Drug Interactions between Aldoril D50 and aspirin / pentazocine

MONITOR: Smoking tobacco may decrease the plasma concentrations and effects of pentazocine by enhancing its metabolic clearance.

MANAGEMENT: The possibility of reduced therapeutic effects of pentazocine should be considered in smokers.

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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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GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

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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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GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.

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ADJUST DOSING INTERVAL: The oral bioavailability and pharmacologic effects of methyldopa may be decreased during concurrent administration with iron-containing products. The proposed mechanism is chelation of methyldopa by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In one study, five hypertensive patients receiving chronic methyldopa therapy (250 mg to 1500 mg daily) all had elevated blood pressure following the addition of ferrous sulfate 325 mg three times daily for 2 weeks. The systolic pressure had increased by more than 15 mmHg in three of the patients and the diastolic pressure increased by more than 10 mmHg in two. Blood pressure returned to baseline within 7 days of discontinuing the iron. In 12 normal subjects, administration of methyldopa 500 mg with ferrous sulfate 325 mg or ferrous gluconate 600 mg resulted in an 88% and 79% reduction, respectively, in the renal excretion of unmetabolized, free methyldopa compared to administration of methyldopa alone. In another study, administration of ferrous sulfate simultaneously with methyldopa reduced the bioavailability of methyldopa by 83%, while administration one hour or two hours before methyldopa reduced its bioavailability by 55% and 42%, respectively.

MANAGEMENT: Until more information is available, patients receiving methyldopa in combination with iron-containing products should be advised to separate the times of administration by as much as possible. Patients should be monitored closely for altered hypertensive effect and methyldopa dosage increased as necessary. Selection of an alternative antihypertensive therapy may be necessary.

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One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

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