Extract from the Clinical Evaluation Report for Armodafinil
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Modafinil Tablets
PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION PrAURO-MODAFINIL Modafinil Tablets 100 mg House Standard Central Nervous System Stimulant Auro Pharma Inc. 3700 Steeles Avenue West, Suite # 402 Date of Revision: Woodbridge, ON, L4L 8K8, August 8, 2019. CANADA Submission Control Number: 230314 Page 1 of 41 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION ......................................................... 3 SUMMARY PRODUCT INFORMATION .................................................................... 3 INDICATIONS AND CLINICAL USE .......................................................................... 3 CONTRAINDICATIONS ............................................................................................... 4 WARNINGS AND PRECAUTIONS .............................................................................. 4 ADVERSE REACTIONS .............................................................................................. 12 DRUG INTERACTIONS .............................................................................................. 16 DOSAGE AND ADMINISTRATION .......................................................................... 19 OVERDOSAGE ............................................................................................................ 21 ACTION AND CLINICAL PHARMACOLOGY ........................................................ 21 STORAGE AND STABILITY ...................................................................................... 23 DOSAGE FORMS, COMPOSITION AND PACKAGING -
These Highlights Do Not Include All the Information Needed to Use PROVIGIL Safely and Effectively
PROVIGIL- modafinil tablet Bryant Ranch Prepack ---------- HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use PROVIGIL safely and effectively. See full prescribing information for PROVIGIL. PROVIGIL® (modafinil) tablets, for oral use, C-IV Initial U.S. Approval: 1998 INDICATIONS AND USAGE PROVIGIL is indicated to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (OSA), or shift work disorder (SWD). (1) Limitations of Use In OSA, PROVIGIL is indicated to treat excessive sleepiness and not as treatment for the underlying obstruction. DOSAGE AND ADMINISTRATION The recommended dosage of PROVIGIL for each indication is as follows: • Narcolepsy or OSA: 200 mg once a day in the morning. (2.1) • SWD: 200 mg once a day, taken approximately one hour prior to start of the work shift. (2.2) • Severe Hepatic Impairment: reduce dose to half the recommended dose. (2.3, 12.3) • Geriatric Patients: consider lower dose. (2.4, 12.3) DOSAGE FORMS AND STRENGTHS Tablets: 100 mg and 200 mg. (3) CONTRAINDICATIONS PROVIGIL is contraindicated in patients with known hypersensitivity to modafinil or armodafinil. (4) WARNINGS AND PRECAUTIONS • Serious Rash, including Stevens-Johnson Syndrome: Discontinue PROVIGIL at the first sign of rash, unless the rash is clearly not drug-related. (5.1) • Angioedema and Anaphylaxis Reactions: If suspected, discontinue PROVIGIL. (5.2) • Multi-organ Hypersensitivity Reactions: If suspected, discontinue PROVIGIL. (5.3) • Persistent Sleepiness: Assess patients frequently for degree of sleepiness and, if appropriate, advise patients to avoid driving or engaging in any other potentially dangerous activity. (5.4) • Psychiatric Symptoms: Use caution in patients with a history of psychosis, depression, or mania. -
Wo 2010/075090 A2
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 1 July 2010 (01.07.2010) WO 2010/075090 A2 (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07D 409/14 (2006.01) A61K 31/7028 (2006.01) kind of national protection available): AE, AG, AL, AM, C07D 409/12 (2006.01) A61P 11/06 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US2009/068073 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 15 December 2009 (15.12.2009) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (25) Filing Language: English SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, (26) Publication Language: English TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 61/122,478 15 December 2008 (15.12.2008) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (71) Applicant (for all designated States except US): AUS- ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, PEX PHARMACEUTICALS, INC. -
