The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine

Greb, W. H.; Büscher, G.; Dierdorf, H.‐D.; Köster, F. E.; Wolf, David S.; Mellows, G.

doi:10.1111/j.1600-0447.1989.tb07184.x

Cited by 33 publications

(8 citation statements)

References 4 publications

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“…Regarding SSRIs, phenobarbital, phenytoin and carbamazepine have been reported to decrease the plasma levels of paroxetine by about 25%, probably as a result of accelerated metabolism [60,61]. Administration of carbamazepine, an inducer of CYP3A4, was associated with a marked decrease in plasma sertraline concentrations in two patients, resulting in lack of antidepressant efficacy [62].…”

Section: Specific Dis Between Antiepileptics and Antidepressantsmentioning

confidence: 98%

Pharmacokinetic and pharmacodynamic interactions between antiepileptics and antidepressants

Italiano

Spina

León

2014

Expert Opinion on Drug Metabolism & Toxicology

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The clinical relevance of the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone and the inhibitory properties of valproic acid and some antidepressants are well understood; correction factors are provided if appropriate DI studies have been completed. More PK studies are needed for: i) antiepileptics with potent inductive effects for all recently approved antidepressants; ii) high doses of mild CYP3A4 inducers, such as clobazam, eslicarbazepine, oxcarbazepine, rufinamide and topiramate for reboxetine and vilazodone; iii) valproate as a possible inhibitor, mild inducer or both a mild inducer and competitive inhibitor of some antidepressants; and iv) inhibitory effects of long-term fluoxetine use on clobazam, lacosamide, phenobarbital, primidone, carbamazepine, felbamate, tiagabine and zonisamide. Possible synergistic or additive beneficial PD DIs in generalized anxiety disorder, chronic pain, migraine prophylaxis, weight control and menopausal symptoms need study.

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Section: Specific Dis Between Antiepileptics and Antidepressantsmentioning

confidence: 98%

Pharmacokinetic and pharmacodynamic interactions between antiepileptics and antidepressants

Italiano

Spina

León

2014

Expert Opinion on Drug Metabolism & Toxicology

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“…In contrast, a study of seven epilepsy patients with depressive symptoms started on fluvoxamine, 100 mg/day, failed to identify any modification in CBZ or CBZ-10,11-epoxide concentrations (42). Two other SSRIs, paroxetine and sertraline, do not seem to affect the plasma concentration of CBZ (27,47), and paroxetine also was found not to modify the plasma concentration of PHT and VPA (27). Conversely, in a patient with bipolar depression treated with VPA, the addition of sertraline (100 mg/day) resulted in a threefold elevation in serum VPA concentrations associated with signs of VPA intoxication (48).…”

Section: Effects Of Antidepressants On the Pharmacokinetics Of Aedsmentioning

confidence: 98%

Clinical Significance of Pharmacokinetic Interactions Between Antiepileptic and Psychotropic Drugs

2002

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Summary: As antiepileptic drugs (AEDs) and psychotropic agents are increasingly used in combination, the possibility of pharmacokinetic interactions between these compounds is relatively common. Most pharmacokinetic interactions between AEDs and psychoactive drugs occur at a metabolic level, and usually involve changes in the activity of the cytochrome P450 mixed‐function oxidases (CYP) involved in their biotransformation. As a consequence of CYP inhibition or induction, plasma concentrations of a given drug may reach toxic or subtherapeutic levels, and dosage adjustments may be required to avoid adverse effects or clinical failure. Enzyme‐inducing AEDs, such as carbamazepine (CBZ), phenytoin (PHT), and barbiturates, stimulate the oxidative biotransformation of many concurrently prescribed psychotropics. In particular, these AEDs may decrease the plasma concentrations of tricyclic antidepressants, many antipsychotics, including traditional compounds, i.e., haloperidol and chlorpromazine, and newer agents, i.e., clozapine, risperidone, olanzapine, quetiapine, and ziprasidone, and some benzodiazepines. Conversely, new AEDs appear to have a lower potential for interactions with all psychotropic drugs. While antipsychotics and anxiolytics do not significantly influence the pharmacokinetics of most AEDs, some newer antidepressants, such as viloxazine, fluoxetine, and fluvoxamine, may lead to higher serum levels of some AEDs, namely CBZ and PHT, through inhibition of CYP enzymes. No significant pharmacokinetic interactions have been documented between AEDs and lithium. Information about CYP enzymes responsible for the biotransformation of individual agents and about the effects of these compounds on the activity of specific CYP enzymes may help in predicting and avoiding clinically significant interactions. Apart from careful clinical observation, serum level monitoring of AEDs and psychotropic drugs can be useful in determining the need for dosage adjustments, especially if there is any change in seizure control, or possible toxicity.

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“…In addition, paroxetine is associated with few drug interactions, is relatively safe in an overdose, and does not exacerbate suicidal ideation. lo, [64][65][66] The potential to induce seizures, often associated with TCA therapy, is only 0.1% with p a r~x e t i n e .~~ Unlike other antidepressants that are associated with weight gain (TCAS)~~ or loss (fl~oxetine),~', ' O paroxetine does not cause changes in weight. Furthermore, the emergence of mania in patients with bipolar disease that often occurs with TCA therapy (11% of 8 6 patients) is relatively uncommon with paroxetine (2% of 134 patients).71…”

Section: Safetymentioning

confidence: 99%

“…Concurrent administration with phenytoin or phenobarbital produced a 28% reduction in the area under the curve (AUC) for paroxetine. Concurrent administration of cimetidine resulted in a 50% increase in the AUC of p a r~x e t i n e .~~~ 66 In addition, paroxetine (as well as fluoxetine and sertraline) may inhibit the cytochrome P450 IID6 enzyme86, 87 and therefore may increase the concentrations of other hepatically metabolized drugs, including other antidepressants (TCAs) or type IC antiarrhythmics (propafenone, flecainide, encainide). The clinical significance of these interactions has not been fully elucidated.…”

Section: Drug Interactionsmentioning

confidence: 99%

The Clinical Pharmacology and Use of Paroxetine, a New Selective Serotonin Reuptake Inhibitor

Nemeroff

1994

Pharmacotherapy

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Major depression afflicts a significant percentage of the population, and optimum therapy is often limited by the poor tolerability and lethality in overdose of the tricyclic antidepressants. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and, more recently, paroxetine are viewed as welcome additions to existing therapy. The SSRIs are as effective as the tricyclic antidepressants, but are not associated with their adverse effect profile. Paroxetine in dosages of 20–50 mg/day is as effective as the older classic antidepressants, including amitriptyline, imipramine, and doxepin. It is effective in the elderly and in patients with recurrent, resistant, or severe depression.

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The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine

Cited by 33 publications

References 4 publications

Pharmacokinetic and pharmacodynamic interactions between antiepileptics and antidepressants

Pharmacokinetic and pharmacodynamic interactions between antiepileptics and antidepressants

Clinical Significance of Pharmacokinetic Interactions Between Antiepileptic and Psychotropic Drugs

The Clinical Pharmacology and Use of Paroxetine, a New Selective Serotonin Reuptake Inhibitor

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