Reboxetine, sold under the brand name Edronax among others, is a selective norepinephrine reuptake inhibitor (sNRI) medication marketed as an antidepressant by Pfizer for use in the treatment of major depressive disorder, although it has also been used off-label for panic disorder and attention deficit hyperactivity disorder (ADHD).[4] It is approved for use in many countries worldwide, but is not approved for use in the United States.[5]
Medical uses
Major depressive disorder
There has been much debate as to whether reboxetine is more efficacious than placebo in the treatment of depression. According to a 2009 meta-analysis of 12 second-generation antidepressants, reboxetine was no more effective than placebo, and was "significantly less" effective and less acceptable than the other drugs in treating the acute-phase of adults with unipolar major depression.[6]
The British MHRA said in September 2011 that the study had several limitations, and that "Overall the balance of benefits and risks for reboxetine remains positive in its authorised indication."[7] A UK and Europe-wide review of available efficacy and safety data has confirmed that reboxetine has benefit over placebo in its authorised indication. Efficacy was clearly shown in patients with severe or very severe depression.[7]
According to a systematic review and meta-analysis by IQWiG, including unpublished data, published data on reboxetine overestimated the benefit of reboxetine versus placebo by up to 115% and reboxetine versus SSRIs by up to 23%, and also underestimated harm, concluding that reboxetine was an ineffective and potentially harmful antidepressant.
Contraindications
Reboxetine is contraindicated in narrow-angle glaucoma, cardiovascular disease, epilepsy, bipolar disorder, urinary retention, prostatic hypertrophy, those hypersensitive to reboxetine or any of its excipients.[2][25]
There is conflicting information regarding use with MAOIs: one says the combination is possible with monitoring of side effects [26] but the product informations indicate them as contraindicated.[2]
Adverse effects
Very common (>10% incidence) adverse effects include insomnia, dizziness, dry mouth, constipation, nausea, and excessive sweating.[27]
Common (1–10%) adverse effects include loss of appetite, agitation, anxiety, headache, restlessness, tingling sensations, distorted sense of taste, difficulty with seeing near or far (problems with accommodation), fast heart beat, heart palpitations, relaxing of blood vessels leading to low blood pressure, high blood pressure, vomiting, rash, sensation of incomplete bladder emptying, urinary tract infection, painful or difficult urination, urinary retention, erectile dysfunction, ejaculatory pain or delay, and chills.[27]
A 2009 meta-analysis found that reboxetine was significantly less well tolerated than the other 11 second-generation antidepressants compared in the analysis.[6]
Overdose
Reboxetine is considered a relatively low-risk antidepressant in overdose.[28] The symptoms are as follows:[28]
- Sweating
- Tachycardia
- Changes in blood pressure
Interactions
Because of its reliance on CYP3A4, reboxetine O-desethylation is markedly inhibited by papaverine and ketoconazole. It weakly inhibits CYP2D6 and CYP3A4.[27] Reboxetine is an intermediate-level inhibitor of P-glycoprotein, which gives it the potential to interact with ciclosporin, tacrolimus, paroxetine, sertraline, quinidine, fluoxetine, and fluvoxamine.[29]
Pharmacology
Pharmacodynamics
Reboxetine is a fairly selective norepinephrine reuptake inhibitor (NRI), with approximately 20-fold selectivity for the norepinephrine transporter (NET) over the serotonin transporter (SERT).[30] Despite this selectivity, reboxetine does slightly inhibit the reuptake of serotonin at therapeutic doses.[32] It does not interact with or inhibit the dopamine transporter (DAT).[30][31]
Reboxetine has been found to inhibit both brain and cardiac GIRKs, a characteristic it shares with the NRI atomoxetine.[33]
Chemistry
Reboxetine has two chiral centers. Thus, four stereoisomers may exist, the (R,R)-, (S,S)-, (R,S)-, and (S,R)-isomers. The active ingredient of reboxetine is a racemic mixture of two enantiomers, the (R,R)-(–)- and (S,S)-(+)-isomer.[35]
History
Reboxetine was discovered at Farmitalia-Carlo Erba and was first published in 1984; Farmitalia did the first clinical studies.[36][37] Farmitalia was acquired by Pharmacia in 1993,[38] and Pharmacia in turn was acquired by Pfizer in 2003.[39]
It was first approved in Europe in 1997 and was provisionally approved by the FDA in 1999.[40] In 2001 the FDA issued Pfizer a "not approvable" letter based on clinical trials the FDA had required when it issued the preliminary approval letter.[41]
Society and culture
Brand names
Edronax is the brand name of reboxetine in every English-speaking country that has approved it for clinical use. Brand names include (where † denotes a product that is no longer marketed):[4]
- Davedax (IT)
- Edronax (AU, AT, BE, CZ, DK, FI, DE, IE, IL, IT, MX, NZ, NO, PH, PL, PT, RU†, ZA, SE, CH, TH, TR, UK)
- Irenor (ES)
External links
References
- Anvisa. RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial Diário Oficial da União, 2023-03-31, retrieved 2023-08-16^
- PRODUCT INFORMATION EDRONAX® Reboxetine mesilate TGA eBusiness Services, Pfizer Australia Pty Ltd, 17 October 2012, retrieved 10 November 2013^
- Reboxetine CNS Drugs, July 1999