 20 mg of quinapril and 25 mg of hydrochlorothiazide, a switch to ACCURETIC 20/25 may be considered, provided that no significant electrolyte disturbances have occurred.

Contraindications

ACCURETIC is contraindicated in patients with hypersensitivity to quinapril or hydrochlorothiazide, as well as those with a history of angioedema related to previous treatment with an ACE inhibitor. The use of ACCURETIC in combination with a neprilysin inhibitor, such as sacubitril, is contraindicated; it should not be administered within 36 hours of switching to or from sacubitril/valsartan. Additionally, due to the hydrochlorothiazide component, ACCURETIC is contraindicated in patients with anuria or hypersensitivity to sulfonamide-derived drugs. Co-administration with aliskiren is contraindicated in patients with diabetes.

Warnings and Precautions

Patients receiving ACE inhibitors, including ACCURETIC, may experience a range of adverse reactions, some of which can be serious.

Anaphylactoid and Angioedema Reactions Anaphylactoid reactions, including angioedema of the face, extremities, lips, tongue, glottis, and larynx, have been reported in patients treated with ACE inhibitors. Angioedema associated with laryngeal edema can be fatal. In cases of laryngeal stridor or angioedema affecting the face, tongue, or glottis, treatment with ACCURETIC must be discontinued immediately, and the patient should receive appropriate medical care. Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk for similar reactions while on treatment. Additionally, life-threatening anaphylactoid reactions have been documented in patients undergoing desensitization therapy while receiving ACE inhibitors, as well as in those dialyzed with high-flux membranes.

Hepatic and Renal Considerations ACCURETIC has been associated with a syndrome that begins with cholestatic jaundice and can progress to fulminant hepatic necrosis, potentially resulting in death. Patients who develop jaundice or significant elevations in hepatic enzymes should discontinue the medication. Caution is advised when prescribing ACCURETIC to patients with severe renal disease, and renal function should be closely monitored during the initial weeks of therapy. Furthermore, periodic monitoring of white blood cell counts is recommended for patients with collagen vascular disease and/or renal disease due to the risk of neutropenia or agranulocytosis.

Hypotension and Fetal Toxicity ACCURETIC may cause symptomatic hypotension, particularly in patients at risk for excessive drops in blood pressure. These patients should be monitored closely. The use of drugs that affect the renin-angiotensin system during the second and third trimesters of pregnancy can lead to fetal injury or death; therefore, ACCURETIC should be discontinued as soon as pregnancy is detected.

Other Precautions Patients should be monitored for serum electrolyte abnormalities, as hyperkalemia may occur, especially in those with renal insufficiency or diabetes mellitus. Hydrochlorothiazide, a component of ACCURETIC, may alter glucose tolerance and increase serum cholesterol and triglyceride levels. A persistent nonproductive cough has been reported with ACE inhibitors, which typically resolves upon discontinuation of therapy. During surgical procedures or anesthesia, quinapril may inhibit angiotensin II formation, potentially leading to hypotension.

Laboratory Monitoring It is important to monitor serum electrolytes periodically during treatment. The hydrochlorothiazide component may decrease serum PBI levels without causing thyroid disturbances. Additionally, therapy with ACCURETIC should be paused for several days prior to conducting tests of parathyroid function.

Emergency Instructions In cases where angioedema involves the tongue, glottis, or larynx, which may lead to airway obstruction, emergency medical assistance should be sought immediately. Emergency therapy, including subcutaneous epinephrine solution (1:1000, 0.3 to 0.5 mL), should be administered promptly.

Discontinuation of Treatment If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, treatment with ACCURETIC must be stopped immediately, and the patient should contact their healthcare provider without delay.

Side Effects

Common adverse reactions observed in clinical trials (≥1% incidence) include headache (6.7%), dizziness (4.8%), coughing (3.2%), fatigue (2.9%), myalgia (2.4%), viral infection (1.9%), rhinitis (2.0%), nausea and/or vomiting (1.8%), abdominal pain (1.7%), back pain (1.5%), diarrhea (1.4%), upper respiratory infection (1.3%), insomnia (1.2%), somnolence (1.2%), bronchitis (1.2%), dyspepsia (1.2%), asthenia (1.1%), pharyngitis (1.1%), vasodilatation (1.0%), vertigo (1.0%), and chest pain (1.0%).

