Galantamine

2 DOSAGE AND ADMINISTRATION Galantamine tablets: Recommended starting dosage is 4 mg twice daily; increase to initial maintenance dosage of 8 mg twice daily after a minimum of 4 weeks. Based on clinical benefit and tolerability, dosage may be increased to 12 mg twice daily after a minimum of 4 weeks at 8 mg twice daily.

2 Galantamine Immediate-Release Tablets The dosage of galantamine tablets shown to be effective in controlled clinical trials is 16 - 32 mg/day given as twice daily dosing. As the dosage of 32 mg/day is less well tolerated than lower dosages and does not provide increased effectiveness, the recommended dosage range is 16 - 24 mg/day given twice daily.

The dosage of 24 mg/day did not provide a statistically significant greater clinical benefit than 16 mg/day. It is possible, however, that a daily dosage of 24 mg of galantamine tablets might provide additional benefit for some patients.

The recommended starting dosage of galantamine tablets is 4 mg twice a day (8 mg/day). The dosage should be increased to the initial maintenance dosage of 8 mg twice a day (16 mg/day) after a minimum of 4 weeks. A further increase to 12 mg twice a day (24 mg/day) should be attempted after a minimum of 4 weeks at 8 mg twice a day (16 mg/day).

Dosage increases should be based upon assessment of clinical benefit and tolerability of the previous dose. Galantamine tablets should be administered twice a day, preferably with morning and evening meals. Patients and caregivers should be advised to ensure adequate fluid intake during treatment.

If therapy has been interrupted for more than three days, the patient should be restarted at the lowest dosage and the dosage escalated to the current dose. The abrupt withdrawal of galantamine tablets in those patients who had been receiving dosages in the effective range was not associated with an increased frequency of adverse events in comparison with those continuing to receive the same dosages of that drug.

The beneficial effects of galantamine tablets are lost, however, when the drug is discontinued. 3 Dosage in Patients with Hepatic Impairment In patients with moderate hepatic impairment (Child-Pugh score of 7 - 9), the dosage should generally not exceed 16 mg/day.

3) ] . 4 Dosage in Patients with Renal Impairment In patients with creatinine clearance of 9 to 59 mL/min, the dosage should generally not exceed 16 mg/day. 3) ] .

gov/medwatch . 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most common adverse reactions in galantamine-treated patients from double-blind clinical trials (≥ 5%) were nausea, vomiting, diarrhea, dizziness, headache, and decreased appetite. 3%). The safety of the extended-release capsule and immediate-release tablet formulations of galantamine was evaluated in 3956 galantamine-treated patients who participated in 8 placebo-controlled clinical studies and 1454 subjects in 5 open-label clinical studies with mild to moderate dementia of the Alzheimer’s type.

In clinical studies, the safety profile of once-daily treatment with extended-release galantamine was similar in frequency and nature to that seen with tablets. The information presented in this section was derived from pooled double-blind studies and from pooled open-label data.

Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials Table 1 lists the adverse reactions reported in ≥1% of galantamine-treated patients in 8 placebo-controlled, double-blind clinical trials. Table 1.

5 The majority of these adverse reactions occurred during the dose-escalation period. In those patients who experienced the most frequent adverse reaction, nausea, the median duration of the nausea was 5-7 days. Other Adverse Reactions Observed in Clinical Trials of Galantamine The following adverse reactions occurred in <1% of all galantamine-treated patients (N=3956) in the above double-blind, placebo-controlled clinical trial data sets.

In addition, the following also includes all adverse reactions reported at any frequency rate in patients (N=1454) who participated in open-label studies. 2%) placebo patients (N=2546) discontinued due to an adverse reaction. 7%). 7%).

1 Serious Skin Reactions Serious skin reactions (Stevens-Johnson syndrome and acute generalized exanthematous pustulosis) have been reported in patients receiving galantamine tablets. Inform patients and caregivers that the use of galantamine tablets should be discontinued at the first appearance of a skin rash, unless the rash is clearly not drug-related.

If signs or symptoms suggest a serious skin reaction, use of this drug should not be resumed and alternative therapy should be considered. 2 Anesthesia Galantamine, as a cholinesterase inhibitor, is likely to exaggerate the neuromuscular blocking effects of succinylcholine-type and similar neuromuscular blocking agents during anesthesia.

3 Cardiovascular Conditions Because of their pharmacological action, cholinesterase inhibitors have vagotonic effects on the sinoatrial and atrioventricular nodes, leading to bradycardia and AV block. 2) ]. Therefore, all patients should be considered at risk for adverse effects on cardiac conduction.

2% [6/273]). 4 Gastrointestinal Conditions Through their primary action, cholinomimetics may be expected to increase gastric acid secretion due to increased cholinergic activity. , those with a history of ulcer disease or patients using concurrent nonsteroidal anti-inflammatory drugs (NSAIDS).

Clinical studies of galantamine have shown no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding. Galantamine, as a predictable consequence of its pharmacological properties, has been shown to produce nausea, vomiting, diarrhea, anorexia, and weight loss.

During therapy, the patient’s weight should be monitored. 5 Genitourinary Conditions Although this was not observed in clinical trials with galantamine, cholinomimetics may cause bladder outflow obstruction. 2) ] . Seizure activity may also be a manifestation of Alzheimer's disease.

4 CONTRAINDICATIONS Galantamine tablets are contraindicated in patients with known hypersensitivity to galantamine hydrobromide or to any excipients used in the formulation. Known hypersensitivity to galantamine hydrobromide or any excipients ( 4 )