| Active Ingredient | MEMANTINE HYDROCHLORIDE (Tablets) |
|---|
| Drug Name | FDA Application No. | Company | Dosage Form;Route | Strength | RLD Strength | Original Approval or Tentative Approval Date |
Exclusivity Expiration (NCE) |
Exclusivity Expiration (ODE) |
Chemical Type |
Review Classification |
Marketing Status |
TE Code |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NAMENDA | (NDA) 021487 | FOREST LABS LLC | TABLET;ORAL | 5 MG, 10 MG | 10 MG | October 16, 2003 | _ | _ | 1 New molecular entity (NME) | S Standard review drug | Prescription | AB |
| Parameters | Details |
|---|---|
| Structural Formula |
/Structural_Formula.jpg) |
| Chemical Name | 1-amino-3,5-dimethyladamantane hydrochloride |
| CAS No | 19982-08-2 |
| Molecular Formula | C12H21N•HCl |
| Molecular Weight | 215.76 |
| Appearance | Fine white to off-white powder |
| Solubility | - |
| Water Solubility | Soluble in water ( 35 mg/mL (HCl salt), 0.9 mg/mL for free base) |
| Polymorphism | - |
| pKa (Strongest Acidic) | 10.7 |
| pKa (Strongest Basic) | - |
| Log P | 3.28 |
| Identification | - |
| Degradation | - |
| Hygroscopic | Hygroscopic |
| Photostability study | Not sensitive to light |
| Melting Point | 258 °C |
| BCS Class | I |
| Manufacture of API | - |
| Parameters | Details |
|---|---|
| Indications and Usage | NAMENDA is an N-methyl-D-aspartate (NMDA) receptor antagonist indicated for the treatment of moderate to severe dementia of the Alzheimer’s type. |
| Dosage and Administration |
• May be taken with or without food • Initial dose is 5 mg once daily. Increase dose in 5 mg increments to a maintenance dose of 10 mg twice daily. A minimum of 1 week of treatment with the previous dose should be observed before increasing the dose. • Severe renal impairment: recommended dose is 5 mg twice daily. |
| Mechanism of action | Persistent activation of central nervous system N-methyl-D-aspartate (NMDA) receptors by the excitatory amino acid glutamate has been hypothesized to contribute to the symptomatology of Alzheimer’s disease. Memantine is postulated to exert its therapeutic effect through its action as a low to moderate affinity uncompetitive (open-channel) NMDA receptor antagonist which binds preferentially to the NMDA receptor-operated cation channels. There is no evidence that memantine prevents or slows neurodegeneration in patients with Alzheimer’s disease. |
| Absorption | Following oral administration memantine is highly absorbed with peak concentrations reached in about 3-7 hours. Memantine has linear pharmacokinetics over the therapeutic dose range. |
| Food Effect | Food has no effect on the absorption of memantine. |
| Distribution | The mean volume of distribution of memantine is 9-11 L/kg and the plasma protein binding is low (45%). |
| Metabolism |
Memantine undergoes partial hepatic metabolism. The hepatic microsomal CYP450 enzyme system does not play a significant role in the metabolism of memantine. The remainder is converted primarily to three polar metabolites which possess minimal NMDA receptor antagonistic activity: the N-glucuronide conjugate, 6-hydroxy memantine, and 1-nitrosodeaminated memantine. A total of 74% of the administered dose is excreted as the sum of the parent drug and the N-glucuronide conjugate. Renal clearance involves active tubular secretion moderated by pH dependent tubular reabsorption. |
| Elimination | Memantine is excreted predominantly (about 48%) unchanged in urine and has a terminal elimination half- life of about 60-80 hours |
| Peak plasma time (Tmax) | 3-7 hours |
| Half life | 60-80 hours |
| Bioavailability | - |
| Age, gender | Following multiple dose administration of NAMENDA 20 mg daily, females had about 45% higher exposure than males, but there was no difference in exposure when body weight was taken into account. |
| DMF | Status | Type | Submit Date | Holder |
|---|---|---|---|---|
| 18436 | A | II | June 17, 2005 | UNION QUIMICO FARMACEUTICA SA UQUIFA SA |
| 18562 | A | II | July 29, 2005 | OLON SPA |
| 19024 | I | II | December 14, 2005 | ESTEVE QUIMICA SA |
| 19465 | A | II | May 22, 2006 | INDUSTRIALE CHIMICA SRL |
| 19549 | A | II | June 20, 2006 | AMSA ANONIMA MATERIE SINTETICHE AND AFFINI SPA |
| 20151 | I | II | April 2, 2007 | TAI HENG INDUSTRY CO LTD |
| 20362 | A | II | March 23, 2007 | MYLAN LABORATORIES LTD |
| 20388 | A | II | March 30, 2007 | CADILA HEALTHCARE LTD |
