Carbamazepine is a medicine used to control epileptic seizures (convulsions) and to relieve the pain of trigeminal neuralgia. It can cause drowsiness and dizziness at first, and requires regular blood tests (blood counts, liver, sodium).
Also known as: Tegretol
Carbamazepine (a CYP3A4 inducer) lowers Artemether and Lumefantrine levels — risk of malaria treatment failure.
Carbamazepine is a potent inducer of CYP3A4, the pathway that metabolises artemether and lumefantrine; coadministration can substantially reduce antimalarial concentrations and compromise malaria cure. In epileptic patients with malaria, prefer an antimalarial less dependent on CYP3A4 (e.g. atovaquone+proguanil) and, if the combination is unavoidable, monitor the clinical and parasitological response closely.
Carbamazepine + artemether+lumefantrine: carbamazepine induces CYP3A4 and lowers antimalarial levels, with risk of therapeutic failure. Avoid the combination.
Enzymatic induction of CYP3A4: faster metabolism of both components with lower systemic exposure.
Clinical and parasitological response to treatment (fever, parasitaemia).
Persistent or recurrent fever, no improvement after 48–72 h.
Consider an alternative antimalarial regimen or dose adjustment and confirm parasitological cure.
DailyMed/FDA (NIH/NLM) — approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2
Combining Clozapine with Carbamazepine increases the risk of agranulocytosis and also lowers Clozapine concentrations.
Carbamazepine induces CYP1A2 and CYP3A4 and can halve clozapine concentrations, compromising the antipsychotic effect; in addition, both clozapine and carbamazepine are associated with blood dyscrasias (agranulocytosis/neutropenia), and coadministration is traditionally avoided because of the additive haematological risk. Choose an alternative antiepileptic (e.g. valproate, lamotrigine) in patients on clozapine; if unavoidable, monitor the blood count and clozapine levels.
Carbamazepine + clozapine: carbamazepine lowers clozapine levels (CYP1A2/3A4 induction) and both carry additive haematological risk. Avoid the combination.
Both can induce blood dyscrasias; in addition, Carbamazepine induces Clozapine metabolism, lowering its levels.
Regular blood counts (white cells and neutrophils) during combined use.
Fever, sore throat or sudden infection with neutropenia require discontinuation and immediate evaluation.
Avoid the combination whenever possible; if unavoidable, strictly monitor the blood count.
DailyMed/FDA (NIH/NLM) — approved Clozapine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=61fe53d5-ed5c-4e45-9189-709d08d386cb ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Corticosteroid + carbamazepine: CYP3A4 induction reduces corticosteroid effect.
Dexamethasone is metabolised by CYP3A4; carbamazepine, a potent inducer of this enzyme, can lower its concentrations and attenuate the anti-inflammatory/immunosuppressive effect. In patients on long-term corticosteroid therapy (e.g. autoimmune diseases, post-transplant) with epilepsy treated with carbamazepine, monitor the clinical response and consider increasing the dexamethasone dose or preferring a corticosteroid less dependent on CYP3A4.
Carbamazepine + dexamethasone: carbamazepine induces CYP3A4 and lowers dexamethasone levels, potentially reducing the corticosteroid effect. Consider dose adjustment.
Carbamazepine (CYP3A4 inducer) accelerates dexamethasone metabolism.
Clinical response to therapy.
Lack of control of inflammatory/allergic symptoms.
Watch clinical response; a higher corticosteroid dose may be needed.
DailyMed (FDA) — approved Dexamethasone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7cbd9005-7df2-47ee-adb3-7244c1c69bc3 ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=97e6e175-75e8-437b-b457-ddb1ae4e857d — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Fluconazole may raise Carbamazepine levels (metabolic inhibition), with a risk of toxicity.
Fluconazole inhibits CYP3A4, reducing carbamazepine clearance and potentially raising its concentrations to toxic levels (nystagmus, ataxia, diplopia, sedation). The effect depends on the fluconazole dose. Monitor carbamazepine plasma levels and reduce the dose if needed during and after antifungal treatment.
