Lotensin Hct Side Effects Center

SIDE EFFECTS

Lotensin HCT has been evaluated for safety in over 2500 patients with hypertension; over 500 of these patients were treated for at least 6 months, and over 200 were treated for more than 1 year.

The reported side effects were generally mild and transient, and there was no relationship between side effects and age, sex, race, or duration of therapy. Discontinuation of therapy due to side effects was required in approximately 7% of U.S. patients treated with Lotensin HCT and in 4% of patients treated with placebo.

The most common reasons for discontinuation of therapy with Lotensin HCT in U.S. studies were cough (1.0%; see PRECAUTIONS), “dizziness” (1.0%), headache (0.6%), and fatigue (0.6%).

The side effects considered possibly or probably related to study drug that occurred in U.S. placebo-controlled trials in more than 1% of patients treated with Lotensin HCT are shown in the table below.

Reactions Possibly or Probably Drug Related Patients in U.S. Placebo-Controlled Studies

	LOTENSIN HCT N =665		Placebo N =235
	N	%	N	%
“Dizziness”	41	6.3	8	3.4
Fatigue	34	5.2	6	2.6
Postural Dizziness	23	3.5	1	0.4
Headache	20	3.1	10	4.3
Cough	14	2.1	3	1.3
Hypertonia	10	1.5	3	1.3
Vertigo	10	1.5	2	0.9
Nausea	9	1.4	2	0.9
Impotence	8	1.2	0	0.0
Somnolence	8	1.2	1	0.4

Other side effects considered possibly or probably related to study drug that occurred in U.S. placebo-controlled trials in 0.3% to 1.0% of patients treated with Lotensin HCT were the following:

Cardiovascular: Palpitations, flushing.

Gastrointestinal: Vomiting, diarrhea, dyspepsia, anorexia, and constipation.

Neurologic and Psychiatric: Insomnia, nervousness, paresthesia, libido decrease, dry mouth, taste perversion, and tinnitus.

Dermatologic: Rash and sweating.

Other: Urinary frequency, arthralgia, myalgia, asthenia, and pain (including chest pain and abdominal pain).

Other adverse experiences reported in 0.3% or more of Lotensin HCT patients in U.S. controlled clinical trials, and rarer events seen in post-marketing experience, were the following; asterisked entries occurred in more than 1% of patients (in some, a causal relationship to Lotensin HCT is uncertain):

Cardiovascular: Syncope, peripheral vascular disorder, and tachycardia.

Body as a Whole: Infection, back pain*, flu syndrome*, fever, chills, and neck pain.

Dermatologic: Photosensitivity and pruritus.

Gastrointestinal: Gastroenteritis, flatulence, and tooth disorder.

Neurologic and Psychiatric: Hypesthesia, abnormal vision, abnormal dreams, and retinal disorder.

Respiratory: Upper respiratory infection*, epistaxis, bronchitis, rhinitis*, sinusitis*, and voice alteration.

Other: Conjunctivitis, arthritis, urinary tract infection, alopecia, and urinary frequency*.

Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of either benazepril or hydrochlorothiazide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure:

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 ≥50,000mg the risk increase was approximately 1 additional SCC case for every 6,700 patients per year.

Benazepril Stevens-Johnson syndrome, pancreatitis, hemolytic anemia, pemphigus, and thrombocytopenia, eosinophilic pneumonitis

Hydrochlorothiazide

Digestive: Pancreatitis, small bowel angioedema, jaundice (intrahepatic cholestatic), sialadenitis, vomiting, diarrhea, cramping, nausea, gastric irritation, constipation, and anorexia.

Neurologic: Vertigo, lightheadedness, transient blurred vision, headache, paresthesia, xanthopsia, weakness, and restlessness.

Musculoskeletal: Muscle spasm.

Hematologic: Aplastic anemia, agranulocytosis, leukopenia, neutropenia and thrombocytopenia.

Metabolic: Hyperglycemia, glycosuria, and hyperuricemia, pyrexia, asthenia, parathyroid gland changes with hypercalcemia and hypophosphatemia.

