- 44 - CENTRAL NERVOUS SYSTEM DRUGS GROUP 7 CENTRAL NERVOUS SYSTEM DRUGS

7.1 GENERAL ANESTHETICS • THIOPENTONE SODIUM Indication: Induction of anesthesia, adjunct for intubation in head injury patients, control of convulsive states and treatment of elevated intracranial pressure. Unlabeled/investigation indication: N/A Usual Dose: Anesthesia ; induction I.V: 3-5 mg/kg, maintenance IV 25-100 mg as needed. Increased intracranial pressure I.V: 1.5-5 mg/kg/dose (repeat as needed to control intracranial pressure). Seizures I.V.: 75-250 mg/dose Adverse Reaction: - Cardiovascular: Bradycardia, hypotension, syncope - Central nervous system: Drowsiness, lethargy, CNS excitation or depression, impaired judgment, hangover effect, confusion, somnolence, agitation, hyperkinesia, ataxia, nervousness, headache, insomnia, nightmares, hallucinations, anxiety, dizziness, shivering - Dermatologic: Rash, exfoliative dermatitis, Stevens-Johnson syndrome - Gastrointestinal: Nausea, vomiting, constipation - Hematologic: Agranulocytosis, thrombocytopenia, megaloblastic anemia, immune hemolytic - Local: Pain at injection site, thrombophlebitis with I.V. use - Renal: Oliguria - Respiratory: Laryngospasm, respiratory depression, apnea (especially with rapid I.V. use), hypoventilation, sneezing, cough, bronchospasm - Miscellaneous: Gangrene with inadvertent intra-arterial injection, , anaphylactic reactions Pregnancy risk factor: C Lactation: N/A Preparations: Injection 1 g ED(>)

7.2 ANALGESICS AND ANTIPYRETICS • (ACETYLSALICYLIC ACID) Indication: Management of rheumatoid arthritis, rheumatic fever, osteoarthritis, and gout (high dose). Unlabeled/investigation indication: Low doses have been used in the prevention of pre-eclampsia, complications associated with autoimmune disorders such as lupus or antiphospholipid syndrome. Usual Dose: Analgesic and antipyretic : Oral325-650 mg every 4-6 hours up to 4 g/day. Anti-inflammatory: Oral Initial: 2.4-3.6 g/day in divided doses, usual maintenance: 3.6-5.4 g/day. Adverse Reaction, Pregnancy risk factor , Lactation, Preparations: See in Section 5 page 35

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- 45 - CENTRAL NERVOUS SYSTEM DRUGS • Indication: Short-term relief of mild to moderate pain including primary dysmenorrheal. Unlabeled/investigation indication: N/A Usual Dose: Oral: Initial: 500 mg, then 250 mg every 4 hours as needed Adverse Reaction: - Central nervous system: Headache, nervousness, dizziness - Dermatologic: Itching, rash - Endocrine & metabolic: Fluid retention - Gastrointestinal: Abdominal cramps, heartburn, , nausea, vomiting, diarrhea, constipation, gastric or duodenal ulcer with bleeding or perforation, gastritis - Hematologic: Bleeding - Hepatic: Elevated LFTs - Otic: Tinnitus Pregnancy risk factor: C/D (full-dose aspirin in 3rd trimester - expert analysis) Lactation: Enters breast milk (trace amounts)/not recommended (AAP rates "compatible") Preparations: Capsules 250 mg NED

• PARACETAMOL (ACETAMINOPHEN) Indication: Treatment of mild-to-moderate pain and fever. Unlabeled/investigation indication: N/A Usual Dose: Oral 325-650 mg every 4-6 hours or 1000 mg 3-4 times/day; do not exceed 4 g/day. IM 300 mg every 4-6 hours. Adverse Reaction: - Dermatologic: Rash - Endocrine & metabolic: Choride/uric acid/glucose increased, Sodium/bicarbonate/calcium decrease - Hematologic: Anemia, blood dyscrasias - Hepatic: Bilirubin increased, alkaline phosphatase increased - Renal: Ammonia increased, nephrotoxicity with chronic overdose, analgesic nephropathy Pregnancy risk factor: B Lactation: Enters breast milk/compatible Preparations: Tablets 500 mg ED(C). Injection 300 mg/2 mL NED

7.3 NARCOTIC ANALGESICS • TRAMADOL HCL Indication: Relief of moderate to moderately-severe pain. Unlabeled/investigation indication: N/A Usual Dose: Oral 50-100 mg every 4-6 hours , not to exceed 400 mg/day .

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- 46 - CENTRAL NERVOUS SYSTEM DRUGS Adverse Reaction: - Cardiovascular: Flushing,chest pain, postural hypotension, vasodilation - Central nervous system: Dizziness, headache, insomnia, somnolence, agitation, anxiety,confusion, coordination impaired, depression - Dermatologic: Pruritus, dermatitis, rash - Gastrointestinal: Constipation, nausea, vomiting, abdominal pain, anorexia, diarrhea, dry mouth, dyspepsia, flatulence - Neuromuscular & skeletal: Weakness, arthralgia, rigors - Endocrine & metabolic: Hot flashes, menopausal symptoms - Ocular: Blurred vision, miosis - Respiratory: Bronchitis, cough, dyspnea, pharyngitis, rhinorrhea - Miscellaneous: Diaphoresis, flu-like syndrome Pregnancy risk factor: C Lactation: Enters breast milk/contraindicated Preparations: Capsules 50 mg ED(>)

7.4 ANTICONVULSANT • Indication: Partial seizures with complex symptomatology, generalized tonic-clonic seizures (grand mal), mixed seizure patterns, trigeminal neuralgia, acute manic and mixed episodes associated with bipolar 1 disorder. Unlabeled/investigation indication: Treatment of resistant schizophrenia, ethanol withdrawal, restless leg syndrome, psychotic behavior associated with dementia, post-traumatic stress disorders. Usual Dose: Epilepsy: Oral Initial: 200 mg twice daily, increase by up to 200 mg/day at weekly, usual dose: 800-1200 mg/day, maximum recommended dose: 1600 mg/day . Trigeminal or glossopharyngeal neuralgia : Oral Initial:100 mg twice daily gradually increasing in increments of 100 mg twice daily as needed, maintenance: usual 400-800 mg daily in 2 divided doses, maximum dose: 1200 mg/day. Bipolar disorder: Oral: Initial: 400 mg/day in divided doses, maximum dose: 1600 mg/day. Adverse Reaction: - Cardiovascular: Arrhythmias, AV block, bradycardia, chest pain (bipolar use), CHF, edema, hyper-/hypotension, lymphadenopathy, syncope, thromboembolism, thrombophlebitis - Central nervous system: Amnesia, anxiety, aseptic meningitis, ataxia, confusion, depression , dizziness, fatigue, headache, sedation, slurred speech, somnolence - Dermatologic: Stevens-Johnson syndrome, alopecia, alterations in skin pigmentation, erythema multiforme, exfoliative dermatitis, photosensitivity reaction, - Endocrine & metabolic: Chills, fever, hyponatremia, syndrome of inappropriate ADH secretion (SIADH) - Gastrointestinal: Abdominal pain, anorexia, constipation, diarrhea, dyspepsia, gastric distress,