Fluconazole + carbamazepine: fluconazole inhibits CYP3A4 and may raise carbamazepine levels, with risk of toxicity. Monitor levels and intoxication signs.
CYP3A4 inhibition by fluconazole reduces carbamazepine metabolism.
Carbamazepine concentration, symptoms (diplopia, nystagmus, ataxia).
Diplopia, nystagmus, ataxia, drowsiness.
Monitor carbamazepine levels and toxicity symptoms; adjust the dose as needed.
DailyMed/FDA (NIH/NLM) — approved Fluconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7961c029-746c-48c3-888b-8f8344102873 ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Haloperidol with Carbamazepine markedly reduces Haloperidol concentrations, risking loss of the antipsychotic effect.
Haloperidol is metabolised by CYP3A4; carbamazepine, a potent inducer, can reduce its concentrations by about 50%, with loss of psychotic control. Conversely, some patients experience more sedation with the combination. Monitor the clinical response, adjust the haloperidol dose (often upwards) and consider an antiepileptic without enzyme induction (e.g. valproate) when the psychiatric picture allows it.
Carbamazepine + haloperidol: carbamazepine lowers haloperidol levels (CYP3A4 induction), potentially reducing the antipsychotic effect. Adjust the dose and monitor.
As an enzyme inducer, Carbamazepine accelerates Haloperidol metabolism, lowering its serum levels.
Monitor the antipsychotic response and signs of relapse.
Psychotic relapse during the combination requires regimen review.
Monitor the clinical response and consider adjusting the Haloperidol dose or using an alternative antipsychotic.
DailyMed/FDA (NIH/NLM) — approved Haloperidol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e2eed126-cb82-42b1-9b48-9cbeb6873b50 ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Isoniazid inhibits Carbamazepine metabolism and may raise its levels — risk of toxicity.
Isoniazid inhibits the enzymes that metabolise carbamazepine (CYP2C19/CYP3A4) and can raise its concentrations to toxic levels (nystagmus, ataxia, sedation); in tuberculosis patients the effect can be clinically relevant in the first weeks. In addition, both drugs are hepatotoxic, with an additive risk of liver injury. Monitor carbamazepine levels and reduce the dose if needed, monitor transaminases and watch for intoxication symptoms.
Isoniazid + carbamazepine: isoniazid inhibits carbamazepine metabolism and raises its levels; both are hepatotoxic. Monitor levels and liver function.
CYP2C19/3A4 inhibition and possible epoxide hydrolase inhibition.
Carbamazepine levels, neurological signs.
Nystagmus, ataxia, drowsiness, diplopia.
Monitor carbamazepine levels and signs of toxicity.
DailyMed/FDA (NIH/NLM) — approved Isoniazid label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=93252cc8-c8d4-401b-bde5-ca8a3b57651e ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2
Carbamazepine lowers Itraconazole levels (induction), increasing the risk of antifungal failure.
Itraconazole is a potent inhibitor of CYP3A4, the main pathway of carbamazepine metabolism; coadministration can raise carbamazepine concentrations and cause intoxication (nystagmus, ataxia, diplopia, sedation). Monitor carbamazepine plasma levels and reduce the dose if needed during antifungal treatment; consider a less inhibitory antifungal (e.g. low-dose fluconazole, with caution) when possible.
Itraconazole + carbamazepine: itraconazole inhibits CYP3A4 and may raise carbamazepine levels, with risk of toxicity. Monitor levels.
Carbamazepine induces CYP3A4, accelerating itraconazole metabolism and reducing its exposure.
Mycosis response; itraconazole levels (if available).
Worsening fungal infection.
Consider an alternative antifungal; if the combination is unavoidable, monitor clinical and mycological response.
DailyMed/FDA (NIH/NLM) — approved Itraconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a4d555fa-787c-40fb-bb7d-b0d4f7318fd0 ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Carbamazepine lowers Mefloquine levels (CYP3A4 inducer) and both lower the seizure threshold — risk of therapeutic failure and seizures.
