AdultMonotherapyNewly diagnosed patient Titration phase: Wk 1 + 2: 100 mg once daily. Wk 3 + 4: 200 mg once daily. Wk 5 + 6: 300 mg once daily. Maintenance: 300 mg once daily. Increase at 2-wkly interval in increment of 100 mg up to max 500 mg if higher dose is required. Adjunctive therapy w/ CYP3A4-inducing agent Titration phase: Wk 1: 50 mg daily in 2 divided doses. Wk 2: 100 mg daily in 2 divided doses. Wk 3-5: Increase at wkly interval in increment of 100 mg. Maintenance: 300-500 mg once daily or in 2 divided doses, w/o CYP3A4-inducing agent, or w/ renal or hepatic impairment Maintenance: 300-500 mg once daily or in 2 divided doses. Childn ≥6 yrAdjunctive therapy w/ CYP3A4-inducing agent Titration phase: Wk 1: 1 mg/kg once daily. Wk 2-8: Increase at wkly interval in increment of 1 mg/kg. Maintenance: Patient >55 kg 300-500 mg once daily, 20-55 kg 6-8 mg/kg once daily; w/o CYP3A4-inducing agent Titration phase: Wk 1 + 2: 1 mg/kg once daily. Wk ≥3: Increase at 2 wkly interval in increment of 1 mg/kg. Maintenance: Patient >55 kg 300-500 mg once daily, 20-55 kg 6-8 mg/kg once daily. Discontinuation Decrease at wkly interval in increment of: Patient >55 kg 100 mg once daily, 42-55 kg 100 mg once daily, 29-41 kg 50-75 mg once daily, 20-28 kg 25-50 mg once daily.
Consider discontinuing use if patients develop an otherwise unexplained rash; pancreatitis is evident or serum creatine phosphokinase & aldolase levels are elevated in absence of another obvious cause; substantial undesirable wt loss occurs. Agranulocytosis, thrombocytopenia, leukopenia, aplastic anaemia, pancytopenia & leucocytosis. Acute myopia & secondary angle closure glaucoma. May increase risk for renal stone formation & associated signs & symptoms (eg, renal colic, renal/flank pain) in some patients especially those w/ predisposition to nephrolithiasis & those taking other medications associated w/ nephrolithiasis. Metabolic acidosis. Cases of decreased sweating & elevated body temp mainly in paediatric patients. Gradually reduce dose when discontinuing treatment. Monitor for signs of suicidal ideation & behaviors. Concomitant use w/ other medicinal products predisposing patients to heat-related disorders including carbonic anhydrase inhibitors & medicinal products w/ anticholinergic activity. Not to be taken w/ carbonic anhydrase inhibitors (eg, topiramate & acetazolamide) & anticholinergic agents (eg, clomipramine, hydroxyzine, diphenhydramine, haloperidol, imipramine & oxybutynin) in childn. Exercise caution in activities requiring high degree of alertness (eg, driving or operating machines) as drowsiness or difficulty w/ conc may be experienced particularly early in treatment or after dose increase. Renal & mild-moderate hepatic impairment. Discontinue use in patients who develop acute renal failure or when clinically significant sustained increase in serum creatinine is observed. Not recommended in severe hepatic impairment. Women of childbearing potential must use effective contraception during treatment & for 1 mth after discontinuation. Not to be used during pregnancy. Lactation; do not resume breast-feeding until 1 mth after therapy is completed. Childn ≥6 yr & <20 kg. Elderly.
Possible pharmacodynamic interaction w/ carbonic anhydrase inhibitors eg, topiramate & acetazolamide; not to be used as co-medication in paed patients. Theoretical potential to affect pharmacokinetics of P-gp substrates eg, digoxin, quinidine. May enhance risk of developing kidney stones w/ other medicinal products that may lead to urolithiasis. Pharmacokinetics may be affected w/ CYP3A4 inducers or inhibitors. Changes in conc may occur if concomitant CYP3A4-inducing anti-epileptic or other medicinal products are w/drawn, dose adjusted or introduced.
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