Carbamazepine is a dibenzapine derivative with antiepileptic and anticonvulsant properties. Carbamazepine is closely related to Imipramine and other antidepressants. Carbamazepine is a tricyclic compound effective in the treatment of bipolar effective disoredrs. It was initally marketed for the treatment of trigeminal neuralgia but has proved useful for epilepsy as well. Carbamazepine is now used as a drug of choice for simple and complex partial seizures and for tonic clonic seizures. It is also used for the management of certain types of nerve pain.
Effects
The severe or irreversible adverse effects of Carbamazepine, which give rise to further complications include Proteinuria, Skin rashes, Stevens johnson syndrome, Bradycardia, Lymphadenopathy, Jaundice, Fatal hepatitis, Lupus erythematosus, Leucopenia, Pruritis, Hyponatremia, Agranulocytosis, Hematuria, Heart failure, Liver dysfunction, Oliguria, Water intoxication, Proteinuria, Hematological toxicities.Carbamazepine produces potentially life-threatening effects which include Coma, Respiratory depression, Aplastic Anemia, Stevens Johnson syndrome, Hyperirritability, Exfoliative dermatitis, increased frequency of seizures, Toxic epidermal necrolysis. which are responsible for the discontinuation of Carbamazepine therapy.The signs and symptoms that are produced after the acute overdosage of Carbamazepine include Convulsions, Unconsciousness, Dilated pupils, Ataxia, Erythema of the face, Muscle hypotonia, Tremor, Psychomotor restlessness, Changes in blood pressure.The symptomatic adverse reactions produced by Carbamazepine are more or less tolerable and if they become severe, they can be treated symptomatically, these include Dizziness, Vertigo, Drowsiness, Ataxia, Nausea, Vomiting, Fever, Blurred vision, Diplopia, Asthenia, Unsteadiness, Hypersensitivity reactions, Hyponatremia, water intoxication.
Interactions
Carbamazepine is known to interact with other drugs, the details of drug interactions is as follows:DrugDetailsSeverityOnsetManagementAfatinibmay decrease the level of afatinibuse alternative or in crease daily dose of afatinibAlbendazoleAlcoholCNS-side effects of Carbamazepine possibly increased by Alcohol.Amitriptyline (HCl)Carbamazepine accelerates metabolism of tricyclics (e.g Amitriptyline); reduced plasma concentration by induction of CYP450 enzymes and reduced effects. ModerateTolerance,patient response,seizure control and monitoring of serum concentration should be done.Amlodipine (Besylate)Carbamazepine may increase the metabolism, via CYP isoenzymes, of Amlodipine.ModerateMonitor for reduced therapeutic effects of Amlodipine if Carbamazepine is initiated or the dose is increased. ArtesunateConcurrent use may decrease artesunate serum concentrations. Avoid co-administration if possible. Monitor closely for therapeutic efficacy. Artesunate dose may need to be increased with co-administration.Atracurium (Besylate)Neuromuscular blocking effect of Atracurium is reduced by carbamazepine.ModerateNeuromuscular blocking effect should be closely monitor. BetamethasoneMetabolism of corticosteroids (e.g Betamethasone) possilbly enhanced by Carbamazipine (reduced effect). MajorBromazepamBupropion (HCl)Plasma concentration of Bupropion reduced by Carbamazepine.CelecoxibChloroquinePossible increased risk of convulsions when antiepileptics given with Chloroquine.MajorChlorpropamideCimetidine (HCl)Cimetidine inhibit the metabolism of carbamazepine.ClarithromycinClarithromycin increses the serum concentration of carbamazepine by inhibiting its hepatic metabolism and decrease its clearance results in severe toxicity ModerateClosely monitor the plasma level of carbamazepine and carefully observed the signs of toxicity. Dose of carbamazipine should reduce if necessary.ClobazamClonazepamCarbamazepine often reduces plasma concentration of Clonazepam.ClozapineCarbamazepine reduces plasma concentration and decrease pharmacological effect of clozapine by induction of CYP450 hepatic metabolism.ModerateMonitor patient response and serum clozapine level.conjugated Estrogens/Bazedoxifenemay reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects monitor closelyCortisone (Acetate)Carbamazepine accelerates metabolism of Corticosteroids (reduced effect).Cyclosporin ACarbamazepine accelerates metabolism of Cyclosporin (reduced plasma concentration)due to hepatic metabolism induction.MajorBetter to avoid this combination or monitor serum concentration of cyclosporine.DabrafenibStrong CYP3A4 inducers may decrease levels of dabrafenib. Consider alternate therapy.Danazoldanazol inhibit the metabolism of cabamazepine ( other anti convulsant drug include phenobarbital) (increased risk of toxicity).MajorDeflazacortDesmopressin (Acetate)DesogestrelDesonideDexamethasonecarbamazepine increase clearance of cortisteroids.DextropropoxypheneEffects of Carbamazepine enhanced by Dextropropoxyphene.MajorDiazepamDiltiazem (HCl)Carbamazepine decrease plasma concentration of diltiazem by induction of CYP450 3A4.ModerateThis combination should be avoided.DisulfiramDolutegravirdecreased level of dolutegravirCoadministration sholud be avoided DoxacuriumNeuromuscular blocking effect of doxacurium is reduced by carbamazepine.ModerateNeuromuscular blocking effect should be closely monitor.Doxicycline HyclateDoxycyclineCarbamazepine accelerates metabolism of Doxycycline (reduced effect) and shortens the half life of doxycycline. DydrogesteroneErythromycinErythromycin may decrease the metabolism of Carbamazepineby increasing its serum levels through CYP450 3A4 inhibition.ModerateConsider selecting a noninteracting macrolide. Monitor for toxic effects of carbamazepine if Erythromycin is initiated or the dose is increased. The dose of carbamazepine will likely need to be altered.EstazolamEstradiol (Valerate)EthosuximideCarbamazepine possibly reduces plasma concentration of Ethosuximide.MajorEthynodiol (Diacetate)FelbamateFelodipineCarbamazepine reduces effects of Felodipine.MajorFludrocortisone (Acetate)Flunarizine (HCl)Fluoxetine (HCl)Plasma concentration of Carbamazepine increased by Fluvoxamine.MajorFluprednisoloneFluticasone PropionateFluvoxamine (Maleate)Plasma concentration of Carbamazepine increased by Fluvoxamine.MajorFosphenytoinFrusemide or Furosemidewith carbamezapine fresemide causes hyponatraemia FurazolidoneMarked adverse affects seen when carbmazepine given with furazolidone including nausea,vomiting,flushing,dizziness,tremor,hyperthermia,rigidity,autonomic instability,hypertensive crises,severe convulsive seizures,coma and death may also reported.MajorThis combination should be avoided or give a gap of atleast 2 weeks before or after use of any of these drugs.GallopamilGestodeneHaloperidolCarbamazepine reduces the plasma concentration of haloperidol.HydrochlorothiazideIncreased risk of hyponatremia when Carbamazepine given with diuretics. HydrocortisoneCarbamazepine accelerates metabolism of Corticosteroids (reduced effect).IloprostIndinavir (Sulphate)Carbamazepine increases the plasma concentration of 9indinavir by induces its hepatic metabolismModerateAdjust the dose of indinavir if necessary. Closely monitor for antiretroviral responsesInfluenza VaccineIprindoleTheoretical potential for CARBAMAZEPINE increasing the CONVULSANT effect of IPRINDOLE.ModerateIproniazid PhosphateTheoretical potential for IPRONIAZID reducing the ANTICONVULSANT effect of CARBAMAZEPINE. Potential risk. AvoidIrinotecan (HCl Trihydrate)IsoniazidPlasma concentration of Carbamazepine increased by Isoniazid also possibly increased isonizid hepatotoxicity by CYP450 3A4 inhibition.ModerateClose monitoring of hepatotoxicity and carbamazepine toxicity should be done and adjust carbamazepine dose.Isosorbide (Dinitrate)Carbamazepine may increase the metabolism of Isosorbide(Dinitrate). ModerateConsider an alternative drug to avoid therapeutic failure of Isosorbide(Dinitrate).Some combinations are specifically contraindicated by manufacturers. Suggested dosage adjustments are also offered by some manufacturers. Please review applicable package inserts. Monitor for decreased effects of Isosorbide(Dinitrate) if Carbamazepine is initiated/dose increased, and increased effects if Carbamazepine is discontinued/dose