Mefloquine is metabolised by CYP3A4; carbamazepine, a potent inducer, can reduce its concentrations below the effective threshold, compromising malaria prophylaxis or treatment. In epileptic patients, mefloquine is also to be avoided because of the seizure risk. Prefer another antimalarial (e.g. atovaquone+proguanil, doxycycline) in patients on carbamazepine.
Carbamazepine + mefloquine: carbamazepine lowers mefloquine levels (CYP3A4 induction), with risk of prophylactic/therapeutic failure. Avoid the combination.
CYP3A4 induction (which metabolises Mefloquine) + additive effects on the seizure threshold.
Clinical response and neurological status.
Seizures, confusion, lack of response to prophylaxis/treatment.
Consider an alternative antimalarial and neurological surveillance.
DailyMed/FDA (NIH/NLM) — approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2
Combining Ritonavir with Carbamazepine increases Carbamazepine concentrations and toxicity, requiring dose adjustment and monitoring.
The interaction is bidirectional and complex: ritonavir (potent CYP3A4 inhibitor) can raise carbamazepine concentrations to toxic levels, while carbamazepine (CYP3A4 inducer) can lower ritonavir and boosted protease inhibitor levels, compromising viral suppression. Monitor carbamazepine levels (reduce the dose if needed) and the virological response; consider an alternative antiepileptic (e.g. levetiracetam) in patients on ritonavir-based antiretroviral therapy.
Ritonavir + carbamazepine: ritonavir inhibits CYP3A4 and raises carbamazepine levels, while carbamazepine lowers antiretroviral levels. Monitor both.
Ritonavir inhibits CYP3A4, the main metabolic pathway of Carbamazepine, lowering its clearance and increasing the risk of adverse effects (neurological, haematological).
Watch for signs of Carbamazepine toxicity: diplopia, ataxia, drowsiness, nausea, hyponatraemia.
Marked drowsiness, ataxia or diplopia require discontinuation and reassessment of the regimen.
Reduce the Carbamazepine dose as needed and, if available, monitor serum concentrations; consider an alternative antiepileptic.
DailyMed/FDA (NIH/NLM) — approved Ritonavir label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2849298e-de6e-47bb-8194-56e075b33fc3 ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Carbamazepine induces hepatic metabolism and may lower theophylline levels; the interaction is bidirectional and variable.
Carbamazepine induces CYP1A2 and CYP3A4, pathways of theophylline metabolism, and can reduce its concentrations by about 50%, compromising asthma/COPD control. Theophylline has a narrow therapeutic window, so monitor its plasma levels and adjust the dose (often upwards) while the combination lasts; consider an antiepileptic without enzyme induction if respiratory control is difficult.
Carbamazepine + theophylline: carbamazepine induces theophylline metabolism and lowers its levels by ~50%, with loss of bronchodilator effect. Monitor theophylline levels.
Carbamazepine is an enzyme inducer (CYP3A4), accelerating theophylline clearance.
Monitor theophylline efficacy and signs of seizures or toxicity.
Loss of asthma control (subtherapeutic theophylline) or toxicity when carbamazepine is stopped.
Monitor levels of both drugs when starting, adjusting or stopping either one.
DailyMed (FDA) — approved Theophylline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5e64036a-ee3e-42e7-9e59-881f88a4e298 ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=97e6e175-75e8-437b-b457-ddb1ae4e857d — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Carbamazepine (a CYP450 inducer) markedly reduces Voriconazole levels, risking antifungal failure.
The interaction is bidirectional and practically contraindicated: voriconazole inhibits CYP3A4 and can raise carbamazepine to toxic levels, while carbamazepine strongly induces CYP3A4 (and other pathways) and reduces voriconazole concentrations to subtherapeutic levels, with risk of antifungal failure. The combination should be avoided; if unavoidable, consider another antifungal (e.g. amphotericin B, echinocandins) or another antiepileptic, with close monitoring of levels and response.
Voriconazole + carbamazepine: voriconazole raises carbamazepine levels (CYP3A4 inhibition) and carbamazepine markedly reduces voriconazole levels (induction). Avoid the combination.
CYP3A4/CYP2C19 induction by carbamazepine accelerates voriconazole elimination.