| 20456 | A | II | March 30, 2007 | LUPIN LTD |
| 20543 | A | II | May 9, 2007 | OLAINFARM JSC |
| 20841 | A | II | September 7, 2007 | DR REDDYS LABORATORIES LTD |
| 20848 | A | II | September 13, 2007 | ORCHID CHEMICALS AND PHARMACEUTICALS LTD |
| 20868 | A | II | September 20, 2007 | TEVA PHARMACEUTICAL INDUSTRIES LTD |
| 20940 | A | II | October 3, 2007 | SUN PHARMACEUTICAL INDUSTRIES LTD |
| 20941 | I | II | October 12, 2007 | RANBAXY LABORATORIES LTD |
| 21199 | A | II | December 21, 2007 | APOTEX PHARMACHEM INC |
| 22112 | A | II | October 23, 2008 | MSN PHARMACHEM PRIVATE LTD |
| 22886 | A | II | June 30, 2009 | UNICHEM LABORATORIES LTD |
| 23108 | A | II | September 11, 2009 | ALEMBIC PHARMACEUTICALS LTD |
| 23567 | A | II | February 22, 2010 | HIKAL LTD |
| 24381 | A | II | November 17, 2010 | MACLEODS PHARMACEUTICALS LTD |
| 24778 | A | II | March 22, 2011 | HETERO DRUGS LTD |
| 25194 | A | II | August 9, 2011 | SHARON BIO MEDICINE LTD |
| 25321 | A | II | October 22, 2011 | EMCURE PHARMACEUTICALS LTD |
| 25402 | A | II | October 14, 2011 | MEGAFINE PHARMA P LTD |
| 26269 | A | II | July 30, 2012 | PROCOS SPA |
| 29180 | A | II | March 16, 2015 | ZCL CHEMICALS LTD |
| 29855 | A | II | October 21, 2015 | MACLEODS PHARMACEUTICALS LTD EXTENDED RELEASE PELLETS 28 MG |
| Parameters | Details | ||
|---|---|---|---|
| Strength | 5 MG | 10 MG | |
| Excipients used | Microcrystalline cellulose/colloidal silicon dioxide, talc, croscarmellose sodium, and magnesium stearate | Microcrystalline cellulose PH 200 (137.3 mg) /colloidal silicon dioxide (0.3 mg), talc (1 mg), croscarmellose sodium (1 mg), and magnesium stearate (0.4mg) | |
| Composition of coating material | Hypromellose, titanium dioxide, polyethylene glycol 400, FD&C yellow #6 and FD&C blue #2 |
Hypromellose, titanium dioxide, macrogol/polyethylene glycol 400 and iron oxide black (Opadry white 5 mg) |
|
| Composition of caspule shell | - | ||
| Pharmaceutical Development | - | ||
| Manufacture of the product | - | ||
| Tablet / Capsule Image |
/5 MG.jpg)
|
/10 MG.jpg)
|
|
| Appearance | Tan, capsule-shaped, film-coated tablets with “5” debossed on one side and FL on the other | Gray, capsule-shaped, film-coated tablets with “10” debossed on one side and FL on the other | |
| Imprint code / Engraving / Debossment | “5” debossed on one side and FL on the other | “10” debossed on one side and FL on the other | |
| Score | No score | No score | |
| Color | Tan | Gray | |
| Shape | Capsule-shaped | Capsule-shaped | |
| Dimension | 10 mm | 12 mm | |
| Mfg by | Forest Laboratories Ireland Ltd | ||
| Mfg for |
Forest Pharmaceuticals, Inc. Subsidiary of Forest Laboratories, Inc. |
||
| Marketed by | - | ||
| Distributed by | - | ||
| Application No. | Prod No | Patent No | Patent Expiration | Drug Substance Claim | Drug Product Claim | Patent Use Code | Delist Requested | Link |
|---|---|---|---|---|---|---|---|---|
| (NDA) 021487 | 1 | 5061703*PED | October 11, 2015 | - | - | - | - | Download |
| USP Apparatus | Speed (RPMs) | Medium | Volume (mL) | Recommended Sampling Times (minutes) | Date Updated |
|---|---|---|---|---|---|
| I (Basket) | 100 | 0.1 N HCl with NaCl (12 g NaCl in 6 L water adjust pH to 1.2 with HCl) | 900 | 10, 20, 30 and 45 | December 16, 2005 |
| Label | Link |
|---|---|
| FDA label | Download |
| FDA chemistry review | Download |
| FDA Pharmacology Review(s) | Download |
| FDA Clinical Pharmacology Biopharmaceutics Review(s) | Download |
| FDA BE Recommendation | Download |
| European Public Assessment Report |
| Territory | Brand name / Generic company name | Link |
|---|---|---|
| EU | - | |
| UK | - | |
| US | AJANTA PHARMA LTD* | |
| US | ALEMBIC PHARMS LTD* | |
| US | AMNEAL PHARMS* | |
| US | APOTEX INC* | |
| US | AUROBINDO PHARMA LTD* | |
| US | DR REDDYS LABS LTD* | |
| US | JUBILANT GENERICS* | |
| US | LUPIN LTD* | |
| US | MACLEODS PHARMS LTD* | |
| US | MYLAN PHARMS INC* | |
| US | NAMENDA | Download |
| US | ORCHID HLTHCARE* | |
| US | PURACAP PHARM LLC* | |
| US | SILARX PHARMS INC* | |
| US | SUN PHARMA GLOBAL* | |
| US | TEVA PHARMS* | |
| US | TORRENT PHARMS LTD* | |
| US | UNICHEM LABS LTD* | |
| US | UPSHER SMITH* | |
| US | WOCKHARDT LTD* | |
| US | ZYDUS PHARMS USA INC* |
| - |
| www.accessdata.fda.gov, www.drugbank.ca, www.ema.europa.eu, www.medicines.org.uk, dailymed.nlm.nih.gov |
