A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine

@article{Fleishaker2004APA,
  title={A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine},
  author={Joseph C. Fleishaker and Laura K. Hulst},
  journal={European Journal of Clinical Pharmacology},
  year={2004},
  volume={46},
  pages={35-39}
}
We have assesed the pharmacokinetic and pharmacodynamic interaction between fluvoxamine, a serotonin reuptake inhibitor, and alprazolam, a triazolobenzodiazepine.Healthy men took fluvoxamine maleate daily for 10 days (50 mg on days 1–3, 100 mg on days 4–10) (n=20), 1 mg of alprazolam four times daily for four days (days 7–10 of the study period) (n=20), or a combination of the two (n=20), according to a parallel study design. Alprazolam and fluvoxamine concentrations were measured in serial… 

Pharmacokinetic and Pharmacodynamic Interactions of Oral Midazolam with Ketoconazole, Fluoxetine, Fluvoxamine, and Nefazodone

TLDR
Results suggest that caution with the use of midazolam is warranted with potent CYP3A4 inhibitors, and pharmacodynamic data are consistent with pharmacokinetic data indicating that nefazodone and ketoconazole resulted in significant increases in midzolam‐related cognition impairment.

Fluvoxamine Affects Sildenafil Kinetics and Dynamics

TLDR
Whereas the pharmacokinetic changes do not suggest a large clinically relevant interaction, it may be prudent to consider a starting dose of 25 mg in patients concurrently treated with fluvoxamine.

Effects of concomitant fluvoxamine on the metabolism of alprazolam in Japanese psychiatric patients: interaction with CYP2C19 mutated alleles

TLDR
Coadministration of FLV significantly increased the plasma concentrations of ALP compared with ALP monotherapy, and wide variations were observed in the drug interactions, with the CYP2C19 genotype possibly being related to these interactions.

Effects of Concomitant Fluvoxamine on the Plasma Concentration of Etizolam in Japanese Psychiatric Patients: Wide Interindividual Variation in the Drug Interaction

TLDR
Wide variations were observed in the drug interactions; however, coadministration with fluvoxamine produced significant changes in the plasma concentrations of etizolam (P < 0.0001).

Different inhibitory effect of fluvoxamine on omeprazole metabolism between CYP2C19 genotypes.

TLDR
A potent inhibitory effect of fluvoxamine on CYP2C19 activity is confirmed and the bioavailability of omeprazole might, to some extent, be increased through inhibition of P-glycoprotein during fluv oxamine treatment.

Fluvoxamine dose-dependent interaction with haloperidol and the effects on negative symptoms in schizophrenia

TLDR
It is indicated that fluvoxamine increases plasma haloperidol concentrations in a dose-dependent manner, however, relatively small elevations in hal operidol concentration did not lead to the development of extrapyramidal symptoms under the conditions of this study.

The relationship between clinical pharmacokinetics of aripiprazole and CYP2D6 genetic polymorphism: effects of CYP enzyme inhibition by coadministration of paroxetine or fluvoxamine

TLDR
Aripiprazole can be used safely in combination with SSRIs that have a CYP enzyme-inhibitory action, and no apparent differences were found between two CYP2D6 genotypes in fluvoxamine coadministration.

In Vitro Inhibition of Pimozide N-Dealkylation by Selective Serotonin Reuptake Inhibitors and Azithromycin

TLDR
In human liver microsomes, coadministration of SSRIs and azithromycin are unlikely to markedly diminish the elimination of pimozide in patients, suggesting that in vivo predictions from in vitro data are not always perfect.

Clinical pharmacology, clinical efficacy, and behavioral toxicity of alprazolam: a review of the literature.

TLDR
An exhaustive review of the literature showed that alprazolam is significantly superior to placebo, and is at least equally effective in the relief of symptoms as tricyclic antidepressants (TCAs) such as imipramine.

Drug Interaction of Fluvoxamine and Fluoxetine with Nevirapine in HIV-1-Infected Individuals

TLDR
It is advised that special attention is paid to HIV-1-infected individuals using a nevirapine-containing regimen and fluvoxamine or fluoxetine concomitantly, since pharmacokinetic interactions have been observed.
...

References

SHOWING 1-10 OF 18 REFERENCES

Influence of dosing regimen on alprazolam and metabolite serum concentrations and tolerance to sedative and psychomotor effects

TLDR
The relationships between alprazolam and metabolite concentrations and CNS effects were determined in a double-blind placebo controlled four-way crossover trial in 16 normal male volunteers, suggesting a tolerance which was sustained during the 10-day washout between phases.

Clinical Pharmacokinetics of Alprazolam

TLDR
Although a therapeutic concentration range is not clearly established, some studies indicate that optimal reduction of anxiety associated with panic disorder occurs at steady-state plasma alprazolam concentrations of 20 to 40 μg/L, which may be needed for suppression of the actual panic attacks.

Single- and multiple-dose pharmacokinetics of oral alprazolam in healthy smoking and nonsmoking men.

TLDR
Steady-state pharmacokinetic values during the multiple-dose phase correlated with values observed following the single dose, and alprazolam elimination was more rapid in smokers than in nonsmokers.

Pharmacokinetics and pharmacodynamics of alprazolam after oral and IV administration

TLDR
With the exception of rapidity of onset, the pharmacodynamic profiles of IV and oral alprazolam are very similar after a 1.0-mg dose and kinetic parameters are not affected by route of administration.

Single- and multiple-dose pharmacokinetics of oral alprazolam in healthy smoking and nonsmoking men.

TLDR
Although not significantly different, alprazolam elimination was more rapid in smokers than in nonsmokers and Steady-state pharmacokinetic values during the multiple-dose phase correlated with values observed following the single dose.

Single and Multiple Oral Dose Fluvoxamine Kinetics in Young and Elderly Subjects

TLDR
The results suggest that it is not necessary to adjust the dosage of fluvoxamine in elderly depressed patients, on the basis of pharma-cokinetic arguments.

Fluoxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness.

TLDR
Fluoxetine has overall therapeutic efficacy comparable with imipramine, amitriptyline and doxepin in patients with unipolar depression treated for 5 to 6 weeks, although it may be less effective than tricyclic antidepressants in relieving sleep disorders in depressed patients.

Fluvoxamine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness.

TLDR
In patients with depressive illness, fluvoxamine offers a suitable alternative to tricyclic antidepressants and may be especially valuable in patients with concomitant cardiovascular disease, and those unresponsive to or unable to tolerate tricyClic antidepressants.

Clinical Pharmacokinetics of Selective Serotonin Reuptake Inhibitors

TLDR
Although many attempts were made, to date no convincing evidence exists of a relationship between plasma concentrations of any of the SSRIs and clinical efficacy, and available data indicate that metabolism ofSSRIs is impaired with reduced liver function.

Determination of clovoxamine concentration in human plasma by electron capture gas chromatography.

TLDR
When this assay was applied to plasma from individuals involved in an early clinical trial of clovoxamine, steady-state plasma concentrations ranged from 50 to 77 micrograms/L 3 h after a 50-mg oral dose of clvoxamine fumarate.