lofepramine lofepramine lofepramine, sold under the brand names gamanil, lomont, and tymelyt among others, is a tricyclic antidepressant (tca) which is used to treat depression. the tcas are so named as they share the common property of having three rings in their chemical structure. like most tcas lofepramine is believed to work in relieving depression by increasing concentrations of the neurotransmitters norepinephrine and serotonin in the synapse, by inhibiting their reuptake. it is usually considered a third-generation tca, as unlike the first- and second-generation tcas it is relatively safe in overdose and has milder and less frequent side effects. lofepramineclinical datatrade namesgamanil, lomont, tymelyt, othersother nameslopramine; db-2182; leo-460; whr-2908aahfs/drugs.cominternational drug namesroutes ofadministrationoralatc coden06aa07 (who) legal statuslegal status uk: pom (prescription only) pharmacokinetic databioavailability7%protein binding99%metabolismhepatic (via cytochrome p450, including cyp2d6)metabolitesdesipramine (major)elimination half-lifeup to 5 hours; 12–24 hours (active metabolites)excretionurine, feces (mostly as metabolites)identifiers iupac name n-(4-chlorobenzoylmethyl)-3-(10,11-dihydro-5h-dibenzoazepin-5-yl)-n-methylpropan-1-amine cas number23047-25-8 n 26786-32-3 (hydrochloride)pubchem cid3947iuphar/bps7551chemspider3810 yuniioca4jt7pawkeggd08140 ychebichebi:47782 ychemblchembl87708 ycomptox dashboard (epa)dtxsid2023220 echa infocard100.041.254 chemical and physical dataformulac26h27cln2omolar mass418.97 g·mol−13d model (jsmol)interactive image smiles clc1ccc(cc1)c(=o)cn(c)cccn4c2ccccc2ccc3c4cccc3 inchi inchi=1s/c26h27cln2o/c1-28(19-26(30)22-13-15-23(27)16-14-22)17-6-18-29-24-9-4-2-7-20(24)11-12-21-8-3-5-10-25(21)29/h2-5,7-10,13-16h,6,11-12,17-19h2,1h3 ykey:sapnxpwpaufaju-uhfffaoysa-n y ny (what is this?) (verify) lofepramine is not available in the united states, canada, australia or new zealand, although it is available in ireland, japan, south africa and the united kingdom, among other countries. depression in the united kingdom, lofepramine is licensed for the treatment of depression which is its primary use in medicine. lofepramine is an efficacious antidepressant with about 64% patients responding to it. contraindications to be used with caution, or not at all, for people with the following conditions: heart disease impaired kidney or liver function narrow angle glaucoma in the immediate recovery period after myocardial infarction in arrhythmias (particularly heart block) mania in severe liver and/or severe renal impairment and in those being treated with amiodarone or terfenadine. pregnancy and lactation lofepramine use during pregnancy is advised against unless the benefits clearly outweigh the risks. this is because its safety during pregnancy has not been established and animal studies have shown some potential for harm if used during pregnancy. if used during the third trimester of pregnancy it can cause insufficient breathing to meet oxygen requirements, agitation and withdrawal symptoms in the infant. likewise its use by breastfeeding women is advised against, except when the benefits clearly outweigh the risks, due to the fact it is excreted in the breast milk and may therefore adversely affect the infant. although the amount secreted in breast milk is likely too small to be harmful. side effects the most common adverse effects (occurring in at least 1% of those taking the drug) include agitation, anxiety, confusion, dizziness, irritability, abnormal sensations, like pins and needles, without a physical cause, sleep disturbances (e.g. sleeplessness) and a drop in blood pressure upon standing up. less frequent side effects include movement disorders (like tremors), precipitation of angle closure glaucoma and the potentially fatal side effects paralytic ileus and neuroleptic malignant syndrome. dropout incidence due to side effects is about 20%. side effects with unknown frequency include (but are not limited to): digestive effects: constipation diarrhoea dry mouth nausea taste disturbances vomiting effects on the heart: arrhythmia ecg changes abnormal heart rhythm heart block sudden cardiac death high heart rate blood abnormalities: abnormal blood cell counts blood sugar changes low blood sodium levels breast effects: breast enlargement, including in males. spontaneous breast milk secretion that is unrelated to breastfeeding or pregnancy effects on the skin: abnormal sweating hair loss hives increased light sensitivity itching rash mental / neurologic effects: delusions hallucinations headache hypomania/mania seizures suicidal behaviour other effects: appetite changes blurred vision difficulty emptying the bladder difficulty talking due to difficulties in moving the required muscles liver problems ringing in the ears sexual dysfunction, such as impotence swelling weight changes withdrawal if abruptly stopped after regular use it can cause withdrawal effects such as sleeplessness, irritability and excessive sweating. overdose main article: tricyclic antidepressant overdose compared to other tcas, lofepramine is considered to be less toxic in overdose. its treatment is mostly a matter of trying to reduce absorption of the drug, if possible, using gastric lavage and monitoring for adverse effects on the heart. interactions lofepramine is known to interact with: alcohol. increased sedative effect. altretamine. risk of severe drop in blood pressure upon standing. analgesics (painkillers). increased risk of ventricular arrhythmias. anticoagulants (blood thinners). lofepramine may inhibit the metabolism of certain anticoagulants leading to a potentially increased risk of bleeding. anticonvulsants. possibly reduce the anticonvulsant effect of antiepileptics by lowering the seizure threshold. antihistamines. possible increase of antimuscarinic (potentially increasing risk of paralytic ileus, among other effects) and sedative effects. antimuscarinics. possible increase of antimuscarinic side-effects. anxiolytics and hypnotics. increased sedative effect. apraclonidine. avoidance advised by manufacturer of apraclonidine. brimonidine. avoidance advised by manufacturer of brimonidine. clonidine. lofepramine may reduce the antihypertensive effects of clonidine. diazoxide. enhanced hypotensive (blood pressure-lowering) effect. digoxin. may increase risk of irregular heart rate. disulfiram. may require a reduction of lofepramine dose. diuretics. increased risk of reduced blood pressure on standing. cimetidine, diltiazem, verapamil. may increase concentration of lofepramine in the blood plasma. hydralazine. enhanced hypotensive effect. monoamine oxidase inhibitors (maois). advised not to be started until at least 2 weeks after stopping maois. maois are advised not to be started until at least 1–2 weeks after stopping tcas like lofepramine. moclobemide. moclobemide is advised not to be started until at least one week after treatment with tcas is discontinued. nitrates. could possibly reduce the effects of sublingual tablets of nitrates (failure to dissolve under tongue owing to dry mouth). rifampicin. may accelerate lofepramine metabolism thereby decreasing plasma concentrations of lofepramine. ritonavir. may increase lofepramine concentration in the blood plasma. sodium nitroprusside. enhanced hypotensive effect. thyroid hormones. effects on the heart of lofepramine may be exacerbated. pharmacology pharmacodynamics