Thiazide Diuretic

Vaseretic

Approved 31 Oct 1986OralTablet

The FDA lists this product in 2 strengths and forms.

Indications

VASERETIC is indicated for the treatment of hypertension. This fixed dose combination is not indicated for initial treatment (see DOSAGE AND ADMINISTRATION ). In using VASERETIC, consideration should be given to the fact that another angiotensin converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen vascular disease, and that available data are insufficient to show that enalapril does not have a similar risk (see WARNINGS ).

In considering use of VASERETIC, it should be noted that black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to non-blacks (see WARNINGS, Head and Neck Angioedema ).

Contraindications

VASERETIC is contraindicated in patients who are hypersensitive to any component of this product and in patients with a history of angioedema related to previous treatment with an angiotensin converting enzyme inhibitor and in patients with hereditary or idiopathic angioedema. Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

VASERETIC is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer VASERETIC within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor (see WARNINGS ) . Do not co-administer aliskiren with VASERETIC in patients with diabetes (see PRECAUTIONS, Drug Interactions ).

Warnings and precautions

General Enalapril Maleate Hypotension: Excessive hypotension was rarely seen in uncomplicated hypertensive patients but is a possible consequence of enalapril use in severely salt/volume depleted persons such as those treated vigorously with diuretics or patients on dialysis. Syncope has been reported in 1.3 percent of patients receiving VASERETIC. In patients receiving enalapril alone, the incidence of syncope is 0.5 percent.

The overall incidence of syncope may be reduced by proper titration of the individual components (see PRECAUTIONS, Drug Interactions , ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION ). In patients with severe congestive heart failure, with or without associated renal insufficiency, excessive hypotension has been observed and may be associated with oliguria and/or progressive azotemia, and rarely with acute renal failure and/or death.

Interactions

Drug Interactions Neprilysin Inhibitors Patients taking concomitant neprilysin inhibitors may be at increased risk for angioedema. (see WARNINGS ). Enalapril Maleate Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.

Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function, and electrolytes in patients on VASERETIC and other agents that affect the RAS. Do not coadminister aliskiren with VASERETIC in patients with diabetes. Avoid use of aliskiren with VASERETIC in patients with renal impairment (GFR <60 mL/min).

Hypotension – Patients on Diuretic Therapy Patients on diuretics and especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with enalapril. The possibility of hypotensive effects with enalapril can be minimized by either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with enalapril.

If it is necessary to continue the diuretic, provide medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour (see WARNINGS and DOSAGE AND ADMINISTRATION ). Agents Causing Renin Release The antihypertensive effect of enalapril is augmented by antihypertensive agents that cause renin release (e.g., diuretics). Non-steroidal Anti-inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including enalapril, may result in deterioration of renal function, including possible acute renal failure.

These effects are usually reversible. Monitor renal function periodically in patients receiving enalapril and NSAID therapy. In a clinical pharmacology study, indomethacin or sulindac was administered to hypertensive patients receiving enalapril maleate. In this study there was no evidence of a blunting of the antihypertensive action of enalapril maleate. However, reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors.

Other Cardiovascular Agents Enalapril has been used concomitantly with beta adrenergic-blocking agents, methyldopa, nitrates, calcium-blocking agents, hydralazine and prazosin without evidence of clinically significant adverse interactions. Agents Increasing Serum Potassium Enalapril attenuates diuretic-induced potassium loss. Potassium-sparing diuretics (e.g., spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium.

Therefore, if concomitant use of these agents is indicated because of demonstrated hypokalemia they should be used with caution and with frequent monitoring of serum potassium. Lithium Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs which cause elimination of sodium, including ACE inhibitors. A few cases of lithium toxicity have been reported in patients receiving concomitant enalapril and lithium and were reversible upon discontinuation of both drugs.