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- 47 - CENTRAL NERVOUS SYSTEM DRUGS nausea , pancreatitis, vomiting, xerostomia - Genitourinary: Azotemia, impotence, renal failure, urinary frequency, urinary retention - Hematologic: Acute intermittent porphyria, agranulocytosis, aplastic anemia, bone marrow suppression, eosinophilia, leukocytosis, leukopenia, pancytopenia, thrombocytopenia - Hepatic: Abnormal liver function tests, hepatic failure, hepatitis, jaundice - Neuromuscular & skeletal: Back pain, pain, peripheral neuritis, weakness - Ocular: Blurred vision, conjunctivitis, lens opacities, nystagmus - Otic: Hyperacusis, tinnitus - Miscellaneous: Diaphoresis, hypersensitivity Pregnancy risk factor: D Lactation: Enters breast milk/not recommended (AAP rates "compatible") Preparations: Tablets 200 mg ED(C). Tablets(controlled release tablets) 200, 400mg ED(G)

• Indication: Alone or as an adjunct in the treatment of petit mal variant, akinetic, and myoclonic seizures, petit mal (absence) seizures unresponsive to succimides, panic disorder with or without agoraphobia. Unlabeled/investigation indication: Restless legs syndrome, neuralgia, multifocal tic disorder, parkinsonian dysarthria, bipolar disorder, adjunct therapy for schizophrenia. Usual Dose: Seizure disorders : Oral 0.05-0.2 mg/kg, do not exceed 20 mg/day . Panic disorder : Oral 0.25 mg twice daily, increase in increments of 0.125-0.25 mg twice daily every 3 days, target dose: 1 mg/day, maximum 4 mg/day. Adverse Reaction: - Cardiovascular: Edema (ankle or facial), palpitation - Central nervous system: Amnesia, ataxia, behavior problems, coma, confusion, depression, dizziness, drowsiness, emotional lability, fatigue, nervousness, psychosis, slurred speech, somnolence, suicidal attempt, vertigo - Dermatologic: Hair loss, hirsutism, skin rash - Endocrine & metabolic: Dysmenorrhea, libido increased/decreased - Gastrointestinal: Abdominal pain, anorexia, appetite increased/decreased, coated tongue, constipation, dehydration, diarrhea, nausea, weight changes (loss/gain), xerostomia - Genitourinary: Colpitis, dysuria, ejaculation delayed, enuresis, impotence, micturition frequency, nocturia, urinary retention, urinary tract infection - Hematologic: Anemia, eosinophilia, leukopenia, thrombocytopenia - Hepatic: Alkaline phosphatase increased, hepatomegaly, transaminases increased - Neuromuscular & skeletal: Choreiform movements, coordination abnormal, dysarthria, muscle pain, muscle weakness, myalgia, tremor - Ocular: Blurred vision, eye movements abnormal, diplopia, nystagmus - Respiratory: Chest congestion, cough, bronchitis, hypersecretions, pharyngitis, respiratory depression, respiratory tract infection, rhinitis, rhinorrhea, shortness of breath, sinusitis      .. 2553            !

- 48 - CENTRAL NERVOUS SYSTEM DRUGS - Miscellaneous: Allergic reaction, aphonia, dysdiadochokinesis, encopresis, "glassy-eyed" appearance, hemiparesis, lymphadenopathy Pregnancy risk factor: D Lactation: Enters breast milk/not recommended Preparations: Tablets 0.5mg , 2 mg ED(C)

• Indication: Adjunct for treatment of partial seizures with and without secondary generalized seizures in patients >12 years of age with epilepsy. Adjunct for treatment of partial seizures in pediatric patients 3-12 years of age. Management of postherpetic neuralgia (PHN) in adults. Unlabeled/investigation indication: Social phobia, chronic pain. Usual Dose: Anticonvulsant : Oral Initial 300 mg 3 times/day, may be increased up to 1800 mg/day. Maintenance: 900-1800 mg/day in divided doses, doses of up to 2400 mg/day have been tolerated in long- term clinical studies. Postherpetic neuralgia : range 1800-3600 mg/day. Adverse Reaction: - Central nervous system: Somnolence, dizziness, ataxia, fatigue, fatigue, headache, ataxia, abnormal thinking - Cardiovascular: Peripheral edema, vasodilatation - Gastrointestinal: Diarrhea, nausea/vomiting, abdominal pain, weight gain, dyspepsia, flatulence, dry throat, xerostomia, constipation, dental abnormalities - Genitourinary: Impotence - Hematologic: Leukopenia, decreased WBC - Neuromuscular & skeletal: Tremor , weakness, hyperkinesia, abnormal gait, back pain, myalgia, fracture - Ocular: Nystagmus, diplopia, blurred vision, conjunctivitis - Otic: Otitis media - Respiratory: Rhinitis, bronchitis, respiratory infection, pharyngitis, cough - Miscellaneous: Infection (children 11%) Pregnancy risk factor: C Lactation: Enters breast milk/use caution Preparations: Capsules 300 mg ED(K)

• Indication: Adjunctive therapy in the treatment of generalized seizures of Lennox- Gastaut syndrome, primary generalized tonic-clonic seizures, and partial seizures in adults and children 2 years of age. Unlabeled/investigation indication: N/A Usual Dose : Monotherapy ; Initial 25 mg once a day for 2 weeks, followed by 50 mg once for 2 weeks.Thereafter, the dose should be increase by a maximum of 50-100 mg every 1-2 weeks until the

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- 49 - CENTRAL NERVOUS SYSTEM DRUGS optimal response is achieve. The usual maintenance dose is 100-200 mg/day. With Valproic acid ; Initial 12.5 mg once a day( given 25 mg alternate days) for 2 weeks, followed by 25 mg once for 2 weeks.Thereafter , the dose should be increase by a maximum of 25-50 mg every 1-2 weeks until the optimal response is achieve. The usual maintenance dose is 100-200 mg/day. With out Valproic ; Initial 50 mg once a day for 2 weeks, followed by 100 mg two divided dosed for 2 weeks. Thereafter , the dose should be increase by a maximum of 100 mg every 1-2 weeks until the optimal response is achieve. The usual maintenance dose is 200-400 mg/day. Adverse Reaction: - Cardiovascular: Chest pain, peripheral edema, edema - Central nervous system: Somnolence, fatigue, dizziness, anxiety, insomnia - Dermatologic: Rash, dermatitis, dry skin - Endocrine & metabolic: Dysmenorrhea - Gastrointestinal: Nausea( >10%), vomiting, dyspepsia,adominal pain, xerostomia - Genitourinary: Urinary frequency - Neuromuscular & skeletal: Back pain, coordination abnormal, weakness, arthralgia - Ocular: Nystagmus, vision abnormal, amblyopia - Respiratory: Rhinitis, cough, pharyngitis, bronchitis, dyspnea, epistaxis - Miscellaneous: Infection, diaphoresis, reflexes increased Pregnancy risk factor: C Lactation: Enters breast milk/not recommended (AAP rates "of concern") Preparations: Tablets 50 mg ED(K)

