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Galantamine Hydrobromide

FDA Drug Information • Also known as: Galantamine Hydrobromide

Brand Names
Galantamine Hydrobromide
Dosage Form
POWDER
Product Type
BULK INGREDIENT

Description

11 DESCRIPTION Galantamine Oral Solution, USP contains galantamine hydrobromide, USP, a reversible, competitive acetylcholinesterase inhibitor, as the hydrobromide salt. Galantamine hydrobromide is known chemically as (4a S ,6 R ,8a S )-4a,5,9,10,11,12-hexahydro-3-methoxy-11-methyl-6 H -benzofuro[3a,3,2- ef ][2]benzazepin-6-ol hydrobromide. It has an empirical formula of C 17 H 21 NO 3

  • HBr and a molecular weight of 368.27. Galantamine hydrobromide, USP is a white to off-white powder and is sparingly soluble in water. The structural formula is: Galantamine Oral Solution, USP contains 4 mg (as 5.13 mg galantamine hydrobromide, USP) per mL. The inactive ingredients are methylparaben, propylparaben, purified water and saccharin sodium. Galantamine may contain hydrochloric acid and/or sodium hydroxide to adjust pH. Chemical Structure

    • What Is Galantamine Hydrobromide Used For?

    1 INDICATIONS AND USAGE Galantamine is indicated for the treatment of mild to moderate dementia of the Alzheimer’s type. Galantamine is a cholinesterase inhibitor indicated for the treatment of mild to moderate dementia of the Alzheimer’s type. ( 1 )

    Dosage and Administration

    2 DOSAGE AND ADMINISTRATION

  • Galantamine Oral Solution: Recommended starting dosage is 4 mg (1 mL) twice daily; increase dose to initial maintenance dosage of 8 mg (2 mL) twice daily after a minimum of 4 weeks. Based on clinical benefit and tolerability, dosage may be increased to 12 mg (3 mL) twice daily after a minimum of 4 weeks at 8 mg (2 mL) twice daily. ( 2.2 )
  • Take with meals; ensure adequate fluid intake during treatment. ( 2.2 )
  • Hepatic Impairment: should not exceed 16 mg (4 mL)/day for moderate hepatic impairment; do not use in patients with severe hepatic impairment. ( 2.3 )
  • Renal Impairment: should not exceed 16 mg (4 mL)/day for creatinine clearance 9 mL to 59 mL/min; do not use in patients with creatinine clearance less than 9 mL/min. ( 2.4 ) 2.2 Galantamine Oral Solution The dosage of galantamine tablets shown to be effective in controlled clinical trials is 16 mg to 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 mg to 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 might provide additional benefit for some patients. The recommended starting dosage of galantamine oral solution is 4 mg (1 mL) twice a day (8 mg (2 mL)/day). The dosage should be increased to the initial maintenance dosage of 8 mg (2 mL) twice a day (16 mg (4 mL)/day) after a minimum of 4 weeks. A further increase to 12 mg (3 mL) twice a day (24 mg (6 mL)/day) should be attempted after a minimum of 4 weeks at 8 mg (2 mL) twice a day (16 mg (4 mL)/day). Dosage increases should be based upon assessment of clinical benefit and tolerability of the previous dose. Galantamine oral solution 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 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 are lost, however, when the drug is discontinued. 2.3 Dosage in Patients with Hepatic Impairment In patients with moderate hepatic impairment (Child-Pugh score of 7 to 9), the dosage should generally not exceed 16 mg (4 mL)/day. The use of galantamine in patients with severe hepatic impairment (Child-Pugh score of 10 to 15) is not recommended [see Clinical Pharmacology (12.3) ]. 2.4 Dosage in Patients with Renal Impairment In patients with creatinine clearance of 9 mL to 59...

    • Side Effects (Adverse Reactions)

    6 ADVERSE REACTIONS Serious adverse reactions are discussed in more detail in the following sections of the labeling:

  • Serious Skin Reactions [see Warnings and Precautions (5.1) ]
  • Cardiovascular Conditions [see Warnings and Precautions (5.3) ]
  • Gastrointestinal Conditions [see Warnings and Precautions (5.4) ]
  • Genitourinary Conditions [see Warnings and Precautions (5.5) ]
  • Neurological Conditions [see Warnings and Precautions (5.6) ]
  • Pulmonary Conditions [see Warnings and Precautions (5.7) ]
  • Deaths in Subjects with Mild cognitive impairment (MCI) [see Warnings and Precautions (5.8) ] The most common adverse reactions (≥5%) were nausea, vomiting, diarrhea, dizziness, headache, and decreased appetite. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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. The most common adverse reactions associated with discontinuation (≥1%) in galantamine-treated patients from double-blind clinical trials were nausea (6.2%), vomiting (3.3%), decreased appetite (1.5%), and dizziness (1.3%). 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: Adverse Reactions Reported by ≥1% of Galantamine-Treated Patients in Pooled Placebo-Controlled, Double-Blind Clinical Trials System/Organ Class Adverse Reaction Galantamine (n=3956) % Placebo (n=2546) % Metabolism and Nutrition Disorders Decreased Appetite 7.4 2.1 Psychiatric Disorders Depression 3.6 2.3 Nervous System Disorders Headache 7.1 5.5 Dizziness 7.5 3.4 Tremor 1.6 0.7 Somnolence 1.5 0.8 Syncope 1.4 0.6 Lethargy 1.3 0.4 Cardiac Disorders Bradycardia 1.0 0.3 Gastrointestinal Disorders Nausea 20.7 5.5 Vomiting 10.5 2.3 Diarrhea 7.4 4.9 Abdominal Discomfort 2.1 0.7 Abdominal Pain 3.8 2.0 Dyspepsia 1.5 1.0 Musculoskeletal and Connective Tissue Disorders Muscle Spasms 1.2 0.5 General Disorders and Administration Site Conditions Fatigue 3.5 1.8 Asthenia 2.0 1.5 Malaise 1.1 0.5 Investigations Decreased Weight 4.7 1.5 Injury, Poisoning and Procedural Complications Fall 3.9 3.0 Laceration 1.1 0.5 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 to 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. Adverse reactions listed in Table 1 above were not included below: Metabolism...

