Drug Interaction Report

ADJUST DOSE: The central nervous system and respiratory depressant effects of meperidine may be potentiated by concomitant use of other agents with CNS depressant effects. An increased risk of serious adverse reactions such as respiratory depression, hypotension, profound sedation, syncope, coma, and even death should be considered, particularly in elderly or debilitated patients.

MANAGEMENT: Caution and dosage adjustments are advisable when meperidine is used in combination with other narcotic analgesics, general anesthetics, phenothiazines, sedative-hypnotics, tranquilizers, tricyclic antidepressants, or other CNS depressants such as alcohol. A lower dosage of meperidine should be considered initially, then titrated carefully according to pain level and clinical response. Meperidine dosage reductions of 25% to 50% have been recommended for patients receiving phenothiazines and other tranquilizers. Patients should be advised to avoid rising abruptly from a sitting or recumbent position, and to notify their physician if they experience dizziness, lightheadedness, orthostasis, syncope, tachycardia, or excessive CNS effects that interfere with their normal activities. Patients should also avoid driving or operating hazardous machinery until they know how these medications affect them.

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. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

MONITOR: Phenothiazines, tricyclic antidepressants (TCAs), and some antipsychotic (neuroleptic) agents may potentiate the blood pressure lowering capabilities of other drugs with hypotensive effects due to their peripheral alpha-1 adrenergic blocking activity. Orthostatic hypotension and syncope associated with vasodilation may occur, particularly during initial dosing and/or parenteral administration of the phenothiazine, TCA, or neuroleptic. The severity of this interaction may be affected by the agent's affinity for the alpha-1 adrenoceptor. One in vitro study demonstrated an affinity for the alpha-1 adrenoceptor for some of these medications that was similar to, or greater than, those of alpha blocker medications used to treat hypertension. Examples of drugs evaluated in this study with a high affinity included amitriptyline, clomipramine, chlorpromazine, clozapine, doxepin, flupenthixol, lurasidone, nortriptyline, perphenazine, paliperidone, quetiapine, risperidone, sertindole, and ziprasidone. On the other hand, examples of those with lower affinities included aripiprazole, lofepramine, protriptyline, sulpiride, and amisulpride.

MANAGEMENT: Close clinical monitoring for development of hypotension is recommended if phenothiazines, tricyclic antidepressants (TCAs), or certain antipsychotic (neuroleptic) agents are used in patients receiving antihypertensive medications or vasodilators. A lower starting dosage and slower titration of the phenothiazine, TCA, or neuroleptic may be appropriate, especially in the elderly. It may also be advisable to consider using a phenothiazine, TCA, or neuroleptic medication with a lower affinity for the alpha-1 adrenoceptor when possible. Patients should be counseled to avoid rising abruptly from a sitting or recumbent position and to notify their healthcare provider if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

GENERALLY AVOID: Moderate-to-high dietary intake of potassium can cause hyperkalemia in some patients who are using angiotensin converting enzyme (ACE) inhibitors. In some cases, affected patients were using a potassium-rich salt substitute. ACE inhibitors can promote hyperkalemia through inhibition of the renin-aldosterone-angiotensin (RAA) system.

ADJUST DOSING INTERVAL: Administration with food decreased the biotransformation of perindopril to its active metabolite, perindoprilat, resulting in a decrease of perindoprilat bioavailability by 35% and a reduction in the plasma ACE inhibition curve of approximately 20%. When administered as part of a combination product with amlodipine and taken with food, perindopril and perindoprilat absorption rates have decreased by 18% and 14%, respectively, versus fasting. No effect of food on the extent of unmetabolized perindopril absorption has been observed.

MANAGEMENT: It is recommended that patients who are taking ACE inhibitors be advised to avoid moderately high or high potassium dietary intake. Particular attention should be paid to the potassium content of salt substitutes. Some authorities recommend administering perindopril before a meal, preferably in the morning. According to the prescribing information, the combination product containing perindopril and amlodipine may be taken with or without food.

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.

GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.