Galantamine 8 mg Tablets

Brand Name

This pharmaceutical product is marketed under various trade names, with Galantamine being one of the recognized labels in clinical practice.

International Non-Proprietary Name

The active substance is universally identified as galantamine, following the standardized naming convention for medicinal compounds.

Form of Release

The drug is available in multiple oral forms to suit different patient needs. It comes as immediate-release tablets in strengths of 4 milligrams, 8 milligrams, and 12 milligrams. Extended-release capsules are offered in 8-milligram, 16-milligram, and 24-milligram doses for once-daily use. Additionally, an oral solution at 4 milligrams per milliliter provides an alternative for precise dosing or swallowing difficulties.

Composition

The core ingredient is galantamine hydrobromide, which delivers its therapeutic effects through enzyme inhibition. Immediate-release tablets include excipients like lactose monohydrate, microcrystalline cellulose, magnesium stearate, and crospovidone to ensure stability and disintegration. Extended-release capsules contain similar components plus a controlled-release matrix, such as hypromellose, to prolong action. The oral solution incorporates propylene glycol, sodium benzoate, and purified water, with flavoring to improve palatability.

Pharmacologic Properties

Pharmacodynamics

This medication functions as a reversible, competitive inhibitor of acetylcholinesterase, an enzyme that degrades acetylcholine in the brain. By blocking this enzyme, it increases acetylcholine levels, enhancing cholinergic transmission critical for memory and cognitive processes. It also modulates nicotinic receptors, amplifying neurotransmitter release, which further supports cognitive function. This dual mechanism distinguishes it from other agents in its class, offering a broader impact on neural activity.

Clinical findings show it improves attention, memory retention, and daily functioning in patients with cognitive decline. The effect is temporary, aimed at symptom relief rather than disease reversal, focusing on brain regions like the cortex and hippocampus. Its receptor modulation may provide additional benefits in maintaining mental clarity, making it a practical choice for managing cognitive symptoms.

Pharmacokinetics

After oral administration, the drug absorbs efficiently from the gastrointestinal tract, with peak plasma levels reached in about 1 hour for immediate-release forms and 4 to 6 hours for extended-release versions. Food slows absorption slightly but does not reduce overall uptake, with bioavailability averaging 85 to 100 percent. This high absorption supports its effectiveness across formulations.

The substance distributes widely, with a volume of distribution around 175 liters, indicating good tissue penetration, including the central nervous system. It binds to plasma proteins at approximately 18 percent, leaving most of the drug free to act. Metabolism occurs primarily in the liver via cytochrome P450 enzymes CYP2D6 and CYP3A4, producing metabolites with minimal activity. The half-life is about 7 to 8 hours, allowing for flexible dosing schedules depending on the form used.

Excretion is predominantly renal, with over 90 percent eliminated through urine as unchanged drug or metabolites within 72 hours. A small fraction exits via feces. Clearance decreases with reduced kidney function, necessitating adjustments in certain cases to prevent accumulation.

Indications for Use

Conditions and Disorders

The medication is prescribed for mild to moderate dementia associated with Alzheimer’s disease, a progressive condition impairing cognitive abilities. It targets symptoms like memory loss, confusion, and difficulty with reasoning or language, helping patients maintain independence longer. By boosting acetylcholine, it supports mental function in affected individuals.

Galantamine has a well-established role in this context, backed by clinical evidence showing improved cognitive scores and daily performance. Some physicians may consider it for other cognitive impairments, such as vascular dementia, though such uses lack formal approval and require further study.

Contraindications

Conditions Prohibiting Use

The drug is not suitable for patients with known hypersensitivity to galantamine hydrobromide or related compounds, as allergic reactions could range from rashes to anaphylaxis. Severe renal impairment, with creatinine clearance below 9 milliliters per minute, precludes its use due to risks of accumulation. Similarly, severe hepatic dysfunction contraindicates administration, given its reliance on liver metabolism.

It should be avoided in patients with active peptic ulcers or gastrointestinal bleeding, as cholinergic stimulation may worsen these conditions. Uncontrolled asthma or chronic obstructive pulmonary disease also prohibits use, as the drug could exacerbate respiratory distress. Cardiac conditions like severe bradycardia or heart block further restrict its application due to potential vagotonic effects.

