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 phenelzine. 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 phenelzine (100%). We do not expect any change in exposure for phenelzine, 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.
The bioavailability of phenelzine is unknown. The terminal half-life [ t12 ] is 11.6 hours and constant plasma levels [ Css ] are reached after approximately 46.4 hours. Protein binding [ Pb ] is not known. The metabolism via cytochromes is currently still being worked on.
|Serotonergic Effects a||5||++||+++|
Recommendation: The combination of the serotonergic drugs should be avoided to this extent. In order to be able to assess whether the criteria for a serotonergic syndrome have already been met, an exact answers to the cognitive, vegative and neuromuscular symptom quenstions are necessary.
Rating: Lorcaserin modulates the serotonergic system to a moderate extent. Phenelzine greatly increases serotonergic activity.
|Kiesel & Durán b||1||Ø||+|
Recommendation: As a precaution, attention should be paid to anticholinergic symptoms, especially after increasing the dose and at doses in the upper therapeutic range.
Rating: Phenelzine only has a mild effect on the anticholinergic system. The risk of anticholinergic syndrome with this medication is rather low if the dosage is in the usual range. According to our knowledge, lorcaserin does not increase anticholinergic activity.
QT time prolongation
We do not know of any QT-prolonging potential for lorcaserin and phenelzine.
General adverse effects
|Side effects||∑ frequency||lor||phe|
|Orthostatic hypotension||1.0 %||n.a.||+|
|Abdominal pain||1.0 %||n.a.||+|
|Weight gain||1.0 %||n.a.||+|
Abnormal ejaculation: phenelzine
Erectile dysfunction: phenelzine
Orgasm disorder: phenelzine
Suicidal: phenelzine, lorcaserin
Depression: phenelzine, lorcaserin
Hypertensive crisis: phenelzine
Liver failure: phenelzine
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: OBJECTIVE: To report a serious drug interaction possibly occurring with the monoamine oxidase inhibitor phenelzine and the selective serotonin reuptake inhibitor sertraline. CASE SUMMARY: A 61-year-old woman with treatment-refractory major depressive disorder was being treated unsuccessfully with lithium, phenelzine, thioridazine, and doxepin. Sertaline 100 mg/d was added to the patient's therapy. Within three hours of ingesting the first dose, the patient experienced a dramatic increase in her temperature, pulse, and respirations along with labile blood pressure, and symptoms of rigidity, diaphoresis, shivering, and decreased sensorium. The patient was transported to the emergency room and treated with diazepam 10 mg iv, followed by midazolam 10 mg iv for control of rigidity. She was also intubated. The patient then experienced precipitous falls in her blood pressure and respiratory rate. Ice packs combined with a cooling blanket and dantrolene 80 mg iv were administered to control fever and rigidity, respectively. She had an initial working diagnosis of neuroleptic malignant syndrome, which was later changed to serotonin syndrome. Dantrolene was continued for 72 hours at which time the patient was extubated and transferred to a psychiatric unit. CONCLUSIONS: Selective serotonin reuptake inhibitor antidepressants should not be combined with monoamine oxidase inhibitor antidepressants because of the risk of serotonin syndrome.
Abstract: Anticholinergic Drug Scale (ADS) scores were previously associated with serum anticholinergic activity (SAA) in a pilot study. To replicate these results, the association between ADS scores and SAA was determined using simple linear regression in subjects from a study of delirium in 201 long-term care facility residents who were not included in the pilot study. Simple and multiple linear regression models were then used to determine whether the ADS could be modified to more effectively predict SAA in all 297 subjects. In the replication analysis, ADS scores were significantly associated with SAA (R2 = .0947, P < .0001). In the modification analysis, each model significantly predicted SAA, including ADS scores (R2 = .0741, P < .0001). The modifications examined did not appear useful in optimizing the ADS. This study replicated findings on the association of the ADS with SAA. Future work will determine whether the ADS is clinically useful for preventing anticholinergic adverse effects.
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.
Abstract: A 27-year-old Caucasian female with a history of depression was admitted to our local hospital with vague events that occurred a day before. This included an episode of dysarthria, and unsteadiness, followed by feeling generally unwell. Two weeks prior to presentation she was commenced on phenelzine. During clinical assessment she suddenly deteriorated with a dramatic fall in her conscious level. Moreover, she became hyperthermic, tachycardic, and diaphoretic, and developed increased tone in all muscles and ocular clonus. Rectal diazepam was administered but failed to control the symptoms. Consequently, she was transferred to the intensive care unit for intubation and muscle relaxants were commenced. She responded well and recovered next day without complications. Her symptoms and signs were consistent with the serotonin syndrome with phenelzine being the likely cause. To the best of our knowledge, this is the first reported case to associate the condition with phenelzine alone at therapeutic dose.