Drug Interactions between bendroflumethiazide / nadolol and methoxsalen

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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GENERALLY AVOID: The ingestion of foods containing photosensitizing components (e.g., limes, figs, parsley, parsnips, rue (Ruta graveolens), mustard, carrots and celery) may increase the risk of photosensitivity and severe burning during methoxsalen therapy. Two cases of photosensitivity involving rue and a soup containing celery, parsley, and parsnip have been reported in PUVA patients.

MANAGEMENT: Patients who are undergoing PUVA treatment and taking methoxsalen should be advised to avoid eating large quantities of these foods.

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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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