Memry Special Precautions

Tablet: Caution is recommended in patients with epilepsy, past history of convulsions or patients with predisposing factors for epilepsy.
Treatment with memantine hydrochloride should be initiated and supervised by a physician experienced in the diagnosis and treatment of dementia; diagnosis should be based on current guidelines. Therapy should be initiated only when a caregiver is available who will monitor patient compliance. Treatment with memantine hydrochloride should be continued only where there is a therapeutic benefit to the patient; therapeutic benefit should be reassessed on a regular basis.
The clearance of memantine hydrochloride was reduced by about 80% under alkaline urine conditions (pH 8). Thus, alterations of urine pH towards the alkaline condition may lead to an accumulation of the drug with a possible increase in adverse effects. Some factors that may raise urine pH may require careful patient monitoring. These factors include drastic changes in diet (e.g., from a carnivore to a vegetarian diet, or a massive ingestion of alkalizing gastric buffers), drugs (e.g., carbonic anhydrase inhibitors, sodium bicarbonate) and the clinical state of the patient (e.g., renal tubular acidosis or severe infections of the urinary tract with Proteus bacteria).
Moderate to severe Alzheimer's disease usually causes impairment of driving performance and compromises the ability to use machinery. Furthermore, memantine hydrochloride may change reactivity and therefore patients should be warned to take special care when driving a vehicle or operating heavy machinery.
Patients with recent myocardial infarction, uncompensated congestive heart failure (NYHA III-IV) or uncontrolled hypertension were excluded in most clinical trials. As a result, only limited data are available and patients with these conditions should be closely supervised.
Ocular toxicity: Animal studies have shown adverse effects of memantine hydrochloride on the visual system. Dietary administration of memantine hydrochloride to rats for one year was associated with abnormal lysosomal storage in ganglion cells and retinal pigment cells at systemic exposures (plasma AUC) of 10-fold the anticipated clinical exposure at the recommended dose, while administration for eight weeks was associated with lens opacity, increased corneal and lens capsular densities, and histological changes in corneal and lens at exposures (plasma AUC) of 20-fold the clinical exposure. Oral administration of memantine hydrochloride to dogs with systemic exposures (plasma AUC) of 3- to 8-fold the clinical exposure was associated with corneal clouding/opacity and baboons showed swollen lenticular fibers in the eyes after oral memantine hydrochloride for three months at less than clinical exposure.
In a 6-month double-blind, placebo-controlled clinical study, specific ophthalmological examinations including slit lamp tests did not show any ocular changes. In the following 6-month open-label extension period, 368 patients underwent eye examinations. At the end of open label treatment, the incidence of cataract (lens previously clear but unclear at end of open label treatment) was reported in 11 of 197 patients (6%) treated with memantine hydrochloride for 12 months compared with 5 of 171 patients (3%) who received placebo in the double-blind period and then memantine hydrochloride for 6 months (p=0.3059).
Oral soln: Serious Hypersensitivity Reactions: Serious skin reactions (Stevens-Johnson syndrome and acute generalized exanthematous pustulosis) and other less serious skin reactions (e.g., erythema multiforme) have been rarely reported in patients receiving memantine. Patients or caregivers should be instructed to inform the physicians of any skin reactions that occur during treatment with memantine. Treatment should be discontinued at the first appearance of skin rash or any signs of a hypersensitivity reaction.
Neurological Conditions: The use of memantine has not been systematically evaluated in patients with seizure disorder. Seizure activity may be a manifestation of Alzheimer's disease. The risks and benefits of memantine treatment must epilepsy be carefully evaluated in patients with epilepsy, with a history of seizure disorder, or predisposing factors for Memantine should be administered with caution in these patients.
Genitourinary Conditions: Conditions that increase urinary pH by a factor of 7 to 9, such as drastic changes in diet (e.g., from a high-protein to a vegetarian diet), concurrent use of medications that alkalinize the urine [e.g., carbonic anhydrase inhibitors, sodium bicarbonate (see Interactions)], renal tubular acidosis, and severe urinary tract infections with Proteus bacteria, may reduce the elimination of memantine, resulting in increased plasma levels of the drug. Memantine should be used with caution in patients with these conditions. Careful monitoring is also recommended.
Cardiovascular Conditions: Since patients with recent myocardial infarction, uncompensated congestive heart failure (NYHA III-IV), or uncontrolled hypertension were excluded in most clinical trials, patients with these conditions should be closely supervised during memantine therapy.
Low incidences of cardiovascular adverse events occurred during clinical trials in patients with moderate to severe Alzheimer's disease. However, increased frequencies of hypertension, angina, bradycardia, and cardiac failure adverse events were reported in patients treated with memantine compared to those treated with placebo. Caution should be observed when memantine treatment is initiated with cardiovascular conditions.
Ophthalmic Conditions: In an open-label study, the administration of memantine 20 mg daily in elderly patients for approximately 48 months resulted to threefold higher concentrations of the drug in the lacrimal fluid than in plasma; no ophthalmologic effects were seen. In another 6-month trial, worsening of the corneal condition was reported for slightly more patients administered with memantine than placebo.
Ocular changes were not seen with specific ophthalmological examinations, including slit lamp examinations, in a 6-month clinical study with memantine. In the following 6-month open label extension period of the study, the incidence of cataract (i.e., lens previously clear but unclear at end of open label treatment) was reported in 6% of patients treated with memantine for 12 months compared to 3% of patients who received placebo in the first 6 months and then memantine for the next 6 months.
Periodic monitoring for ophthalmic conditions is recommended during memantine therapy.
Use in patients with serious comorbidities: Since there is limited information on its safety when given to patients with moderate to severe Alzheimer's disease and serious comorbidities, careful risk/benefit assessment should be done prior to initiation. Dose escalation should be done with caution in this patient population.
Concomitant use with other drugs: The concomitant use of memantine with drugs chemically related to NMDA antagonists should be avoided, as this may result to more frequent or pronounced adverse drug reactions, particularly CNS-related adverse reactions (see Interactions).
Effects on Ability to Drive and Use Machines: Moderate to severe Alzheimer's disease usually impairs the driving performance and compromises the ability to use machines. In addition, memantine has minor or moderate influence on the ability to drive and use machines. Patients on memantine therapy should be warned to take special care in driving a vehicle or operating heavy machinery.
Use in Children: Tablet: There are no adequate and well-controlled studies on the efficacy and safety of memantine hydrochloride in any illness occurring in children.
Oral soln: The safety and effectiveness of memantine in pediatric patients have not been established. The use of memantine in children is not recommended. Women taking memantine should not breastfeed. The clinical need of the mother for memantine, together with the benefits of breastfeeding and the potential adverse effects of memantine to the breastfed infant, must also be considered.
Use in the Elderly: Oral soln: There were no clinically significant differences in most adverse events reported between patients ≥65 years old and younger adults. There is limited safety information on the use of memantine in patients ≥80 years old. The use of memantine in Alzheimer's patients with chronic comorbidities common among the elderly should only be considered after a proper benefit-risk assessment. In addition, the potential for compromised renal function in elderly patients should be considered when memantine is concomitantly used with other drugs eliminated through renal mechanism.