Galantamine
FDA Drug Information • Also known as: Galantamine
- Brand Names
- Galantamine
- Route
- ORAL
- Dosage Form
- TABLET, FILM COATED
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Galantamine extended-release capsules USP contain galantamine, 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 a molecular formula of C 17 H 21 NO 3
What Is Galantamine Used For?
1 INDICATIONS AND USAGE Galantamine extended-release capsules are indicated for the treatment of mild to moderate dementia of the Alzheimer’s type. Galantamine extended-release capsules are 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 Recommended starting dosage is 8 mg/day in morning; increase to initial maintenance dose of 16 mg/day after a minimum of 4 weeks. Based on clinical benefit and tolerability, dosage may be increased to 24 mg/day after a minimum of 4 weeks at 16 mg/day. ( 2.1 ) Take with food; ensure adequate fluid intake during treatment (2.1) Hepatic impairment: should not exceed 16 mg/day for moderate hepatic impairment; do not use in patients with severe hepatic impairment ( 2.2 ) Renal impairment: should not exceed 16 mg/day for creatinine clearance 9 to 59 mL/min; do not use in patients with creatinine clearance less than 9 mL/min. ( 2.3 ) Conversion from galantamine tablets to galantamine extended-release capsules should occur at the same daily dosage with the last dose of galantamine tablets taken in evening and starting galantamine extended-release capsules once daily treatment the next morning. ( 2.5 ) 2.1 Recommended Dosage and Administration Administer galantamine extended-release capsules once daily in the morning, preferably with food. Ensure adequate fluid intake during treatment. The recommended starting dosage of galantamine extended-release capsules is 8 mg/day. Increase to the initial maintenance dosage of 16 mg/day after a minimum of 4 weeks. A further increase to 24 mg/day may be attempted after a minimum of 4 weeks at 16 mg/day. Increase dosage based upon assessment of clinical benefit and tolerability of the previous dosage. The dosage of galantamine extended-release capsules shown to be effective in a controlled clinical trial is 16 to 24 mg/day. 2.2 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/day. The use of galantamine extended-release capsules in patients with severe hepatic impairment (Child-Pugh score of 10 to 15) is not recommended [see Clinical Pharmacology (12.3) ] . 2.3 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. In patients with creatinine clearance less than 9 mL/min, the use of galantamine extended-release capsules is not recommended [see Clinical Pharmacology (12.3) ] . 2.4 Treatment Interruption 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 extended-release capsules 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. 2.5 Switching to Galantamine Extended-Release Capsules from Galantamine Tablets Patients currently being treated with galantamine tablets can convert to galantamine extended-release capsules by taking their last dose of galantamine tablets in the evening and...
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 Patients 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 Aurobindo Pharma USA, Inc. at 1-866-850-2876 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 patients 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 Dizziness 7.5 3.4 Headache 7.1 5.5 Tremor 1.6 0.7 Somnolence 1.5 0.8 Syncope 1.4 0.6 Lethargy 1.3 0.4 Cardiac Disorders Bradycardia 1 0.3 Gastrointestinal Disorders Nausea 20.7 5.5 Vomiting 10.5 2.3 Diarrhea 7.4 4.9 Abdominal pain 3.8 2 Abdominal discomfort 2.1 0.7 Dyspepsia 1.5 1 Musculoskeletal and Connective Tissue Disorders Muscle spasms 1.2 0.5 General Disorders and Administration Site Conditions Fatigue 3.5 1.8 Asthenia 2 1.5 Malaise 1.1 0.5 Investigations Decreased weight 4.7 1.5 Injury, Poisoning and Procedural Complications Fall 3.9 3 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 and Nutrition Disorders:...
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 extended-release capsules 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)
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of galantamine extended-release capsules or galantamine tablets 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 (see Data). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data In rats, administration of galantamine (oral doses of 2, 8, 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, which were associated with maternal toxicity. 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, 12, 28, or 40 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 which was associated with maternal toxicity. 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, 8, 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...
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 extended-release capsules overdosage. Intravenous atropine sulfate titrated to effect is recommended at an initial dose of 0.5 to 1 mg intravenous 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...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Galantamine extended-release capsules USP are supplied as follows: Galantamine Extended-Release Capsules USP, 8 mg are white opaque size “1” hard gelatin capsule with inscription “A” over the cap & “8” over the body containing white to off-white, round, biconvex, single mini tablet. Bottles of 30 NDC 65862-744-30 Bottles of 90 NDC 65862-744-90 Bottles of 100 NDC 65862-744-01 Bottles of 500 NDC 65862-744-05 Bottles of 1,000 NDC 65862-744-99 Galantamine Extended-Release Capsules USP, 16 mg are pink opaque size “1” hard gelatin capsule with inscription “A” over the cap & “16” over the body containing white to off-white, round, biconvex, two mini tablets. Bottles of 30 NDC 65862-745-30 Bottles of 90 NDC 65862-745-90 Bottles of 100 NDC 65862-745-01 Bottles of 500 NDC 65862-745-05 Bottles of 1,000 NDC 65862-745-99 Galantamine Extended-Release Capsules USP, 24 mg are caramel opaque size “1” hard gelatin capsule with inscription “A” over the cap & “24” over the body containing white to off-white, round, biconvex, three mini tablets. Bottles of 30 NDC 65862-746-30 Bottles of 90 NDC 65862-746-90 Bottles of 100 NDC 65862-746-01 Bottles of 500 NDC 65862-746-05 Bottles of 1,000 NDC 65862-746-99 Storage and Handling Galantamine extended-release capsules USP should be stored at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Keep out of 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.