Galantamine Hydrobromide

Pronunciation: (gah-LAN-tah-meen HIGH-droe-BRO-mide)Class: Cholinesterase inhibitor

Trade Names:Razadyne- Tablets 4 mg (as base)- Tablets 8 mg (as base)- Tablets 12 mg (as base)- Oral Solution 4 mg/mL

Trade Names:Razadyne ER- Capsules, extended-release 8 mg (as base)- Capsules, extended-release 16 mg (as base)- Capsules, extended-release 24 mg (as base)

Reminyl (Canada)Reminyl ER (Canada)

Pharmacology

May enhance cholinergic function by increasing acetylcholine.

Pharmacokinetics

Absorption

Absolute bioavailability is about 90%. T _max is about 1 h. Food decreases C _max 25% and delayed T _max 1.5 h.

Distribution

Mean Vd is 175 L. Protein binding is 18%.

Metabolism

Metabolized by hepatic CYP-450 2D6 and 3A4 enzymes and glucuronidated.

Elimination

T _½ is about 7 h. Approximately 95% is excreted in urine and 5% in feces.

Special Populations

Renal Function Impairment

AUC increased 37% and 67% in moderate and severe renal function impairment.

Hepatic Function Impairment

Cl decreased about 25% in moderate (Child-Pugh 7 to 9) hepatic function impairment.

Elderly

Concentrations are about 30% to 40% higher.

Gender

Cl is about 20% lower in women than in men.

CYP2D6 poor metabolizers

Approximately 35% increase in AUC of unchanged drug and 25% decrease in median Cl.

Indications and Usage

Treatment of mild to moderate dementia of the Alzheimer type.

Contraindications

Standard considerations.

Dosage and Administration

Renal/Hepatic Function Impairment

In patients with moderately impaired hepatic function (Child-Pugh score 7 to 9) and those with moderate renal function impairment, the dose should not exceed 16 mg/day. Not recommended for patients with severe renal (CrCl less than 9 mL/min) or severe hepatic function impairment (Child-Pugh 10 to 15).

Immediate-Release Tablets and Oral SolutionAdults

PO 4 mg twice daily. May increase to 8 mg twice daily after 4 wk. A further increase to 12 mg twice daily may be attempted after min 4 wk at previous dose.

Extended-Release TabletsAdults

PO 8 mg/day. Increase to 16 mg/day after min 4 wk. A further increase to 24 mg/day may be attempted after min 4 wk at previous dose.

General Advice

• Administer immediate-release tablets and oral solution twice daily, preferably with morning and evening meal.
• Administer extended-release tablets once daily in the morning, preferably with food.

Storage/Stability

Store at controlled room temperature (59° to 86°F). Do not freeze oral solution.

Drug Interactions

Bethanechol, succinylcholine

May act synergistically with galantamine.

CYP2D6 inhibitors (eg, amitriptyline, fluoxetine, fluvoxamine, quinidine)

May decrease galantamine Cl.

Erythromycin; ketoconazole; paroxetine

May elevate galantamine levels, increasing the risk of adverse reactions.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Chest pain, hypertension (at least 2%); bradycardia, syncope (2%).

CNS

Dizziness, somnolence (9%); headache (8%); depression (7%); fatigue, insomnia (5%); tremor (3%); agitation, anxiety, confusion, hallucinations (at least 2%).

Dermatologic

Purpura (at least 2%).

GI

Nausea (24%); vomiting (13%); diarrhea (12%); anorexia (9%); abdominal pain, dyspepsia (5%); constipation (at least 2%); flatulence (at least 1%).

Genitourinary

UTI (8%); hematuria (3%); urinary incontinence (at least 2%).

Hematologic

Anemia (3%).

Metabolic

Weight decrease (7%).

Respiratory

Rhinitis (4%); bronchitis, coughing, upper respiratory tract infection (at least 2%).

Miscellaneous

Asthenia, back pain, falling, injury, peripheral edema (at least 2%).

Precautions

Monitor Monitor for symptoms of active or occult GI bleeding. Evaluate patient's mental status and function prior to initiation of therapy. Monitor patient for signs of improvement after therapy is started.

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

Use with caution in patients with moderately impaired function; not recommended in severe impairment.

Hepatic Function

Use with caution in patients with moderately impaired function; not recommended in severe impairment.

Bladder outflow obstruction

May occur.

Cardiac effects

May cause bradycardia and/or AV block. All patients should be considered at risk for adverse reactions or cardiac conditions.

Discontinuation

The beneficial effects of galantamine are lost when the drug is discontinued.

GI effects

May increase gastric acid secretion.

Pulmonary

Use with caution in patients with a history of severe asthma or obstructive pulmonary disease.

Seizures

May cause generalized convulsions.

Overdosage

Symptoms

Cholinergic crisis (eg, bradycardia, collapse, convulsions, defecation, GI cramping, hypotension, lacrimation, muscle weakness, respiratory depression, salivation, severe nausea, sweating, urination, vomiting).

Patient Information

• Advise patient, family or caregiver that this drug does not alter the Alzheimer process and that the efficacy of the medication may lessen over time.
• Advise patient or caregiver that medication is started at a low dose and gradually increased (up to every 4 wk) as tolerated.
• Caution patient or caregiver that if medication has been stopped for several days or longer, it must be restarted at the lowest dose and gradually increased to the current dose.
• Advise patient or caregiver that nausea and vomiting are the most common adverse reactions and that taking the medication with food and ensuring adequate fluid intake reduces these adverse reactions. If nausea and vomiting become a problem, patient or caregiver should inform health care provider.
• Advise patient, family, or caregiver to not discontinue the drug or change dose unless advised by health care provider.

Copyright © 2009 Wolters Kluwer Health.