Label Changes for:
Lotensin HCT (benazepril HCl and hydrochlorothiazide) Tablets
Changes have been made to the WARNINGS, PRECAUTIONS and ADVERSE REACTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) – June 2011 and February 2012
Impaired Renal Function
- Monitor renal function periodically in patients treated with Lotensin HCT. Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics…Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Lotensin HCT.
- Thiazides can cross the placenta, and concentrations reached in the umbilical vein approach those in the maternal plasma Hydrochlorothiazide, like other diuretics, can cause placental hypoperfusion…Use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice or thrombocytopenia. Since they do not prevent or alter the course of EPH (Edema, Proteinuria, Hypertension) gestosis (pre-eclampsia), these drugs must not be used to treat hypertension in pregnant women. The use of hydrochlorothiazide for other indications (e.g. heart disease) in pregnancy should be avoided.
Serum Electrolyte Abnormalities
- …Hydrochlorothiazide can cause hypokalemia and hyponatremia. Hypomagnesema can result in hypokalemia which appears difficult to treat despite potassium repletion. Drugs that inhibit the renin-angiotensin system can cause hyperkalemia. Monitor serum electrolytes periodically.
Metabolic Disturbances: Hydrochlorothiazide
- Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides…may raise the serum uric acid level due to reduced clearance of uric acid and may cause or exacerbate hyperuricemia and precipitate gout in susceptible patients.
- Thiazides decrease urinary calcium excretion and may cause mild elevation of serum calcium. Avoid using Lotensin HCT in patients with hypercalcemia.
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.
- Lithium: Renal clearance of lithium is reduced by thiazides and increase the risk of lithium toxicity…Monitor lithium levels when used concomitantly with Lotensin HCT.
- Ion exchange resins: Stagger the dosage of hydrochlorothiazide and ion exchange resins such that hydrochlorothiazide is administered at least 4 hours before or 4-6 hours after the administration of resins…
- 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.
Non-clinical safety data
Carcinogenesis, Mutagenicity, Fertility
- Fertility: There are no human fertility data for hydrochlorothiazide…
Use In Specific Populations
- Safety and effectiveness of Lotensin HCT in patients with severe renal impairment (CrCL ≤ 30 ml/min) have not been established. No dose adjustment is required in patients with mild (CrCL 60-90 ml/min) or moderate (CrCL 30-60) renal impairment.
- No adjustment of the initial dose is required for patients with mild to moderate hepatic impairment
- Hydrochlorothiazide: Minor alterations of fluid and electrolyte imbalance may precipitate hepatic coma in patients with impaired hepatic function or progressive liver disease.
- The following adverse reactions have been identified during post-approval use of either benazapril 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:
- Metabolic: … pyrexia, asthenia, parathyroid gland changes with hypercalcemia and hypophosphatemia.
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, co-administration 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 ACE inhibitors, including benazepril may be attenuated by NSAIDs.