Modafinil: a Review of Neurochemical Actions and Effects on Cognition
Neuropsychopharmacology (2008) 33, 1477–1502 & 2008 Nature Publishing Group All rights reserved 0893-133X/08 $30.00 www.neuropsychopharmacology.org Perspective Modafinil: A Review of Neurochemical Actions and Effects on Cognition ,1 1 Michael J Minzenberg* and Cameron S Carter 1Imaging Research Center, Davis School of Medicine, UC-Davis Health System, University of California, Sacramento, CA, USA Modafinil (2-[(Diphenylmethyl) sulfinyl] acetamide, Provigil) is an FDA-approved medication with wake-promoting properties. Pre-clinical studies of modafinil suggest a complex profile of neurochemical and behavioral effects, distinct from those of amphetamine. In addition, modafinil shows initial promise for a variety of off-label indications in psychiatry, including treatment-resistant depression, attention- deficit/hyperactivity disorder, and schizophrenia. Cognitive dysfunction may be a particularly important emerging treatment target for modafinil, across these and other neuropsychiatric disorders. We aimed to comprehensively review the empirical literature on neurochemical actions of modafinil, and effects on cognition in animal models, healthy adult humans, and clinical populations. We searched PubMed with the search term ‘modafinil’ and reviewed all English-language articles for neurochemical, neurophysiological, cognitive, or information-processing experimental measures. We additionally summarized the pharmacokinetic profile of modafinil and clinical efficacy in psychiatric patients. Modafinil exhibits robust effects on catecholamines, serotonin, glutamate, gamma amino-butyric acid, orexin, and histamine systems in the brain. Many of these effects may be secondary to catecholamine effects, with some selectivity for cortical over subcortical sites of action. In addition, modafinil (at well-tolerated doses) improves function in several cognitive domains, including working memory and episodic memory, and other processes dependent on prefrontal cortex and cognitive control. -
Methylxanthines and Neurodegenerative Diseases: an Update
nutrients Review Methylxanthines and Neurodegenerative Diseases: An Update Daniel Janitschke 1,† , Anna A. Lauer 1,†, Cornel M. Bachmann 1, Heike S. Grimm 1, Tobias Hartmann 1,2 and Marcus O. W. Grimm 1,2,* 1 Experimental Neurology, Saarland University, 66421 Homburg/Saar, Germany; [email protected] (D.J.); [email protected] (A.A.L.); [email protected] (C.M.B.); [email protected] (H.S.G.); [email protected] (T.H.) 2 Deutsches Institut für DemenzPrävention (DIDP), Saarland University, 66421 Homburg/Saar, Germany * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: Methylxanthines (MTX) are purine derived xanthine derivatives. Whereas naturally occurring methylxanthines like caffeine, theophylline or theobromine are widely consumed in food, several synthetic but also non-synthetic methylxanthines are used as pharmaceuticals, in particular in treating airway constrictions. Besides the well-established bronchoprotective effects, methylxanthines are also known to have anti-inflammatory and anti-oxidative properties, mediate changes in lipid homeostasis and have neuroprotective effects. Known molecular mechanisms include adenosine receptor antagonism, phosphodiesterase inhibition, effects on the cholinergic system, wnt signaling, histone deacetylase activation and gene regulation. By affecting several pathways associated with neurodegenerative diseases via different pleiotropic mechanisms and due to its moderate side effects, intake of methylxanthines have been suggested to be an interesting approach in dealing with neurodegeneration. Especially in the past years, the impact of methylxanthines in neurodegenerative diseases has been extensively studied and several new aspects have been elucidated. In this review Citation: Janitschke, D.; Lauer, A.A.; Bachmann, C.M.; Grimm, H.S.; we summarize the findings of methylxanthines linked to Alzheimer´s disease, Parkinson’s disease Hartmann, T.; Grimm, M.O.W. -
