Drug Interactions between canagliflozin and hydrochlorothiazide / propranolol

Using propranolol and hydroCHLOROthiazide together may lower your blood pressure and slow your heart rate. This can cause dizziness, or feeling like you might pass out, weakness, fainting, fast or irregular heartbeats, or loss of blood glucose control. If you take both medications together, tell your doctor if you have any of these symptoms. You may need a dose adjustment or need your blood pressure checked more often to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Consumer information for this interaction is not currently available.

MONITOR: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors may potentiate the hypotensive effects of antihypertensive agents, including beta-blockers. Inhibition of glucose and sodium co-transport produces mild diuresis and transient natriuresis, resulting in intravascular volume contraction. Volume depletion-related adverse reactions including hypotension, postural dizziness, orthostatic hypotension, syncope, and dehydration can occur after initiating treatment with SGLT-2 inhibitors, and the risk may be increased with concomitant use of other agents that can lower blood pressure.

MONITOR: Beta-blockers may inhibit some of the normal physiologic responses to hypoglycemia, which, when combined with antidiabetic agents such as sodium-glucose co-transporter 2 (SGLT-2) inhibitors, may potentiate the risk for adverse events. Symptoms of hypoglycemia, such as tremors and tachycardia, may be absent, making it more difficult for patients to recognize an oncoming episode. In addition, multiple effects on glucose metabolism have been reported, usually with the noncardioselective beta-blockers (e.g., propranolol, pindolol, timolol) but occasionally also with relatively beta-1 selective agents (e.g., atenolol, metoprolol, nebivolol). Specifically, inhibition of catecholamine-mediated glycogenolysis and glucose mobilization in association with beta-blockade can potentiate insulin-induced hypoglycemia in diabetics and delay the recovery of normal blood glucose levels. Prolonged and severe hypoglycemia may occur, although these events have rarely been reported. Significant increases in blood pressure and bradycardia can also occur during hypoglycemia in diabetics treated with insulin and beta-blockers due to the antagonism of epinephrine's effect on beta-2 adrenergic receptors, which leads to unopposed alpha-adrenergic effects, including vasoconstriction. On the other hand, decreased glucose tolerance and decreased glucose-induced insulin secretion have also been reported with various beta-blockers. For example, cardioselective beta-blockers like atenolol have been noted to increase insulin resistance while others such as metoprolol and the noncardioselective propranolol are known to increase hepatic glycogenolysis and gluconeogenesis, which may contribute to hyperglycemia. However, beta-blockers with intrinsic sympathomimetic activity and alpha-adrenergic activity, such as pindolol, or those with alpha-blocking effects, such as carvedilol, are reported to have a lesser impact on insulin sensitivity and may even have neutral or mildly positive effects on glycemic control due to vasodilating and insulin-sensitizing effects. The extent to which these opposing effects manifest clinically and whether one effect will predominate are unclear.

MANAGEMENT: Caution is advised if SGLT-2 inhibitors are coadministered with beta-blockers, particularly in the elderly and patients with impaired renal function. Prior to initiating SGLT-2 inhibitors, volume status should be assessed and corrected, if necessary. If volume depletion occurs, treatment with SGLT-2 inhibitors should be interrupted until the condition is corrected. Clinical and laboratory monitoring are recommended during therapy, including electrolytes, fluid status, renal function, and blood pressure. In addition, cardioselective beta-blockers are generally considered safer than noncardioselective agents in the treatment of diabetic patients. Nevertheless, caution is advised if they are prescribed to patients on SGLT-2 inhibitor therapy, as cardioselectivity is not absolute and larger doses of beta-1 selective agents may pose some of the same risks as nonselective agents. Patients should be advised of the need for regular blood glucose monitoring, due to the potential for developing hypoglycemia or hyperglycemia. They should also be made aware that certain symptoms of hypoglycemia such as tremor and tachycardia may be masked. However, other symptoms such as headache, dizziness, drowsiness, confusion, nausea, hunger, weakness, and perspiration may be unaffected. The same precautions are applicable in diabetic patients treated with ophthalmic beta-blockers.

Canagliflozin may add to the diuretic effects of hydroCHLOROthiazide. This may increase the risk of dehydration, kidney problems, and low blood pressure. You may experience headache, dizziness, lightheadedness, fainting, and/or changes in pulse or heart rate. Use caution when getting up from a sitting or lying position, and let your doctor know if you develop these symptoms. Keep yourself hydrated by drinking plenty of fluids unless otherwise directed. You should seek medical advice immediately if you have reduced oral intake (for example, due to acute illness) or increased fluid loss (for example, due to vomiting, diarrhea, or excessive heat exposure), as it may be appropriate to interrupt one or both medications temporarily under these circumstances. In addition, hydroCHLOROthiazide may interfere with blood glucose control and reduce the effectiveness of canagliflozin and other diabetic medications. Monitor your blood sugar levels closely. You may need a dose adjustment of your diabetic medications during and after treatment with hydroCHLOROthiazide. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.