Additional adverse reactions occurring at a frequency of ≥0.5% to <1.0% include asthenia and malaise (body as a whole), palpitations, tachycardia, heart failure, hyperkalemia, myocardial infarction, cerebrovascular accident, hypertensive crisis, angina pectoris, orthostatic hypotension, and cardiac rhythm disturbance (cardiovascular), dry mouth or throat, gastrointestinal hemorrhage, pancreatitis, and abnormal liver function tests (gastrointestinal), nervousness, vertigo, and paresthesia (nervous/psychiatric), sinusitis and dyspnea (respiratory), pruritus, increased sweating, erythema multiforme, exfoliative dermatitis, photosensitivity reaction, alopecia, and pemphigus (integumentary), acute renal failure and impotence (urogenital system), agranulocytosis, thrombocytopenia, and arthralgia (other).

Serious adverse reactions include angioedema, reported in 0.1% of patients receiving quinapril, and hypotension, which occurred in 1.2% of patients during clinical trials. Neutropenia and agranulocytosis have been rarely associated with ACE inhibitors, particularly in patients with renal impairment or collagen vascular disease.

Postmarketing experience has revealed additional adverse reactions, including shock, accidental injury, neoplasm, cellulitis, ascites, generalized edema, hernia, and anaphylactoid reactions (body as a whole). Cardiovascular events such as bradycardia, cor pulmonale, vasculitis, and deep vein thrombosis have also been reported. Digestive system issues include gastrointestinal carcinoma, cholestatic jaundice, hepatitis, esophagitis, vomiting, and diarrhea. Eye disorders such as acute myopia and acute angle closure glaucoma, as well as anemia (hemic system), weight loss (metabolic and nutritional disorders), myopathy, myositis, and arthritis (musculoskeletal system) have been noted. Neurological events include paralysis, hemiplegia, speech disorder, abnormal gait, meningism, and amnesia. Respiratory system reactions such as pneumonia, asthma, respiratory infiltration, and lung disorder have been documented. Skin and appendage reactions include urticaria, macropapular rash, and petechiae. Abnormal vision (special senses) and urogenital system issues such as kidney function abnormalities, albuminuria, pyuria, hematuria, and nephrosis have also been reported.

Warnings include fetal toxicity, as the use of drugs acting on the renin-angiotensin system during the second and third trimesters of pregnancy can cause injury and death to the developing fetus. Hepatic failure has been rarely associated with a syndrome starting with cholestatic jaundice and progressing to fulminant hepatic necrosis. Hypotension can cause symptomatic hypotension, particularly in patients with certain conditions or characteristics.

Persistent nonproductive cough has been reported with all ACE inhibitors, resolving after discontinuation of therapy. Hyperkalemia occurred in approximately 2% of patients receiving quinapril. Additionally, hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides.

Drug Interactions

Coadministration of ACCURETIC with other medications that elevate serum potassium levels may lead to hyperkalemia; therefore, it is advised to monitor serum potassium levels in these patients.

When ACCURETIC is used in conjunction with lithium, there is an increased risk of elevated serum lithium levels and potential lithium toxicity. This risk is further heightened due to the renal clearance reduction of lithium caused by thiazides. Caution is warranted when coadministering ACCURETIC and lithium, and frequent monitoring of serum lithium levels is recommended.

The dual blockade of the renin-angiotensin system (RAS) through the use of angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with heightened risks of hypotension, hyperkalemia, and alterations in renal function, including acute renal failure, compared to monotherapy. Most patients do not experience additional benefits from the combination of two RAS inhibitors. Therefore, the combined use of RAS inhibitors should generally be avoided. Patients receiving ACCURETIC alongside other RAS-affecting agents should be closely monitored for blood pressure, renal function, and electrolyte levels. Specifically, aliskiren should not be coadministered with ACCURETIC in patients with diabetes or those with renal impairment (GFR <60 mL/min/1.73 m²).

The simultaneous administration of tetracycline with quinapril may reduce the absorption of tetracycline by approximately 28% to 37%, likely due to the high magnesium content in quinapril tablets. This interaction should be considered when prescribing these medications together.

Rare instances of nitritoid reactions, characterized by facial flushing, nausea, vomiting, and hypotension, have been reported in patients receiving injectable gold (sodium aurothiomalate) alongside ACE inhibitors.

In elderly patients, those who are volume-depleted (including individuals on diuretic therapy), or those with compromised renal function, the coadministration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors such as quinapril may lead to renal function deterioration, potentially resulting in acute renal failure. These effects are typically reversible, but renal function should be monitored periodically in patients receiving quinapril and NSAID therapy. Additionally, the antihypertensive effect of ACE inhibitors may be diminished by NSAIDs.

Patients undergoing treatment with mTOR inhibitors (e.g., temsirolimus) or neprilysin inhibitors may face an increased risk of angioedema when using ACCURETIC.

