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Drug Interactions between perphenazine and pseudoephedrine / terfenadine

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

terfenadine perphenazine

Applies to: pseudoephedrine / terfenadine and perphenazine

MONITOR: 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. The risk of an individual agent or a combination of these agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Caution and clinical monitoring are recommended if multiple agents associated with QT interval prolongation are prescribed together. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References (7)
  1. Glassman AH, Bigger JT Jr (2001) "Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death." Am J Psychiatry, 158, p. 1774-82
  2. Witchel HJ, Hancox JC, Nutt DJ (2003) "Psychotropic drugs, cardiac arrhythmia, and sudden death." J Clin Psychopharmacol, 23, p. 58-77
  3. Iannini PB (2002) "Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval." Expert Opin Drug Saf, 1, p. 121-8
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  5. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  6. Cerner Multum, Inc. "Australian Product Information."
  7. EMA. European Medicines Agency. European Union (2013) EMA - List of medicines under additional monitoring. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852
Moderate

pseudoephedrine perphenazine

Applies to: pseudoephedrine / terfenadine and perphenazine

GENERALLY AVOID: Phenothiazines may antagonize the pharmacologic effects of amphetamine, amphetamine derivatives, and other centrally-acting sympathomimetic agents (i.e., CNS stimulants). Conversely, these agents may diminish the neuroleptic efficacy of phenothiazines. The exact mechanism of interaction is unknown but may involve opposing effects on dopaminergic activity. Several clinical studies have demonstrated the reduction or lack of effect of amphetamines on weight loss in obese psychiatric patients treated with chlorpromazine and other neuroleptic agents. In one of these studies, dextroamphetamine also had no effect on sleep patterns. As for the reverse interaction, it is uncertain whether CNS stimulants actually antagonize the neuroleptic effect of phenothiazines, since CNS stimulants alone have been reported to cause or aggravate preexisting psychotic symptoms. Finally, it is conceivable that, because of their sympathomimetic effects, CNS stimulants may also potentiate the arrhythmogenicity of phenothiazines. A case of fatal ventricular arrhythmia was reported in a patient treated chronically with thioridazine who ingested a single capsule containing phenylpropanolamine 50 mg and chlorpheniramine 4 mg. However, a causal relationship was not established.

MANAGEMENT: Amphetamine, amphetamine derivatives, and other CNS stimulants should generally not be used, particularly for weight reduction, in patients treated with phenothiazines.

References (34)
  1. Reid AA (1964) "Pharmacological antagonism between chlorpromazine and phenmetrazine in mental hospital patients." Med J Aust, 1, p. 187-8
  2. Sletten IW, Ognjanov V, Menendez S, Sundland D, El-Toumi A (1967) "Weight reduction with chlorphentermine and phenmetrazine in obese psychiatric patients during chlorpromazine therapy." Curr Ther Res Clin Exp, 9, p. 570-5
  3. Chouinard G, Ghadirian AM, Jones BD (1978) "Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac*C capsule." Can Med Assoc J, 119, p. 729-31
  4. Casey JF, Hollister LE, Klett CJ, Lasky JJ, Caffey EM (1961) "Combined drug therapy of chronic schizophrenics." Am J Psychiatry, 177, p. 997
  5. Modell W, Hussar AE (1965) "Failure of dextroamphetamine sulfate to incluence eating and sleeping patterns in obese schizophrenic patients." JAMA, 193, p. 275-8
  6. Angrist B, Lee HK, Gershon S (1974) "The antagonism of amphetamine-induced symptomatology by a neuroleptic." Am J Psychiatry, 131, p. 817-9
  7. Cornelius JR, Soloff PH, Reynolds CF, 3d (1984) "Paranoia, homicidal behavior, and seizures associated with phenylpropanolamine." Am J Psychiatry, 141, p. 120-1
  8. Achor MB, Extein I (1981) "Diet aids, mania, and affective illness" Am J Psychiatry, 138, p. 392
  9. Schaffer CB, Pauli MW (1980) "Psychotic reaction caused by proprietary oral diet agents." Am J Psychiatry, 137, p. 1256-7
  10. Grieger TA, Clayton AH, Goyer PF (1990) "Affective disorder following use of phenylpropanolamine" Am J Psychiatry, 147, p. 367-8
  11. Dietz AJ, Jr (1981) "Amphetamine-like reactions to phenylpropanolamine." JAMA, 245, p. 601-2
  12. Norvenius G, Widerlov E, Lonnerholm G (1979) "Phenylpropanolamine and mental disturbances" Lancet, 2, p. 1367-8
  13. Mueller SM (1983) "Neurologic complications of phenylpropanolamine use." Neurology, 33, p. 650-2
  14. Lake CR, Tenglin R, Chernow B, Holloway HC (1983) "Psychomotor stimulant-induced mania in a genetically predisposed patient: a review of the literature and report of a case." J Clin Psychopharmacol, 3, p. 97-100
  15. Lake CR (1991) "Manic psychosis after coffee and phenylpropanolamine." Biol Psychiatry, 30, p. 401-4
  16. Lambert MT (1987) "Paranoid psychoses after abuse of proprietary cold remedies." Br J Psychiatry, 151:, p. 548-50
  17. Wharton BK (1970) "Nasal decongestants and paranoid psychosis." Br J Psychiatry, 117, p. 439-40
  18. Dewsnap P, Libby G (1992) "A case of affective psychosis after routine use of proprietary cold remedy containing phenylpropanolamine" Hum Exp Toxicol, 11, p. 295-6
  19. Finton CK, Barton M, Chernow B (1982) "Possible adverse effects of phenylpropanolamine (diet pills) on sympathetic nervous system function--caveat emptor!" Mil Med, 147, p. 1072
  20. Stroe AE, Hall J, Amin F (1995) "Psychotic episode related to phenylpropanolamine and amantadine in a healthy female." Gen Hosp Psychiatry, 17, p. 457-8
  21. Marshall RD, Douglas CJ (1994) "Phenylpropanolamine-induced psychosis: potential predisposing factors." Gen Hosp Psychiatry, 16, p. 358-60
  22. (2001) "Product Information. Fastin (phentermine)." SmithKline Beecham
  23. (2001) "Product Information. Cylert (pemoline)." Abbott Pharmaceutical
  24. (2001) "Product Information. Ritalin (methylphenidate)." Novartis Pharmaceuticals
  25. (2001) "Product Information. Desoxyn (methamphetamine)." Abbott Pharmaceutical
  26. (2001) "Product Information. Dexedrine (dextroamphetamine)." SmithKline Beecham
  27. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  28. (2001) "Product Information. Didrex (benzphetamine)." Pharmacia and Upjohn
  29. (2001) "Product Information. Prelu-2 (phendimetrazine)." Boehringer-Ingelheim
  30. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  31. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  32. Markowitz JS, Patrick KS (2001) "Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder." Clin Pharmacokinet, 40, p. 753-72
  33. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  34. (2007) "Product Information. Vyvanse (lisdexamfetamine)." Shire US Inc

