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Drug Interactions between amitriptyline and Guaifenex

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

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Interactions between your drugs

Major

amitriptyline phenylephrine

Applies to: amitriptyline and Guaifenex (guaifenesin / phenylephrine / phenylpropanolamine)

GENERALLY AVOID: Tricyclic antidepressants (TCAs) may markedly enhance the pressor response to parenteral direct-acting sympathomimetic agents and vasoconstrictor-containing local anesthetics. Several-fold increases in the effects of norepinephrine and, to a lesser extent, epinephrine and phenylephrine were reported in healthy subjects pretreated with desipramine, imipramine, or nortriptyline. The mechanism is TCA inhibition of norepinephrine reuptake in adrenergic neurons, resulting in increased stimulation of adrenergic receptors. Clinically, hypertension, throbbing headache, tremor, palpitation, chest pain, and cardiac dysrhythmia have been reported in association with this interaction. Various TCAs have been implicated including amitriptyline, desipramine, imipramine, nortriptyline, and protriptyline. It is not known whether the interaction also occurs with mixed-acting sympathomimetic agents (e.g., dopamine, ephedrine, metaraminol).

MANAGEMENT: Parenteral administration of direct-acting sympathomimetic agents should preferably be avoided during therapy with tricyclic antidepressants except in cases of emergency (e.g., treatment of anaphylaxis). If concomitant use is necessary, initial dose and rate of administration of the sympathomimetic should be reduced, and cardiovascular status including blood pressure should be monitored closely. Although clinical data are lacking, it may be prudent to follow the same precaution with mixed-acting sympathomimetic agents.

References (11)
  1. Mitchell JR, Cavanaugh JH, Arias L, Oates JA (1970) "Guanethidine and related agents. III: antagonism by drugs which inhibit the norepinephrine pump in man." J Clin Invest, 49, p. 1596-604
  2. Svedmyr N (1968) "The influence of a tricyclic antidepressive agent (protriptyline) on some of the circulatory effects of noradrenaline and adrenaline in man." Life Sci, 7, p. 77-84
  3. Boakes AJ, Laurence DR, Teoh PC, Barar FS, Benedikter LT, Pritchard BN (1973) "Interactions between sympathomimetic amines and antidepressant agents in man." Br Med J, 1, p. 311-5
  4. Borg KO, Johnsson G, Jordo L, Lundborg P, Ronn O, Welin-Fogelberg I (1979) "Interaction studies between three antidepressant drugs (zimelidine, imipramine and chlorimipramine) and noradrenaline in healthy volunteers and some pharmacokinetics of the drugs studied." Acta Pharmacol Toxicol (Copenh), 45, p. 198-205
  5. Linnoila M, Karoum F, Calil HM, Kopin IJ, Potter WZ (1982) "Alteration of norepinephrine metabolism with desipramine and zimelidine in depressed patients." Arch Gen Psychiatry, 39, p. 1025-8
  6. ed., Boakes AJ. Vasoconstrictors in local anaesthetics and tricyclic antidepressants. In: Grahame-Smith, DG (1977) "Drug Interactions. QV 38 D7932 1975." Baltimore, MD: University Park Press, p. 275-83
  7. Fritz H, Hagstam KE, Lindqvist B (1965) "Local skin necrosis after intravenous infusion of norepinephrine, and the concept of endotoxinaemia. A clinical study on 10 cases." Acta Med Scand, 178, p. 403-16
  8. Teba L, Schiebel F, Dedhia HV, Lazzell VA (1988) "Beneficial effect of norepinephrine in the treatment of circulatory shock caused by tricyclic antidepressant overdose." Am J Emerg Med, 6, p. 566-8
  9. Goulet JP, Perusse R, Turcotte JY (1992) "Contraindications to vasoconstrictors in dentistry: Part III. Pharmacologic interactions." Oral Surg Oral Med Oral Pathol, 74, p. 692-7
  10. Niemegeers CJ, Lenaerts FM, Artois KS, Janssen PA (1977) "Interaction of drugs with apomorphine, tryptamine and norepinephrine. A new 'in vivo' approach: the ATN-test in rats." Arch Int Pharmacodyn Ther, 227, p. 238-53
  11. Ghose K (1980) "Sympathomimetic amines and tricyclic antidepressant drugs." Neuropharmacology, 19, p. 1251-4
Moderate

amitriptyline phenylpropanolamine

Applies to: amitriptyline and Guaifenex (guaifenesin / phenylephrine / phenylpropanolamine)

MONITOR: The use of tricyclic antidepressants in combination with amphetamines or sympathomimetic appetite suppressants may produce additive cardiovascular effects, increasing the risk of hypertension, cardiac arrhythmias, tachycardia, and fever. The mechanism involves additive pharmacodynamic effects resulting from increased norepinephrine release by sympathomimetic agents and inhibition of norepinephrine reuptake by tricyclic antidepressants. A pharmacokinetic interaction is also possible between tricyclic antidepressants and amphetamines, since many of these agents are metabolized by CYP450 2D6. Increased plasma levels of one or both drugs may occur during coadministration.