decreased.IsotretinoinItopride (HCl)ItraconazoleCarbamazepine possibly reduces plasma concentration of Itraconazole.ModerateKetoconazoleCo administration results in decreased plasma concentration of azole agent by accelerating azole clearance due to induction of enzymatic pathway by carbamazepine.ModerateMonitor cabamazepine toxicity and failure of ketoconazole treatment so dose adjustment is required. Less reactive like Terbinafine or fluconazole may be prescribed.LamotrigineWhen lamotrigine is used with carbamazepine therapy, CNS adverse effects such as dizziness and diplopia become more common.Lercanidipine (HCl)Liothyronine (Na)LithiumNeurotoxicity,lethargy,muscular weakness,ataxia,dystonia,tremor and sinus node dysfunction may occur when Carbamazepine given with Lithium.ModerateAdverse neurologic and cardiac effects,lithium toxicity and altered thyroxine levels must be monitor.Lofepramine (HCl)Theoretical potential for CARBAMAZEPINE increasing the CONVULSANT effect of LOFEPRAMINE. ModerateLynoestrenolLypressinMebendazoleMegestrol (Acetate)MestranolMethylprednisoloneCarbamazepine accelerates metabolism of Corticosteroids (reduced effect).MajorMethylprednisoloneMetronidazoleMetronidazole enhances the serum concentration of carbamazepine.ModerateDuring coadministration carbamazepine serum kevel and clinical effects should be closely monitored.Miconazole (Nitrate)Plasma concentration of Carbamazepine possibly increased by Miconazole.MajorMorphineNicotinamideNicoumaloneNitrendipineCarbamazepine may decrease the levels/effects of nitrendipine.NorgestimateOndansetron (HCl)By concurrent use the clearance of ondansetron was significantly increased and ondansetron blood concentrations were decreased. However, on the basis of available data, no dosage adjustment for ondansetron is recommended for patients on these drugs.No dosage adjustment for ondansetron is recommended for patients on these drugs.OxymorphoneCentral nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients.ModerateDuring concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Ambulatory patients should be made aware of the possibility of additive CNS effects (e.g., drowsiness, dizziness, lightheadedness, confusion) and counseled to avoid activities requiring mental alertness until they know how these agents affect them. Patients should also be advised to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.Pancuronium (Br)Carbamazepine reduces the duration effect of pancuronium.ModerateDuring coadministration close observation for decreasing effect of pancuronium is recommended.PapaveretumParacetamolplasma concentration of paracetamol may be reduced by anti epileptic such as carbamazepine, phenobarbital , phenytoin or primidoneMinorParoxetineThese drugs act synergistically result in depression of central nervous system and respiratory system.ModerateClosely monitor for CNS and respiratory depression.PericyazineThese drugs shouldnot be taken concurrently without doctors prescription.PhenindionePhenobarbitonePhenobarbitone may decreases Carbamazepine levels. The mechanism may be related to induction of CYP450 hepatic metabolism of Carbamazepine.PhenylalaninePhenylalanine may enhance the tardive dyskinesia side effects of Carbamazepine.Phenytoin (Na)Phenytoin may decrease Carbamazepine levels, and Carbamazepine may have variable effects on Phenytoin levels. The mechanism may be related to induction of CYP450 hepatic metabolism of Carbamazepine and alteration of Phenytoin metabolism. ModerateClose observation for clinical and laboratory evidence of altered effects is recommended, perticularly when one drug is started or discontinued. Patients should be advised to notify their physician if they experience loss of seizure control or symptoms of Phenytoin toxicity (nausea, drowsiness, visual disturbances, change in mental status, ataxia).PioglitazonePraziquantel Prednisolone and PrednisonePrimidonePrimidone, ethosuximide, methsuximide, ethylphenacemide will decrease carbamazepine plasma concentration.PrimidoneProcarbazineCoadministration enhances the excessive serotonergic activity in CNS i.e. serotonin syndrome