GALANTAMINE HYDROBROMIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GALANTAMINE HYDROBROMIDE (GALANTAMINE HYDROBROMIDE).
Reversible competitive acetylcholinesterase inhibitor; also modulates nicotinic acetylcholine receptors, increasing acetylcholine concentration in synaptic clefts.
| Metabolism | Primarily hepatic via CYP2D6 and CYP3A4; also glucuronidation. |
| Excretion | Renal (approximately 95% of administered dose, with 20-25% as unchanged drug and the remainder as metabolites, mainly O-desmethylgalantamine glucuronide and other conjugates); biliary/fecal: <5%. |
| Half-life | Terminal elimination half-life is approximately 7 hours (range 5-9 hours) in patients with normal renal function; in moderate renal impairment (CrCl 30-50 mL/min), half-life increases to about 10 hours. |
| Protein binding | 18% bound to plasma proteins (mainly albumin) over a concentration range of 15-50 ng/mL. |
| Volume of Distribution | 2.6 L/kg (mean), indicating extensive distribution into tissues including brain. |
| Bioavailability | Oral: 88-100% absolute bioavailability (tablets); food does not affect absorption. Oral extended-release: approximately 90% bioavailability relative to immediate-release. |
| Onset of Action | Immediate-release tablets: clinical effects may be observed within 30-60 minutes; extended-release capsules: peak effects occur within 4-6 hours after dosing. |
| Duration of Action | Immediate-release: 8-12 hours (tid dosing); extended-release: 24 hours (once-daily dosing with consistent plasma levels). |
16 mg orally once daily, increased to 24 mg once daily after 4 weeks. Extended-release: 8 mg once daily, titrate to 16 mg then 24 mg as tolerated. Immediate-release: 4 mg twice daily, titrate to 8 mg, then 12 mg twice daily.
| Dosage form | TABLET |
| Renal impairment | CrCl ≥ 9 mL/min: no adjustment. CrCl < 9 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: max 16 mg/day. Child-Pugh C: not recommended. |
| Pediatric use | Not FDA approved for pediatric use; safety and efficacy not established. Dosing not defined. |
| Geriatric use | Same as adult dosing; monitor for cholinergic side effects and weight loss. Titrate slowly due to increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GALANTAMINE HYDROBROMIDE (GALANTAMINE HYDROBROMIDE).
| Breastfeeding | Excretion into human milk unknown; M/P ratio not available. Due to potential for serious adverse reactions (e.g., cholinergic toxicity, seizures) in nursing infants, breastfeeding is not recommended during therapy. |
| Teratogenic Risk | Pregnancy Category B. In animal studies, no evidence of teratogenicity at doses up to 50 times the human AUC; however, fetal body weights were reduced at maternally toxic doses. First trimester: Limited human data; risk cannot be excluded. Second and third trimesters: No specific studies; potential for increased cholinergic effects. Overall, use only if benefit outweighs risk. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to galantamine or any excipients","Severe hepatic impairment (Child-Pugh score >9)","Severe renal impairment (CrCl <9 mL/min)"]
| Precautions | ["Serious skin reactions (Stevens-Johnson syndrome, acute generalized exanthematous pustulosis)","Bradycardia and heart block","Gastrointestinal bleeding (increased risk with NSAIDs)","Seizures","Urinary retention","Pulmonary effects (e.g., exacerbation of asthma or COPD)"] |
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| Fetal Monitoring | Monitor for cholinergic adverse effects (e.g., bradycardia, hypotension, GI distress) in mother. Fetal monitoring includes fetal heart rate and uterine activity during third trimester due to potential for premature labor from cholinergic stimulation. |
| Fertility Effects | No human data. In animal studies, no impairment of fertility at doses up to 10 mg/kg/day (approximately 8 times the maximum recommended human dose). Theoretical risk of cholinergic effects on reproductive function. |