• Indication: Adjunctive therapy in the treatment of partial onset seizures, myoclonic seizures. Unlabeled/investigation indication: Bipolar disorder. Usual Dose : Oral Initial 500 mg twice daily, increase every 2 weeks by 500 mg/dose to a maximum of 1500 mg twice daily . Adverse Reaction: - Central nervous system: Behavioral symptoms, somnolence , headache - Gastrointestinal: Vomiting, anorexia - Neuromuscular & skeletal: Weakness - Respiratory: Rhinitis, cough - Miscellaneous: Accidental injury, infection Pregnancy risk factor: C Lactation: Enters breast milk/not recommended Preparations: Tablets 500 mg NED

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- 50 - CENTRAL NERVOUS SYSTEM DRUGS • SULFATE Indication: Prevention seizure in severe pre-eclampsia or eclampsia, pediatric acute nephritis, torsade de pointes and hypomagnesemia. Treatment of cardiac arrhythmias (VT/VF) caused by hypomagnesemia. Unlabeled/investigation indication: N/A Usual Dose: Eclampsia, pre-eclampsia : I.V. 4-6 g over 15-20 minutes followed by 2 g/hour. Torsade de pointes : Pulseless: I.V 1-2 g over 5-20 minutes, With pulse: IV 1-2 g over 5-60 minutes. Parenteral nutrition supplementation (elemental magnesium): I.V.: 8-20 mEq/day. Hypomagnesemia Severe or symptomatic : IV 1- 2 g over 5-60 minutes. Hypomagnesemia with seizures : IV 2 g over 10 minutes. Adverse Reaction: - Cardiovascular: Complete heart block. - Central nervous system: Depresses CNS , somnolence - Gastrointestinal: Diarrhea (excessive oral doses) - Respiratory :Respiratory paralysis Pregnancy risk factor: A/C (manufacturer dependent) Lactation: Enters breast milk/compatible Preparations: Injection 50% (10 mL) ED(C)

• Indication: Monotherapy or adjunctive therapy in the treatment of partial seizures in adults and children with epilepsy . Unlabeled/investigation indication: Bipolar disorder, neuropathic pain. Usual Dose: Adjunctive therapy : Oral: Initial: 300 mg twice daily, recommended daily dose is 1200 mg/day in 2 divided doses. Monotherapy: Oral: Patients receiving concomitant antiepileptic drugs (AEDs) : Initial: 300 mg twice daily while simultaneously reducing the dose of concomitant AEDs. Withdraw concomitant AEDs completely over 3-6 weeks, while increasing the oxcarbazine dose in increments of 600 mg/day at weekly intervals, reaching the maximum oxcarbazine dose (2400 mg/day) in about 2-4 weeks (lower doses have been effective in patients in whom monotherapy has been initiated). Oral: Patients not receiving prior AEDs : 300 mg twice daily (total dose 600 mg/day). Increase dose by 300 mg/day every third day to a dose of 1200 mg/day. Higher dosages (2400 mg/day) have been shown to be effective in patients converted to monotherapy from other AEDs. Adverse Reaction: > 10% - Central nervous system: Dizziness, somnolence, headache, ataxia, fatigue, vertigo - Gastrointestinal: Vomiting, nausea, abdominal pain - Neuromuscular & skeletal: Abnormal gait, tremor - Ocular: Diplopia, nystagmus, abnormal vision Pregnancy risk factor: C Lactation: Enters breast milk/not recommended Preparations: Tablets 600 mg NED

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- 51 - CENTRAL NERVOUS SYSTEM DRUGS • PHENOBARBITAL Indication: Management of generalized tonic-clonic(grand mal) and partial seizures, for nervous insomnia. Unlabeled/investigation indication: Febrile seizures in children, prevention and treatment of neonatal hyperbilirubinemia and lowering of bilirubin in chronic cholestasis, neonatal seizures and management of sedative/hypnotic withdrawal. Usual Dose: Sedation : Oral 30-120 mg/day in 2-3 divided doses. Hypnotic : Oral 100-320 mg at bedtime. Anticonvulsant/status epilepticus : Oral 50-100 mg 2-3 times/day. Adverse Reactions: - Cardiovascular: Bradycardia, hypotension, syncope - Central nervous system: Drowsiness, lethargy, CNS excitation or depression, "hangover" effect, confusion, somnolence, agitation - Dermatologic: Rash, exfoliative dermatitis, Stevens-Johnson syndrome - Gastrointestinal: Nausea, vomiting, constipation - Hematologic: Agranulocytosis, thrombocytopenia, megaloblastic anemia - Renal: Oliguria - Respiratory: Laryngospasm, respiratory depression Pregnancy risk factor: D Lactation: Enters breast milk/not recommended (AAP recommends use "with caution") Preparations: Tablet 60 mg ED(C)

• Indication: Management of generalized tonic-clonic (grand mal), complex partial seizures. Prevention of seizures following head trauma/neurosurgery . Unlabeled/investigation indication: Ventricular arrhythmias, including those associated with digitalis intoxication, prolonged QT interval and surgical repair of congenital heart diseases in children and epidermolysis bullosa. Usual Dose: Oral: Loading dose : 15-20 mg/kg (based on phenytoin serum concentrations and recent dosing history). Maintenance dose : 300 mg/day or 5-6 mg/kg/day in 3 divided doses or 1-2 divided doses using extended release, range 200-1200 mg/day. Therapeutic range: 10-20 mcg/mL Adverse Reaction: Related to elevated concentrations: >20 mcg/mL: Far lateral nystagmus, >30 mcg/mL: 45º lateral gaze nystagmus and ataxia, >40 mcg/mL: Decreased mentation, >100 mcg/mL: Death - Cardiovascular: Hypotension, bradycardia, cardiac arrhythmia, cardiovascular collapse - Central nervous system: Psychiatric changes, slurred speech, dizziness, drowsiness - Dermatologic: Rash - Gastrointestinal: Constipation, nausea, vomiting, gingival hyperplasia, enlargement of lips - Hematologic: Leukopenia, thrombocytopenia, agranulocytosis - Hepatic: Hepatitis

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- 52 - CENTRAL NERVOUS SYSTEM DRUGS - Local: Thrombophlebitis - Neuromuscular & skeletal: Tremor, peripheral neuropathy, paresthesia - Ocular: Diplopia, nystagmus, blurred vision Pregnancy risk factor: D Lactation: Enters breast milk/not recommended (AAP rates "compatible") Preparations: Tablets (Immediate release) 50 mg ED(C) ,Capsules(Immediate release) 100 mg ED(C) ,Capsules (Controlled release) 100 mg ED(C)

• Indication: Monotherapy or adjunctive therapy for partial onset seizures and primary generalized tonic-clonic seizures adjunctive treatment of seizures associated with Lennox-Gastaut syndrome. Unlabeled/investigation indication: Infantile spasms, neuropathic pain, cluster headache. Usual Dose: Monotherapy : Partial onset seizure and primary generalized tonic-clonic seizure: Initial: 25 mg twice daily; may increase weekly by 50 mg/day up to 100 mg twice daily (week 4 dose); thereafter, may further increase weekly by 100 mg/day up to the recommended maximum of 200 mg twice daily . Adjunctive therapy : Partial onset seizures : Oral: Initial: 25-50 mg/day for 1 week, increase at weekly intervals by 25-50 mg/day until response, usual maintenance dose: 100-200 mg twice daily. Primary generalized tonic-clonic seizures : Oral: Initial dose as listed above for partial onset seizures, but use slower initial titration rate; titrate upwards to recommended dose by the end of 8 weeks; usual maintenance dose: 200 mg twice daily . Adverse Reaction: >10% - Central nervous system: Dizziness, ataxia, somnolence, psychomotor slowing , nervousness , memory difficulties, speech problems, fatigue, difficulty concentrating, depression, confusion - Endocrine & metabolic: Serum bicarbonate decreased - Gastrointestinal: Nausea, weight loss, anorexia - Neuromuscular & skeletal: Paresthesia - Ocular: Nystagmus, abnormal vision - Respiratory: Upper respiratory infection - Miscellaneous: Injury Pregnancy risk factor: C Lactation: Enters breast milk/not recommended Preparations: Tablets 50, 100 mg ED(K)