Voriconazole levels, mycological response, liver function tests.
Persistent or worsening fungal infection.
Avoid the combination; if unavoidable, monitor voriconazole levels and clinical response, adjusting the dose.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Carbamazepine (a CYP2C8/3A4 inducer) accelerates Amodiaquine metabolism — risk of subtherapeutic levels and treatment failure.
Carbamazepine induces the monooxygenases (including CYP3A4) involved in the metabolism of artesunate (and its active metabolite dihydroartemisinin) and amodiaquine; antimalarial levels can fall below the therapeutic threshold and compromise response. Prefer an alternative antimalarial in patients on carbamazepine and, if the combination is unavoidable, monitor the clinical and parasitological response.
Carbamazepine + artesunate+amodiaquine: carbamazepine induces antimalarial metabolism, with risk of subtherapeutic levels and failure. Avoid if possible.
Enzymatic induction reducing exposure to Amodiaquine (the ACT component).
Clinical and parasitological response to treatment.
Persistent or recurrent fever, no improvement after 48–72 h.
Consider an alternative ACT and confirm parasitological cure.
WHO — WHO Guidelines for malaria: https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria ; DailyMed/FDA (NIH/NLM) — approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2
Carbamazepine (an inducer) lowers Piperaquine and Dihydroartemisinin levels — risk of treatment failure.
Carbamazepine induces CYP3A4, an important pathway in dihydroartemisinin and piperaquine metabolism; antimalarial levels can fall below the therapeutic threshold, compromising cure. In addition, piperaquine prolongs the QT — in epileptic patients treated with carbamazepine, prefer an alternative antimalarial (e.g. atovaquone+proguanil, which is also less CYP3A4-dependent) and monitor the clinical and parasitological response if the combination is unavoidable.
Carbamazepine + dihydroartemisinin+piperaquine: carbamazepine induces antimalarial metabolism, with risk of subtherapeutic levels. Avoid if possible.
Enzymatic induction (CYP3A4) accelerating metabolism of the ACT components.
Clinical and parasitological response.
Persistent or recurrent fever.
Consider an alternative ACT and confirm parasitological cure.
EMA — EPAR Eurartesim (dihydroartemisinin + piperaquine): https://www.ema.europa.eu/en/medicines/human/EPAR/eurartesim ; DailyMed/FDA (NIH/NLM) — approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2
Two-way interaction: Rifampin lowers Carbamazepine levels and Carbamazepine lowers Rifampin levels — possible loss of efficacy of both.
Rifampicin is a potent inducer of CYP3A4 and can reduce carbamazepine concentrations by more than 50%, with risk of seizure relapse; the effect develops over days to weeks and persists after rifampicin discontinuation. Both are hepatotoxic, with an additive risk. Monitor carbamazepine plasma levels and increase the dose as needed during and after antituberculosis treatment, monitoring transaminases.
Rifampicin + carbamazepine: rifampicin strongly induces CYP3A4 and lowers carbamazepine levels, with risk of losing seizure control. Monitor levels and adjust the dose.
Mutual enzymatic induction (CYP3A4/2C9).
Carbamazepine levels, seizure control, TB response.
Seizures, persistent TB fever.
Monitor carbamazepine levels and clinical response; adjust doses.
DailyMed/FDA (NIH/NLM) — approved Rifampin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2
Carbamazepine lowers ketoconazole levels (induction) while ketoconazole can raise carbamazepine; reciprocal effects.
Carbamazepine is metabolised by CYP3A4; ketoconazole is a potent inhibitor of this enzyme and can raise carbamazepine concentrations, with risk of intoxication (nystagmus, ataxia, diplopia, sedation and, in severe cases, arrhythmias and seizures). Monitor carbamazepine plasma levels, reduce the dose if needed and watch for toxicity signs while the antifungal lasts.
Ketoconazole + carbamazepine: ketoconazole inhibits CYP3A4 and may raise carbamazepine levels, with risk of toxicity (nystagmus, ataxia, sedation). Monitor levels.
Carbamazepine induces ketoconazole metabolism; ketoconazole inhibits CYP3A4, reducing carbamazepine metabolism.
