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Drug Interactions between Anafranil and dyphylline / ephedrine / guaifenesin / phenobarbital

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

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Interactions between your drugs

Major

ePHEDrine clomiPRAMINE

Applies to: dyphylline / ephedrine / guaifenesin / phenobarbital and Anafranil (clomipramine)

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

  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
View all 11 references

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Moderate

PHENobarbital clomiPRAMINE

Applies to: dyphylline / ephedrine / guaifenesin / phenobarbital and Anafranil (clomipramine)

MONITOR: Tricyclic antidepressants may counteract the anticonvulsive effects of barbiturates by lowering the seizure threshold. Barbiturates may decrease the serum levels and effects of tricyclic antidepressants by induction of hepatic metabolism. In addition, the respiratory-depressant effects of both agents may be increased due to additive pharmacologic effects.

MANAGEMENT: If the barbiturate is being taken for a seizure disorder, patients should be closely monitored for loss of seizure control. Dose adjustments may be required. Monitoring for clinical evidence of additive toxicity and for clinical and/or laboratory evidence of reduced antidepressant effect is also advisable.

References

  1. Crocker J, Morton B (1969) "Tricyclic (antidepressant) drug toxicity." Clin Toxicol, 2, p. 397-402
  2. Burrows GD, Davies B (1971) "Antidepressants and barbiturates." Br Med J, 4, p. 113
  3. Silverman G, Braithwaite R (1972) "Interaction of benzodiazepines with tricyclic antidepressants." Br Med J, 4, p. 111
  4. Spina E, Avenoso A, Campo GM, Caputi AP, Perucca E (1996) "Phenobarbital induces the 2-hydroxylation of desipramine." Ther Drug Monit, 18, p. 60-4
  5. Garey KW, Amsden GW, Johns CA (1997) "Possible interaction between imipramine and butalbital." Pharmacotherapy, 17, p. 1041-2
View all 5 references

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Minor

ePHEDrine dyphylline

Applies to: dyphylline / ephedrine / guaifenesin / phenobarbital and dyphylline / ephedrine / guaifenesin / phenobarbital

Ephedrine-methylxanthine combinations are used for the treatment of asthma but the efficacy of the combination has been questioned. This combination may lead to increased xanthine side effects. The mechanism is unknown, but may be related to synergistic pharmacologic effects. Patients using this combination should be closely monitored for side effects such as nausea, vomiting, tachycardia, nervousness, or insomnia. If side effects are noted, the dosage of the xanthine may need to be decreased.

References

  1. Weinberger M, Bronsky E, Bensch GW, Bock GN, Yecies JJ (1975) "Interaction of ephedrine and theophylline." Clin Pharmacol Ther, 17, p. 585-92
  2. Sims JA, doPico GA, Reed CE (1978) "Bronchodilating effect of oral theophylline-ephedrine combination." J Allergy Clin Immunol, 62, p. 15-21
  3. Tinkelman DG, Avner SE (1977) "Ephedrine therapy in asthmatic children. Clinical tolerance and absence of side effects." JAMA, 237, p. 553-7
  4. Weinberger MM, Brousky EA (1974) "Evaluation of oral bronchodilator therapy in asthmatic children: bronchodilators in asthmatic children." J Pediatr, 84, p. 421-7
  5. Badiei B, Faciane J, Sly M (1975) "Effect of throphylline, ephedrine and theri combination upon exercise-induced airway obstruction." Ann Allergy, 35, p. 32-6
View all 5 references

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Drug and food interactions

Major

PHENobarbital food

Applies to: dyphylline / ephedrine / guaifenesin / phenobarbital

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

References

  1. Gupta RC, Kofoed J (1966) "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J, 94, p. 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS (1971) "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med, 51, p. 346-51
  3. Saario I, Linnoila M (1976) "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh), 38, p. 382-92
  4. Stead AH, Moffat AC (1983) "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol, 2, p. 5-14
  5. Seixas FA (1979) "Drug/alcohol interactions: avert potential dangers." Geriatrics, 34, p. 89-102
View all 5 references

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Moderate

clomiPRAMINE food

Applies to: Anafranil (clomipramine)

MONITOR: Limited data suggest that the administration of clomipramine with grapefruit juice or cranberry juice may significantly increase plasma drug concentrations of clomipramine. Clomipramine is initially demethylated by CYP450 1A2, 3A3 and 3A4 before undergoing further metabolism to 8-hydroxyclomipramine. The increase in clomipramine bioavailability may stem from inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The precise mechanism by which cranberry juice exerts its effects is unknown, but may involve inhibition of CYP450 isoenzymes. This interaction has occasionally been exploited in attempts to improve symptomatic control of obsessive compulsive disorder.

MANAGEMENT: Patients receiving clomipramine therapy who ingest cranberry juice, grapefruits, or grapefruit juice should be monitored for adverse effects and undue fluctuations in plasma drug levels.

References

  1. Oesterheld J, Kallepalli BR (1997) "Grapefruit juice and clomipramine: shifting metabolitic ratios." J Clin Psychopharmacol, 17, p. 62-3
  2. 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
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Cerner Multum, Inc. "Australian Product Information."
View all 4 references

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Moderate

clomiPRAMINE food

Applies to: Anafranil (clomipramine)

GENERALLY AVOID: The combination of ethanol and a tricyclic antidepressant may result in additive impairment of motor skills, especially driving skills. Also, one study has suggested that clomipramine metabolism is significantly impaired for several weeks or more following discontinuation of chronic alcohol consumption.

MANAGEMENT: Patients should be warned of this interaction and advised to limit their ethanol intake while taking tricyclic antidepressants. Monitoring for TCA toxicity (CNS depression, excessive anticholinergic effects, hypotension, arrhythmias) is recommended during alcohol withdrawal.

References

  1. 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
  2. Berlin I, Cournot A, Zimmer R, et al. (1990) "Evaluation and comparison of the interaction between alcohol and moclobemide or clomipramine in healthy subjects." Psychopharmacology (Berl), 100, p. 40-5
  3. Balant-Gorgia AE, Gay M, Gex-Fabry M, Balant LP (1992) "Persistent impairment of clomipramine demethylation in recently detoxified alcoholic patients." Ther Drug Monit, 14, p. 119-24

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Moderate

ePHEDrine food

Applies to: dyphylline / ephedrine / guaifenesin / phenobarbital

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 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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