| Active Ingredient | LURASIDONE HYDROCHLORIDE |
|---|
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| LATUDA | (NDA) 200603 | SUNOVION PHARMS INC | TABLET;ORAL | 20MG, 40MG, 60MG, 80MG, 120MG | 20MG, 40MG (RS), 60MG, 80MG, 120MG | October 28, 2010 | - | - | 1 New molecular entity (NME) | S Standard review drug | Prescription | None |
| Parameters | Details |
|---|---|
| Structural Formula |
 |
| Chemical Name | (3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1ylmethyl] cyclohexylmethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione hydrochloride |
| CAS No | 367514-87-2 |
| Molecular Formula | C28H36N4O2S·HCl |
| Molecular Weight | 529.14 |
| Appearance | a white to off-white powder |
| Solubility | It is very slightly soluble in water, practically insoluble or insoluble in 0.1 N HCl, slightly soluble in ethanol, sparingly soluble in methanol, practically insoluble or insoluble in toluene and very slightly soluble in acetone. |
| Water Solubility | 0.00789 mg/mL (Predicted) |
| Polymorphism | Only one crystal form has been produced under the manufacturing conditions. No polymorphism has been observed by powder X-ray diffraction measurements, infrared absorption spectrometry or thermal analysis under various crystallisation conditions. |
| pKa (Strongest Acidic) | - |
| pKa (Strongest Basic) | 8.5 (Predicted) |
| Log P | 5.25 (Predicted) |
| Identification | (IR, HPLC and chloride anion method |
| Degradation | - |
| Hygroscopic | non-hygroscopic |
| Photostability study | - |
| Melting Point | 205-210°C |
| BCS Class | IV |
| Manufacture of API | Lurasidone hydrochloride is synthesised according to a nine-step process using three well-defined starting materials with acceptable specifications and three intermediates are isolated. Brief descriptions of the manufacture of the starting materials have been provided and the active substance synthesis has been described in detail including process controls. |
| Parameters | Details |
|---|---|
| Indications and Usage | LATUDA is indicated for the treatment of patients with schizophrenia. The efficacy of LATUDA in schizophrenia was established in five 6-week controlled studies of adult patients with schizophrenia. The effectiveness of LATUDA for longer-term use, that is, for more than 6 weeks, has not been established in controlled studies. Therefore, the physician who elects to use LATUDA for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient. LATUDA is indicated as monotherapy for the treatment of patients with major depressive episodes associated with bipolar I disorder (bipolar depression). The efficacy of LATUDA was established in a 6-week monotherapy study in adult patients with bipolar depression. LATUDA is indicated as adjunctive therapy with either lithium or valproate for the treatment of patients with major depressive episodes associated with bipolar I disorder (bipolar depression). The efficacy of LATUDA was established in a 6-week study in adult patients with bipolar depression who were treated adjunctively with lithium or valproate. The effectiveness of LATUDA for longer-term use, that is, for more than 6 weeks, has not been established in controlled studies. Therefore, the physician who elects to use LATUDA for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient. The efficacy of LATUDA in the treatment of mania associated with bipolar disorder has not been established. |
| Dosage and Administration |
The recommended starting dose of LATUDA is 40 mg once daily. Initial dose titration is not required. LATUDA has been shown to be effective in a dose range of 40 mg per day to 160 mg per day. The maximum recommended dose is 160 mg per day. The recommended starting dose of LATUDA is 20 mg given once daily as monotherapy or as adjunctive therapy with lithium or valproate. Initial dose titration is not required. LATUDA has been shown to be effective in a dose range of 20 mg per day to 120 mg per day as monotherapy or as adjunctive therapy with lithium or valproate. The maximum recommended dose, as monotherapy or as adjunctive therapy with lithium or valproate, is 120 mg per day. In the monotherapy study, the higher dose range (80 mg to 120 mg per day) did not provide additional efficacy on average, compared to the lower dose range (20 to 60 mg per day). LATUDA should be taken with food (at least 350 calories). Administration with food substantially increases the absorption of LATUDA. Administration with food increases the AUC approximately 2-fold and increases the Cmax approximately 3-fold. In the clinical studies, LATUDA was administered with food. |
