| Active Ingredient | AMANTADINE (EXTENDED RELEASE 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OSMOLEX ER | (NDA): 209410 | OSMOTICA PHARM US | TABLET, EXTENDED RELEASE;ORAL | 129MG, 193MG, 258MG | 258 MG | February 16, 2018 | _ | _ | Type 3 - New Dosage Form | STANDARD | Prescription | None |
| Parameters | Details |
|---|---|
| Structural Formula |
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| Chemical Name | Tricyclo [3.3.1.1 3,7] decan-1-amine,hydrochloride or 1-adamantanamine hydrochloride |
| CAS No | 768-94-5 |
| Molecular Formula | C10H17N•HCl |
| Molecular Weight | 187.71 (g/mol) |
| Appearance | Wite or nearly white crystalline powder |
| Solubility | Alcohol, and soluble in chloroform |
| Water Solubility | Freely soluble in water. 6290 mg/L (freely soluble) |
| Polymorphism | - |
| pKa (Strongest Acidic) | - |
| pKa (Strongest Basic) | 10.71 (Predicted) |
| Log P | 2.44 |
| Identification | - |
| Degradation | - |
| Hygroscopic | - |
| Photostability study | - |
| Melting Point | 180-192 |
| BCS Class | BCS Class I |
| Manufacture of API | - |
| Parameters | Details |
|---|---|
| Indications and Usage | OSMOLEX ER is indicated for the treatment of: • Parkinson's disease • Drug-induced extrapyramidal reactions in adult patients |
| Dosage and Administration |
• The initial dosage is 129 mg orally once daily in the morning • The dosage may be increased in weekly intervals to a maximum daily dose of 322 mg once daily in the morning • Swallow tablets whole; do not chew, crush, or divide • Dosing frequency reduction and monitoring required for renal impairment |
| Mechanism of action |
The mechanism by which amantadine exerts efficacy in the treatment of Parkinson’s disease and drug-induced extrapyramidal reactions is unknown. Amantadine is a weak uncompetitive antagonist of the NMDA receptor; however, it exhibits anticholinergic-like side effects such as dry mouth, urinary retention, and constipation in humans. Amantadine may have direct and indirect effects on dopamine neurons; it exerts dopaminergic-like side effects such as hallucinations and dizziness in humans. |
| Absorption |
OSMOLEX ER tablet consists of an immediate-release outer layer and an extended-release core.The pharmacokinetics of amantadine from OSMOLEX ER is dose proportional across the dose range of 129 mg to 322 mg. Absorption Following oral administration of OSMOLEX ER, peak concentration of amantadine was observed in a median time of 7.5 hours (range 5.5 to 12 hours). After a single oral administration of the 129 mg dose, the mean (CV%) Cmax and AUC were 328 ng/ml (18%) and 8263 ng.h/ml (18%) respectively. Cmax and AUC with other dose levels of OSMOLEX ER increase proportionally. |
| Food Effect | Food does not affect the rate or the extent of absorption of OSMOLEX ER. |
| Distribution | Amantadine is 67% bound to plasma proteins over a concentration range of 0.1 to 2.0 μg/mL.The volume of distribution after intravenous administration is 3-8 L/kg, suggesting potential extravascular distribution. |
| Metabolism | Metabolism accounts for only 5-15% of the total clearance for amantadine. Eight metabolites of amantadine have been identified in human urine. One metabolite, an N-acetylated compound,was quantified in human urine and accounted for 0-15% of the administered dose in multiple studies. The contribution of this metabolite to efficacy or toxicity is not known. |
| Elimination |
Amantadine is mainly eliminated renally, and approximately 85% of the administered dose is excreted unchanged in urine. After oral administration of a single 129 mg OSMOLEX ER tablet, the apparent oral clearance was approximately11 L/h. The half-life was approximately 16 hours. Amantadine is primarily excreted by glomerular filtration and tubular secretion. The pH of the urine has been reported to influence the excretion rate of amantadine |
| Peak plasma time (Tmax) | 7.5 hours (range 5.5 to 12 hours) |