• SODIUM (VALPROIC ACID) Indication: Monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures, simple and complex absence seizures. Adjunctive therapy in patients with multiple seizure types that include absence seizures ,mania associated with bipolar disorder. Prophylaxis of migrainesyndrome. Unlabeled/investigation indication: Status epilepticus

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- 53 - CENTRAL NERVOUS SYSTEM DRUGS Usual Dose: Simple and complex absence seizure : Oral Initial: 15 mg/kg/day, maximum: 60 mg/kg/day. Complex partial seizure : Oral Initial: 10-15 mg/kg/day, maximum: 60 mg/kg/day . Bipolar disorder : Oral: Initial: 750 mg/day in divided doses, maximum recommended dosage: 60 mg/kg/day . Migraine prophylaxis : Oral controlled-release tabs 500 mg once daily for 7 days, then increase to 1000 mg once daily; adjust dose based on patient response, usual dosage range 500-1000 mg/day . Therapeutic: Epilepsy: 50-100 mcg/mL (SI: 350-690 µmol/L), Mania: 50-125 mcg/mL (SI: 350-860 µmol/L). Adverse Reaction: - Cardiovascular: Chest pain, hypertension, palpitation, peripheral edema, tachycardia - Central nervous system: Somnolence, dizziness, insomnia, nervousness - Dermatologic: Alopecia, bruising, dry skin, petechia, pruritus, rash - Endocrine & metabolic: Amenorrhea, dysmenorrhea - Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain, dyspepsia, anorexia - Genitourinary: Urinary frequency, urinary incontinence, vaginitis - Hematologic: Thrombocytopenia - Hepatic: AST/ALT increased - Neuromuscular & skeletal: Tremor, weakness - Ocular: Abnormal vision, amblyopia/blurred vision, nystagmus - Otic: Deafness, otitis media, tinnitus - Respiratory: Dyspnea, epistaxis, increased cough, pharyngitis, pneumonia, sinusitis - Miscellaneous: Infection Pregnancy risk factor: D Lactation: Enters breast milk/not recommended. Preparations: Tablets 200 mg (immediated release) ED(C/K). Tablets 200, 500 (controlled release) ED(C/K) Solutions 200 mg/mL ED(C).

7.5 CENTRALLY ACTING RELAXANTS • TYPE A Indication: Treatment of blepharospasm, hemifacial spasm, spasmodic torticollis Unlabeled/investigation indication: Treatment of oromandibular dystonia, spasmodic dysphonia (laryngeal dystonia) and other dystonias, migraine treatment and prophylaxis. Usual Dose: Cervical dystonia : I.M.: the mean dose is 236 units divided among the affected muscles in patients previously treated with botulinum toxin. Initial dose in previously untreated patients should be lower. The total dose injected into the sternocleidomastoid muscles should be 100 units to decrease the occurrence of dysphagia. Blepharospasm : I.M.: Initial dose: 1.25-2.5 units injected into the medial and lateral pretarsal orbicularis oculi of the upper and lower lid, maximum dose per site: 5 units; cumulative dose in a 30-day period: 200 units. Strabismus : I.M.: Initial dose vertical muscles and for horizontal strabismus <20 prism diopters: 1.25-2.5 units in any one muscle, Horizontal strabismus of 20-50 prism diopters: 2.5-5 units in any one muscle, Persistent VI nerve palsy >1 month: 1.5-2.5 units in the medial rectus muscle.Subsequent

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- 54 - CENTRAL NERVOUS SYSTEM DRUGS doses: The maximum recommended dose as a single injection for any one muscle is 25 units. Primary axillary hyperhidrosis : Intradermal: 50 units/axilla. Adverse Reaction: - Central nervous system: Headache, anxiety, dizziness, drowsiness, fever, speech disorder - Dermatologic: Pruritus - Gastrointestinal: Dysphagia, nausea - Ocular: Dry eyes, Ptosis, vertical deviation - Respiratory: Upper respiratory infection, cough, rhinitis - Local: Injection site reaction - Miscellaneous: Flu syndrome Pregnancy risk factor: C Lactation: Excretion in breast milk unknown/not recommended Preparations: Injection 500 units ED(P)

• HCL Indication: Improvement of myotonic symtoms associated with stiff shoulders, headache, cervical syndrome and lumbago, spasticity associated with cerebrospinal disturbances. Unlabeled/investigation indication: N/A Usual Dose: Oral 50 mg 3 times/day Adverse Reaction: - Central nervous system: Dizziness, drowsiness, fatigue, insomnia, headache - Gastrointestinal: GI disturbances - Dermatologic: Rash - Hepatic: Hepatic dysfunction - Hematology: RBC count abnormal - Neuromuscular & skeletal: Numbness and tembling Pregnancy risk factor: N/A Lactation: N/A Preparations: Tablets 50 mg NED

• TOLPERISONE HCL Indication: Symtomatic treatment of musculoskeletal conditions associated with painful muscle spasm. Unlabeled/investigation indication: N/A Usual Dose: Oral 50-150 mg 3 times/day Adverse Reaction: - Central nervous system: Dizziness, drowsiness, headache - Gastrointestinal: Nausea, vomiting, heartburn, abdominal discomfort, constipation - Respiratory: Respiratory disorder

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- 55 - CENTRAL NERVOUS SYSTEM DRUGS Pregnancy risk factor: N/A Lactation: N/A Preparations: Tablets 50 mg NED

7.6 PSYCHOTHERAPEUTIC AGENTS 7.6.1 ANTIDEPRESSANT GROUP (, , , NORTRYPTYLINE) Adverse Reaction: - Cardiovascular: Postural hypotension, arrhythmia, hypertension, heart block, tachycardia,palpitation. MI - Central nervous system: Confusion, delirium, hallucinations, restlessness, insomnia,disorientation, delusions, anxiety, agitation, panic, nightmares, hypomania, exacerbation of psychosis, incoordination, ataxia, extrapyramidal symptoms, seizure - Dermatologic: Alopecia, photosensitivity, rash, petechiae, urticaria, itching - Endocrine & metabolic: Sexual dysfunction, gynecomastia, breast enlargement, galactorrhea, increase or decrease in libido, increase in blood sugar, SIADH - Gastrointestinal: Xerostomia, constipation, vomiting, anorexia, diarrhea, abdominal cramps, black tongue, nausea, unpleasant taste, weight gain/loss - Genitourinary: Urinary retention, delayed micturition, impotence, testicular edema - Hematologic: Rarely agranulocytosis, eosinophilia, purpura, thrombocytopenia - Hepatic: Increased liver enzymes, cholestatic jaundice - Neuromuscular & skeletal: Tremor, numbness, tingling, paresthesia, peripheral neuropathy - Ocular: Blurred vision, eye pain, disturbances in accommodation, mydriasis - Otic: Tinnitus - Miscellaneous: Diaphoresis, allergic reactions

