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Drug Interaction Report

8 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Moderate

pyrilamine pheniramine

Applies to: pheniramine / phenylpropanolamine / pyrilamine, pheniramine / phenylpropanolamine / pyrilamine

MONITOR: Agents with anticholinergic properties (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; disopyramide) may have additive effects when used in combination. Excessive parasympatholytic effects may result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures. Central nervous system-depressant effects may also be additively or synergistically increased when these agents are combined, especially in elderly or debilitated patients. Use of neuroleptics in combination with other neuroleptics or anticholinergic agents may increase the risk of tardive dyskinesia. In addition, some neuroleptics and tricyclic antidepressants may cause prolongation of the QT interval and theoretically, concurrent use of two or more drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Caution is advised when agents with anticholinergic properties are combined, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A reduction in anticholinergic dosages may be necessary if excessive adverse effects develop.

References

  1. Stadnyk AN, Glezos JD (1983) "Drug-induced heat stroke." Can Med Assoc J, 128, p. 957-9
  2. Zelman S, Guillan R (1970) "Heat stroke in phenothiazine-treated patients: a report of three fatalities." Am J Psychiatry, 126, p. 1787-90
  3. Mann SC, Boger WP (1978) "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry, 135, p. 1097-100
  4. Warnes H, Lehmann HE, Ban TA (1967) "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J, 96, p. 1112-3
  5. Gershon S, Neubauer H, Sundland DM (1965) "Interaction between some anticholinergic agents and phenothiazines." Clin Pharmacol Ther, 6, p. 749-56
  6. Sarnquist F, Larson CP Jr (1973) "Drug-induced heat stroke." Anesthesiology, 39, p. 348-50
  7. Johnson AL, Hollister LE, Berger PA (1981) "The anticholinergic intoxication syndrome: diagnosis and treatment." J Clin Psychiatry, 42, p. 313-7
  8. Lee BS (1986) "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry, 47, p. 571
  9. Forester D (1978) "Fatal drug-induced heat stroke." JACEP, 7, p. 243-4
  10. Moreau A, Jones BD, Banno V (1986) "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry, 31, p. 339-41
  11. Hvizdos AJ, Bennett JA, Wells BG, Rappaport KB, Mendel SA (1983) "Anticholinergic psychosis in a patient receiving usual doses of haloperidol." Clin Pharm, 2, p. 174-8
  12. Cohen MA, Alfonso CA, Mosquera M (1994) "Development of urinary retention during treatment with clozapine and meclizine [published erratum appears in Am J Psychiatry 1994 Jun;151(6):952]." Am J Psychiatry, 151, p. 619-20
  13. (2001) "Product Information. Cogentin (benztropine)." Merck & Co., Inc
  14. Kulik AV, Wilbur R (1982) "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry, 6, p. 75-82
  15. (2001) "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories
View all 15 references

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Moderate

pyrilamine flibanserin

Applies to: pheniramine / phenylpropanolamine / pyrilamine, flibanserin

MONITOR: The central nervous system (CNS) effects of flibanserin such as somnolence and fatigue may be potentiated by concomitant use of other agents with CNS depressant effects. In five 24-week clinical trials, the incidence of somnolence, sedation, or fatigue was 21% and 8% in patients treated with flibanserin 100 mg once daily at bedtime and placebo, respectively. The risk of CNS depression is increased if flibanserin is taken during waking hours or with alcohol or other CNS depressants.

MANAGEMENT: Patients receiving flibanserin with other agents that can cause CNS depression should be apprised of the potential for increased adverse effects such as drowsiness, dizziness, lightheadedness, and fatigue. Patients should not drive, operate machinery, or engage in hazardous activities requiring mental alertness and motor coordination for at least 6 hours after taking flibanserin and until they know how the medication affects them.

References

  1. (2015) "Product Information. Addyi (flibanserin)." Sprout Pharmaceuticals

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Moderate

pheniramine flibanserin

Applies to: pheniramine / phenylpropanolamine / pyrilamine, flibanserin

MONITOR: The central nervous system (CNS) effects of flibanserin such as somnolence and fatigue may be potentiated by concomitant use of other agents with CNS depressant effects. In five 24-week clinical trials, the incidence of somnolence, sedation, or fatigue was 21% and 8% in patients treated with flibanserin 100 mg once daily at bedtime and placebo, respectively. The risk of CNS depression is increased if flibanserin is taken during waking hours or with alcohol or other CNS depressants.