It is recommended that serum lithium levels be monitored frequently if enalapril is administered concomitantly with lithium. Gold Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including VASERETIC. mTOR (mammalian target of rapamycin) inhibitors: Patients receiving coadministration of ACE inhibitor and mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema (see WARNINGS ).

Hydrochlorothiazide When administered concurrently the following drugs may interact with thiazide diuretics: Alcohol, barbiturates, or narcotics Potentiation of orthostatic hypotension may occur. Anti-diabetic drugs (oral agents and insulin) Dosage adjustment of the anti-diabetic drug may be required. Other anti-hypertensive drugs Additive effect or potentiation. Cholestyramine and colestipol resins Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins.

Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85 and 43 percent, respectively. Corticosteroids, ACTH Intensified electrolyte depletion, particularly hypokalemia. Pressor amines (e.g., norepinephrine) Possible decreased response to pressor amines but not sufficient to preclude their use. Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine) Possible increased responsiveness to the muscle relaxant.

Lithium Should not generally be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations before use of such preparations with VASERETIC. Non-steroidal Anti-inflammatory Drugs In some patients, the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics.

Therefore, when VASERETIC and non-steroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.

Adverse reactions

VASERETIC has been evaluated for safety in more than 1500 patients, including over 300 patients treated for one year or more. In clinical trials with VASERETIC no adverse experiences peculiar to this combination drug have been observed. Adverse experiences that have occurred have been limited to those that have been previously reported with enalapril or hydrochlorothiazide. The most frequent clinical adverse experiences in controlled trials were: dizziness (8.6 percent), headache (5.5 percent), fatigue (3.9 percent) and cough (3.5 percent).

Generally, adverse experiences were mild and transient in nature. Adverse experiences occurring in greater than two percent of patients treated with VASERETIC in controlled clinical trials are shown below. Percent of Patients in Controlled Studies VASERETIC (n=1580) Incidence (discontinuation) Placebo (n=230) Incidence Dizziness 8.6 (0.7)

4.3 Headache 5.5 (0.4)

9.1 Fatigue 3.9 (0.8)

2.6 Cough 3.5 (0.4)

0.9 Muscle Cramps 2.7 (0.2)

0.9 Nausea 2.5 (0.4)

1.7 Asthenia 2.4 (0.3)

0.9 Orthostatic Effects 2.3 (<0.1)

0.0 Impotence 2.2 (0.5)

0.5 Diarrhea 2.1 (<0.1)

1.7 Clinical adverse experiences occurring in 0.5 to 2.0 percent of patients in controlled trials included: Body as a Whole: Syncope, chest pain, abdominal pain Cardiovascular: Orthostatic hypotension, palpitation, tachycardia Digestive: Vomiting, dyspepsia, constipation, flatulence, dry mouth Nervous/Psychiatric: Insomnia, nervousness, paresthesia, somnolence, vertigo Skin: Pruritus, rash Other: Dyspnea, gout, back pain, arthralgia, diaphoresis, decreased libido, tinnitus, urinary tract infection Angioedema: Angioedema has been reported in patients receiving VASERETIC, with an incidence higher in black than in non-black patients.

Angioedema associated with laryngeal edema may be fatal. If angioedema of the face, extremities, lips, tongue, glottis and/or larynx occurs, treatment with VASERETIC should be discontinued and appropriate therapy instituted immediately (see WARNINGS ). Hypotension: In clinical trials, adverse effects relating to hypotension occurred as follows: hypotension (0.9 percent), orthostatic hypotension (1.5 percent), other orthostatic effects (2.3 percent).

In addition syncope occurred in 1.3 percent of patients (see WARNINGS ). Cough: See PRECAUTIONS, Cough . Clinical Laboratory Test Findings Serum Electrolytes: See PRECAUTIONS . Creatinine, Blood Urea Nitrogen: In controlled clinical trials minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 0.6 percent of patients with essential hypertension treated with VASERETIC.

