Clinical Pharmacology Details


CARBAMAZEPINE


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Indications & Dose:

Focal and secondary generalised tonic-clonic seizures


Primary generalised tonic-clonic seizures 



Adult: Initially 100–200 mg 1–2 times a day, increased in steps of 100–200 mg every 2 weeks; usual dose 0.8–1.2 g daily in divided doses; increased if necessary up to 1.6–2 g daily in divided doses Elderly: Reduce initial dose



Adult: Up to 1 g daily in 4 divided doses for up to 7 days, for short-term use when oral therapy temporarily not possible



Adult: Initially 100 mg 1–2 times a day, some patients may require higher initial dose, increase gradually according to response; usual dose 200 mg 3–4 times a day, increased if necessary up to 1.6 g daily


Prophylaxis of bipolar disorder unresponsive to lithium



Adult: Initially 400 mg daily in divided doses, increased until symptoms controlled; usual dose 400–600 mg daily; maximum 1.6 g per day


Adjunct in acute alcohol withdrawal


BY MOUTH


Adult: Initially 800 mg daily in divided doses, then reduced to 200 mg daily for usual treatment duration of 7–10 days, dose to be reduced gradually over 5 days Diabetic neuropathy



Adult: Initially 100 mg 1–2 times a day, increased gradually according to response; usual dose 200 mg 3–4 times a day, increased if necessary up to 1.6 g daily.


Focal and generalised tonic-clonic seizures



Child 1 month–11 years: Initially 5 mg/kg once daily, dose to be taken at night, alternatively initially 2.5 mg/kg twice daily, then increased in steps of 2.5–5 mg/kg every 3–7 days as required; maintenance 5 mg/kg 2–3 times a day, increased if necessary up to 20 mg/kg daily Child 12–17 years: Initially 100–200 mg 1–2 times a day, then increased to 200–400 mg 2–3 times a day, increased if necessary up to 1.8 g daily, dose should be increased slowly


Focal and secondary generalised tonic-clonic seizures


Primary generalised tonic-clonic seizures



Adult: Initially 100–400 mg daily in 1–2 divided doses, increased in steps of 100–200 mg every 2 weeks, dose should be increased slowly; usual dose 0.8–1.2 g daily in 1–2 divided doses, increased if necessary up to 1.6–2 g daily in 1–2 divided doses


Elderly: Reduce initial dose


Trigeminal neuralgia



Adult: Initially 100–200 mg daily in 1–2 divided doses, some patients may require higher initial dose, increase gradually according to response; usual dose 600–800 mg daily in 1–2 divided doses, increased if necessary up to 1.6 g daily in 1–2 divided doses


Prophylaxis of bipolar disorder unresponsive to lithium



Adult: Initially 400 mg daily in 1–2 divided doses, increased until symptoms controlled; usual dose 400–600 mg daily in 1–2 divided doses; maximum 1.6 g per day


Focal and generalised tonic-clonic seizures Prophylaxis of bipolar disorder



Child 5–11 years: Initially 5 mg/kg daily in 1–2 divided doses, then increased in steps of 2.5–5 mg/kg every 3–7 days as required, dose should be increased slowly; maintenance 10–15 mg/kg daily in continued 1–2 divided doses, increased if necessary up to 20 mg/kg daily in 1–2 divided doses


Child 12–17 years: Initially 100–400 mg daily in 1–2 divided doses, then increased to 400–1200 mg daily in 1–2 divided doses, increased if necessary up to 1.8 g daily in 1–2 divided doses, dose should be increased slowly


Focal and secondary generalised tonic-clonic seizures


Primary generalised tonic-clonic seizures



Adult: Initially 100–400 mg daily in 2 divided doses, increased in steps of 100–200 mg every 2 weeks, dose should be increased slowly; usual dose 0.8–1.2 g daily in 2 divided doses, increased if necessary up to 1.6–2 g daily in 2 divided doses


Elderly: Reduce initial dose


Focal and generalised tonic-clonic seizures Prophylaxis of bipolar disorder



Child 5–11 years: Initially 5 mg/kg daily in 2 divided doses, then increased in steps of 2.5–5 mg/kg every 3–7 days as required; maintenance 10–15 mg/kg daily in 2 divided doses, increased if necessary up to 20 mg/kg daily in 2 divided doses


Child 12–17 years: Initially 100–400 mg daily in 2 divided doses, dose should be increased slowly; maintenance 400–1200 mg daily in 2 divided doses, increased if necessary up to 1.8 g daily in 2 divided doses


