Carbamazepine Drug Information PDF

Treatment of seizures. oral suspensions, chewable tablets, Many dosage forms oral immediate release tablets extended release tablets extended release capsules. Effective dose for seizure disorders : 15 to 25 mg/kg/day. Metabolized by P450 isozymeCYP3A4. Intro: Having some anticonvulsant activity...

Treatment of seizures. oral suspensions, chewable tablets, Many dosage forms oral immediate release tablets extended release tablets extended release capsules. Effective dose for seizure disorders : 15 to 25 mg/kg/day. Metabolized by P450 isozymeCYP3A4. Intro: Having some anticonvulsant activity. Formation of carbamazepine-10,11-epoxide : higher in infants Ratio of carbamazepine-10,11epoxide to carbamazipine and preschool children than in adults. So faster metabolized in infants And preschooler children Less than 2% carbamazepine excreted unchanged in urine. Exclusively by metabolic route, plasma albumin Bound to Less than 2% of an oral dose being excreted unchanged in urine. Clearance values difficult to estimate because bioavailability uncertain. Approximately (0.064 L/kg/hr α1 –acid glycoprotein to a significant extent. Approximately 0.2 to 0.3, / 20-30% unbound & 70-80% bound Clearance : Free fraction : Alteration in serum protein concentration may affect therapeutic range. ) in adult patients who have Therapeutic plasma concentration received the drug chronically. 4-12 mg/L. Average clearance value : In patients who are taking other enzyme inducing antiepileptic drugs concurrently, clearance increased to 0.1L/kg/hr. Higher in children : (0.11L/kg/hr. 80% ) Bioavailability factor (F) Reach blood circulation (in oral form) = increase Cl , no sufficient = increase dose needed When drug induces its own metabolism Auto induction of its metabolic enzymes. Increase in clearance : Key Parameters: 1.0 Chemical form (S) (administered as active form) Potent inducer of drug metabolizing enzymes Important to initiate patients with relatively low dose to avoid side effects early in the therapy. Available in pure form 1.4L/kg Volume of distribution(V)(based on oral administered data) Multiply by patient body weight Maintenance dose increased at 1-week to 2- week intervals. Monotherapy = 0.064L/kg/hr Autoinduction of metabolism commonly causes changes in steady-state carbamazepine levels Polytherapy = 0.1L/kg/hr (increase dose since faster metabolism) Clearance: (no need number Less than proportional to an increase in the maintenance dose. Carbamazipine principle example of drug that displays autoinduction: Children (Monotherapy) = 0.11L/kg/hr (increase dose since faster metabolism) α (freefraction) = 0.2-0.3 (i.e. enhanced metabolism) of other anti convulsants. Adult monotherapy = 15 hr Cross-induction Whenever added to anticonvulsant regimen or other agents are added T 1/2 : Additional plasma level monitoring Adult polytherapy = 10 hr Polytherapy Ensures maintenance regimen optimal for therapeutic control. Since low metabolism 4-12 mg/L. THERAPEUTIC AND TOXIC PLASMA CONCENTRATIONS: Plasma concentration exceeds 9 mg/L. Many clinicians prefer to use a therapeutic range of approximately Symptoms of toxicity : Reported steady-state half-lives of 4-12 hours. Since higher metabolism a patient receiving other enzyme inducing anticonvulsant. Therapeutic plasma concentration Children metabolize more rapidly than adults 15 hrs. ) 4-8 mg/L. So doctor need to stick to this range (4-8) Half life (t 1/2): Adult patients receiving carbamazepine monotherapy,-half life : Inhibit carbamazepine metabolism Higher toxic conc = higher frequency CYP 3A4 inhibitors: 10 hrs Increase plasma carbamazepine levels; (any 4 Adult patients receiving other enzyme inducing antiepileptic drugs (eg.phenytoin,phenobarbital), half-life : Carbamazepine Within first few weeks useful Carbamazepine drug interaction: cimetidine, diltiazem, erythromycin, clarithromycin, fluoxetine, loratadine, verapamil, valproate. ) Induce rate of metabolism Early morning before the first dose is administered, or Decrease plasma carbamazepine levels : (any 4 ) CYP 3A4 inducers: Later in the day before the next dose. Rifampicin,Theophylline. Most sensible time : Such samples reflect trough conc. cisplatin, doxorubicin, felbamate, phenobarbital, phenytoin, primidone, Potent inducer Blurred vision Comparable from day to day. Drowsiness, Time to sample: Autoinduction, Ataxia, Limitations: ♦ ♦ ♦♦♦ ♦ ♦ ⛔♦♦ ♦ ♦ ♦ ♦ ♦ CNS: Many drug interactions, toxicities and teratogenicity (in pregnancy) ⛔ Nystagmus, ⛔ ♦ Skin rashes, Chemically similar to carbamazepine Syndrome of inappropriate antidiuretic hormone(SIADH) Oxcarbazepine (Trileptal): Improved safety profile. ADVERSE DRUG REACTIONS Hyponatremia. Alternative for Carbamazepine. Dermatological and hematological side effects. Many patients, develop symptoms of toxicity when plasma concentration exceeds 9 mg/L. Mild leukopenia-10% of patients. Others : Carbamazepine, is primarily bound to albumin and α1- acid glycoprotein and has a free fraction of approximatly 0.2 to 0.3. Teratogenic. Conclusion : Not to pregnant Children metabolize carbamazepine more rapidly than adults Lipid soluble compound = in adipose tissue Adult patients receiving other enzyme inducing antiepileptic drugs (eg.phenytoin,phenobarbital), half-life of approximately10 hrs. Slowly and variably absorbed from GIT approximately 0.8 when administered as oral tablet, Bioavailability factor (F) : chewable tablet or suspension. well absorbed , Controlled release product : Bioavailability 89% of the suspension Bioavailability: What is the absorption? Q.1: Slowly absorbed, Calculation : Changes in gastrointestinal function could decrease bioavailability Result in variable plasma concentration Estimated to be greater than 75%. Effects of gender and race not been systematically studied Q.2: Approximatly 1.4L/kg. Solution: Wide range of reported values (0.8-1.9L/kg), Volume of Distribution: Variability due to in plasma binding. Primarily bound to albumin and α1- acid glycoprotein Has free fraction of approximately 0.2 to 0.3. ♦ ⛔ # ⛔