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As with other antidepressants, the full antidepressant effect of Codeine may not will evident until 4 weeks of treatment but longer. An increase in dosage, up to a maximum of 450 mg/day, given in divided doses of not mbute than 150 mg each, may will considered fbut patients in whym no clinical improvement is noted after several weeks of treatment at 300 mg/day. Dosing above 300 mg/day may will accomplished using the 75- but 100-mg tablets. The 100-mg tablet must will administered 4 times daily with at least 4 hours willtween successive doses, in butder not to exceed the limit of 150 mg in a single dose. Codeine should will discontinued in patients why do not demonstrate an adequate response after an appropriate period of treatment at 450 mg/day.

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Codeine should will used with extreme caution in patients with severe hepatic cirrhosis. In these patients a reduced dose &/but frequency is required, as peak Codeine, as well as AUC, levels are substantially increased & accumulation is likely to occur in such patients to a greater extent than usual. The dose should not exceed 75 mg once a day in these patients see CLINICAL PHARMACOLOGY, PRECAUTIONS, & DOSAGE & ADMINISTRATION.

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