MANAGEMENT: Close monitoring of cardiovascular status is recommended for patients receiving this combination. Patients should be advised to promptly report symptoms such as fever, headache, or fast or irregular heartbeats.

References (8)
  1. Raisfeld IH (1972) "Cardiovascular complications of antidepressant therapy: interactions at the adrenergic neuron." Am Heart J, 83, p. 129-33
  2. Limbird LE eds., Gilman AG, Hardman JG (1995) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: McGraw-Hill
  3. Nielsen KK, Flinois JP, Beaune P, Brosen K (1996) "The biotransformation of clomipramine in vitro, identification of the cytochrome p450s responsible for the separate metabolic pathways." J Pharmacol Exp Ther, 277, p. 1659-64
  4. Gunne LM, Antonijevic S, Jonsson J (1975) "Effect of fenfluramine on steady state plasma levels of amitriptyline." Postgrad Med J, 51 Suppl 1, p. 117
  5. Markowitz JS, Patrick KS (2001) "Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder." Clin Pharmacokinet, 40, p. 753-72
  6. Kirchheiner J, Muller G, Meineke I, Wernecke KD, Roots I, Brockmoller J (2003) "Effects of polymorphisms in CYP2D6, CYP2C9, and CYP2C19 on trimipramine pharmacokinetics." J Clin Psychopharmacol, 23, p. 459-66
  7. Kirchheiner J, Meineke I, Muller G, Roots I, Brockmoller J (2002) "Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers." Pharmacogenetics, 12, p. 571-80
  8. Haritos VS, Ghabrial H, Ahokas JT, Ching MS (2000) "Role of cytochrome P450 2D6 (CYP2D6) in the stereospecific metabolism of E- and Z-doxepin." Pharmacogenetics, 10, p. 591-603
Moderate

phenylephrine phenylpropanolamine

Applies to: Guaifenex (guaifenesin / phenylephrine / phenylpropanolamine) and Guaifenex (guaifenesin / phenylephrine / phenylpropanolamine)

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

Drug and food interactions

Moderate

phenylpropanolamine food

Applies to: Guaifenex (guaifenesin / phenylephrine / phenylpropanolamine)

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 (3)
  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
Moderate

amitriptyline food

Applies to: amitriptyline

GENERALLY AVOID: Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

MANAGEMENT: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.

References (7)
  1. Dorian P, Sellers EM, Reed KL, et al. (1983) "Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction." Eur J Clin Pharmacol, 25, p. 325-31
  2. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  3. Sandoz M, Vandel S, Vandel B, Bonin B, Allers G, Volmat R (1983) "Biotransformation of amitriptyline in alcoholic depressive patients." Eur J Clin Pharmacol, 24, p. 615-21
  4. Ciraulo DA, Barnhill JG, Jaffe JH (1988) "Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers." Clin Pharmacol Ther, 43, p. 509-18
  5. Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M (1975) "Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving." Clin Pharmacol Ther, 17, p. 515-22
  6. Ciraulo DA, Barnhill JG, Jaffe JH, Ciraulo AM, Tarmey MF (1990) "Intravenous pharmacokinetics of 2-hydroxyimipramine in alcoholics and normal controls." J Stud Alcohol, 51, p. 366-72
  7. Ciraulo DA, Alderson LM, Chapron DJ, Jaffe JH, Subbarao B, Kramer PA (1982) "Imipramine disposition in alcoholics." J Clin Psychopharmacol, 2, p. 2-7
Moderate

phenylephrine food

Applies to: Guaifenex (guaifenesin / phenylephrine / phenylpropanolamine)

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
Moderate

phenylpropanolamine food

Applies to: Guaifenex (guaifenesin / phenylephrine / phenylpropanolamine)

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
Moderate

amitriptyline food

Applies to: amitriptyline

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.

References (4)
  1. (2024) "Product Information. Cytisine (cytisinicline)." Consilient Health Ltd
  2. jeong sh, Newcombe D, sheridan j, Tingle M (2015) "Pharmacokinetics of cytisine, an a4 b2 nicotinic receptor partial agonist, in healthy smokers following a single dose." Drug Test Anal, 7, p. 475-82
  3. Vaughan DP, Beckett AH, Robbie DS (1976) "The influence of smoking on the intersubject variation in pentazocine elimination." Br J Clin Pharmacol, 3, p. 279-83
  4. Zevin S, Benowitz NL (1999) "Drug interactions with tobacco smoking: an update" Clin Pharmacokinet, 36, p. 425-38

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.

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