Carbamazepine concentration, toxicity symptoms (diplopia, nystagmus, ataxia), mycosis response.
Diplopia, nystagmus, ataxia, drowsiness; or worsening fungal infection.
Monitor carbamazepine levels and antifungal response; adjust doses; consider a non-CYP3A4-inducing alternative.
DailyMed/FDA (NIH/NLM) — approved Ketoconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f162e616-21b4-49b1-b437-15e21001a6f0 ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Carbamazepine + vitamin D3: carbamazepine accelerates vitamin D metabolism, risking deficiency.
Carbamazepine is an enzyme inducer (CYP3A4 and others) that accelerates vitamin D catabolism, reducing 25-hydroxyvitamin D levels and, long-term, serum calcium and bone density — with risk of osteomalacia and fractures in patients on prolonged antiepileptic therapy. Monitor vitamin D and serum calcium, supplement vitamin D preventively (and calcium when indicated) and consider bone density assessment in chronic carbamazepine patients, especially older people and postmenopausal women.
Carbamazepine + vitamin D3: carbamazepine accelerates vitamin D metabolism — risk of deficiency.
Enzyme-inducing antiepileptics increase vitamin D and calcium catabolism.
25(OH)D, calcium and bone density in chronic use.
Vitamin D deficiency, osteomalacia, fractures.
Consider a higher vitamin D dose and monitor levels/25(OH)D in at-risk patients.
DailyMed (FDA) — approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=97e6e175-75e8-437b-b457-ddb1ae4e857d ; approved Cholecalciferol (vitamin D3) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3822c324-e22a-4ac4-ac1c-9b63983b516a — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Combining Efavirenz with Carbamazepine reduces the concentrations of both drugs, risking failure in controlling epilepsy and HIV.
The interaction is bidirectional: carbamazepine induces CYP3A4 and lowers efavirenz concentrations, and efavirenz also induces CYP3A4, lowering carbamazepine levels. The result can be simultaneous loss of virological control and of seizure control. Whenever possible, choose another antiepileptic (e.g. levetiracetam, valproate) in patients on efavirenz; if the combination is unavoidable, monitor the viral load and carbamazepine levels, adjusting doses.
Efavirenz + carbamazepine: mutual CYP3A4 induction — both drugs can become subtherapeutic. Monitor levels and clinical response.
Efavirenz induces Carbamazepine metabolism and Carbamazepine induces Efavirenz metabolism, mutually lowering exposure.
Monitor seizure control and HIV viral load.
Worsening seizures or a detectable viral load require reassessment of the antiepileptic/antiretroviral regimen.
With no reliable dose recommendation, prefer an alternative antiepileptic when possible (e.g. valproate, levetiracetam).
DailyMed/FDA (NIH/NLM) — approved Efavirenz label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92603fa5-7a2c-4bfb-9a70-aadb4fba952c ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Lamotrigine with Carbamazepine reduces Lamotrigine concentrations, possibly requiring a higher dose; Lamotrigine may also increase the toxicity of the Carbamazepine metabolite.
The interaction is bidirectional: carbamazepine induces lamotrigine glucuronidation and reduces its concentrations by about 40–50%, potentially requiring a lamotrigine dose increase; conversely, lamotrigine inhibits epoxide hydrolase and can raise the active metabolite carbamazepine-10,11-epoxide, causing toxicity (nystagmus, ataxia, diplopia) even with carbamazepine levels in range. Titrate lamotrigine according to response, watch for epoxide toxicity signs and consider epoxide monitoring if available.
Carbamazepine + lamotrigine: carbamazepine lowers lamotrigine levels (glucuronidation induction) and lamotrigine may raise carbamazepine-epoxide. Monitor both.
Carbamazepine induces the glucuronidation of Lamotrigine, lowering its levels; Lamotrigine may raise carbamazepine-10,11-epoxide, increasing toxicity.
Monitor seizure control and signs of neurological toxicity (diplopia, ataxia).
Rash or signs of a serious reaction require discontinuation and evaluation.
