Razadyne

Galantamine improves the function of nerve cells in the brain. It works by preventing the breakdown of a chemical called acetylcholine (ah see til KO leen). People with dementia usually have lower levels of this chemical, which is important for the processes of memory, thinking, and reasoning.

Galantamine is used to treat mild to moderate dementia caused by Alzheimer's disease.

Galantamine may also be used for purposes not listed in this medication guide.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

You should not use galantamine if you are allergic to it.

To make sure galantamine is safe for you, tell your doctor if you have:

• urination problems;
• heart disease or a heart rhythm disorder;
• a history of stomach ulcer or bleeding;
• seizures or epilepsy;
• kidney disease;
• liver disease; or
• a history of asthma or chronic obstructive pulmonary disease (COPD).

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether galantamine passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Contraindications

Hypersensitivity

Cautions

Moderate hepatic or renal impairment: max 8 mg q12hr (conventional) or 16 mg qDay (ER)

Not recommended in severe hepatic or renal impairment

Renamed Razadyne from Reminyl in the US to avoid confusion with Amaryl

Serious skin reactions may occur; discontinue at first appearance of skin rash

All patients should be considered at risk for adverse effects on cardiac conduction, including bradycardia and AV block, due to vagotonic effects on sinoatrial and atrioventricular nodes

Active or occult gastrointestinal bleeding: monitor, especially those with an increased risk for developing ulcers

Cholinomimetics may cause bladder outflow obstruction

Monitor for respiratory adverse events in patients with a history of severe asthma or obstructive pulmonary disease

Galantamine improves the function of nerve cells in the brain. It works by preventing the breakdown of a chemical called acetylcholine (ah see til KO leen). People with dementia usually have lower levels of this chemical, which is important for the processes of memory, thinking, and reasoning.

Galantamine is used to treat mild to moderate dementia caused by Alzheimer's disease.

Galantamine may also be used for purposes not listed in this medication guide.

• Janssen Pharmaceuticals, Inc.

Serious side effects have been reported with Razadyne. See the "Razadyne Drug Precautions" section.

Common side effects of Razadyne include the following:

• Nausea
• Vomiting
• Dizziness
• Diarrhea
• Loss of appetite
• Weight loss
• Tiredness
• Headache
• Stomach upset
• Decreased heart rate
• Uncontrollable shaking in a part of your body
• Depression

This is not a complete list of Razadyne side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• anticholinergics such as glycopyrrolate (Cuvposa, Robinul), trospium (Sanctura), oxybutynin (Anturol, Gelnique, Oxytrol, Ditropan), solifenacin (Vesicare), dicyclomine (Bentyl), propantheline (Pro-Banthine), and atropine (Atropen, Sal-Tropine)
• medications that block a protein in the body (CYP3A4) such as some macrolide antibiotics (clarithromycin, telithromycin), some HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (boceprevir, telaprevir), some azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), conivaptan (Vaprisol), delavirdine (Rescriptor), and nefazodone
• medications that block a protein in the body (CYP2D6) such as quinidine (Qualaquin), fluoxetine (Prozac, Sarafem), amitriptyline (Elavil, Amitril), and paroxetine (Paxil)
• Cimetidine
• Cholinergics such as bethanechol (Urecholine), cevimeline (Evoxac), pilocarpine (Salagen)

This is not a complete list of drug interactions. Ask your doctor or pharmacist for more information.

• Store Razadyne at room temperature.
• Keep this and all medicines out of the reach of children.

Absorption

Bioavailability

Absolute oral bioavailability about 90%.1 Bioavailabilities of oral solution and tablets are equivalent.1 Extended-release capsules (24 mg once daily) and conventional tablets (12 mg twice daily) are bioequivalent when administered under fasting conditions.1

Peak plasma concentrations attained within 1 or 4.5–5 hours after administration of conventional tablets or extended-release capsules, respectively.1

Food

Conventional tablets or oral solution: Food did not affect the AUC, but peak plasma concentrations were decreased by 25% and time to peak plasma concentrations was delayed by 1.5 hours.1

Extended-release capsules: No appreciable differences in pharmacokinetic parameters following administration with food.1

Maximum inhibition of acetylcholinesterase (about 40%) achieved about 1 hour after a single 8-mg oral dose.1