No pharmacokinetic interactions were observed when single doses of quinapril were administered with propranolol or cimetidine. Furthermore, the anticoagulant effect of a single dose of warfarin, as measured by prothrombin time, was not significantly altered by the coadministration of quinapril.

Thiazide-induced electrolyte disturbances, such as hypokalemia and hypomagnesemia, can increase the risk of digoxin toxicity, potentially leading to fatal arrhythmic events.

No pharmacokinetic interaction was noted when single doses of quinapril and hydrochlorothiazide were administered together.

Concomitant use of alcohol, barbiturates, or narcotics may enhance the risk of orthostatic hypotension.

For patients taking antidiabetic medications (oral hypoglycemic agents and insulin), dosage adjustments may be necessary.

The absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins such as cholestyramine and colestipol. Single doses of cholestyramine or colestipol can bind hydrochlorothiazide, reducing its gastrointestinal absorption by up to 85% and 43%, respectively.

Corticosteroids and ACTH may lead to intensified electrolyte depletion, particularly hypokalemia.

The response to pressor amines (e.g., norepinephrine) may be diminished, although this is not sufficient to preclude their therapeutic use.

There is a potential for increased responsiveness to nondepolarizing skeletal muscle relaxants (e.g., tubocurarine) when used concurrently.

The diuretic, natriuretic, and antihypertensive effects of thiazide diuretics may be reduced by the concurrent administration of nonsteroidal anti-inflammatory drugs (NSAIDs).

Packaging & NDC

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

Pediatric Use

The safety and effectiveness of ACCURETIC in pediatric patients have not been established. In neonates with a history of in utero exposure to ACCURETIC, if oliguria or hypotension occurs, it is crucial to provide support for blood pressure and renal perfusion. In such cases, exchange transfusions or dialysis may be necessary to address hypotension and/or substitute for impaired renal function. It is important to note that the removal of quinapril, which crosses the placenta, from the neonatal circulation is not significantly accelerated by these interventions.

Geriatric Use

Clinical studies of quinapril HCl/hydrochlorothiazide did not include a sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, other reported clinical experience has not identified significant differences in responses between elderly patients and younger patients.

In general, dose selection for geriatric patients should be approached with caution. It is recommended 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. Careful monitoring of these patients is advised to ensure safety and efficacy.

Pregnancy

Pregnant patients should be informed that the safety of ACCURETIC during pregnancy has not been established, as carcinogenicity, mutagenicity, and fertility studies have not been conducted in animals. Quinapril hydrochloride, a component of ACCURETIC, was not found to be carcinogenic in long-term studies involving mice and rats at doses significantly higher than the maximum human daily dose. However, female rats receiving the highest dose exhibited an increased incidence of mesenteric lymph node hemangiomas and skin/subcutaneous lipomas.

In terms of genetic toxicity, neither quinapril nor its active metabolite, quinaprilat, demonstrated mutagenic potential in various assays, including the Ames test and other in vitro and in vivo genetic toxicology studies. Additionally, no adverse effects on fertility or reproduction were observed in rats at doses up to 100 mg/kg/day.

Hydrochlorothiazide, another component of ACCURETIC, has been evaluated under the National Toxicology Program, with studies indicating no evidence of carcinogenic potential in rats or female mice, although equivocal evidence of hepatocarcinogenicity was noted in male mice. Hydrochlorothiazide was not found to be genotoxic in several in vitro assays, but positive results were obtained in specific clastogenicity and mutagenicity tests at high concentrations.

Overall, there is no evidence of adverse effects on fertility in animal studies involving hydrochlorothiazide. Given the lack of comprehensive studies in pregnant patients and the potential risks, ACCURETIC should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Healthcare providers are advised to discuss these considerations with women of childbearing potential and pregnant patients.

Lactation

Because quinapril and hydrochlorothiazide are secreted in human milk, caution should be exercised when ACCURETIC is administered to lactating mothers. Due to the potential for serious adverse reactions in breastfed infants from hydrochlorothiazide and the unknown effects of quinapril in infants, a decision should be made whether to discontinue nursing or to discontinue ACCURETIC, taking into account the importance of the drug to the mother.

Renal Impairment

ACCURETIC should be used with caution in patients with severe renal disease, as thiazides may precipitate azotemia in these individuals, and the effects of repeated dosing may be cumulative. In patients with severe congestive heart failure, where renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin-converting enzyme inhibitors, including quinapril, may lead to oliguria, progressive azotemia, and, in rare cases, acute renal failure or death.