and may produce adverse effects like tremor,dizziness,myoclonus,diaphoresis,hyperthermia and coma.MajorCoadministration in general must not be used.If necessary 14 days gap must be given and both drugs started at low doses.ProgesteroneCarbamazepine accelerates metabolism of Progesterone (reduced contraceptive effect).MajorWomen recieving carbamazepine should be given a contraceptive pill containing 50 mcg of estrogen together with a high dose of progesterone.PropoxyphenePropoxyphene interferes with metabolism and clearance of carbamazepine producing toxic effect like headache, dizziness, ataxia.PropoxypheneADVICE: Generally avoid. The co-administration of Propoxyphene and Carbamazepine may result in significantly elevated plasma Carbamazepine concentrations. This interaction has been reported in various case reports and studies, with increases in Carbamazepine levels by up to 6-folds and associated toxicity in some cases. The proposed mechanism is decreased clerance of Carbamazepine due to inhibition of CYP450 3A4 enzymatic activity by Propoxyphene. RepaglinideCarbamazepine may decrease the levels/effects of repaglinide.RitonavirCoadministration decreases the plasma level of ritonavir due to cabamazepine induction of CYP450 3A4 which also metabolizes ritonavir.ModerateCare must be taken during coadministration and carbamazepine serum level must be closely monitored.RizatriptanConcurrent use may increase drowsiness.Salicylic AcidSaquinavirPlasma concentration of Carbamazepine possibly increased by Saquinavir.MajorSelegiline (HCl)Concomitant use of carbamazepine and monoamine oxidase inhibitors (e.g. selegiline, tranylcypromine) increases the incidence of cardiac arrythmias.Sodium ValproateSorafenibmay also increase metabolism of sorafenib and thus decrease sorafenib concentrations.SulfapyridineConcurrent use with sulfonamides may result in an increased incidence of hepatotoxicity. Patients, especially those on prolonged administration or those with a history of liver disease.Should be carefully monitored.SulphamethizoleCarbamazepine may be displaced from protein binding sites or their metabolism may be inhibited by some sulfonamides, resulting in increased or prolonged effects or toxicity.Dosage adjustments may be necessary during and after sulfonamide therapySunitinibMay decrease sunitinib concentrations.TacrolimusTelithromycinCarbamazepine is likely to result in subtherapeutic levels of telithromycin and loss of effect.TerfenadineCoadministration may increases free cabamazepine levels and clinical toxicity.ModerateClose monitoring for free level of cabamazepine must be done.TheophyllineBoth agents decreases their serum levels due to inhibition of hepatic metabolism.ModerateClose observation for altered effects of both agents is recommended.Thyroxine (Na)Carbamazepine accelerates metabolism of Theophylline (reduced effect).Tiagabine (HCl)Carbamazepine reduces plasma concentration of Tigabine.TiboloneCarbamazepine accelerates metabolism of Tibolone (reduced plasma concentration).TopiramateCarbamazepine lowers the plasma concentration of topiramate.TopiramateTramadol (HCl)Carbamazepine reduces effects of Tramadol.Tranylcypromine (Sulphate)VasopressinVemurafenibCarbamazepine induces P-gp and CYP3A4.Verapamil (HCl)Effects of Carbamazepine enhanced by Verapamil MajorVORICONAZOLECarbamazepine may reduce serum concentrations and efficacy of voriconazole likely by increasing its metabolism. Concomitant voriconazole and carbamazepine therapy is contraindicated.Warfarin (Na)Carbamazepine may decrease the serum concentration of Warfarin. Patients on anticoaggulant therapy will suffer a serious bleeding disorder if carbamazepine is suddenly withdrawn.Moderate (Sequence important)Monitor for decreased therapeutic effects/prothrombin time of Warfarin if Carbamazepine is initiated/dose increased, or increased effects/prothrombin time if carbamazepine is discontinued/dose decreased. Patients stabilized on carbamazepine prior to warfarin initiation will not likely note this interaction.Zolpidem (Tartrate)Zopiclone These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.