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Drug Interactions between Maxolon and Zoloft

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

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Interactions between your drugs

Moderate

metoclopramide sertraline

Applies to: Maxolon (metoclopramide) and Zoloft (sertraline)

MONITOR: Coadministration of metoclopramide with serotonin reuptake inhibitors has been associated with development of the serotonin syndrome and severe extrapyramidal reactions. The exact mechanism is unknown but may involve a pharmacodynamic interaction between serotonergic and antidopaminergic effects of the drugs. A pharmacokinetic interaction is also possible, since metoclopramide and most serotonin reuptake inhibitors are primarily or at least partially metabolized by the CYP450 2D6 isoenzyme. Theoretically, competitive and/or noncompetitive inhibition may lead to elevated plasma levels of one or both drugs, resulting in excessive central serotonergic and antidopaminergic effects. A pharmacokinetic study conducted in 24 young, healthy, nonsmoking volunteers found that administration of a single 20 mg dose of metoclopramide following pretreatment with fluoxetine (60 mg/day for 8 days) resulted in a 42% and 89% increase in metoclopramide peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, compared to metoclopramide administered alone. In a published case report, a 72-year-old woman treated with sertraline and a 32-year-old woman treated with venlafaxine developed movement disorders and symptoms consistent with the serotonin syndrome shortly after single doses of metoclopramide. Both cases resolved following treatment with diazepam, and the patients resumed their sertraline and venlafaxine therapy without further incident. Serotonin syndrome is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucinations, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: Caution is advised if metoclopramide is prescribed in combination with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Patients should be monitored for symptoms of the serotonin syndrome as well as development of extrapyramidal reactions such as involuntary twitching of the jaw and limbs, teeth clenching, severe jerking, trismus, and tongue and neck stiffness. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures.

References

  1. Otton SV, Wu D, Joffe RT, Cheung SW, Sellers EM "Inhibition by fluoxetine of cytochrome P450 2D6 activity." Clin Pharmacol Ther 53 (1993): 401-9
  2. Crewe HK, Lennard MS, Tucker GT, Woods FR, Haddock RE "The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes." Br J Clin Pharmacol 34 (1992): 262-5
  3. Riesenman C "Antidepressant drug interactions and the cytochrome p450 system: a critical appraisal." Pharmacotherapy 15 (1995): s84-99
  4. Nemeroff CB, Devane CL, Pollock BG "Newer antidepressants and the cytochrome p450 system." Am J Psychiatry 153 (1996): 311-20
  5. Otton SV, Ball SE, Cheung SW, Inaba T, Rudolph RL, Sellers EM "Venlafaxine oxidation in vitro is catalysed by CYP2D6." Br J Clin Pharmacol 41 (1996): 149-56
  6. Palop V, Jimenez MJ, Catalan C, MartinezMir I "Acute dystonia associated with fluvoxamine-metoclopramide." Ann Pharmacother 33 (1999): 382
  7. Margolis JM, ODonnell JP, Mankowski DC, Ekins S, Obach RS "(R)-, (S)-, and racemic fluoxetine N-demethylation by human cytochrome P450 enzymes." Drug Metab Disposition 28 (2000): 1187-91
  8. Ereshefsky L, Riesemman C, Lam YW "Antidepressant drug interactions and the cytochrome P450 system. The role of cytochrome P450 2D6." Clin Pharmacokinet 29(Suppl 1) (1995): 10-8; discussion 18-9
  9. Amchin J, Ereshefsky L, Zarycranski W, Taylor K, Albano D, Klockowski PM "Effect of venlafaxine versus fluoxetine on metabolism of dextromethorphan, a CYP2D6 probe." J Clin Pharmacol 41 (2001): 443-51
  10. Sproule BA, Otton SV, Cheung SW, et al. "CYP2D6 inhibition in patients treated with sertraline." J Clin Psychopharmacol 17 (1997): 102-6
  11. Fisher AA, Davis MW "Serotonin syndrome caused by selective serotonin reuptake-inhibitors-metoclopramide interaction." Ann Pharmacother 36 (2002): 67-71
  12. Desta Z, Wu GM, Morocho AM, Flockhart DA "The gastroprokinetic and antiemetic drug metoclopramide is a substrate and inhibitor of cytochrome P450 2D6." Drug Metab Dispos 30 (2002): 336-343
  13. Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6
View all 13 references

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Drug and food interactions

Moderate

metoclopramide food

Applies to: Maxolon (metoclopramide)

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

sertraline food

Applies to: Zoloft (sertraline)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of sertraline. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills. In addition, limited clinical data suggest that consumption of grapefruit juice during treatment with sertraline may result in increased plasma concentrations of sertraline. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit. An in-vitro study demonstrated that grapefruit juice dose-dependently inhibits the conversion of sertraline to its metabolite, desmethylsertraline. In a study with eight Japanese subjects, mean plasma levels of sertraline increased by approximately 100% and maximum plasma concentrations increased by 66% after the ingestion of three 250 mL glasses of grapefruit juice per day for 5 days and administration of a single dose of sertraline 75 mg on the sixth day. In another small study with 5 patients, mean sertraline trough levels increased by 47% after taking sertraline for at least 6 weeks, then taking sertraline with 240 mL grapefruit juice daily for 1 week. The clinical significance is unknown; however, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability. The possibility of significant interaction in some patients should be considered.

MANAGEMENT: Patients receiving sertraline should be 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 sertraline affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. Some authorities recommend that consumption of grapefruit juice should be avoided during sertraline therapy.

References

  1. "Product Information. Zoloft (sertraline)." Roerig Division PROD (2001):
  2. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther 21 (1999): 1890-9
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Ueda N, Yoshimura R, Umene-Nakano W, et al. "Grapefruit juice alters plasma sertraline levels after single ingestion of sertraline in healthy volunteers." World J Biol Psychiatry 10(4 Pt 3) (2009): 832-5
View all 4 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

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