Hypersensitivity: Anaphylactoid reactions, necrotizing angiitis, respiratory distress (including pneumonitis and pulmonary edema), purpura, urticaria, rash, and photosensitivity.

Skin: Erythema multiforme including Stevens-Johnson syndrome, and exfoliative dermatitis including toxic epidermal necrolysis.

Clinical Laboratory Test Findings

Serum Electrolytes: see PRECAUTIONS.

Creatinine and BUN: Minor reversible increases in serum creatinine and BUN were observed in patients with essential hypertension treated with Lotensin HCT. Such increases occurred most frequently in patients with renal artery stenosis (see PRECAUTIONS).

To report SUSPECTED ADVERSE REACTIONS, contact Validus Pharmaceuticals LLC at 1-866-982-5438 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Neprilysin Inhibitors

Patients taking concomitant neprilysin inhibitors may be at increased risk for angioedema.

Interactions Common For Both Benazepril And Hydrochlorothiazide

Potassium Supplements And Potassium-Sparing Diuretics

Concomitant use with Lotensin HCT may effect potassium levels. Monitor potassium periodically.

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).

Lithium

Renal clearance of lithium is reduced by thiazides and increase the risk of lithium toxicity. Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium. Monitor lithium levels when used concomitantly with Lotensin HCT.

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 hypertension, 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 Lotensin HCT and other agents that affect the RAS.

Do not coadminister aliskiren with Lotensin HCT in patients with diabetes. Avoid use of aliskiren with Lotensin HCT in patients with renal impairment (GFR < 60 mL/min).

NSAIDs And Cox-2 Selective Agents

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 benazepril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving benazepril and NSAID therapy.

The antihypertensive effect of benazepril and hydrochlorothiazide may be attenuated by NSAIDs.

Benazepril

Benazepril has been used concomitantly with beta-adrenergic-blocking agents, calcium-blocking agents, cimetidine, diuretics, digoxin, hydralazine, and naproxen without evidence of clinically important adverse interactions. Other ACE inhibitors have had less than additive effects with beta-adrenergic blockers, presumably because drugs of both classes lower blood pressure by inhibiting parts of the renin-angiotensin system.

Interaction studies with warfarin and acenocoumarol have failed to identify any clinically important effects of benazepril on the serum concentrations or clinical effects of these anticoagulants.

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.

Hydrochlorothiazide

Ion Exchange Resins

Stagger the dosage of hydrochlorothiazide and ion exchange resins such that hydrochlorothiazide is administered at least 4 hours before or 4 to 6 hours after the administration of 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%, respectively.

Digitalis Glycosides

Thiazide-induced hypokalemia or hypomagnesemia may predispose the patients to digoxin toxicity

Skeletal Muscle Relaxants

Possible increased responsiveness to muscle relaxants such as curare derivatives.

Antidiabetic Agents

Dosage adjustment of antidiabetic drug may be required.

Antineoplastic Agents (e.g., cyclophosphamide, methotrexate)

Concomitant use of thiazide diuretics may reduce renal excretion of cytotoxic agents and enhance their myelosuppressive effects.

Drugs That Alter Gastrointestinal Motility

The bioavailability of thiazide-type diuretics may be increased by anticholinergic agents (e.g., atropine, biperiden), apparently due to a decrease in gastrointestinal motility and the stomach emptying rate. Conversely, pro-kinetic drugs may decrease the bioavailability of thiazide diuretics.

Cyclosporin

Concomitant treatment with diuretics may increase the risk of hyperuricaemia and gout-type complications.

Alcohol, Barbiturates Or Narcotics

Concomitant administration of thiazide diuretics with alcohol, barbiturates, or narcotics may potentiate orthostatic hypotension.

Pressor Amines

Hydrochlorothiazide may reduce the response to pressor amines such as noradrenaline but the clinical significance of this effect is not sufficient to preclude their use.

Read the entire FDA prescribing information for Lotensin Hct (Benazepril HCl and HCTZ)