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Drug Interactions between fluvoxamine and Theolair

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

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Interactions between your drugs

Major

theophylline fluvoxaMINE

Applies to: Theolair (theophylline) and fluvoxamine

GENERALLY AVOID: Coadministration with fluvoxamine may significantly increase the serum concentrations of theophylline and the associated risk of toxicity. The mechanism is fluvoxamine inhibition of theophylline metabolism via CYP450 1A2. Case reports and pharmacokinetic studies indicate that fluvoxamine 50 to 100 mg/day can reduce the clearance of theophylline by 50% to 70%, resulting in toxic theophylline levels and/or clinical toxicity in some patients. Two- to fourfold increases in theophylline serum levels or systemic exposure (AUC) and half-life have been reported, with onset of clinical toxicity as early as two to three days and typically within a week of initiating fluvoxamine. Patients with liver dysfunction may be less susceptible to the interaction. In a study consisting of 10 healthy subjects, 10 subjects with mild hepatic impairment (Child class A) and 10 subjects with severe hepatic impairment (Child class C), fluvoxamine-induced inhibition of theophylline clearance was reduced from 62% in healthy subjects to 52% and 12% in subjects with mild and severe cirrhosis, respectively. These differences may be due to reduced hepatic uptake of fluvoxamine as well as reduced hepatic expression of CYP450 1A2 in the cirrhotic liver.

MANAGEMENT: The use of theophylline or its salts in combination with fluvoxamine should generally be avoided. If coadministration is required, a reduction of theophylline dosage by one-half to two-thirds should be considered. Pharmacologic response and serum levels should be closely monitored following initiation, discontinuation or change of dosage of fluvoxamine, and the theophylline dosage adjusted accordingly. Patients should be advised to contact their physician if they experience signs and symptoms suggestive of theophylline toxicity such as nausea, vomiting, diarrhea, anorexia, headache, tremor, irritability, confusion, insomnia, seizure, palpitation, and arrhythmia. Other selective serotonin reuptake inhibitors including citalopram, escitalopram, fluoxetine, paroxetine, and sertraline do not significantly inhibit CYP450 1A2 and may be safer alternatives in theophylline-treated patients.

References

  1. Brosen K, Skjelbo E, Rasmussen BB, Poulsen HE, Loft S "Fluvoxamine is a potent inhibitor of cytochrome P4501A2." Biochem Pharmacol 45 (1993): 1211-4
  2. Sperber AD "Toxic interaction between fluvoxamine and sustained release theophylline in an 11-year-old boy." Drug Saf 6 (1991): 460-2
  3. "Product Information. Luvox (fluvoxamine)." Solvay Pharmaceuticals Inc PROD (2001):
  4. Rasmussen BB, Maenpaa J, Pelkonen O, et al. "Selective serotonin reuptake inhibitors and theophylline metabolism in human liver microsomes: potent inhibition by fluvoxamine." Br J Clin Pharmacol 39 (1995): 151-9
  5. Limbird LE eds., Gilman AG, Hardman JG "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: McGraw-Hill (1995):
  6. Nemeroff CB, Devane CL, Pollock BG "Newer antidepressants and the cytochrome p450 system." Am J Psychiatry 153 (1996): 311-20
  7. Devane CL, Markowitz JS, Hardesty SJ, Mundy S, Gill HS "Fluvoxamine-induced theophylline toxicity." Am J Psychiatry 154 (1997): 1317-8
  8. Rasmussen BB, Jeppesen U, Gaist D, Brosen K "Griseofulvin and fluvoxamine interactions with the metabolism of theophylline." Ther Drug Monit 19 (1997): 56-62
  9. Yao C, Kunze KL, Kharasch ED, et al. "Fluvoxamine-theophylline interaction: Gap between in vitro and in vivo inhibition constants toward cytochrome P4501A2." Clin Pharmacol Ther 70 (2001): 415-24
  10. Orlando R, Padrini R, Perazzi M, De Martin S, Piccoli P, Palatini P "Liver dysfunction markedly decreases the inhibition of cytochrome P450 1A2-mediated theophylline metabolism by fluvoxamine." Clin Pharmacol Ther 79 (2006): 489-99
  11. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  12. van den Brekel AM, Harriington L "Toxic effects of theophylline caused by fluoxamine." CMAJ 151 (1994): 1289-90
View all 12 references

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Drug and food interactions

Moderate

theophylline food

Applies to: Theolair (theophylline)

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

ADJUST DOSING INTERVAL: Administration of theophylline with continuous enteral nutrition may reduce the serum levels or the rate of absorption of theophylline. The mechanism has not been reported. In one case, theophylline levels decreased by 53% in a patient receiving continuous nasogastric tube feedings and occurred with both theophylline tablet and liquid formulations, but not with intravenous aminophylline.

MANAGEMENT: When administered to patients receiving continuous enteral nutrition , some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of theophylline is given; rapid-release formulations are preferable, and theophylline levels should be monitored.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8
  3. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67

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Moderate

fluvoxaMINE food

Applies to: fluvoxamine

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

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Moderate

theophylline food

Applies to: Theolair (theophylline)

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8

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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.

See also

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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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