More marked increases have been reported in other enalapril experience. Increases are more likely to occur in patients with renal artery stenosis (see PRECAUTIONS ). Serum Uric Acid, Glucose, Magnesium, and Calcium: See PRECAUTIONS . Hemoglobin and Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.3 g percent and 1.0 vol percent, respectively) occur frequently in hypertensive patients treated with VASERETIC but are rarely of clinical importance unless another cause of anemia coexists.

In clinical trials, less than 0.1 percent of patients discontinued therapy due to anemia. Liver Function Tests: Rarely, elevations of liver enzymes and/or serum bilirubin have occurred (see WARNINGS, Hepatic Failure ). Other adverse reactions that have been reported with the individual components are listed below and, within each category, are in order of decreasing severity. Enalapril Maleate – Enalapril has been evaluated for safety in more than 10,000 patients.

In clinical trials adverse reactions which occurred with enalapril were also seen with VASERETIC. However, since enalapril has been marketed, the following adverse reactions have been reported: Body As A Whole: Anaphylactoid reactions (see WARNINGS, Anaphylactoid Reactions During Membrane Exposure ); Cardiovascular: Cardiac arrest; myocardial infarction or cerebrovascular accident, possibly secondary to excessive hypotension in high risk patients (see WARNINGS, Hypotension ); pulmonary embolism and infarction; pulmonary edema; rhythm disturbances including atrial tachycardia and bradycardia; atrial fibrillation; hypotension; angina pectoris, Raynaud's phenomenon; Digestive: Ileus, pancreatitis, hepatic failure, hepatitis (hepatocellular [proven on rechallenge] or cholestatic jaundice) (see WARNINGS, Hepatic Failure ), melena, anorexia, glossitis, stomatitis, dry mouth; Hematologic: Rare cases of neutropenia, thrombocytopenia and bone marrow depression.

Hemolytic anemia, including cases of hemolysis in patients with G6PD deficiency, has been reported; a causal relationship to enalapril cannot be excluded. Nervous System/Psychiatric: Depression, confusion, ataxia, peripheral neuropathy (e.g., paresthesia, dysesthesia), dream abnormality; Urogenital: Renal failure, oliguria, renal dysfunction, (see PRECAUTIONS and DOSAGE AND ADMINISTRATION ), flank pain, gynecomastia; Respiratory: Pulmonary infiltrates, eosinophilic pneumonitis, bronchospasm, pneumonia, bronchitis, rhinorrhea, sore throat and hoarseness, asthma, upper respiratory infection; Skin: Exfoliative dermatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, herpes zoster, erythema multiforme, urticaria, pemphigus, alopecia, flushing, photosensitivity; Special Senses: Blurred vision, taste alteration, anosmia, conjunctivitis, dry eyes, tearing.

Miscellaneous: A symptom complex has been reported which may include some or all of the following: a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia/myositis, fever, serositis, vasculitis, leukocytosis, eosinophilia, photosensitivity, rash and other dermatologic manifestations. Hydrochlorothiazide – Body as a Whole: Weakness; Digestive: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation, anorexia; Hematologic: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia; Hypersensitivity: Purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions; Musculoskeletal: Muscle spasm; Nervous System/Psychiatric: Restlessness; Renal: Renal failure, renal dysfunction, interstitial nephritis (see WARNINGS ); Skin: Erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis, alopecia; Special Senses: Transient blurred vision, xanthopsia.

Postmarketing Experience Non-melanoma Skin Cancer: Hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer. In a study conducted in the Sentinel System, increased risk was predominantly for squamous cell carcinoma (SCC) and in white patients taking large cumulative doses. The increased risk for SCC in the overall population was approximately 1 additional case per 16,000 patients per year, and for white patients taking a cumulative dose of ≥50,000 mg the risk increase was approximately 1 additional SCC case for every 6,700 patients per year.

To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Vaseretic

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Interactions

Pregnancy and breastfeeding

Adverse reactions

Composition

Strengths and forms

Official product information

At a glance

Guidelines