Drug Interactions between bendroflumethiazide / nadolol and Byetta

GENERALLY AVOID: Coadministration with green tea may significantly decrease the plasma concentrations of nadolol. The mechanism of interaction has not been established, but may involve inhibition of OATP1A2-mediated uptake of nadolol in the intestine by catechins in green tea. In a study with ten healthy volunteers, administration of a single 30 mg oral dose of nadolol following repeated consumption of green tea (700 mL/day for 14 days) resulted in decreases of 85% in nadolol peak plasma concentration (Cmax) and systemic exposure (AUC) compared to administration with water. The renal clearance of nadolol was not altered. Green tea also markedly reduced the effects of nadolol on systolic blood pressure.

MANAGEMENT: Based on available data, patients should be advised to limit their consumption of green tea and green tea extracts during treatment with nadolol.

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ADJUST DOSING INTERVAL: Exenatide slows gastric emptying and may reduce the extent and rate of absorption of concomitantly administered oral medications. When acetaminophen 1000 mg was administered simultaneously with exenatide 10 mcg and also one hour, 2 hours, and 4 hours after exenatide injection, acetaminophen systemic exposure (AUC) was decreased by 21%, 23%, 24%, and 14%, respectively; peak plasma concentration (Cmax) was decreased by 37%, 56%, 54%, and 41%, respectively; and time to peak plasma concentration (Tmax) was increased from 0.6 hours in the control period to 0.9 hours, 4.2 hours, 3.3 hours, and 1.6 hours, respectively. These values were not significantly changed when acetaminophen was given one hour before exenatide injection.

MANAGEMENT: Concomitantly administered oral medications that are dependent on threshold concentrations for efficacy (e.g., antibiotics, contraceptives) or that require rapid gastrointestinal absorption (e.g., hypnotics, pain medications) should be administered at least 1 hour before exenatide. If such medications are to be administered with food, patients should be advised to take them with a meal or snack when exenatide is not administered.

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MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

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MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

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ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.

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