Monograph
N06AB06 - Sertraline |
Propably not porphyrinogenic |
PNP |
Important Information
Risk for gastrointestinal adverse events in the form of nausea and diarrhoea motivates vigilance against insufficient intake of food, especially of carbohydrate.
Side effects
Common adverse reactions of sertraline that can be confused with an acute porphyric attack are diarrhoea, nausea, vomiting, constipation, abdominal pains and decreased appetite. These side effects may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake.
Rationale
Sertraline is not suspected to be an inducer of CYP450 enzymes. Although sertraline has been reported to be a mechanism-based inhibitor of CYP3A4 in vitro, this was not found to be clinically relevant. No pharmacokinetic porphyrinogenic effects are thus suspected.
Chemical description
Naphthalenamine derivative
Therapeutic characteristics
Sertraline is a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of depression, panic disorder, obsessive compulsive disorder, social anxiety disorder and post-traumatic stress disorder. It is administered orally.
Metabolism and pharmacokinetics
Sertraline is metabolized by CYP3A4, 2C19 and 2B6, and the main pathway is demethylation to inactive desmethylsertraline (SPC).
In vitro, sertraline is reported to be an inhibitor of CYP2D6, 3A4 and 2B6, but only the inhibition of CYP2D6 is found to be clinically significant (DeVane 2002). Sertraline is classified as a weak inhibitor of CYP2D6 in vivo (FDA, Liston 2002). This drug possesses a secondary amine group, which is a common structure generating MI complexes causing mechanism-based inhibition (Fontana 2005). An in vitro study found that sertraline was a mechanism-based inhibitor of CYP3A4 (Masubuchi 2013). However, this was at concentrations much higher than plasma concentrations obtained in clinical use, and sertraline is not suspected to be an inhibitor of CYP3A4 in vivo (Preskorn 1997, Hassan 2000).
In vivo interaction studies also report that sertraline is not an inhibitor of CYP2C9 and 2C19 (SPC), and not an inducer of CYP3A4 (DeVane 2004).
Published experience
One case report of uneventful use in a patient with manifest AIP (Holroyd 1999).
IPNet drug reports
Uneventful use reported in 4 patients with acute porphyria.
References
| # | Citation details | PMID |
|---|---|---|
| * | Scientific articles | |
| 1. | Fontana E1, Dansette PM, et al. Cytochrome p450 enzymes mechanism based inhibitors: common sub-structures and reactivity.
Curr Drug Metab. 2005 Oct;6(5):413-54 |
|
| 2. | The Impact of Sertraline Co-Administration on the Pharmacokinetics of Olanzapine: A Population Pharmacokinetic Analysis of the STOP-PD.
Davies SJ, Mulsant BH, et al. Clin Pharmacokinet. 2015 May 14 |
25971243 |
| 3. | Comparative CYP3A4 inhibitory effects of venlafaxine, fluoxetine, sertraline, and nefazodone in healthy volunteers.
DeVane CL, Donovan JL, et al. J Clin Psychopharmacol. 2004 Feb;24(1):4-10. |
14709940 |
| 4. | Clinical pharmacokinetics of sertraline.
DeVane CL, Liston HL, et al. Clin Pharmacokinet. 2002;41(15):1247-66. |
|
| 5. | Dose-response evaluation of the interaction between sertraline and alprazolam in vivo.
Hassan PC, Sproule BA, et al. J Clin Psychopharmacol. 2000 Apr;20(2):150-8. |
10770452 |
| 6. | Psychotropic drugs in acute intermittent porphyria.
Holroyd S, Seward RL. Clin Pharmacol Ther. 1999 Sep;66(3):323-5. |
10511069 |
| 7. | Differential time course of cytochrome P450 2D6 enzyme inhibition by fluoxetine, sertraline, and paroxetine in healthy volunteers.
Liston HL, DeVane CL, et al. J Clin Psychopharmacol. 2002 Apr;22(2):169-73. |
11910262 |
| 8. | Time-dependent inhibition of CYP3A4 by sertraline, a selective serotonin reuptake inhibitor.
Masubuchi Y, Kawaguchi Y. Biopharm Drug Dispos. 2013 Nov;34(8):423-30. |
23929629 |
| 9. | Sertraline does not inhibit cytochrome P450 3A-mediated drug metabolism in vivo.
Preskorn SH, Alderman J, et al. Psychopharmacol Bull. 1997;33(4):659-65. |
|
| * | Summary of Product Characteristics | |
| 10. | The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). (Lustral).
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