| Mechanism of action | The mechanism of action of LATUDA in the treatment of schizophrenia and bipolar depression is unknown. However, its efficacy in schizophrenia and bipolar depression could be mediated through a combination of central dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptor antagonism. |
| Absorption | The activity of LATUDA is primarily due to the parent drug. The pharmacokinetics of LATUDA is dose-proportional within a total daily dose range of 20 mg to 160 mg. Steady-state concentrations of LATUDA are reached within 7 days of starting LATUDA. LATUDA is absorbed and reaches peak serum concentrations in approximately 1-3 hours. It is estimated that 9-19% of an administered dose is absorbed. |
| Food Effect |
In a food effect study, LATUDA mean Cmax and AUC were about 3-times and 2-times, respectively, when administered with food compared to the levels observed under fasting conditions. LATUDA exposure was not affected as meal size was increased from 350 to 1000 calories and was independent of meal fat content. In clinical studies, establishing the safety and efficacy of LATUDA, patients were instructed to take their daily dose with food |
| Distribution | Following administration of 40 mg of LATUDA, the mean (%CV) apparent volume of distribution was 6173 (17.2) L. LATUDA is highly bound (~99%) to serum proteins. |
| Metabolism | LATUDA is metabolized mainly via CYP3A4. The major biotransformation pathways are oxidative N-dealkylation, hydroxylation of norbornane ring, and S-oxidation. LATUDA is metabolized into two active metabolites (ID-14283 and ID-14326) and two major non-active metabolites (ID-20219 and ID-20220). Based on in vitro studies, LATUDA is not a substrate of CYP1A1, CYP1A2, CYP2A6, CYP4A11, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP2E1 enzymes. Because LATUDA is not a substrate for CYP1A2, smoking is not expected to have an effect on the pharmacokinetics of LATUDA. |
| Elimination | Total excretion of radioactivity in urine and feces combined was approximately 89%, with about 80% recovered in feces and 9% recovered in urine, after a single dose of [14C]-labeled LATUDA. Following administration of 40 mg of LATUDA, the mean (%CV) apparent clearance was 3902 (18.0) mL/min. Following administration of 40 mg of LATUDA, the mean (%CV) elimination half-life was 18(7) hours. |
| Peak plasma time (Tmax) | 1-3 hours |
| Half life | 18(7) hours |
| Bioavailability | - |
| Age, gender | - |
| DMF | Status | Type | Submit Date | Holder |
|---|---|---|---|---|
| 26700 | A | II | March 22, 2013 | DR REDDYS LABORATORIES LTD |
| 27452 | A | II | September 20, 2013 | GLENMARK PHARMACEUTICALS LTD |
| 27570 | A | II | September 30, 2013 | MSN PHARMACHEM PRIVATE LTD |
| 27584 | A | II | December 5, 2013 | ALP PHARM BEIJING CO LTD |
| 27898 | A | II | April 30, 2014 | AMSA SPA |
| 27963 | A | II | April 11, 2014 | LUPIN LTD |
| 27970 | A | II | February 20, 2014 | HETERO DRUGS LTD |
| 28076 | A | II | April 21, 2014 | APOTEX PHARMACHEM INDIA PVT LTD |
| 28126 | A | II | April 18, 2014 | MYLAN LABORATORIES LTD |
| 28164 | A | II | April 22, 2014 | TORRENT PHARMACEUTICALS LTD |
| 28178 | A | II | April 28, 2014 | TEVA PHARMACEUTICAL INDUSTRIES LTD |
| 28252 | A | II | June 4, 2014 | RAKS PHARMA PVT LTD |
| 28281 | A | II | June 12, 2014 | CADILA HEALTHCARE LTD |
| 28417 | A | II | July 21, 2014 | SUN PHARMACEUTICAL INDUSTRIES LTD |
| 28447 | A | II | July 9, 2014 | INTAS PHARMACEUTICALS LTD |
| 28448 | A | II | July 22, 2014 | AUROBINDO PHARMA LTD |
| 28723 | A | II | September 30, 2014 | EDMOND PHARMA SRL |
| 29163 | A | II | March 30, 2015 | PIRAMAL ENTERPRISES LTD |
| 29191 | A | II | March 31, 2015 | UNICHEM LABORATORIES LTD |
| 29794 | A | II | May 7, 2016 | NEULAND LABORATORIES LTD |
| 30092 | A | II | December 29, 2015 | ALEMBIC PHARMACEUTICALS LTD |
| 30464 | A | II | April 5, 2016 | STRIDES SHASUN LTD |
| 31381 | A | II | March 23, 2017 | JUBILANT GENERICS LTD |
| Parameters | Details | |||||
|---|---|---|---|---|---|---|
| Strength | 20MG | 40MG | 60MG | 80MG | 120MG | |
| Excipients used | mannitol, pregelatinized starch, croscarmellose sodium, hypromellose, magnesium stearate | mannitol (65.7mg), pregelatinized starch (40mg), croscarmellose sodium (7.3mg), hypromellose (5mg), magnesium stearate (2mg) | mannitol, pregelatinized starch, croscarmellose sodium, hypromellose, magnesium stearate | mannitol (131.4mg), pregelatinized starch (80mg), croscarmellose sodium (14.6mg), hypromellose (10mg), magnesium stearate (4mg) | mannitol, pregelatinized starch, croscarmellose sodium, hypromellose, magnesium stearate | |