Clinical studies involving hypertensive patients with unilateral renal artery stenosis have shown that treatment with ACE inhibitors can result in increases in blood urea nitrogen and serum creatinine; these changes were reversible upon discontinuation of the ACE inhibitor, concomitant diuretic, or both. Therefore, renal function should be closely monitored during the initial weeks of therapy in such patients receiving ACCURETIC.

Additionally, some hypertensive patients treated with quinapril, even in the absence of apparent preexisting renal vascular diseases, have experienced minor and transient increases in blood urea nitrogen and serum creatinine, particularly when quinapril is administered alongside a diuretic. This occurrence is more likely in patients with pre-existing renal impairment, and dosage reduction of ACCURETIC may be necessary. Regular assessment of renal function is recommended for hypertensive patients.

Hepatic Impairment

Patients with hepatic impairment should use ACCURETIC with caution due to the potential for minor alterations in fluid and electrolyte balance, which may precipitate hepatic coma. The metabolism of quinapril to its active form, quinaprilat, is primarily dependent on hepatic esterases; therefore, patients with compromised liver function may experience significantly elevated plasma levels of quinapril.

Currently, no pharmacokinetic studies have been conducted specifically in hypertensive patients with impaired liver function, which limits the understanding of the drug's behavior in this population. Additionally, there is a rare association between ACE inhibitors and a syndrome that begins with cholestatic jaundice and can progress to fulminant hepatic necrosis, potentially resulting in death.

Patients receiving ACCURETIC who develop jaundice or exhibit marked elevations in hepatic enzymes should discontinue the use of the ACE inhibitor and receive appropriate medical follow-up to ensure safety and manage any complications. Regular monitoring of liver function is advised for patients with hepatic impairment to detect any adverse effects promptly.

Overdosage

In cases of overdosage with ACCURETIC or quinapril monotherapy, specific treatment information is limited. Management should focus on symptomatic and supportive care. It is recommended that therapy with ACCURETIC be discontinued, and the patient should be closely monitored. Key concerns include dehydration, electrolyte imbalances, and hypotension, which should be addressed according to established medical protocols.

The oral median lethal dose of the quinapril/hydrochlorothiazide combination has been observed to range from 1063/664 to 4640/2896 mg/kg in animal studies involving mice and rats. Notably, doses of quinapril between 1440 to 4280 mg/kg have resulted in significant lethality in these models. In contrast, single-dose studies of hydrochlorothiazide indicate that most rats survived doses up to 2.75 g/kg.

Human data regarding overdoses of ACE inhibitors, including quinapril, are limited. The most common manifestation of quinapril overdosage in humans is hypotension. In cases of hydrochlorothiazide overdose, symptoms typically include dehydration and electrolyte depletion, such as hypokalemia, hypochloremia, and hyponatremia. It is important to note that if digitalis has been administered concurrently, hypokalemia may exacerbate the risk of cardiac arrhythmias.

Laboratory assessments of serum levels of quinapril and its metabolites are not routinely available, and such determinations do not have a defined role in the management of quinapril overdose. Furthermore, there is no evidence to support the use of physiological maneuvers, such as altering urine pH, to enhance the elimination of quinapril and its metabolites. Both hemodialysis and peritoneal dialysis have been shown to have minimal impact on the clearance of quinapril and quinaprilat.

While angiotensin II could theoretically act as a specific antagonist or antidote in the event of quinapril overdose, it is largely unavailable outside of specialized research settings. Given that the hypotensive effects of quinapril result from vasodilation and effective hypovolemia, it is advisable to manage quinapril overdose through the infusion of normal saline solution to restore fluid balance.

Nonclinical Toxicology

Carcinogenicity, mutagenicity, and fertility studies have not been conducted in animals with ACCURETIC. Quinapril hydrochloride demonstrated no carcinogenic potential in mice or rats when administered at doses up to 75 or 100 mg/kg/day for 104 weeks, which corresponds to 50 or 60 times the maximum human daily dose on a mg/kg basis and 3.8 or 10 times the maximum human daily dose on a mg/m² basis. However, an increased incidence of mesenteric lymph node hemangiomas and skin/subcutaneous lipomas was observed in female rats receiving the highest dose level.

In terms of mutagenicity, neither quinapril nor quinaprilat exhibited mutagenic effects in the Ames bacterial assay, both with and without metabolic activation. Quinapril was also found to be negative in several genetic toxicology studies, including in vitro mammalian cell point mutation, sister chromatid exchange in cultured mammalian cells, micronucleus test in mice, in vitro chromosome aberration tests with V79 cultured lung cells, and in vivo cytogenetic studies using rat bone marrow.

Fertility and reproduction studies in rats indicated no adverse effects at doses up to 100 mg/kg/day, which is equivalent to 60 and 10 times the maximum daily human dose based on mg/kg and mg/m², respectively.