Adjust the Lamotrigine dose according to response and, if available, serum levels; watch for neurological toxicity.
DailyMed/FDA (NIH/NLM) — approved Lamotrigine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57f04b9b-06cd-8044-e063-6394a90ae733 ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Carbamazepine can reduce the effectiveness of levonorgestrel (including emergency contraception). If you take both, talk to your doctor or pharmacist.
Carbamazepine induces CYP3A4 and glucuronidation, accelerating levonorgestrel elimination and reducing contraceptive effectiveness — the levonorgestrel OTC label explicitly warns that seizure medicines can reduce effectiveness, and the Prontuário states that enzyme inducers (barbiturates, phenytoin, primidone, carbamazepine, rifampicin) reduce the effectiveness of progestogens. In regular hormonal contraception, an alternative or complementary method is recommended; for emergency contraception, the copper IUD is the reliable alternative.
Enzyme inducers (carbamazepine, phenytoin, rifampicin, barbiturates) accelerate progestogen metabolism and reduce contraceptive effectiveness. For emergency contraception with levonorgestrel, consider an alternative (ulipristal acetate is not a reliable alternative with inducers; copper IUD).
CYP3A4 induction, accelerating levonorgestrel metabolism.
Contraceptive effectiveness; irregular cycles may indicate reduced hormonal exposure.
Unplanned pregnancy; irregular bleeding.
Use a non-hormonal contraceptive (copper IUD) or an additional barrier method; for emergency contraception, prefer the copper IUD.
DailyMed/FDA (NIH/NLM) — approved Levonorgestrel label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=07567b80-d8a1-41c0-95e4-33afa584bbc4 ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2 ; PubMed — https://pmc.ncbi.nlm.nih.gov/articles/PMC2848501/ ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Carbamazepine can reduce the effect of estradiol (hormone therapy), lowering effectiveness and changing the bleeding pattern. Tell your doctor.
The approved estradiol label (DailyMed) documents that oestrogens are partially metabolised by CYP3A4 and that inducers of this enzyme — such as carbamazepine, phenytoin, barbiturates and rifampicin — can reduce plasma concentrations, decreasing the therapeutic effect and changing the uterine bleeding pattern. In hormone replacement therapy, a dose adjustment or another route may be needed; in hormonal contraceptives, contraceptive effectiveness may be compromised.
CYP3A4 inducers (carbamazepine, phenytoin, rifampicin) reduce oestrogen concentrations, decreasing the therapeutic effect and changing the bleeding pattern. Consider a dose adjustment or an alternative.
CYP3A4 induction, accelerating oestrogen metabolism.
Vasomotor symptoms, bleeding pattern and contraceptive effectiveness.
Irregular bleeding, return of menopausal symptoms, unplanned pregnancy.
Monitor the therapeutic effect; consider an estradiol dose adjustment or non-hormonal contraception when applicable.
DailyMed/FDA (NIH/NLM) — approved Estradiol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5718f042-e8c0-b721-e063-6294a90a5bef ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Carbamazepine toxicity. Clarithromycin inhibits CYP3A4 and greatly raises Carbamazepine levels.
Carbamazepine is extensively metabolised by CYP3A4 and clarithromycin is a potent inhibitor of this isoenzyme and of P-glycoprotein. The combination can double or more than double serum carbamazepine levels, with toxicity symptoms such as diplopia, nystagmus, ataxia, sedation and nausea; severe cases may progress to seizures or coma. Whenever possible, an alternative antibiotic that does not inhibit CYP3A4 should be chosen (e.g. azithromycin); if the combination is necessary, reduce the carbamazepine dose, monitor serum levels and clinical signs of toxicity.
Clarithromycin inhibits CYP3A4 and greatly increases carbamazepine concentrations, with risk of toxicity (diplopia, ataxia, sedation, nausea). Prefer an alternative antibiotic; if unavoidable, reduce the carbamazepine dose and monitor.
Carbamazepine is metabolised by CYP3A4, potently inhibited by Clarithromycin.
Carbamazepine levels and toxicity signs in the first days.
Nystagmus, diplopia, ataxia, sedation, nausea.