| Composition of coating material | Opadry and carnauba wax | Opadry (3.2mg) and carnauba wax | Opadry and carnauba wax | Opadry (6.304mg) and carnauba wax, yellow ferric oxide and FD&C Blue No. 2 Aluminum Lake | Opadry and carnauba wax | |
| Composition of caspule shell | - | |||||
| Pharmaceutical Development | The objective of the pharmaceutical development was to obtain an immediate release solid dosage form of lurasidone as active substance for the treatment of schizophrenia. The finished product comprises immediate release film-coated tablets containing 20 mg, 40 mg and 80 mg lurasidone hydrochloride packaged in aluminium/aluminium blisters. With respect to the free base the content of the tablets for the respective strengths is 18.6 mg (18.5 mg), 37.2 mg (37 mg) and 74.5 mg (74 mg). | |||||
| Manufacture of the product | The finished product is manufactured by a standard process consisting of the following main steps: wet granulation, drying, sizing, blending, compression and film-coating. Standard equipment is utilised. The three strengths are manufactured from a common granulate. | |||||
| Tablet / Capsule Image |
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| Appearance | white to off-white, film-coated round tablets debossed with “L20” one side and plain other side | white to off-white, film-coated round tablets debossed with “L40” one side and plain other side | white to off-white, film-coated oval tablets debossed with “L60” one side and plain other side | pale green, film-coated oval tablets debossed with “L80” one side and plain other side | white to off-white, film-coated oval tablets debossed with “L60” one side and plain other side | |
| Imprint code / Engraving / Debossment | debossed with “L20” one side and plain other side | debossed with “L40” one side and plain other side | debossed with “L60” one side and plain other side | debossed with “L80” one side and plain other side | debossed with “L120” one side and plain other side | |
| Score | no score | no score | no score | no score | no score | |
| Color | WHITE | WHITE | WHITE | PALE GREEN | WHITE | |
| Shape | ROUND | ROUND | OVAL | OVAL | OVAL | |
| Dimension | 6mm | 8mm | 13mm | 12mm | 15mm | |
| Mfg by | Takeda Limited (EU) | |||||
| Mfg for | Sunovion Pharmaceuticals Inc. (US) | |||||
| Marketed by | Sunovion Pharmaceuticals Inc. (US, EU) | |||||
| Distributed by | - | |||||
| Application No. | Prod No | Patent No | Patent Expiration | Drug Substance Claim | Drug Product Claim | Patent Use Code | Delist Requested | Link |
|---|---|---|---|---|---|---|---|---|
| N200603 | 1 | 5532372 | July 2, 2018 | Y | - | - | - | Download |
| N200603 | 1 | 8729085 | May 26, 2026 | - | Y | - | - | Download |
| N200603 | 1 | 8883794 | May 26, 2026 | - | Y | - | - | Download |
| N200603 | 1 | 9174975 | June 25, 2026 | - | - | U - 1770 | - | Download |
| N200603 | 1 | RE45573 | June 23, 2025 | Y | - | - | - | Download |
| N200603 | 3 | 9259423 | May 23, 2031 | - | - | U-1822 | - | Download |
| N200603 | 3 | 9555027 | May 26, 2026 | - | DP | U-543 | - | Download |
| USP Apparatus | Speed (RPMs) | Medium | Volume (mL) | Recommended Sampling Times (minutes) | Date Updated |
|---|---|---|---|---|---|
| II (Paddle) | 50 | McIlvaine buffer, pH 3.8 [(0.0.025 M Citric acid Solution + 0.05M Na2HPO4 solution (3:2)] Measure the pH and adjust to 3.8, if necessary. Degas before use. | 900 | 5, 10, 15, 20 and 30 | January 31, 2013 |
| 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 | Download |
| Territory | Brand name / Generic company name | Link |
|---|---|---|
| EU | LATUDA | Download |
| UK | LATUDA | Download |
| US | ACCORD HLTHCARE INC (ANDA # 208049)* | |
| US | AMNEAL PHARMS CO (ANDA # 208002)* | |
| US | AUROBINDO PHARMA LTD (ANDA #208045)* | |
| US | EMCURE PHARMS LTD (ANDA # 208058)* | |
| US | EMCURE PHARMS LTD (ANDA #208058)* | |
| US | INVAGEN PHARMS (ANDA #208028)* | |
| US | LATUDA | Download |
| US | LUPIN LTD (ANDA # 208031)* | |
| US | MSN LABORATORIES (ANDA # 208037)* | |
| US | PAR PHARM INC (ANDA #207948)* | Download |
| US | SUN PHARMA GLOBAL (ANDA # 208066)* | |
| US | TORRENT PHARMS LTD (ANDA #208055) | |
| US | WATSON LABS INC ( ANDA #208016)* | |
| US | ZYDUS PHARMS USA (ANDA #208052)* |
| Exclusivity Code: Exclusivity Expiration M-195: Jan 27, 2020; NPP: Jan 27, 2020, PED:Jul 27, 2020 |
| www.accessdata.fda.gov, www.drugbank.ca, www.ema.europa.eu, www.medicines.org.uk, dailymed.nlm.nih.gov |