Comparison of Caffeine and D-Amphetamine in Cocaine-Dependent Subjects: Differential Outcomes on Subjective and Cardiovascular Effects, Reward Learning, and Salivary
NIH Public Access Author Manuscript J Addict Res Ther. Author manuscript; available in PMC 2014 November 18. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: J Addict Res Ther. 2014 ; 5(2): 176–. doi:10.4172/2155-6105.1000176. Comparison of Caffeine and d-amphetamine in Cocaine- Dependent Subjects: Differential Outcomes on Subjective and Cardiovascular Effects, Reward Learning, and Salivary Paraxanthine Scott D Lane1,*, Charles E Green1, Joy M Schmitz1, Nuvan Rathnayaka1, Wendy B Fang2, Sergi Ferré3, and F Gerard Moeller4 1Center for Neurobehavioral Research on Addictions, Department of Psychiatry & Behavioral Sciences, University of Texas Health Science Center – Houston, Houston, TX USA 2Center for Human Toxicology, University of Utah, Salt Lake City, UT, USA 3Integrative Neurobiology, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA 4Division on Addictions, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA Abstract Due to indirect modulation of dopamine transmission, adenosine receptor antagonists may be useful in either treating cocaine use or improving disrupted cognitive-behavioral functions associated with chronic cocaine use. To compare and contrast the stimulant effects of adenosine antagonism to direct dopamine stimulation, we administered 150 mg and 300 mg caffeine, 20 mg amphetamine, and placebo to cocaine-dependent vs. healthy control subjects, matched on moderate caffeine use. Data were obtained on measures -
(12) Patent Application Publication (10) Pub. No.: US 2011/0142957 A1 VAN KEMPEN (43) Pub
US 2011 O142957A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0142957 A1 VAN KEMPEN (43) Pub. Date: Jun. 16, 2011 (54) METHOD OF TREATING PARTURIENT Publication Classification PLACENTAL MAMMALS IN ORDER TO (51) Int. Cl. REDUCE MATERNAL AND/OR UTERINE A633/42 (2006.01) EXHAUSTION A633/04 (2006.01) A633/00 (2006.01) (76) Inventor: Theo VAN KEMPEN, Sint Stevens A6II 3/522 (2006.01) Woluwe (BE) A63L/35 (2006.01) (21) Appl. No.: 13/030,422 (52) U.S. Cl. ... 424/601; 424/709: 424/722: 514/263.34; 514/654 (22) Filed: Feb. 18, 2011 (57) ABSTRACT Related U.S. Application Data The present invention relates to a method of facilitating the birth process of placental mammals, especially to a method of (62) Division of application No. 12/063,830, filed on Aug. reducing delays in the birth process and, thereby, complica 4, 2008, now Pat. No. 7,893,070, filed as application tions resulting there from that may negatively affect the health No. PCT/NL2006/050201 on Aug. 14, 2006. and wellbeing of the mother and increase the incidence of stillbirths and/or neonatal mortality. According to the present (60) Provisional application No. 60/707,954, filed on Aug. invention delays in parturition that result from maternal and/ 15, 2005. or uterine exhaustion may be prevented or reduced by the administration of an effective amount of one or more psycho (30) Foreign Application Priority Data motor stimulants to the parturient mammal prior to and/or during parturition. Said psychomotor stimulant is selected Aug. -
The Transcriptional Repressor Orphan Nuclear Receptor TLX Is Responsive to Caffeine and Istradefylline
The transcriptional repressor orphan nuclear receptor TLX is responsive to caffeine and istradefylline Giuseppe Faudonea, Whitney Kilua, Xiaomin Nia,b, Apirat Chaikuada,b, Sridhar Sreeramuluc, Pascal Heitela, Harald Schwalbec, Stefan Knappa,b, Manfred Schubert-Zsilavecza, Jan Heeringd, and Daniel Merka* a Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt, Germany b Structural Genomics Consortium, BMLS, Goethe University Frankfurt, Max-von-Laue-Str. 15, D-60438 Frankfurt, Germany c Center for Biomolecular Magnetic Resonance (BMRZ), Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, Max-von-Laue-Str. 7, D-60438 Frankfurt, Germany d Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, D-60596 Frankfurt, Germany * Correspondence to: [email protected] Abstract. The orphan nuclear receptor TLX is expressed almost exclusively in neural stem cells. TLX acts as an essential factor for neural stem cell survival and is hence considered as a promising drug target in neurodegeneration. However, few studies have characterized the roles of TLX due to a lack of ligands and limited functional understanding. Here, we identify caffeine and istradefylline as TLX ligands that counteract the receptor’s intrinsic repressor activity in reporter gene assays and modulate TLX regulated SIRT1 and p21 expression. Mutagenesis of residues lining a cavity within the TLX ligand binding domain altered activity of these ligands suggesting direct interactions with helix 5. Using istradefylline as a tool compound, we observed ligand-sensitive recruitment of the co-repressor SMRT and heterodimerization of TLX with RXR. Both protein-protein complexes evolve as factors that modulate TLX function and suggest an unprecedented role of TLX in directly repressing other nuclear receptors. -
US 2002/0103350 A1 Lyles (43) Pub
US 2002O103350A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2002/0103350 A1 Lyles (43) Pub. Date: Aug. 1, 2002 (54) MATERIALS AND METHODS FOR BINDING Publication Classification NUCLECACDS TO SURFACES (51) Int. CI.7. ... C12O 1/68; CO7H 21/04 (76) Inventor: Mark B. Lyles, San Antonio, TX (US) (52) U.S. Cl. ............................................... 536/23.1; 435/6 Correspondence Address: (57) ABSTRACT Baker Botts L.L.P. Surfaces containing high purity Silica (Silicon dioxide) One Shell Plaza exhibit high loading potential for nucleic acids. 901 Louisiana Houston, TX 77002-4995 (US) Formulations containing nucleic acids and materials which mask the electroStatic interactions between the nucleic acids (21) Appl. No.: 09/910,697 and Surfaces are disclosed. By masking the phosphate charges of the nucleic acids, undesired interactions may be (22) Filed: Jul. 20, 2001 minimized or eliminated, thereby allowing the covalent bonding of the nucleic acids to the Surface to proceed. The use of Such formulations additionally minimizes nonspecific Related U.S. Application Data binding of the nucleic acids to the Surface. Examples of materials to be included in Such formulations include cat (60) Provisional application No. 60/220,096, filed on Jul. ions, Xanthines, heXOSes, purines, arginine, lysine, polyargi 21, 2000. nine, polylysine, and quaternary ammonium Salts. US 2002/0103350 A1 Aug. 1, 2002 MATERIALS AND METHODS FOR BINDING DETAILED DESCRIPTION OF THE NUCLEIC ACIDS TO SURFACES INVENTION 0009. The prior art materials and formulations have been FIELD OF THE INVENTION plagued with two general problems; a) low loading potential 0001. The invention relates to silica Surfaces useful for of the Surfaces, and b) nonspecific binding of nucleic acids binding nucleic acids, and formulations to improve the to the Surface. -
PROVIGIL® (Modafinil) Tablets [C-IV] Rx Only
PI + MG October 2010 PROVIGIL® (modafinil) Tablets [C-IV] Rx Only DESCRIPTION PROVIGIL (modafinil) is a wakefulness-promoting agent for oral administration. Modafinil is a racemic compound. The chemical name for modafinil is 2-[(diphenylmethyl)sulfinyl]acetamide. The molecular formula is C15H15NO2S and the molecular weight is 273.35. The chemical structure is: OO CH S CH2 CNH2 Modafinil is a white to off-white, crystalline powder that is practically insoluble in water and cyclohexane. It is sparingly to slightly soluble in methanol and acetone. PROVIGIL tablets contain 100 mg or 200 mg of modafinil and the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, pregelatinized starch, croscarmellose sodium, povidone, and magnesium stearate. CLINICAL PHARMACOLOGY Mechanism of Action and Pharmacology The precise mechanism(s) through which modafinil promotes wakefulness is unknown. Modafinil has wake-promoting actions similar to sympathomimetic agents like amphetamine and methylphenidate, although the pharmacologic profile is not identical to that of sympathomimetic amines. Modafinil has weak to negligible interactions with receptors for norepinephrine, serotonin, dopamine, GABA, adenosine, histamine-3, melatonin, and