MANAGEMENT: Patients receiving flibanserin with other agents that can cause CNS depression should be apprised of the potential for increased adverse effects such as drowsiness, dizziness, lightheadedness, and fatigue. Patients should not drive, operate machinery, or engage in hazardous activities requiring mental alertness and motor coordination for at least 6 hours after taking flibanserin and until they know how the medication affects them.

References

  1. (2015) "Product Information. Addyi (flibanserin)." Sprout Pharmaceuticals

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Drug and food interactions

Major

flibanserin food

Applies to: flibanserin

CONTRAINDICATED: Grapefruit juice may increase the plasma concentrations of flibanserin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In 26 healthy female subjects, administration of a single 100 mg dose of flibanserin with 240 mL grapefruit juice increased flibanserin peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.1- and 1.4-fold, respectively, compared to administration of flibanserin alone. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

ADJUST DOSING INTERVAL: Coadministration of flibanserin with alcohol may potentiate the risk of severe hypotension, syncope, and central nervous system depression. In a dedicated alcohol interaction study, hypotension or syncope requiring therapeutic intervention (ammonia salts and/or placement in supine or Trendelenberg position) occurred in 4 (17%) of 23 subjects given flibanserin 100 mg with 0.4 g/kg alcohol (equivalent to two 12 ounce cans of beer containing 5% alcohol content, two 5 ounce glasses of wine containing 12% alcohol content, or two 1.5 ounce shots of 80-proof spirit in a 70 kg person) consumed over 10 minutes in the morning. In these four subjects, systolic blood pressure reductions ranged from 28 to 54 mmHg and diastolic blood pressure reductions ranged from 24 to 46 mmHg. In addition, 6 (25%) of 24 subjects coadministered flibanserin with 0.8 g/kg alcohol experienced orthostatic hypotension when standing from a sitting position. Systolic and diastolic blood pressure reductions in these 6 subjects ranged from 22 to 48 mmHg and 0 to 27 mmHg, respectively, with one requiring therapeutic intervention. No adverse events requiring therapeutic intervention were observed when flibanserin or alcohol was administered alone. Somnolence was reported in 67%, 74%, and 92% of subjects who received flibanserin alone, flibanserin with 0.4 g/kg ethanol, and flibanserin with 0.8 g/kg ethanol, respectively. Subsequent data from postmarketing trials showed that the risk of severe hypotension and syncope was reduced when women who consumed up to two alcoholic drinks waited at least two hours before taking flibanserin.

MANAGEMENT: Concomitant use of flibanserin with moderate or potent CYP450 3A4 inhibitors such as grapefruit juice is considered contraindicated. The patient should be advised to avoid the consumption of grapefruit and grapefruit juice during treatment, and to take flibanserin at bedtime to minimize the risk of hypotension, syncope, accidental injury, and central nervous system depression. In addition, patients should consume no more than 1 to 2 alcoholic drinks and discontinue drinking alcohol at least two hours before taking flibanserin at bedtime; otherwise, they should skip the flibanserin dose that evening. Alcohol should not be consumed until at least the morning after taking flibanserin at bedtime. A standard alcoholic drink contains 14 g of pure alcohol and is equivalent to one 12-ounce regular beer (5% alcohol), 5-ounces wine (12% alcohol), or 1.5 ounces of distilled spirits/shot (40% alcohol).

References

  1. (2015) "Product Information. Addyi (flibanserin)." Sprout Pharmaceuticals

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Moderate

phenylpropanolamine food

Applies to: pheniramine / phenylpropanolamine / pyrilamine

GENERALLY AVOID: Alcohol may potentiate the central nervous system and cardiovascular effects of centrally-acting appetite suppressants. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state.

MANAGEMENT: Concomitant use of centrally-acting appetite suppressants and alcohol should be avoided if possible, especially in patients with a history of cardiovascular disease. Patients should be counselled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Mendelson J, Jones RT, Upton R, Jacob P 3rd (1995) "Methamphetamine and ethanol interactions in humans." Clin Pharmacol Ther, 57, p. 559-68
  2. (2001) "Product Information. Didrex (benzphetamine)." Pharmacia and Upjohn
  3. (2012) "Product Information. Suprenza (phentermine)." Akrimax Pharmaceuticals

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Moderate

pyrilamine food

Applies to: pheniramine / phenylpropanolamine / pyrilamine

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
View all 4 references

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Moderate

pheniramine food

Applies to: pheniramine / phenylpropanolamine / pyrilamine

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
View all 4 references

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Moderate

phenylpropanolamine food

Applies to: pheniramine / phenylpropanolamine / pyrilamine

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References

  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
  3. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  4. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  5. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  6. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  7. (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
View all 7 references

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Therapeutic duplication warnings

No duplication warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

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Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.