• AMITRIPTYLINE Indication: Relief of symptoms of depression. Unlabeled/investigation indication: Analgesic for certain chronic and neuropathic pain. Prophylaxis against migraine headaches and treatment of depressive disorders in children. Usual Dose: Oral 50-150 mg/day, dose may be gradually increased up to 300 mg/day. Pregnancy risk factor: C Lactation: Enters breast milk/not recommended (AAP rates "of concern") Preparations: Tablets 10, 25 mg ED(C)

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- 56 - CENTRAL NERVOUS SYSTEM DRUGS • CLOMIPRAMINE HCL Indication: Treatment of obsessive-compulsive disorder (OCD) Unlabeled/investigation indication: Depression, panic attacks, chronic pain Usual Dose: Oral: Initial: 25 mg/day and gradually increase, as tolerated, to 100 mg/day the first 2 weeks, maximum of 250 mg/day Pregnancy risk factor: C Lactation: Enters breast milk/contraindicated (AAP rates "of concern") Preparations: Tablets 25, 50 mg ED(C)

• IMIPRAMINE HCL Indication: Treatment of depression, nocturnal enuresis in children. Unlabeled/investigation indication: Analgesic for certain chronic and neuropathic pain, panic disorder, attention-deficit/hyperactivity disorder (ADHD). Usual Dose: Antidepressant Oral: Initial: 25 mg 3-4 times/day; increase dose gradually, total dose may be given at bedtime, maximum: 300 mg/day . Enuresis : Oral: Children 6 years: Initial: 25 mg at bedtime, increase by 25 mg/day, not exceed 2.5 mg/kg/day or 50 mg at bedtime if 6-12 years of age or 75 mg at bedtime if 12 years of age. Pregnancy risk factor: D Lactation: Enters breast milk/not recommended (AAP rates "of concern") Preparations: Tablets 25, 50 mg ED(C)

• Indication: Treatment of depression . Unlabeled/investigation indication: Chronic pain, anxiety disorders, enuresis, attention-deficit/hyperactivity disorder (ADHD), adjunctive therapy for smoking cessation. Usual Dose: Oral: 25 mg 3-4 times/day up to 150 mg/day. Pregnancy risk factor: D Lactation: Enters breast milk/contraindicated (AAP rates "of concern") Preparations: Tablets 25mg ED(C)

TETRACYCLIC ANTIDEPRESSANT GROUP • MIRTAZAPINE Indication: Treatment of depression. Unlabeled/investigation indication: N/A Usual Dose: Oral: Initial 15 mg/day titrate up to 15-45 mg/day.

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- 57 - CENTRAL NERVOUS SYSTEM DRUGS Adverse Reactions: - Cardiovascular: Hypertension, vasodilatation, peripheral edema - Central nervous system: Somnolence (54%), dizziness, abnormal dreams , confusion, malaise - Endocrine & metabolic: increased (>10%), triglycerides increased - Gastrointestinal: Constipation , xerostomia, appetite increased, vomiting, anorexia, abdominal pain - Genitourinary: Urinary frequency - Neuromuscular & skeletal: Myalgia, back pain, arthralgia, tremor, weakness - Respiratory: Dyspnea Pregnancy risk factor: C Lactation: Excretion in breast milk unknown/not recommended Preparations: Tablets 30mg NED

SEROTONIN SELECTIVE REUPTAKE INHIBITOR GROUP (SSRIs) Adverse Reactions: >10%: - Central nervous system: Insomnia, headache, anxiety, nervousness, somnolence - Endocrine & metabolic: Libido decreased - Gastrointestinal: Nausea, diarrhea, anorexia, xerostomia - Neuromuscular & skeletal: Weakness, tremor - Respiratory: Pharyngitis,yawn 1% to 10%: - Cardiovascular: Vasodilation, fever, chest pain, hemorrhage, hypertension, palpitation - Central nervous system: Dizziness, dream abnormality, thinking abnormality, agitation, amnesia, chills, confusion, emotional lability, sleep disorder - Dermatologic: Rash, pruritus - Endocrine & metabolic: Ejaculation abnormal, impotence - Gastrointestinal: Dyspepsia, constipation, flatulence, vomiting, weight loss, appetite increased, taste perversion, weight gain - Genitourinary: Urinary frequency - Ocular: Vision abnormal - Otic: Ear pain, tinnitus - Respiratory: Sinusitis - Miscellaneous: Flu-like syndrome , diaphoresis

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- 58 - CENTRAL NERVOUS SYSTEM DRUGS • DULOXETINE Indication: Treatment of major depressive disorder. Unlabeled/investigation indication: Treatment of stress incontinence, chronic pain syndromes and fibromyalgia. Usual Dose: Oral: Initial: 40-60 mg/day, maximum dose: 60 mg/day Pregnancy risk factor: C Lactation: Excretion in breast milk unknown/not recommended Preparations: Capsules 60 mg NED

• ESCITALOPRAM OXALATE Indication: Treatment of major depressive episode and panic disorder with or without agoraphobia Unlabeled/investigation indication: N/A Usual Dose: Oral: Initial 10 mg/day, dose may be increased to 20 mg/day Pregnancy risk factor: C Lactation: Excretion breast milk/not recommended Preparations: Tablets 10 mg NED

• HCL Indication: Treatment of major depressive disorder (MDD), binge-eating and vomiting in patients with moderate-to-severe bulimia nervosa, obsessive-compulsive disorder (OCD), premenstrual dysphoric disorder (PMDD) and panic disorder with or without agoraphobia. Unlabeled/investigation indication: Selective mutism Usual Dose: Depression, OCD, PMDD, bulimia : 20 mg/day in the morning, maximum 80 mg/day . Panic disorder : Initial: 10 mg/day, increase to 20 mg/day. Pregnancy risk factor: C Lactation: Enters breast milk/not recommended (AAP rates "of concern") Preparations: Tablets 20 mg ED(C), Capsules 20 mg ED(C)

• FLUVOXAMINE Indication : Treatment of obsessive-compulsive disorder (OCD) in children 8 years of age and adults Unlabeled/investigation indication: Treatment of major depression, panic disorder and anxiety disorders in children. Usual Dose: Oral: Initial: 50 mg at bedtime, usual dose range: 100-300 mg/day in divide dose. Pregnancy risk factor: C Lactation: Enters breast milk/not recommended (AAP rates "of concern") Preparations: Tablets 20 mg ED(C), Capsules 20 mg ED(C)

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- 59 - CENTRAL NERVOUS SYSTEM DRUGS • PAROXETINE Indication: Treatment of depression in adults, panic disorder with or without agoraphobia, obsessive- compulsive disorder (OCD) in adults, social anxiety disorder (social phobia), generalized anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Unlabeled/investigation indication: Useful in eating disorders, impulse control disorders, self-injurious behavior, premenstrual disorders, vasomotor symptoms of menopause, treatment of depression and obsessive-compulsive disorder (OCD) in children. Usual Dose: Depression/OCD : Oral: Initial: 50 mg/day a maximum of 200 mg/day . Panic disorder, PTSD, social anxiety disorder : Oral: Initial: 25 mg once daily, increased to 50 mg once daily. Premenstrual dysphoric disorder (PMDD) : 50 mg/day. Pregnancy risk factor: D Lactation: Enters breast milk/use caution (AAP rates "of concern") Preparations: Tablets 20 mg NED