benzodiazepines. Modafinil also does not inhibit the activities of MAO-B or phosphodiesterases II-V. 1 PI + MG October 2010 Modafinil-induced wakefulness can be attenuated by the α1-adrenergic receptor antagonist prazosin; however, modafinil is inactive in other in vitro assay systems known to be responsive to α-adrenergic agonists, such as the rat vas deferens preparation. Modafinil is not a direct- or indirect-acting dopamine receptor agonist. However, in vitro, modafinil binds to the dopamine transporter and inhibits dopamine reuptake. This activity has been associated in vivo with increased extracellular dopamine levels in some brain regions of animals. -
Simultaneous Quantification of Antioxidants Paraxanthine
antioxidants Article Simultaneous Quantification of Antioxidants Paraxanthine and Caffeine in Human Saliva by Electrochemical Sensing for CYP1A2 Phenotyping Rozalia-Maria Anastasiadi 1,*, Federico Berti 2 , Silvia Colomban 3 , Claudio Tavagnacco 2, Luciano Navarini 3 and Marina Resmini 1,* 1 Department of Chemistry, Queen Mary University of London, Mile End Road, London E1 4NS, UK 2 Department of Chemical and Pharmaceutical Sciences, University of Trieste, via L. Giorgieri 1, 34127 Trieste, Italy; [email protected] (F.B.); [email protected] (C.T.) 3 Aromalab, illycaffè S.p.A., Area Science Park, Localita’ Padriciano 99, 34149 Trieste, Italy; [email protected] (S.C.); [email protected] (L.N.) * Correspondence: [email protected] (R.-M.A.); [email protected] (M.R.) Abstract: The enzyme CYP1A2 is responsible for the metabolism of numerous antioxidants in the body, including caffeine, which is transformed into paraxanthine, its main primary metabolite. Both molecules are known for their antioxidant and pro-oxidant characteristics, and the paraxanthine- to-caffeine molar ratio is a widely accepted metric for CYP1A2 phenotyping, to optimize dose– response effects in individual patients. We developed a simple, cheap and fast electrochemical based method for the simultaneous quantification of paraxanthine and caffeine in human saliva, by differ- ential pulse voltammetry, using an anodically pretreated glassy carbon electrode. Cyclic voltammetry experiments revealed for the first time that the oxidation of paraxanthine is diffusion controlled with an irreversible peak at ca. +1.24 V (vs. Ag/AgCl) in a 0.1 M H2SO4 solution, and that the mechanism occurs via the transfer of two electrons and two protons. -
Download Product Insert (PDF)
PRODUCT INFORMATION Paraxanthine Item No. 21068 CAS Registry No.: 611-59-6 Formal Name: 3,7-dihydro-1,7-dimethyl-1H-purine-2,6-dione O Synonyms: 1,7-Dimethylxanthine, NSC 400018 N MF: C7H8N4O2 N FW: 180.2 Purity: ≥98% N N O UV/Vis.: λmax: 269 nm Supplied as: A crystalline solid H Storage: -20°C Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures Paraxanthine is supplied as a crystalline solid. A stock solution may be made by dissolving the paraxanthine in the solvent of choice. Paraxanthine is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide, which should be purged with an inert gas. The solubility of paraxanthine in these solvents is approximately 0.5, 30, and 20 mg/ml, respectively. Paraxanthine is sparingly soluble in aqueous buffers. For maximum solubility in aqueous buffers, paraxanthine should first be dissolved in DMSO and then diluted with the aqueous buffer of choice. Paraxanthine has a solubility of approximately 0.25 mg/ml in a 1:3 solution of DMSO:PBS (pH 7.2) using this method. We do not recommend storing the aqueous solution for more than one day. Description Paraxanthine is an inhibitor of phosphodiesterase 9 (PDE9) and an antagonist of adenosine receptors 1,2 A1 and A2 (Kis = 35 and 22 μM, respectively in equine forebrain tissues). It is the main metabolite of caffeine (Item No. 14118) in humans, making up 80% of the three dimethylxanthine metabolites produced by caffeine demethylation.1,3 Paraxanthine increases locomotor activity and counteracts adenosine receptor agonist-induced motor depression in rats not habituated to caffeine.1 At a dose of 30 mg/kg, paraxanthine induces a significant increase in striatal cGMP and extracellular striatal dopamine concentrations in vivo.