Galantamine Other names: Galantamine hydrobromide Galanthamine

Caution should be taken with medicinal products that have potential to cause torsades de pointes. In such cases an ECG should be considered.

Formal drug interaction studies showed an increase in galantamine bioavailability of about 40% during co-administration of paroxetine (a potent CYP2D6 inhibitor) and of 30% and 12% during co-treatment with ketoconazole and erythromycin (both CYP3A4 inhibitors). Therefore, during initiation of treatment with potent inhibitors of CYP2D6 (e.g. quinidine, paroxetine or fluoxetine) or CYP3A4 (e.g. ketoconazole or ritonavir) patients may experience an increased incidence of cholinergic adverse reactions, predominantly nausea and vomiting. Under these circumstances, based on tolerability, a reduction of the galantamine maintenance dose can be considered.

In patients with moderately impaired hepatic function (Child-Pugh score 7-9), based on pharmacokinetic modelling, it is recommended that dosing should begin with 8 mg prolonged-release capsule once every other day, preferably taken in the morning, for 1 week. Thereafter, patients should proceed with 8 mg once daily for 4 weeks. In these patients, daily doses should not exceed 16 mg.

Galantamine has the potential to antagonise the effect of anticholinergic medication. Should anticholinergics such as atropine be abruptly stopped, there is a potential risk that galantamine’s effects could be exacerbated.

Because of its mechanism of action, galantamine should not be given concomitantly with other cholinomimetics (such as ambenonium, donepezil, neostigmine, pyridostigmine, rivastigmine or systemically administered pilocarpine).

As expected with cholinomimetics, a pharmacodynamic interaction is possible with medicinal products that significantly reduce the heart rate such as digoxin, beta-blockers, certain calcium-channel blocking agents and amiodarone.

Patients at increased risk of developing peptic ulcers, e.g. those with a history of ulcer disease or those predisposed to these conditions, including those receiving concurrent non-steroidal anti-inflammatory drugs (NSAIDs), should be monitored for symptoms. The use of galantamine is not recommended in patients with gastrointestinal obstruction or recovering from gastrointestinal surgery.

Cholinomimetics should be prescribed with care for patients with a history of severe asthma or obstructive pulmonary disease or active pulmonary infections (e.g. pneumonia).

The use of galantamine is not recommended in patients with urinary outflow obstruction or recovering from bladder surgery.

Because of their pharmacological action, cholinomimetics may have vagotonic effects on heart rate, including bradycardia and all types of atrioventricular node block. The potential for this action may be particularly important to patients with ‘sick sinus syndrome’ or other supraventricular cardiac conduction disturbances or in those who use medicinal products that significantly reduce heart rate concomitantly, such as digoxin and beta-blockers or for patients with an uncorrected electrolyte disturbance (e.g. hyperkalaemia, hypokalaemia).

Caution should therefore be exercised when administering galantamine to patients with cardiovascular diseases, e.g. immediate post-myocardial infarction period, new- onset atrial fibrillation, second degree heart block or greater, unstable angina pectoris or congestive heart failure, especially NYHA group III – IV.

In a pooled analysis of placebo-controlled studies in patients with Alzheimer’s dementia treated with galantamine an increased incidence of certain cardiovascular adverse events were observed.

Galantamine, as a cholinomimetic, is likely to exaggerate succinylcholine-type muscle relaxation during anaesthesia, especially in cases of pseudocholinesterase deficiency.

For galantamine no clinical data on exposed pregnancies are available. Studies in animals have shown reproductive toxicity. Caution should be exercised when prescribing to pregnant women.

It is not known whether galantamine is excreted in human breast milk and there are no studies in lactating women. Therefore, women on galantamine should not breast-feed.

Fertility

The effect of galantamine on human fertility has not been evaluated.

Galantamine has minor or moderate influence on the ability to drive and use machines. Symptoms include dizziness and somnolence, especially during the first weeks after initiation of treatment.