• SERTRALINE Indication: Treatment of symptoms of depression. Unlabeled/investigation indication: Eating disorders, generalized anxiety disorder (GAD) and impulse control disorders. Usual Dose: Oral: Initial: 50 mg/day, maximum of 200 mg/day . Pregnancy risk factor: C Lactation: Enters breast milk/not recommended (AAP rates "of concern") Preparations: Tablets 50, 100 mg NED

MISCELLANEOUS • BUPROPION HCL Indication: Treatment of nicotine dependence as an aid to smoking cessation. Unlabeled/investigation indication: Attention-deficit/hyperactivity disorder (ADHD), depression associated with bipolar disorder. Usual Dose: Oral: Initiate with 150 mg once daily for 3 days, increase to 150 mg twice daily for 7-12 weeks. Adverse Reactions: - Cardiovascular: Tachycardia, palpitation, arrhythmias, chest pain, hyper/hypotension, flushing - Central nervous system: Headache, insomnia, dizziness, confusion, anxiety, hostility, nervousness, sleep disturbance - Dermatologic: Rash, pruritus, urticaria - Endocrine & metabolic: Menstrual complaints, hot flashes, libido decreased - Gastrointestinal: Xerostomia, weight loss, nausea, abdominal pain, diarrhea, flatulence, anorexia, appetite increased - Genitourinary: Urinary frequency, urinary urgency, vaginal hemorrhage      .. 2553            !

- 60 - CENTRAL NERVOUS SYSTEM DRUGS - Neuromuscular & skeletal: Tremor, myalgia, weakness, arthralgia, arthritis, akathisia, - Ocular: Amblyopia, blurred vision - Otic: Tinnitus, auditory disturbance - Respiratory: Pharyngitis, Upper respiratory infection, cough increased, sinusitis Pregnancy risk factor: C Lactation: Enters breast milk/not recommended (AAP rates "of concern") Preparations: Tablets 150 mg (sustained-release) NED

• DESVENLAFAXINE Indication: Major depressive disorder, moderate to severe vasomotor symptoms associated with menopause. (Note: vasomotor symptoms associated with menopause approved by Thai FDA) Unlabeled/investigation indication: N/A Usual Dose: Major depressive disorder : Oral 50 mg once daily. Moderate to severe vasomotor symptoms associated with menopause : Oral 100 mg once daily. Adverse Reactions: - Cardiovascular: Palpitations, tachycardia - Central nervous system: Fatigue, dizziness, insomnia, somnolence - Dermatologic: Rash, pruritus, urticaria - Endocrine & metabolic: Weight changes, increased blodd pressure and blood cholesterol, decreased libido, anorgasmia, abnormal orga - Gastrointestinal: Nausea, dry mouth, constipation, diarrhea, vomiting, decreased appetite - Genitourinary: Urinary frequency, urinary urgency, vaginal hemorrhage - Neuromuscular & skeletal: Tremor - Ocular: Blurred vision, mydriasis - Otic: Tinnitus - Skin: Rash Pregnancy risk factor: C Lactation: N/A Preparations: Tablets 50 mg (extended-release) NED

• TIANEPTINE Indication: Treatment of major depressive disorders. Unlabeled/investigation indication: N/A Usual Dose: Oral 12.5 mg 3 times/day. Adverse Reactions: - Cardiovascular: Tachycardia - Central nervous system: Headache, vertigo, insomnia, dry mouth, drowsiness - Gastrointestinal: Abdominal pain, nausea, vomiting, constipation

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- 61 - CENTRAL NERVOUS SYSTEM DRUGS - Respiratory: Respiratory discomfort - Neuromuscular & skeletal: Tremor Pregnancy risk factor: N/A Lactation: N/A Preparations: Tablets 12.5 mg NED

• TRAZODONE HYDROCHLORIDE Indication: Treatment of depression. Unlabeled/investigation indication: Potential augmenting agent for antidepressants and hypnotic . Usual Dose: Oral: Initial: 150 mg/day in 3 divided doses, maximum 600 mg/day . Adverse Reactions: - Cardiovascular: Syncope, hyper-/hypotension, edema - Central nervous system: Dizziness, headache, sedation, confusion, fatigue - Gastrointestinal: Nausea, xerostomia, diarrhea, constipation, weight gain/loss - Ocular: Blurred vision - Neuromuscular & skeletal: Tremor, myalgia - Respiratory: Nasal congestion Pregnancy risk factor: C Lactation: Enters breast milk/use caution (AAP rates "of concern") Preparations: Tablets 50, 100 mg ED(>)

• VENLAFAXINE Indication: Treatment of depression and anxiety. Unlabeled/investigation indication: Obsessive-compulsive disorder (OCD), hot flashes, neuropathic pain, attention-deficit/hyperactivity disorder (ADHD). Usual Dose: Oral 75 mg once daily (may be desirable to start at 37.5 mg/day for 4-7 days) before increasing to 75 mg once daily, a recommended maximum of 225 mg/day . Adverse Reactions: - Cardiovascular: Hyper/hypotension, vasodilation, palpitation, tachycardia, chest pain - Central nervous system: Headache, insomnia, somnolence, dizziness, nervousness - Dermatologic: Rash, pruritus, bruising - Gastrointestinal: Nausea, xerostomia, anorexia, constipation, diarrhea, vomiting, dyspepsia - Genitourinary: Abnormal ejaculation/orgasm,impotence, urinary frequency, impaired urination - Neuromuscular & skeletal: Weakness, tremor, hypertonia, paresthesia - Ocular: Abnormal or blurred vision, mydriasis - Otic: Tinnitus - Respiratory: Pharyngitis, sinusitis, cough increased, dyspnea Pregnancy risk factor: C

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- 62 - CENTRAL NERVOUS SYSTEM DRUGS Lactation: Enters breast milk/not recommended. Preparations: Capsules 37.5 mg , 75 mg (extended-release) NED

7.6.2 ANTIPSYCHOTIC AGENT • ARIPIPRAZOLE Indication: Treatment of schizophrenia. Unlabeled/investigation indication: Depression with psychotic features, aggression (children), bipolar disorder (children), conduct disorder (children), Tourette syndrome (children) Usual Dose: Oral: 10-15 mg once daily; may be increased to a maximum of 30 mg once daily . Adverse Reactions: - Cardiovascular: Edema, hypertension, tachycardia, hypotension, bradycardia, chest pain - Central nervous system: Headache, agitation, anxiety, insomnia, extrapyramidal symptoms, somnolence, akathisia, lightheadedness - Dermatologic: Dry skin, skin ulcer - Endocrine & metabolic: Dehydration - Gastrointestinal: Nausea, dyspepsia, constipation, vomiting, weight gain, salivation increased, weight loss - Genitourinary: Urinary incontinence, pelvic pain - Hematologic: Anemia, bruising - Neuromuscular & skeletal: Tremor, weakness, myalgia, neck pain, neck rigidity, muscle cramp, CPK increased, abnormal gait - Ocular: Blurred vision, conjunctivitis - Respiratory: Rhinitis, pharyngitis, cough, asthma, dyspnea, pneumonia, sinusitis Pregnancy risk factor: C Lactation: Excretion in breast milk unknown/not recommended Preparations: Tablets 10, 15 mg. NED

