Remcept 8mg. 16mg. 24mg Capsules

REMCEPT XL is indicated for the symptomatic treatment of mild to moderately severe dementia of the Alzheimer type. Efficacy data beyond 6 months has not been established (see WARNINGS AND SPECIAL PRECAUTIONS).

Adults: Administration: REMCEPT XL prolonged release capsules should be administered once daily in the morning, preferably with food.

Starting dose: The recommended starting dose is 8 mg/day for 4 weeks.

Maintenance dose:

• The initial maintenance dose is 16 mg/day and patients should be maintained on 16 mg/day for at least 4 weeks.
• An increase to the maintenance dose of 24 mg/day should be considered after appropriate assessment including evaluation of clinical benefit and tolerability.
• In individual patients not showing an increased response or not tolerating 24 mg/day, a dose reduction to 16 mg/day should be considered.
• Maintenance treatment can be continued for as long as therapeutic benefit for the patient exists. Therefore, the clinical benefit of REMCEPT XL should be reassessed on a regular basis. Discontinuation should be considered when evidence of a therapeutic effect is no longer present.
• There is no rebound effect after abrupt discontinuation of treatment (e.g. in preparation for surgery).

Children: Use of REMCEPT XL in children is not recommended. No data on the use of REMCEPT XL in paediatric patients are available.

Hepatic and renal impairment: REMCEPT XL plasma levels may be increased in patients with moderate to severe hepatic or renal impairment. In patients with moderately impaired hepatic function, based on pharmacokinetic modelling, dosing should begin with 8 mg every other day for at least one week, preferably taken in the morning. Thereafter, patients should proceed with 8 mg once daily for at least four weeks. In these patients total daily doses should not exceed 16 mg. In patients with severe hepatic impairment (Child Pugh score greater than 9), the use of REMCEPT XL is contraindicated. For patients with a creatinine clearance greater than 9 ml/min, no dosage adjustment is required. In patients, with severe renal impairment (creatinine clearance less than 9 ml/min), the use of REMCEPT XL is contraindicated.

• REMCEPT XL should not be administered to patients with a known hypersensitivity to galantamine hydrobromide or to any excipients used in the formulations.
• Severe impaired hepatic function (Child Pugh score > 9)
• Severe impaired renal function (Cl CR = 9 u2013 51 ml/min)
• The use of REMCEPT XL is not recommended in patients with urinary outflow obstruction or recovering from bladder surgery.

Types of dementia: REMCEPT XL is indicated for a patient with mild to moderately severe dementia of the Alzheimer type. The benefit of REMCEPT XL in patients with other types of dementia or other types of memory impairment has not been demonstrated. A diagnosis of Alzheimer's dementia should be made according to current guidelines by an experienced medical practitioner. Therapy with REMCEPT XL should occur under the supervision of a medical practitioner and should only be initiated if a caregiver is available who will regularly monitor medicine intake by the patient.

Mild Cognitive Impairment (MCI): REMCEPT XL is not indicated for individuals with mild cognitive impairment (MCI), i.e. those who demonstrate isolated memory impairment greater than expected for their age and education, but do not meet criteria for Alzheimeru2019s disease.

Serious skin reactions: Serious skin reactions (Stevens Johnson syndrome and acute generalised exanthematous pustulosis) have been reported in patients receiving REMCEPT XL (see SIDE EFFECTS). It is recommended that patients be informed about the signs of serious skin reactions, and that use of REMCEPT XL be discontinued at the first appearance of skin rash.

Weight monitoring: Treatment with cholinesterase inhibitors, including REMCEPT XL, has been associated with weight loss in these patients. During therapy, patient's weight should be monitored.

Conditions requiring caution: REMCEPT XL should be given with caution in the following conditions:

• Cardiac disorders: Cholinomimetics may have vagotonic effects on heart rate (e.g. bradycardia). The potential for this action may be particularly important to patients with u201csick sinus syndromeu201d or other supraventricular cardiac conduction disturbances or in those who use medicines 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 REMCEPT XL 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 u2013 IV.
• Gastrointestinal disorders: 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 REMCEPT XL is not recommended in patients with gastro-intestinal obstruction or recovering from gastro-intestinal surgery.
• Nervous system disorders: Seizures have been reported with REMCEPT XL (see section SIDE EFFECTS). Seizure activity may also be a manifestation of Alzheimer's disease. In some cases an increase in cholinergic tone may worsen Parkinsonian symptoms.
• Respiratory, thoracic and mediastinal disorders: 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).
• Renal and urinary disorders: The use of REMCEPT XL is not recommended in patients with urinary outflow obstruction or recovering from bladder surgery (see CONTRAINDICATIONS).
• Surgical and medical procedures: REMCEPT XL, as a cholinomimetic, is likely to exaggerate succinylcholine-type muscle relaxation during anaesthesia, especially in cases of pseudocholinesterase deficiency.

Pharmacodynamic interactions: Because of its mechanism of action, REMCEPT XL should not be given concomitantly with other cholinomimetics (such as ambenonium, donepezil, neostigmine, pyridostigmine, rivastigmine or systemically administered pilocarpine). REMCEPT XL has the potential to antagonise the effect of anticholinergic medicine. Should anticholinergic medicine such as atropine be abruptly stopped there is a potential risk that REMCEPT XL effects could be exacerbated. As expected with cholinomimetics, a pharmacodynamic interaction is possible with medicines that significantly reduce the heart rate such as digoxin, beta-blockers, certain calcium-channel blocking medicines and amiodarone (see WARNINGS AND SPECIAL PRECAUTIONS). Caution should be taken with medicines that have potential to cause torsadeu2019s de pointes. In such cases an ECG should be considered.