| Half life | Approximately 16 hours |
| Bioavailability | - |
| Age, gender | In a study of young healthy subjects (n=20), mean renal clearance of amantadine, normalized for body mass index, was 1.5 fold higher in males compared to females. No dose adjustment by gender is warranted. |
| DMF | Status | Type | Submit Date | Holder |
|---|---|---|---|---|
| 23528 | A | II | February 11, 2010 | OLAINFARM JSC AMANTADINE HYDROCHLORIDE |
| 25151 | A | II | July 21, 2011 | ZHEJIANG APELOA KANGYU PHARMACEUTICAL CO LTD AMANTADINE HYDROCHLORIDE USP |
| 2817 | I | II | January 7, 1977 | CILAG CHEMIE AG AMANTADINE HCL |
| 29486 | A | II | September 1, 2015 | ANONIMA MATERIE SINTETICHE AND AFFINI (AMSA) SPA AMANTADINE HYDROCHLORIDE |
| 3739 | I | II | February 21, 1980 | CHEMOSWED AB 1-AMINOADAMANTANE HCL (AMANTADINE HCL) |
| 6924 | A | II | April 8, 1987 | MOEHS IBERICA SL AMANTADINE HYDROCHLORIDE |
| 9665 | I | II | April 28, 1992 | NORTHEAST GENERAL PHARMACEUTICAL FACTORY AMANTADINE HYDROCHLORIDE |
| Parameters | Details | |||
|---|---|---|---|---|
| Strength | 129MG | 193MG | 258MG | |
| Excipients used |
colloidal silicon dioxide, copovidone magnesium stearate, microcrystalline cellulose, sodium chloride |
|||
| Composition of coating material | Cellulose acetate, D&C Yellow No. 10, FD&C Yellow No. 6, ferrosoferric oxide, hypromellose polyethylene glycol, polysorbate 80, propylene glycol and titanium dioxide, lactose monohydrate and triacetin |
Cellulose acetate, D&C Yellow No. 10, FD&C Yellow No. 6, ferrosoferric oxide, hypromellose polyethylene glycol, polysorbate 80, propylene glycol and titanium dioxide, FD&C Blue No. 2 and FD&C Red No.40. |
Cellulose acetate, D&C Yellow No. 10, FD&C Yellow No. 6, ferrosoferric oxide, hypromellose polyethylene glycol, polysorbate 80, propylene glycol and titanium dioxide, FD&C Blue No. 1, FD&C Red No. 40, and ferric oxide yellow. |
|
| Composition of caspule shell | NA | |||
| Pharmaceutical Development | Updated soon | |||
| Manufacture of the product | Updated soon | |||
| Tablet / Capsule Image | ||||
| Appearance | Round, biconvex, white coated tablets, imprinted on one side with a black “VP” over “075” | Round, biconvex, green coated tabled, imprinted on one side with a black “VP” over “076” | Round, biconvex, blue coated tablets, imprinted on one side with a black “VP” over “077” | |
| Imprint code / Engraving / Debossment | Imprinted on one side with a black “VP” over “075” | Imprinted on one side with a black “VP” over “076” | Imprinted on one side with a black “VP” over “077” | |
| Score | No score | No score | No score | |
| Color | White | Green | Blue | |
| Shape | Round | Round | Round | |
| Dimension | 8 mm | 10 mm | 11 mm | |
| Mfg by |
Vertical Pharmaceuticals, LLC Bridgewater, NJ 08807 USA |
|||
| Mfg for | - | |||
| Marketed by | - | |||
| Distributed by | - | |||
| Application No. | Prod No | Patent No | Patent Expiration | Drug Substance Claim | Drug Product Claim | Patent Use Code | Delist Requested | Link |
|---|---|---|---|---|---|---|---|---|
| N209410 | 1 | 8252331 | March 13, 2030 | - | DP | - | - | Download |
| N209410 | 1 | 8574626 | November 28, 2025 | - | DP | U-20 | - | Download |
| N209410 | 1 | 10213393 | February 15, 2038 | - | - | U-20 | - | Download |
| N209410 | 1 | 10213394 | February 15, 2038 | - | - | U-2497 | - | Download |
| USP Apparatus | Speed (RPMs) | Medium | Volume (mL) | Recommended Sampling Times (minutes) | Date Updated |
|---|---|---|---|---|---|
| USP Type II (Paddle) | 50 | Water | 900 mL | Time point: 0.5 hour, 1 hour, 2.5 hours, 4 hours, 6 hours | As per SBOA |
| Label | Link |
|---|---|
| FDA label | Download |
| FDA chemistry review | Download |
| FDA Pharmacology Review(s) | Download |
| FDA Clinical Pharmacology Biopharmaceutics Review(s) | Download |
| FDA BE Recommendation | |
| European Public Assessment Report |
| - |
| www.accessdata.fda.gov, www.drugbank.ca, www.ema.europa.eu, www.medicines.org.uk, dailymed.nlm.nih.gov |
