QT time prolongation
Adverse drug events
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Explanations of the substances for patients
We have no additional warnings for the combination of lorcaserin and oxymorphone. Please also consult the relevant specialist information.
The reported changes in exposure correspond to the changes in the plasma concentration-time curve [ AUC ]. We do not expect any change in exposure for lorcaserin, when combined with oxymorphone (100%). We do not expect any change in exposure for oxymorphone, when combined with lorcaserin (100%).
The pharmacokinetic parameters of the average population are used as the starting point for calculating the individual changes in exposure due to the interactions.
The bioavailability of lorcaserin is unknown. The terminal half-life [ t12 ] is 11 hours and constant plasma levels [ Css ] are reached after approximately 44 hours. The protein binding [ Pb ] is rather weak at 70%. The metabolism takes place via CYP1A2, CYP2B6, CYP2C19, CYP2D6 and CYP3A4, among others.
Oxymorphone has a low oral bioavailability [ F ] of 10%, which is why the maximum plasma level [Cmax] tends to change strongly with an interaction. The terminal half-life [ t12 ] is 8 hours and constant plasma levels [ Css ] are reached after approximately 32 hours. The protein binding [ Pb ] is very weak at 10%. The metabolism mainly takes place via CYP3A4.
|Serotonergic Effects a||3||++||+|
Recommendation: The risk of a serotonergic syndrome is increased, but without an exact answers to the cognitive, vegative and neuromuscular symptom questions we cannot make any recommendations for action.
Rating: Oxymorphone has a mild effect on the serotonergic system. Lorcaserin modulates the serotonergic system to a moderate extent.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, neither lorcaserin nor oxymorphone increase anticholinergic activity.
QT time prolongation
We do not know of any QT-prolonging potential for lorcaserin and oxymorphone.
General adverse effects
|Side effects||∑ frequency||lor||oxy|
Diaphoresis (5.5%): oxymorphone
Abdominal pain (5.5%): oxymorphone
Xerostomia (5.5%): oxymorphone
Bowel obstruction: oxymorphone
Confusion (5.5%): oxymorphone
Dyspnea (5.5%): oxymorphone
Respiratory depression: oxymorphone
Adrenal insufficiency: oxymorphone
Hypersensitivity reaction: oxymorphone
Based on your answers and scientific information, we assess the individual risk of undesirable side effects. These recommendations are intended to advise professionals and are not a substitute for consultation with a doctor. In the restricted test version (alpha), the risk of all substances has not yet been conclusively assessed.
Abstract: The nasal bioavailability of oxymorphone HCI was determined. Rats were surgically prepared to isolate the nasal cavity, into which a solution of oxymorphone was administered. A reference group of rats was administered oxymorphone HCl intravenously. Plasma oxymorphone concentrations were determined by HPLC. Nasal absorption was rapid, nasal bioavailability was 43%, and the iv and nasal elimination profiles were similar. Oxymorphone HCI appears to have the solubility, potency, and absorption properties required for efficient nasal delivery, which is an alternative to injections.
Abstract: Lorcaserin, a selective serotonin 5-hydroxytryptamine 2C receptor agonist, is being developed for weight management. The oxidative metabolism of lorcaserin, mediated by recombinant human cytochrome P450 (P450) and flavin-containing monooxygenase (FMO) enzymes, was examined in vitro to identify the enzymes involved in the generation of its primary oxidative metabolites, N-hydroxylorcaserin, 7-hydroxylorcaserin, 5-hydroxylorcaserin, and 1-hydroxylorcaserin. Human CYP1A2, CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4, and FMO1 are major enzymes involved in N-hydroxylorcaserin; CYP2D6 and CYP3A4 are enzymes involved in 7-hydroxylorcaserin; CYP1A1, CYP1A2, CYP2D6, and CYP3A4 are enzymes involved in 5-hydroxylorcaserin; and CYP3A4 is an enzyme involved in 1-hydroxylorcaserin formation. In 16 individual human liver microsomal preparations (HLM), formation of N-hydroxylorcaserin was correlated with CYP2B6, 7-hydroxylorcaserin was correlated with CYP2D6, 5-hydroxylorcaserin was correlated with CYP1A2 and CYP3A4, and 1-hydroxylorcaserin was correlated with CYP3A4 activity at 10.0 μM lorcaserin. No correlation was observed for N-hydroxylorcaserin with any P450 marker substrate activity at 1.0 μM lorcaserin. N-Hydroxylorcaserin formation was not inhibited by CYP1A2, CYP2A6, CYP2B6, CYP2C19, CYP2D6, and CYP3A4 inhibitors at the highest concentration tested. Furafylline, quinidine, and ketoconazole, selective inhibitors of CYP1A2, CYP2D6, and CYP3A4, respectively, inhibited 5-hydroxylorcaserin (IC(50) = 1.914 μM), 7-hydroxylorcaserin (IC(50) = 0.213 μM), and 1-hydroxylorcaserin formation (IC(50) = 0.281 μM), respectively. N-Hydroxylorcaserin showed low and high K(m) components in HLM and 7-hydroxylorcaserin showed lower K(m) than 5-hydroxylorcaserin and 1-hydroxylorcaserin in HLM. The highest intrinsic clearance was observed for N-hydroxylorcaserin, followed by 7-hydroxylorcaserin, 5-hydroxylorcaserin, and 1-hydroxylorcaserin in HLM. Multiple human P450 and FMO enzymes catalyze the formation of four primary oxidative metabolites of lorcaserin, suggesting that lorcaserin has a low probability of drug-drug interactions by concomitant medications.