Fluoxetine Carvedilol

Drugs that may affect carvedilol include cimetidine, rifampin and SSRIs (eg, fluoxetine, paroxetine, diphenhydramine, hydroxychloroquine). 

The drug has a half-life of 6-8 hours. It is extensively metabolized in the liver, and stereoselective metabolism of its two isomers is observed. Since metabolism of ( R)-carvedilol is influenced by polymorphisms in CYP2D6 activity and by drugs that inhibit this enzyme s activity (such as quinidine and fluoxetine, see Chapter 4), drug interactions may occur. Carvedilol also appears to attenuate oxygen free radical-initiated lipid peroxidation and to inhibit vascular smooth muscle mitogenesis independently of adrenoceptor blockade. These effects may contribute to the clinical benefits of the drug in chronic heart failure (see Chapter 13). 

Selective serotonin reuptake inhibitors (SSRIs) [P] Fluoxetine and paroxetine inhibit CYP2D6 and increase concentrations of timolol, propranolol, metoprolol, carvedilol, and labetalol. 

CYP2D6 5 25 S-metoprolol Carvedilol Dextromethorphan Nortriptyline Propanolol Odansetron Chlorpromazine Codeine Flecainide Fluoxetine Haloperidol Amiodarone Fluoxetine Methadone Celecoxib Doxorubicin ... 

Fluoxetine can increase serum pindolol and carvedilol levels, but the clinical effects of this are minimal. Isolated reports describe lethargy and bradycardia in patients taking metoprolol with fluoxetine and propranolol with fluoxetine or fluvoxamine. Flu-voxamine may increase the levels of propranolol, but not atenolol. Paroxetine may increase levels of metoprolol resulting in increased beta-blocking effects. Citalopram and escitalopram may interact similarly. Sertraline does not interact with atenolol. 

Fluoxetine and paroxetine inhibit the cytochrome P450 isoenzyme CYP2D6 thus inhibiting the metabolism of some beta blockers (e.g. propranolol, metoprolol, carvedilol) so that they accumulate, the result being that their effects, such as bradycardia, may be increased. Citalopram and escitalopram may also inhibit CYP2D6. In vitro studies with human liver microsomes found that fluoxetine and paroxetine are potent inhibitors of metoprolol metabolism and fluvoxamine, sertraline and citalopram less potent. However, fluvoxamine also potently inhibits the metabolism of propranolol by CYP1A2. Beta blockers that are not extensively me-... 

Effect of fluoxetine on carvedilol pharmacokinetics, CYP2D6 activity, and autonomic balance in heart failure Clin Pharmacol (2001) 41, 97-106. 

---