Under the National Toxicology Program, hydrochlorothiazide was administered to rats and mice in their feed for 2 years at doses up to 600 mg/kg/day in mice and up to 100 mg/kg/day in rats. These studies did not reveal evidence of carcinogenic potential in rats or female mice; however, there was "equivocal" evidence of hepatocarcinogenicity in male mice.

Hydrochlorothiazide was not found to be genotoxic in various in vitro assays, including the Ames test using strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 of Salmonella typhimurium, the Chinese hamster ovary (CHO) test for chromosomal aberrations, or in vivo assays involving mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Nonetheless, positive results were obtained in the in vitro CHO sister chromatid exchange (clastogenicity) test and in mouse lymphoma cell (mutagenicity) assays at hydrochlorothiazide concentrations ranging from 43 to 1300 µg/mL. Additionally, positive results were noted in the Aspergillus nidulans nondisjunction assay at an unspecified concentration of hydrochlorothiazide.

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 and 4 mg/kg/day, respectively, prior to mating and throughout gestation.

Postmarketing Experience

Postmarketing experience has identified several adverse events reported voluntarily or through surveillance programs.

Hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma (SCC). Data from a study conducted in the Sentinel System indicate that the increased risk is predominantly observed in white patients receiving large cumulative doses. The overall population shows an approximate risk of 1 additional case of SCC per 16,000 patients per year, while white patients with a cumulative dose of ≥50,000 mg exhibit an increased risk of approximately 1 additional SCC case for every 6,700 patients per year.

Additional adverse events reported include:

Body as a Whole: Shock, accidental injury, neoplasm, cellulitis, ascites, generalized edema, hernia, and anaphylactoid reaction.

Cardiovascular System: Bradycardia, cor pulmonale, vasculitis, and deep vein thrombosis.

Digestive System: Gastrointestinal carcinoma, cholestatic jaundice, hepatitis, esophagitis, vomiting, and diarrhea.

Eye Disorders: Acute myopia and acute angle closure glaucoma.

Hemic System: Anemia.

Metabolic and Nutritional Disorders: Weight loss.

Musculoskeletal System: Myopathy, myositis, and arthritis.

Nervous System: Paralysis, hemiplegia, speech disorder, abnormal gait, meningism, and amnesia.

Respiratory System: Pneumonia, asthma, respiratory infiltration, and lung disorder.

Skin and Appendages: Urticaria, macropapular rash, and petechiae.

Special Senses: Abnormal vision.

Urogenital System: Abnormal kidney function, albuminuria, pyuria, hematuria, and nephrosis.

Patient Counseling

Patients receiving ACCURETIC should be advised to immediately report any signs or symptoms suggestive of angioedema, such as swelling of the face, eyes, lips, or tongue, or difficulty in breathing. They should be instructed to temporarily discontinue ACCURETIC until they have consulted with their prescribing physician.

Healthcare providers should discuss with female patients of childbearing age the potential consequences of exposure to ACCURETIC during pregnancy. It is important to explore treatment options with women who are planning to become pregnant and to encourage patients to report any pregnancies to their physicians as soon as possible.

Patients should be informed that lightheadedness may occur, particularly during the initial days of therapy, and they should report this to their prescribing physician. In the event of syncope, patients should discontinue ACCURETIC until they have consulted with their physician. Additionally, patients should be made aware that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to a significant drop in blood pressure due to reduced fluid volume, which may result in lightheadedness and possible syncope.

Patients planning to undergo major surgery or general or spinal anesthesia should be instructed to inform their physicians that they are taking an ACE inhibitor.

It is essential to advise patients receiving ACCURETIC not to use potassium supplements or salt substitutes containing potassium without first consulting their prescribing physician.

Patients should be encouraged to promptly report any signs of infection, such as a sore throat or fever, as these may indicate neutropenia.

Finally, patients taking hydrochlorothiazide should be instructed to protect their skin from sun exposure and to undergo regular skin cancer screenings.

Storage and Handling

The product is supplied in tight containers as defined by the United States Pharmacopeia (USP). It should be stored at a controlled room temperature of 20–25°C (68–77°F) to ensure optimal stability and efficacy.

Additional Clinical Information

The hydrochlorothiazide component of ACCURETIC has been observed to decrease serum protein-bound iodine (PBI) levels; however, this effect does not indicate any signs of thyroid disturbance in patients. Clinicians are advised to interrupt therapy with ACCURETIC for a few days prior to conducting tests related to parathyroid function to ensure accurate results.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Accuretic as submitted by Parke-Davis Div of Pfizer Inc. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)