Method of Administration and Dosage

Administration Guidelines

The medication is taken orally, preferably with meals to reduce stomach upset, though it can be consumed without food if tolerated. Immediate-release tablets require twice-daily dosing, swallowed whole with water. Extended-release capsules are taken once daily in the morning, also with water. The oral solution should be measured accurately with a provided device and mixed with a non-alcoholic beverage if desired, consumed promptly.

Dosage for Adults and Children

For adults with Alzheimer’s, immediate-release therapy starts at 4 milligrams twice daily for four weeks, increasing to 8 milligrams twice daily if tolerated. After another four weeks, it may rise to 12 milligrams twice daily based on response. Extended-release begins at 8 milligrams daily, escalating to 16 milligrams after four weeks, and potentially 24 milligrams if needed. Pediatric use is not approved, as efficacy and safety in children remain unestablished.

Dose Adjustments for Specific Conditions

In moderate renal impairment (creatinine clearance 9 to 59 milliliters per minute), the maximum dose should not exceed 16 milligrams daily for extended-release or 8 milligrams twice daily for immediate-release. Severe kidney issues rule out use entirely. Mild to moderate hepatic impairment may allow standard dosing with caution, but severe liver dysfunction prohibits administration. Adjustments should align with clinical monitoring.

Side Effects

Potential Adverse Reactions

Common effects include nausea, vomiting, and diarrhea, often tied to cholinergic stimulation and most prominent during dose increases. Fatigue, dizziness, and loss of appetite also occur frequently, typically lessening over time. Headache and muscle cramps may arise as the body adjusts to enhanced acetylcholine levels.

Less common reactions involve bradycardia or fainting, particularly in those with heart conditions, requiring attention if persistent. Tremors or sleep disturbances can affect some patients, while rare cases report hallucinations or seizures, especially at higher doses. Severe abdominal pain or allergic skin responses warrant immediate medical evaluation.

Overdose

Symptoms of Excessive Intake

Excessive intake can lead to cholinergic crisis, marked by severe nausea, sweating, slowed heart rate, and muscle weakness. Respiratory difficulty, seizures, or fainting may follow, reflecting overstimulation of cholinergic pathways. In extreme cases, collapse or coma could occur, posing significant risks without prompt care.

First Aid Measures

Stop the drug immediately and contact emergency services. If ingestion occurred within an hour, activated charcoal may limit absorption if the patient is conscious. Atropine may be administered by professionals to reverse critical symptoms like bradycardia or bronchospasm. Supportive measures, such as maintaining airway and monitoring vitals, are essential until help arrives.

Drug Interactions

Effects on Other Medications

The medication can enhance the effects of other cholinergic agents, like bethanechol, increasing risks of gastrointestinal or cardiac issues. It may counteract anticholinergics, such as oxybutynin, reducing their efficacy in conditions needing acetylcholine suppression. CYP2D6 or CYP3A4 inhibitors, like paroxetine or ketoconazole, could elevate its levels, intensifying side effects, while inducers like rifampicin might lower its potency.

Galantamine may amplify bradycardia risk with beta-blockers or other heart-slowing drugs, necessitating caution. Nonsteroidal anti-inflammatory drugs could heighten gastrointestinal irritation when combined, requiring monitoring for ulcer symptoms.

Compatibility with Alcohol and Food

Alcohol does not directly alter its pharmacokinetics but may worsen dizziness or nausea, so moderation is advised. Food slightly delays absorption but enhances tolerability, making it a preferred administration option for many. No specific dietary restrictions apply.

Special Precautions

Use During Pregnancy and Breastfeeding

Limited data exist on pregnancy use, with no clear human evidence of safety or risk. Animal studies suggest no teratogenicity, but the drug should only be used if benefits justify potential fetal exposure, under strict medical oversight. It may pass into breast milk in small amounts, so nursing mothers should consult a physician, possibly suspending breastfeeding during therapy.

Impact on Driving and Machinery Operation

The medication may cause dizziness, fatigue, or slowed reactions, especially during initial use or dose escalation. Patients should assess their response before driving or operating equipment, avoiding these tasks if affected. Caregivers may need to supervise those with significant cognitive or physical limitations.

Considerations for Elderly and Pediatric Patients

Elderly patients, the primary users due to Alzheimer’s prevalence, generally tolerate it well, though reduced kidney or liver function may require dose caps in moderate impairment. Galantamine is not approved for children, as its role in pediatric cognitive conditions lacks evidence, restricting use to adults.