• HCL Indication: Treatment of schizophrenia, control of mania, nausea and vomiting, relief of restlessness and apprehension before surgery, acute intermittent porphyria. Adjunct in the treatment of tetanus, intractable hiccups. Unlabeled/investigation indication: Management of psychotic disorders. Usual Dose: Schizophrenia/psychoses : Oral: 30-800 mg/day in 1-4 divided doses, usual dose: 200-600 mg/day. I.M., I.V.: Initial: 25 mg, may repeat (25-50 mg) in 1-4 hours, usual dose: 300-800 mg/day. Intractable hiccups : Oral, I.M.: 25-50 mg 3-4 times/day. Adverse Reactions: - Cardiovascular: Postural hypotension, tachycardia, dizziness, nonspecific QT changes - Central nervous system: Drowsiness, dystonias, akathisia, pseudoparkinsonism, tardive

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- 63 - CENTRAL NERVOUS SYSTEM DRUGS dyskinesia, neuroleptic malignant syndrome, seizure - Dermatologic: Photosensitivity, dermatitis, skin pigmentation - Endocrine & metabolic: Lactation, amenorrhea, gynecomastia, hyper/ hypoglycemia - Gastrointestinal: Xerostomia, constipation, nausea - Genitourinary: Urinary retention, ejaculatory disorder, impotence - Hematologic: Agranulocytosis, eosinophilia, leukopenia, aplastic anemia, thrombocytopenic - Hepatic: Jaundice - Ocular: Blurred vision Pregnancy risk factor: C Lactation: Enters breast milk/not recommended (AAP rates "of concern") Preparations: Tablets 25, 50, 100 mg. Injection 50 mg/2 mL ED(C)

• Indication: Treatment-resistant schizophrenia. Unlabeled/investigation indication: Schizoaffective disorder, bipolar disorder, childhood psychosis and severe obsessive-compulsive disorder. Usual Dose: Initial:12.5 mg once or twice daily, a target dose of 300-450 mg/day after 2-4 weeks, maximum 600-900 mg/day . Adverse Reactions: - Cardiovascular: Tachycardia, angina, ECG changes, hypertension, hypotension, syncope - Central nervous system: Drowsiness, dizziness, akathisia, seizure, agitation, ataxia, slurred speech - Dermatologic: Rash - Gastrointestinal: Constipation, weight gain, sialorrhea, nausea/vomiting - Gastrointestinal: Abdominal discomfort/heartburn, anorexia, diarrhea - Genitourinary: Urinary abnormalities - Hematologic: Eosinophilia, leukopenia, leukocytosis, agranulocytosis - Hepatic: Liver function tests abnormal - Neuromuscular & skeletal: Tremor, hypokinesia, rigidity, hyperkinesia, weakness, pain - Ocular: Visual disturbances - Respiratory: Dyspnea, nasal congestion - Miscellaneous: Diaphoresis increased, fever, tongue numbness Pregnancy risk factor: B Lactation: Enters breast milk/not recommended (AAP rates "of concern") Preparations: Tablets 25,100 mg. ED(K)

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- 64 - CENTRAL NERVOUS SYSTEM DRUGS • FLUPENTHIXOL DECANOATE Indication: Maintenance therapy of chronic schizophrenic. Unlabeled/investigation indication: N/A Usual Dose: I.M. 20-60 mg every 2-4 weeks. Adverse Reactions: - Central nervous system: Extrapyramidal effects, anxiety/nervousness, insomnia, dizziness - Dermatologic: Rash, pruritus, exfoliative dermatitis, contact dermatitis - Endocrine & metabolic: Weight gain, galactorrhea, gynecomastia, decreased libido - Gastrointestinal: Xerostomia, increased salivation, nausea, vomiting - Genitourinary: Micturition disorder - Neuromuscular & skeletal: Hypertonia, tremor, weakness - Ocular: Abnormal accommodation, abnormal vision - Miscellaneous: Diaphoresis increased Pregnancy risk factor: C Lactation: Enters breast milk/not recommended Preparations: Injection 20 mg (Depot ;long- acting) ED(G)

• Indication: Management of schizophrenia, control of tics and vocal utterances of Tourette's disorder in children and adults, severe behavioral problems in children. Unlabeled/investigation indication: Treatment of psychosis, adjunctive treatment of ethanol dependence, antiemetic. Usual Dose: Oral: 0.5-5 mg 2-3 times/day, maximum 30 mg/day . I.M. (as lactate): 2-5 mg every 4-8 hours as needed. I.M. (as decanoate): Initial: 10-20 times the daily oral dose administered at 4-week intervals. Adverse Reactions: - Cardiovascular: Hyper-/hypotension, tachycardia, arrhythmia, abnormal T waves with prolonged - Central nervous system: Restlessness, anxiety, extrapyramidal reactions,neuroleptic malignant syndrome (NMS),agitation - Dermatologic: Hyperpigmentation, pruritus, rash, contact dermatitis, alopecia, photosensitivity - Endocrine & metabolic: Amenorrhea, galactorrhea, gynecomastia, sexual dysfunction, lactation, hyper/hypo glycemia - Gastrointestinal: Nausea, vomiting, anorexia, constipation, diarrhea, hypersalivation - Genitourinary: Urinary retention, priapism - Hematologic: Cholestatic jaundice, obstructive jaundice - Ocular: Blurred vision - Respiratory: Laryngospasm, bronchospasm - Miscellaneous: Heat stroke, diaphoresis Pregnancy risk factor: C

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- 65 - CENTRAL NERVOUS SYSTEM DRUGS Lactation: Enters breast milk/not recommended (AAP rates "of concern") Preparations: Tablets 0.5, 2, 5 mg. ED(C) Injection 5 mg (as lactate) ED(C), Injection 50 mg (as decanoate) ED(C), Oral solution 2 mg/mL ED(C)

• OLANZAPINE Indication: Treatment of the manifestations of schizophrenia. Unlabeled/investigation indication: Treatment of psychosis/schizophrenia in children or adolescents, chronic pain. Usual Dose: Initial: 5-10 mg once daily, a recommended maximum of 20 mg/day . Adverse Reactions: - Central nervous system: Somnolence, extrapyramidal symptoms, insomnia, dizziness - Cardiovascular: Postural hypotension, tachycardia, peripheral edema, chest pain, hyper- /hypotension - Dermatologic: Bruising - Endocrine & metabolic: Cholesterol increased, prolactin increased - Genitourinary: Incontinence, UTI, vaginitis - Hepatic: ALT increased - Neuromuscular & skeletal: Weakness - Ocular: Amblyopia, conjunctivitis - Respiratory: Rhinitis, cough, pharyngitis, dyspnea Pregnancy risk factor: C Lactation: Enters breast milk/not recommended Preparations: Tablets 10 mg. NED Injection 10mg NED