Trigeminal neuralgia



Adult: Initially 100–200 mg daily in 2 divided doses, some patients may require higher initial dose. After initial dose, increase according to response; usual dose 600–800 mg daily in 2 divided doses, increased if necessary up to 1.6 g daily in 2 divided doses, dose should be increased slowly


Prophylaxis of bipolar disorder unresponsive to lithium



Adult: Initially 400 mg daily in 2 divided doses, increased until symptoms controlled; usual dose 400–600 mg daily in 2 divided doses; maximum 1.6 g per day

Contraindications:

Hypersensitivity to tricyclic antidepressants, bone marrow depression, concomitant use of MAO inhibitor

Side Effects:

Cautions:

Precautions:

Glaucoma, hepatic disease, renal disease, cardiac disease, psychosis, child <6 yr

Interaction:

 Drugs


Acetaminopen: Enhanced hepatotoxic potential; reduced acetaminophen response


Antidepressants, tricyclic: Carbamazepine (educes serum concentrations of imipramine and probably other cyclic antidepressants


Benzodiazepines (alprazolam, diazepam, midazolam, triazolam): Metabolized by CYP3A4; enzyme induced by carbamazepine; reduced benzo effect


Calcium channel blockers: Verapamil and diltiazem reduce the metabolism of carbamazepine leading to increased carbamazepine toxicity when these CCBs are added to chronic carbamazepine therapy; enzyme induction by carbamazepine can reduce the bioBrands Available with Cost of CCBs that undergo extensive 1 stpasa hepatic clearance, like felodipine (94% reduction)


Cimetidine: Transient (1 week) increases in carbsmazepine levels


Corticosteroids: Carbamazepine reduces levels and therapeutic effect


Cyclasporine: Carbamazepine reduces cyclosporine blood levels


Danazol: Increases carbamazepine levels with toxicity expected


Doxycycline: Carbamazepine reduces doxycycline levels and antibiotic effects


Erythromycin, clarithromycin:Increased carbarnazepine levels


Ethinyl Estradiol, Oral contraceptives: Carbamazepineinduced metabolic induction may lead to menstrual irregularities and unplanned pregnancies


Felbamate: Reductions in carbamazepine levels and increases in 10,11-epoxide metabolite, along with decreased felbarnate concentrations


Fluoxetine, fluvoxamine:Inhibits carbamazepine metabolism, increased levels and risk of toxicity


Isoniazid: Increases carbamazepine levels with increased risk of toxicity


Isotretinoin: Reduced carbamazepine bioBrands Available with Cost


Lamotrigine: Increased carbamazepine metab and risk of toxicity; carbamazepine reduces lamotrigine levels


Lithium: Increased potential for neurotoxicity with normal lithium concentrations; reverses carbamazepine induced leukopenia; additive antithyroidal effects


Mebendazole: Carbamazepine decreases mebendazole levels, significant only when large doses given


Methadone: Carbamazepine reduces levels and therapeutic effect


Metronidazole: Increases carbamazepine concentrations with toxicity


Neuroleptics: Reduced concentration of and therapeutic response to these agents when used with carbamazepine


Omeprazole: May increase carbamazepine concentrations


Oral anticoagulants: Decreased prothrombin time


Phenytoin: Concurrent use reduces serum concentrations of both


Propoxyphene: Increases carbamazepine levels


Theophylline: Carbamazepine reduces levels and therapeutic effect


Thyroid: Cxrbamazepine reduces levels and therapeutic effect


Valproic acid: Valproic acid can increase, decrease, or have no effect on carbamazepine, monitor serum levels; carbamazepine decreases levels of valproic acid


 

Warnings:

Adverse Effects:

Lactations:

Concentration in milk approximately 60% of maternal plasma concentration; compatible with breast feeding 


 

Special Precautions:

Counselling:

Side Effects Or Adverse Reactions:

 


CN: Ataxia, confusion, dizziness, drowsiness, fatigue, hallucinations, headache, paralysis


CV: Aggravation of coronary artery disease, CHF, hypertension, hypotension


EENT: Blurred vision, conjunctivitis, diplopia, dry mouth, nystagmus, tinnitus


GI: Abdominal pain, anorexia, constipation, diarrhea, enzymes, glossitis, hepatitis, increased liver enzymes, nausea, stomatitis, vomiting


GU: Albuminuria, frequency, glycosuria, impotence, urinary retention


HEME: Agranulocytosis, aplastic anemia, eosinophilia, leukocytosis, neutropenia, thrombocytopenia


RESP: Pulmonary hypersensitivity (fever, dyspnea, pneumonitis)


SKIN: Rash, Stevens-Johnson syndrome, urticaria 

Patient And Carer Advice: