galantamine

General

Genetic Implications: Genetic Implications

Pronunciation:
ga-lant-a-meen


Trade Name(s)

  • Razadyne
  • Razadyne ER

Ther. Class.

anti-Alzheimers's agents

Pharm. Class.

cholinergics

(cholinesterase inhibitors)

Indications

Mild to moderate dementia/neurocognitive disorder of the Alzheimer's type.

Action

Enhances cholinergic function by reversible inhibition of cholinesterase.

Therapeutic Effect(s):

  • Decreased dementia/cognitive decline (temporary) associated with Alzheimer's disease.
  • Cognitive enhancer.

Pharmacokinetics

Absorption: Well absorbed (90%) following oral administration.

Distribution: Unknown.

Metabolism and Excretion: Mostly metabolized by the liver (primarily by CYP2D6 and CYP3A4 isoenzymes);Genetic implication the CYP2D6 enzyme system exhibits genetic polymorphism; ~7% of population may be poor metabolizers and may have significantly ↑ galantamine concentrations and an ↑ risk of adverse effects. 20% excreted unchanged in urine.

Half-life: 7 hr.

TIME/ACTION PROFILE (anticholinesterase activity)

ROUTEONSETPEAKDURATION
PO unknown1 hr12 hr
PO-ERunknown1 hr24 hr

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity;
  • Severe hepatic or renal impairment.

Use Cautiously in:

  • Patients with supraventricular cardiac conduction defects or concurrent use of drugs that may slow heart rate (↑ risk of bradycardia);
  • History of ulcer disease/GI bleeding/concurrent NSAID use;
  • Severe asthma or obstructive pulmonary disease;
  • Mild to moderate renal impairment (avoid use if CCr <9 mL/min);
  • Mild to moderate hepatic impairment (cautious dose titration recommended);
  • May ↑ risk of cardiovascular mortality;
  • OB:  Safety not established in pregnancy;
  •  Lactation: Use while breast feeding only if potential maternal benefit justifies potential risk to infant;
  • Pedi:   Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: bradycardia, chest pain

Derm: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS (AGEP), STEVENS-JOHNSON SYNDROME (SJS)

GI: nausea, vomiting, anorexia, ↓ weight, diarrhea, dyspepsia, flatulence

GU: bladder outflow obstruction, incontinence

Neuro: extrapyramidal symptoms, tremor, dizziness, fatigue, headache, syncope

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  • Will ↑ neuromuscular blockade from  succinylcholine-type neuromuscular blocking agents.
  • May ↑ effects of other  cholinesterase inhibitors  or other  cholinergic agonists, including  bethanechol.
  • May ↓ effectiveness of  anticholinergic medications.
  • Levels and effects may be ↑ by  ketoconazole,  paroxetine,  amitriptyline,  fluvoxamine, or  quinidine.

Route/Dosage

PO (Adults): Immediate-release tablets– 4 mg twice daily initially, dose increments of 4 mg should be made at 4 wk intervals, up to 12 mg twice daily. Doses up to 16 mg twice daily have been used (range 16–32 mg/day;  Extended-release capsules– 8 mg/day as a single dose in the morning, may be ↑ to 16 mg/day after 4 wk, then up to 24 mg/day after 4 wk; increments based on benefit/tolerability.

Renal Impairment 
PO (Adults): Moderate renal impairment– Daily dose should not exceed 16 mg.

Hepatic Impairment 
PO (Adults): Moderate hepatic impairment– Daily dose should not exceed 16 mg.

Availability (generic available)

Immediate-release tablets: 4 mg, 8 mg, 12 mg

Extended-release capsules: 8 mg, 16 mg, 24 mg

Oral solution: 4 mg/mL

Assessment

  • Assess cognitive function (memory, attention, reasoning, language, ability to perform simple tasks) periodically during therapy.
  • Monitor heart rate periodically during therapy. May cause bradycardia.

Implementation

  • Do not confuse Razadyne with Rozerem (ramelteon).
  • Patient should be maintained on a stable dose for a minimum of 4 wk prior to increasing dose.

    • If dose has been interrupted for several days or longer, restart at the lowest dose and escalate to the current dose.
  • PO Administer twice daily, preferably with morning and evening meal. Administration with food, the use of antiemetic medications, and ensuring adequate fluid intake may decrease nausea and vomiting.
    • Administer extended-release capsules in the morning, preferably with food.  DNC: Swallow whole; do not open, crush, or chew .
  • Use pipette provided with oral solution to administer accurate amount.

Patient/Family Teaching

  • Emphasize the importance of taking galantamine daily, as directed. Instruct patient and/or caregiver in correct use of pipette if using oral solution; review  Oral Solution Instruction Sheet  included with product prior to use. Skip missed doses and return to regular schedule the following day; do not double doses. If >3 days doses are missed, restart at lowest dose. Do not discontinue abruptly; although no increase in frequency of adverse events may occur, beneficial affects of galantamine are lost when the drug is discontinued.
  • Caution patient and caregiver that galantamine may cause dizziness. Monitor and assist with ambulation and caution patient to avoid driving and other activities requiring alertness until response to medication is known.
  • Instruct patient to maintain adequate fluid intake during therapy.
  • Advise patient and caregiver to stop taking galantamine and notify health care professional immediately if rash occurs.
  • Advise patient and caregiver to notify health care professional if nausea or vomiting persists beyond 7 days or if new symptoms occur or previously noted symptoms increase in severity.
  • Advise patient and caregiver to notify health care professional of medication regimen prior to treatment or surgery.
  • Teach patient and caregivers that improvements in cognitive functioning may take wk to mo to stabilize.
  • Caution that disease is not cured and degenerative process is not reversed.
  • Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breast feeding.
  • Emphasize the importance of follow-up exams to monitor progress.

Evaluation/Desired Outcomes

Improvement in cognitive function (memory, attention, reasoning, language, ability to perform simple tasks) in patients with Alzheimer's disease.

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