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

Pharmacokinetic interactions: Multiple metabolic pathways and renal excretion are involved in the elimination of REMCEPT XL. The occurrence of significant interactions may be clinically relevant in individual cases. Concomitant administration with food slows the absorption rate of REMCEPT XL but does not affect the extent of absorption. It is recommended that REMCEPT XL be taken with food in order to minimise cholinergic side effects.

Other medicines affecting the metabolism of galantamine: Formal interaction studies showed an increase in REMCEPT XL 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 REMCEPT XL maintenance dose can be considered (see DOSAGE AND DIRECTIONS FOR USE). Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, at a dose of 10 mg once a day for 2 days followed by 10 mg twice a day for 12 days, had no effect on the pharmacokinetics of galantamine at steady state.

Effect of REMCEPT XL on the metabolism of other medicines: Therapeutic doses of galantamine as in REMCEPT XL 24 mg/day had no effect on the kinetics of digoxin, although pharmacodynamic interactions may occur (see also Pharmacodynamic interactions). Therapeutic doses of galantamine as in REMCEPT XL 24 mg/day had no effect on the kinetics and prothrombin time (INR) of warfarin.

No studies are available on the use of REMCEPT XL in pregnant women. REMCEPT XL should not be used during pregnancy. Animal studies have shown reproductive toxicity. It is not known whether galantamine is excreted in human breast milk and there are no studies in lactating women. Women on REMCEPT XL should not breastfeed their infants.

Alzheimeru2019s disease may cause gradual impairment of driving performance or compromise the ability to use machinery. REMCEPT XL may cause dizziness and somnolence, which could affect the ability to drive or use machines, especially during the first weeks after initiation of treatment.

System Organ Class Frequency Undesirable effects Blood and the lymphatic system disorders Frequent Less frequent Anaemia Thrombocytopenia Immune system disorders Less frequent Hypersensitivity Metabolism and nutrition disorders Frequent Less frequent Decreased appetite, weight decrease Dehydration, hyperglycaemia, increased alkaline phosphate Psychiatric disorders Frequent Less frequent Hallucination, depression, insomnia, anorexia, somnolence, agitation, confusion, anxiety Hallucination visual, hallucination auditory, paranoid reaction, increased libido, delirium, suicidal ideation, suicide Nervous system disorder Frequent Less frequent Headache, somnolence, lethargy, tremor, dizziness, syncope Paraesthesia, dysgeusia, hypersomnia, seizures, vertigo, hypertonia, convulsions, involuntary muscle contractions, ataxia, hyperkinesia, apraxia, aphasia, leg cramps Eye disorders Less frequent Blurred vision Ear and labyrinth disorders Less frequent Tinnitus Cardiac disorders Frequent Less frequent Bradycardia Supraventricular extrasystoles, first degree atrioventricular block, sinus bradycardia, palpitations, cardiac failure, myocardial ischaemia or infarction, atrial dysrhythmias, atrial fibrillation, supraventricular tachycardiau2019s, QT prolonged, bundle branch block, T-wave inversion, ventricular tachycardia Vascular disorders Frequent Less frequent Hypertension, peripheral oedema Hypotension, flushing, postural hypotension, dependent oedema, purpura, epistaxis Gastrointestinal disorders Frequent Less frequent Nausea, vomiting, constipation, flatulence, abdominal pain, upper abdominal pain, diarrhoea, dyspepsia, abdominal discomfort Retching, gastritis, melaena, dysphagia, rectal haemorrhage, dry mouth, increased saliva, diverticulitis, gastroenteritis, hiccup, oesophageal perforation Hepatobiliary disorders Less frequent Hepatitis, elevated liver enzymes Skin and subcutaneous tissue disorders Frequent Hyperhidrosis Less frequent Stevens Johnson syndrome, acute generalised exanthematous pustulosis, erythema multiforme Musculoskeletal, Connective tissue and bone disorders Frequent Less frequent Muscle spasms Muscle weakness Renal and urinary disorders Frequent Less frequent Urinary tract infection, haematuria, urinary incontinence Micturition frequency, cystitis, urinary retention, nocturia, renal calculi Respiratory, thoracic and mediastinal disorders Frequent Rhinitis, upper respiratory tract infection, bronchitis, coughing General disorders and administrative site conditions Frequent Fatigue, syncope, asthenia, malaise, fall, injury, back pain, chest pain, fever Investigations Frequent Hepatic enzyme increase

Symptoms: Signs and symptoms of significant overdosing of REMCEPT XL 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 fasciculationu2019s, some or all of the signs of a cholinergic crisis may develop: severe nausea, vomiting, gastro-intestinal cramping, salivation, lacrimation, urination, defaecation, sweating, bradycardia, hypotension, collapse and convulsions. Increasing muscle weakness together with tracheal hypersecretions and bronchospasms, may lead to vital airway compromise. There have been post-marketing reports of Torsade de Pointes, QT prolongation, bradycardia, ventricular tachycardia and loss of consciousness in association with inadvertent overdoses of REMCEPT XL.

Treatment: General supportive measures should be used. In severe cases, anticholinergics such as atropine can be used as a general antidote for cholinomimetics. An initial dose of 0,5 to 1,0 mg I.V. is recommended, with subsequent doses based on the clinical response. Because strategies for the management of overdose are continually evolving, it is advisable to contact a poison control centre to determine the latest recommendations for the management of an overdose.