    • Drug Interactions

    7 DRUG INTERACTIONS

  • Potential to interfere with the activity of anticholinergic medications. ( 7.1 )
  • Synergistic effect expected when given concurrently with succinylcholine, other cholinesterase inhibitors, similar neuromuscular blocking agents, or cholinergic agonists. ( 7.2 ) 7.1 Use with Anticholinergics Galantamine has the potential to interfere with the activity of anticholinergic medications [see Clinical Pharmacology (12.3) ] . 7.2 Use with Cholinomimetics and Other Cholinesterase Inhibitors A synergistic effect is expected when cholinesterase inhibitors are given concurrently with succinylcholine, other cholinesterase inhibitors, similar neuromuscular blocking agents or cholinergic agonists such as bethanechol [see Clinical Pharmacology (12.3) ] .

    • Contraindications

    4 CONTRAINDICATIONS Galantamine is 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 )

    Pregnancy and Breastfeeding

    8.1 Pregnancy There are no adequate and well-controlled studies in pregnant women. In studies conducted in animals, administration of galantamine during pregnancy resulted in developmental toxicity (increased incidence of morphological abnormalities and decreased growth in offspring) at doses similar to or greater than those used clinically. Galantamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In rats, administration of galantamine (oral doses of 2 mg, 8 mg, or 16 mg/kg/day), from day 14 (females) or day 60 (males) prior to mating and continuing in females through the period of organogenesis, resulted in an increased incidence of fetal skeletal variations at the two highest doses. The no-effect dose for embryo-fetal developmental toxicity in rats (2 mg/kg/day) is approximately equal to the maximum recommended human dose (MRHD of 24 mg/day) on a body surface area (mg/m 2 ) basis. When galantamine (oral doses of 4 mg, 12 mg, 28 mg, or 48 mg/kg/day) was administered to pregnant rabbits throughout the period of organogenesis, small increases in fetal visceral malformations and skeletal variations were observed at the highest dose. The no-effect dose for embryo-fetal developmental toxicity in rabbits (28 mg/kg/day) is approximately 20 times the MRHD on a mg/m 2 basis. In a study in which pregnant rats were orally dosed with galantamine (2 mg, 8 mg, or 16 mg/kg/day) from the beginning of organogenesis through day 21 post-partum, pup weights were decreased at birth and during the lactation period at the two highest doses. The no-effect dose for pre- and postnatal developmental toxicity in rats (2 mg/kg/day) is approximately equal to the MRHD on a mg/m 2 basis.

    8.3 Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when galantamine is administered to a nursing woman.

    Overdosage

    10 OVERDOSAGE Because strategies for the management of overdose are continually evolving, it is advisable to contact a poison control center to determine the latest recommendations for the management of an overdose of any drug. As in any case of overdose, general supportive measures should be utilized. Signs and symptoms of significant overdosing of galantamine are predicted to be similar to those of overdosing of other cholinomimetics. These effects generally involve the central nervous system, the parasympathetic nervous system, and the neuromuscular junction. In addition to muscle weakness or fasciculations, some or all of the following signs of cholinergic crisis may develop: severe nausea, vomiting, gastrointestinal cramping, salivation, lacrimation, urination, defecation, sweating, bradycardia, hypotension, respiratory depression, collapse and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Tertiary anticholinergics such as atropine may be used as an antidote for galantamine overdosage. Intravenous atropine sulfate titrated to effect is recommended at an initial dose of 0.5 mg to 1.0 mg i.v. with subsequent doses based upon clinical response. Atypical responses in blood pressure and heart rate have been reported with other cholinomimetics when co-administered with quaternary anticholinergics. It is not known whether galantamine and/or its metabolites can be removed by dialysis (hemodialysis, peritoneal dialysis, or hemofiltration). Dose-related signs of toxicity in animals included hypoactivity, tremors, clonic convulsions, salivation, lacrimation, chromodacryorrhea, mucoid feces, and dyspnea. In one postmarketing report, one patient who had been taking 4 mg of galantamine daily for a week inadvertently ingested eight 4 mg tablets (32 mg total) on a single day. Subsequently, she developed bradycardia, QT prolongation, ventricular tachycardia and torsades de pointes accompanied by a brief...

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Galantamine Oral Solution, USP 4 mg/mL oral solution is supplied in a 100 mL bottle as a clear, colorless to pale yellow solution with a calibrated (in milliliters) syringe. The minimum calibrated volume is 0.5 mL, while the maximum calibrated volume is 5 mL. NDC 0054-0137-49: Bottle of 100 mL 16.2 Storage and Handling Galantamine Oral Solution, USP should be stored at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] DO NOT FREEZE. Keep this and all drugs out of the reach of children.

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.