Avoid the combination; choose an alternative antibiotic or monitor Carbamazepine levels.
DailyMed/FDA (NIH/NLM) — approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2
Grapefruit juice inhibits CYP3A4, reduces carbamazepine metabolism and raises plasma concentrations, increasing the risk of adverse effects.
Advise avoiding grapefruit juice; if consumed, monitor plasma levels and signs of toxicity (dizziness, drowsiness, ataxia, diplopia).
EMC-UK (MHRA) — approved Carbamazepine SmPC: https://www.medicines.org.uk/emc/product/1040/smpc
Carbamazepine affects cardiac conduction; atrioventricular block is an absolute contraindication.
Do not prescribe to patients with AV block; consider alternative antiepileptic therapy.
EMC-UK (MHRA) — approved Carbamazepine SmPC: https://www.medicines.org.uk/emc/product/1040/smpc
Carbamazepine is contraindicated in patients with a history of bone marrow depression; agranulocytosis and aplastic anaemia may occur.
Do not use in these patients; during therapy, monitor the blood count and stop if severe or progressive leucopenia develops.
EMC-UK (MHRA) — approved Carbamazepine SmPC: https://www.medicines.org.uk/emc/product/1040/smpc
Hepatic porphyrias (acute intermittent, variegate and cutanea tarda) contraindicate carbamazepine.
Do not prescribe to patients with a history of hepatic porphyria.
EMC-UK (MHRA) — approved Carbamazepine SmPC: https://www.medicines.org.uk/emc/product/1040/smpc
Carbamazepine can cause hyponatraemia, with increased risk in renal disease, diuretic use or elderly patients.
Check serum sodium before start, at 2 weeks and then monthly for the first months; institute fluid restriction if hyponatraemia occurs.
EMC-UK (MHRA) — approved Carbamazepine SmPC: https://www.medicines.org.uk/emc/product/1040/smpc
The HLA-B*1502 allele is strongly associated with Stevens-Johnson syndrome risk with carbamazepine in Han Chinese, Thai and Malay populations.
Screen for the allele before starting whenever possible; if positive, do not start the drug unless no alternative exists.
EMC-UK (MHRA) — approved Carbamazepine SmPC: https://www.medicines.org.uk/emc/product/1040/smpc
First-trimester exposure increases the risk of major malformations (neural tube defects, orofacial clefts, cardiovascular malformations), with a dose-dependent risk.
Use only if benefit clearly outweighs risk, as monotherapy at the lowest effective dose and with specialised antenatal surveillance; do not stop abruptly. Folate supplementation is recommended before and during pregnancy and vitamin K1 at the end of pregnancy.
Breastfeeding is possible if benefits are weighed; observe the infant for adverse reactions, including hepatobiliary effects.
Carbamazepine induces enzymes and can fail hormonal contraception; use highly effective contraception (e.g. IUD) or complementary methods, with at least 50 µg of oestrogen if hormonal.
EMC-UK (MHRA) — approved Carbamazepine SmPC: https://www.medicines.org.uk/emc/product/1040/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Anticonvulsant and mood stabiliser. The therapeutic effect in epilepsy relates to maintenance of plasma concentrations within the range usually considered to be 4 to 12 mcg/ml. Metabolism is auto-induced over 3 to 5 weeks, often requiring dose adjustment.
Blocks voltage-dependent sodium channels, reducing sustained high-frequency neuronal firing and stabilising neuronal membranes. It also has effects on calcium channels and on GABAergic and serotoninergic systems.
Oral absorption is slow and irregular, with peak plasma concentrations 4 to 8 hours after tablet intake (about 1.5 hours for the suspension). Plasma protein binding is about 76%.
Metabolised in the liver, with formation of carbamazepine-10,11-epoxide, an active metabolite. Carbamazepine is a potent inducer of cytochrome P450 enzymes (including CYP3A4), accelerating its own metabolism and that of many other drugs. The metabolites are eliminated in urine and faeces.
The initial half-life is 25 to 65 hours; after enzyme auto-induction (3 to 5 weeks) it falls to about 12 to 17 hours.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