Drug and food interactions

Major

terfenadine food

Applies to: pseudoephedrine / terfenadine

CONTRAINDICATED: The consumption of grapefruit juice has been associated with significantly increased plasma concentrations of terfenadine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. Terfenadine in high serum levels has been associated with prolongation of the QT interval and development of torsade de pointes, a potentially fatal ventricular arrhythmia.

MANAGEMENT: Due to the risk of cardiotoxicity, patients receiving the drug should be advised to avoid consumption of grapefruit products. Loratadine, cetirizine, and fexofenadine may be safer alternatives in patients who may have trouble adhering to the dietary restriction.

References (17)
  1. Honig PK, Woosley RL, Zamani K, Conner DP, Cantilena LR Jr (1992) "Changes in the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine with concomitant administration of erythromycin." Clin Pharmacol Ther, 52, p. 231-8
  2. Zimmermann M, Duruz H, Guinand O, et al. (1992) "Torsades de Pointes after treatment with terfenadine and ketoconazole." Eur Heart J, 13, p. 1002-3
  3. Mathews DR, McNutt B, Okerholm R, et al. (1991) "Torsades de pointes occurring in association with terfenadine use." JAMA, 266, p. 2375-6
  4. Monahan BP, Ferguson CL, Killeavy ES, et al. (1990) "Torsades de pointes occurring in association with terfenadine use." JAMA, 264, p. 2788-90
  5. Honig PK, Wortham DC, Zamani K, et al. (1993) "Terfenadine-ketoconazole interaction: pharmacokinetic and electrocardiographic consequences." JAMA, 269, p. 1513-8
  6. Pohjola-Sintonen S, Viitasalo M, Toivonene L, Neuvonen P (1993) "Torsades de pointes after terfenadine-itraconazole interaction." BMJ, 306, p. 186
  7. Cortese LM, Bjornson DC (1992) "Potential interaction between terfenadine and macrolide antibiotics." Clin Pharm, 11, p. 675
  8. Paris DG, Parente TF, Bruschetta HR, Guzman E, Niarchos AP (1994) "Torsades-de-pointes induced by erythromycin and terfenadine." Am J Emerg Med, 12, p. 636-8
  9. Zechnich AD, Haxby DG (1996) "Drug interactions associated with terfenadine and related nonsedating antihistamines." West J Med, 164, p. 68-9
  10. Honig PK, Wortham DC, Lazarev A, Cantilena LR (1996) "Grapefruit juice alters the systemic bioavailability and cardiac repolarization of terfenadine in poor metabolizers of terfenadine." J Clin Pharmacol, 36, p. 345-51
  11. Woosley RL (1996) "Cardiac actions of antihistamines." Annu Rev Pharmacol Toxicol, 36, p. 233-52
  12. Benton RE, Honig PK, Zamani K, Cantilena LR, Woosley RL (1996) "Grapefruit juice alters terfenadine pharmacokinetics resulting in prolongation of repolarization on the electrocardiogram." Clin Pharmacol Ther, 59, p. 383-8
  13. Hsieh MH, Chen SA, Chiang CE, et al. (1996) "Drug-induced torsades de pointes in one patient with congenital long QT syndrome." Int J Cardiol, 54, p. 85-8
  14. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
  15. Rau SE, Bend JR, Arnold JMO, Tran LT, Spence JD, Bailey DG (1997) "Grapefruit juice terfenadine single-dose interaction: Magnitude, mechanism, and relevance." Clin Pharmacol Ther, 61, p. 401-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  17. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
Moderate

perphenazine food

Applies to: perphenazine

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.

References (2)
  1. Lutz EG (1976) "Neuroleptic-induced akathisia and dystonia triggered by alcohol." JAMA, 236, p. 2422-3
  2. Freed E (1981) "Alcohol-triggered-neuroleptic-induced tremor, rigidity and dystonia." Med J Aust, 2, p. 44-5
Moderate

pseudoephedrine food

Applies to: pseudoephedrine / terfenadine

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 (7)
  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

Therapeutic duplication warnings

No 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.

Further information

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

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