Approximately 50% higher systemic exposure following administration of extended-release capsules in patients with reduced levels of CYP2D6 (also known as poor metabolizers); however, dosage adjustment is not necessary.1

Distribution

Extent

In whole blood, galantamine is mainly distributed to blood cells (52.7%).1 Blood to plasma concentration ratio is 1.2.1

Plasma Protein Binding

18% at therapeutically relevant concentrations.1

Elimination

Metabolism

Metabolized in the liver by CYP isoenzymes (principally CYP2D6 and 3A4).1

Clearance decreased 25% in patients with reduced levels of CYP2D6 activity; however, dosage adjustment is not necessary.1

Elimination Route

Principally in urine.1

Half-life

Terminal elimination half-life of about 7 hours.1

Special Populations

In patients with moderate hepatic impairment (Child-Pugh score of 7–9), clearance decreased by about 25% compared with healthy individuals.1 Exposure to the drug would be expected to increase further with increasing degree of hepatic impairment.1

In patients with moderate or severe renal impairment, AUC following a single 8-mg dose of galantamine (as conventional tablets) increased by 37% or 67%, respectively, compared with values in healthy individuals.1

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to check for unwanted effects.

Serious skin reactions can occur with this medicine. Check with your doctor right away if you have blistering, peeling, or loose skin, red skin lesions, severe acne or skin rash, sores or ulcers on the skin, or fever or chills while you are using this medicine.

Galantamine may cause stomach or bowel problems. Check with your doctor right away if you have nausea, vomiting, diarrhea, stomach pain, loss of appetite, or weight loss.

If you think you or someone else may have taken an overdose of galantamine, get emergency help at once. Taking an overdose of galantamine may lead to convulsions (seizures) or shock. Some signs of shock are large pupils, irregular breathing, and fast weak pulse. Other signs of an overdose are severe nausea and vomiting, increasing muscle weakness, greatly increased sweating, and greatly increased watering of the mouth.

Do not take other medicines unless they have been discussed with your doctor. This especially includes nonprescription medicines, such as aspirin, and medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems.

Because strategies for the management of overdose are continually evolving, it is advisable to contact a poison control center to determine the latest recommendations for the management of an overdose of any drug.

As in any case of overdose, general supportive measures should be utilized. Signs and symptoms of significant overdosing of galantamine are predicted to be similar to those of overdosing of other cholinomimetics. These effects generally involve the central nervous system, the parasympathetic nervous system, and the neuromuscular junction. In addition to muscle weakness or fasciculations, some or all of the following signs of cholinergic crisis may develop: severe nausea, vomiting, gastrointestinal cramping, salivation, lacrimation, urination, defecation, sweating, bradycardia, hypotension, respiratory depression, collapse and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved.

Tertiary anticholinergics such as atropine may be used as an antidote for Razadyne® ER and Razadyne® (galantamine hydrobromide) overdosage. Intravenous atropine sulfate titrated to effect is recommended at an initial dose of 0.5 to 1.0 mg i.v. with subsequent doses based upon clinical response. Atypical responses in blood pressure and heart rate have been reported with other cholinomimetics when co-administered with quaternary anticholinergics. It is not known whether galantamine and/or its metabolites can be removed by dialysis (hemodialysis, peritoneal dialysis, or hemofiltration). Dose-related signs of toxicity in animals included hypoactivity, tremors, clonic convulsions, salivation, lacrimation, chromodacryorrhea, mucoid feces, and dyspnea.

In one postmarketing report, one patient who had been taking 4 mg of galantamine daily for a week inadvertently ingested eight 4 mg tablets (32 mg total) on a single day. Subsequently, she developed bradycardia, QT prolongation, ventricular tachycardia and torsades de pointes accompanied by a brief loss of consciousness for which she required hospital treatment. Two additional cases of accidental ingestion of 32 mg (nausea, vomiting, and dry mouth; nausea, vomiting, and substernal chest pain) and one of 40 mg (vomiting), resulted in brief hospitalizations for observation with full recovery. One patient, who was prescribed 24 mg/day and had a history of hallucinations over the previous two years, mistakenly received 24 mg twice daily for 34 days and developed hallucinations requiring hospitalization. Another patient, who was prescribed 16 mg/day of oral solution, inadvertently ingested 160 mg (40 mL) and experienced sweating, vomiting, bradycardia, and near-syncope one hour later, which necessitated hospital treatment. His symptoms resolved within 24 hours.