Scribd Logo
Upload

Welcome to Scribd!

  • Memry

    Uploaded by

    Manice Bastinen
    12 views1 page

    Original Title

    memry

    Copyright

    © © All Rights Reserved

    Available Formats

    PDF or read online from Scribd

    Did you find this document useful?

    Is this content inappropriate?

    Report this Document

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    12 views1 page

    Memry

    Uploaded by

    Manice Bastinen

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    of 1
    MEMANTINE HCI MEMRY* 10 mg FILM-COATED TABLET ANTI-DEMENTIA FORMULATION Each fim-coated tablet contains: Memantine hydrochloride, USP........snsnnsese Mg PRODUCT DESCRIPTION Memantine hydrochloride 10mg Tabletisawhite, oblong, biconvex,film-coated tablet, scored onboth sides. PHARMACOLOGY Evidence suggests that malfunctioning of glutamatergic neurotransmission, particulary the N-methy/-D-aspartate (NMDA)-eceptors, contributes to both expression ofsymptoms and disease progression in neurodegenerative dementia, Memantine hydrochloride isa rapid, strongly votage-dependent, low to moderate affnity uncompettve (open-channel) NMDA-receptor antagonist which binds preferential to the NMDA receplor-operated cation channels, Prolonged increased levels of glutamate in the brain of demented patients are sufficient to counter the Mg” ions voltage-dependent block of NMDA receptors and allow continuous influx of Ca" ions into cells which lead to neuronal degeneration. Studies showed that memantine hydrochloride binds more effectvaly than Mg” ions atthe NMDA receptor, and thereby effectively blocks this prolonged influx of Ca’ ions through the NMDA channels while preserving the transient physiological acvation of the channels by higher concentrations of synapticaly released glstamate, Thus, memantine hydrochloride modulates the effects of pathologically elevated tonic levels of glutamate that may lead toneuronal dysfunction, ‘Thereisno evidence that memantine hydrochioride prevents or slows neurodegenerationin patients with Alzheimer’s disease. However, studies show that ‘memantine hydrochloride produced statistically significant effects in preventing worsening in three endpoints (eg., cognitive, global and functional) in patients with moderate to severe Alzheimers disease (MMSE total score <20), Memantine hydrochloride showed low to negligible affity for GABA, benzodiazepine, dopamine, adrenergo, histamine, and glycine receptors and for voltage-dependent Ca”, Na’ orK’ channels. Memantine hydrochloride also showed antagonistic effects atthe SHT, receptors with a potency similar t that forthe NMDA receptors and blocked nicotinic acetylcholine receptors with one-sixth to one-tenth the potency. In vio studies have shown that memantine hydrochloride does notaffecthe reversible inhibition of acetycholinesterase by donepezil, galantamineortacrine, PHARMACOKINETICS Memantine hydrochloride is completely absorbed after oral administration; absolute bioavailability is approximately 100%. Ithas linear pharmacokinetics ‘ver the therapeutic dose range of 10 to 40 mg, Maximum plasma concentration is achieved in to 8 hours. Food tended to slow the rate butnotthe extent ‘ofmemantine hydrochloride absorption, Daily doses of 20 mg lead to steady-state piasma concentrations ranging from 70 to 150 ngimL. (05-1 uM) with large interindividual variations. A mean ccrebrospinal ud (CSF)/serum ratio 00.52 was obtained when dally doses of Sto 30 mg were administered. The volume of istrbution is approximately 410 Lika. Protein binding varied from 42 to 54% and no relationship was observed between plasma memantine hydrochloride concentration and protein binding Memantine hydrochloride undergoes partial hepaticmetabalism. tis excreted mainly (60 to 80%) nits unchanged form in urine. Human metabolites are 1- amino-3-nydroxymethy-S-methy-adamantane, 3-amino-1-hydroxy'5,7-dimethy-adamantane and various secondary hydroxylated not yet definitively identfied memantine nydrochiride derivatives; phase II metabolism amounts for upto 10%. The known metabolites do not have any NMDA-antagonistc activity, n vitro studios have shown that memantine hydrochloride isnot metabolized by cytochrome P450 (CYP) isoenzymes 1A2, 2A6, 2B6, 2C9, 2019, 208, 261, and 3A4, Memantine hydrochloride is eliminated predominantly by the kidneys in a mono-exponential manner with a terminal hattife of 60 to 100 hours. In volunteers with normal kidney function, systemic clearance amounts to 170 mLImin. In a study on the absorption, metabolism and excretion of orally ‘administered “C-memantine, amean of 84% ofthe dose was recovered within 20 days, the majority being excreted unchanged renal, Renal clearance has been shown to depend on the pH ofthe urine. Under alkaline conditions, the renal clearance of unchanged memantine hydrochloride is markedly reduced compared to neutral oracidc urine conditions dv to tubular reabsorption of memantine hydrochloride under alkaline conditions, ‘Special Population: Hepatic Impairment: Ater single oral dose administration of 20 mg memantine hydrochloride in subjects wih moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) and subjects who were age-, gender- and weight-matched to the hepaticallyimpaired subjects, no change in memantine hhydrochioride exposure (based on C,,, and AUC) was seenin subjects with moderate hepatic impairments compared with healthy subjects. However, the terminal elimination hal-ife increasedby about 16% in subjects with moderate hepaticimpairmentas compared with heathy subject. Renal Impairment: Ate single oral dose administration of 20 mg memantine hydrochloride in subjects with mild enal impairment (creatinine clearance, CL, >50 to 80 mL), moderate renal impairment (Cl, 30 to 49 mL/min), severe renal impairment (CL, 5 to 29mLImin),orin healthy subjects (Cl, 80 mL/min) matched as closely as possible by age, weight and gender to the subjects with renal impairment, the mean AUC, . increased by 4%, 60% ot 115% in subjects with mild, moderate or severe renalimpairment, respectively, compared to healthy subjects. The terminal hal-ife increased by 18%, 41% or 95% in subjects wth mild, moderate or severe renalimpairment, respectively, comparedtoheatthy subjects In the eldery with impaired renal function [creatinine clearance (CL): 50 mL/min], a significant correlation was observed between CL, and total renal

    You might also like