• PERPHENAZINE Indication: Treatment of schizophrenia, nausea and vomiting. Unlabeled/investigation indication: Ethanol withdrawal, dementia in elderly, Tourette's syndrome, Huntington's chorea, spasmodic torticollis, Reye's syndrome, psychosis. Usual Dose: Schizophrenia/psychoses :Oral: 4-16 mg 2-4 times/day not to exceed 64 mg/day . Nausea/vomiting: Oral: 8-16 mg/day in divided doses up to 24 mg/day . Adverse Reactions: - Cardiovascular: Hyper-/hypotension, orthostatic hypotension, tachycardia, bradycardia - Central nervous system: Extrapyramidal symptoms, dizziness, drowsiness, NMS - Dermatologic: Rash, discoloration of skin (blue-gray), photosensitivity - Endocrine & metabolic: Hypo/hyper glycemia,galactorrhea, lactation, menstrual irregularity, amenorrhea - Gastrointestinal: Constipation, weight gain, vomiting, stomach pain, nausea, xerostomia, salivation, diarrhea, anorexia, ileus

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- 66 - CENTRAL NERVOUS SYSTEM DRUGS - Genitourinary: Difficulty in urination, ejaculatory disturbances, incontinence, priapism - Hematologic: Agranulocytosis, leukopenia, eosinophilia, hemolytic anemia, thrombocytopenic - Hepatic: Cholestatic jaundice, hepatotoxicity - Neuromuscular & skeletal: Tremor - Ocular: Pigmentary retinopathy, blurred vision - Respiratory: Nasal congestion - Miscellaneous: Diaphoresis Pregnancy risk factor: C Lactation: Enters breast milk/not recommended (AAP rates "of concern") Preparations: Tablets 2, 4,8 mg. ED(C)

• PALIPERIDONE Indication: For the acute and maintenance treatment of schizophrenia. Unlabeled/investigation indication: N/A Usual Dose: Oral 1 tablet morning with or without food. If clinical assessment warrants, increase the dose at increments of 3 mg/day at intervals of more than 5 days. Maximum recommended dose is 12 mg/day. Adverse Reactions: Extrapyramidal symptoms, tachycardia, somnolence, dyspepsia, constipation, weight increased, and nasopharyngitis Pregnancy risk factor: C Lactation: Enters breast milk/use caution Preparations: Tablets (extended-release) 6 mg NED

• QUETIAPINE Indication: Treatment of schizophrenia and manic episodes associated with bipolar disorder. Unlabeled/investigation indication: Autism, psychosis (children) Usual Dose: Oral: Initial: 25 mg twice daily, increase in increments of 25-50 mg 2-3 times/day on the second and third day, a target dose of 300-400 mg in 2-3 divided doses. Usual maintenance range 300-800 mg/day. Adverse Reactions: - Cardiovascular: Palpitation, peripheral edema, postural hypotension, tachycardia - Central nervous system: Agitation, dizziness, headache, somnolence - Dermatologic: Rash - Endocrine & metabolic: Cholesterol increased, triglycerides increased - Gastrointestinal: Weight gain , xerostomia, abdominal pain, anorexia, constipation, dyspepsia - Hematologic: Leukopenia - Hepatic: AST increased, ALT increased, GGT increased - Neuromuscular & skeletal: Back pain, dysarthria, hypertonia, tremor, weakness - Ocular: Amblyopia - Respiratory: Cough, dyspnea, pharyngitis, rhinitis

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- 67 - CENTRAL NERVOUS SYSTEM DRUGS Pregnancy risk factor: C Lactation: Excretion in breast milk unknown/not recommended Preparations: Tablets 200mg. 300 mg (XR) NED

• RISPERIDONE Indication: Treatment of schizophrenia. Unlabeled/investigation indication: Behavioral symptoms associated with dementia in elderly, Tourette's disorder and pervasive developmental disorder. Usual Dose: Usual range: 4-8 mg/day. Oral Initial: 1 mg twice daily, a target dose of 6 mg/day . I.M. (Long- acting): 25 mg every 2 weeks, maximum dose not to exceed 50 mg every 2 weeks. Adverse Reactions: - Cardiovascular: Tachycardia, hypertension, chest pain, hypotension - Central nervous system: Fatigue, extrapyramidal symptoms, somnolence, insomnia, agitation, anxiety, headache, dizziness - Dermatologic: Rash, acne, pruritus, pigmentation increased, photosensitivity - Endocrine & metabolic: Sexual dysfunction, menorrhagia, galactorrhea, gynecomastia - Gastrointestinal: Appetite increased, salivation increased, weight gain, constipation, xerostomia, dyspepsia, nausea - Genitourinary: Micturition disturbances - Hematologic: Anemia ( I.M. injection) - Hepatic: Transaminases increased (I.M. injection) - Neuromuscular & skeletal: Tremor - Ocular: Abnormal vision, accommodation disturbances - Respiratory: Upper respiratory infection - Renal: Polydipsia, polyuria Pregnancy risk factor: C Lactation: Enters breast milk/not recommended Preparations: Tablets 1, 2 mg (Quicklet tablets) NED . Injection 25 mg (Long-acting) NED

• Indication: Treatment of schizophrenic. Unlabeled/investigation indication: Psychosis Usual Dose: Oral Initial: 50-100 mg 3 times/day maximum: 800 mg/day in 2-4 divided doses . Adverse Reactions: - Cardiovascular: Hypotension, orthostatic hypotension, peripheral edema, ECG changes - Central nervous system: EPS, NMS, dizziness, drowsiness, impairment of temperature regulation, lowering of seizure threshold - Dermatologic: Increased sensitivity to sun, rash, discoloration of skin (blue-gray)

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- 68 - CENTRAL NERVOUS SYSTEM DRUGS - Endocrine & metabolic: Changes in menstrual cycle, libido, galactorrhea, amenorrhea - Gastrointestinal: Constipation, weight gain, nausea, vomiting, stomach pain, xerostomia, diarrhea - Genitourinary: Difficulty in urination, ejaculatory disturbances, urinary retention, priapism - Hematologic: Agranulocytosis, leucopenia - Hepatic: Cholestatic jaundice, hepatotoxicity - Neuromuscular & skeletal: Tremor, seizure - Ocular: Pigmentary retinopathy, blurred vision, cornea and lens changes - Respiratory: Nasal congestion Pregnancy risk factor: C Lactation: Excretion in breast milk unknown/not recommended Preparations: Tablets 25, 50, 100mg ED(G)

• ZUCLOPENTHIXOL Indication: Management of schizophrenia Unlabeled/investigation indication: Bipolar disorder, psychoses, agitated states Usual Dose: Short-term management : I.M. (acetate): 50-150 mg, maximum dose during course of treatment: 400 mg . Long-term management : I.M (decanoate) 100 mg, maximum weekly dose 600 mg, usual maintenance dose: 150-300 mg every 2 weeks. Adverse Reactions: - Central nervous system: Somnolence/drowsiness, anxiety/nervousness, insomnia, akathisia , extrapyramidal effects, dizziness - Dermatologic: Seborrhea , pruritus - Endocrine & metabolic: Decreased libido, menstrual disorder - Gastrointestinal: Xerostomia, constipation, increased salivation, anorexia - Genitourinary: Micturition disorder - Neuromuscular & skeletal: Hypokinesia, abnormal gait, myalgia - Ocular: Abnormal accommodation, abnormal vision Pregnancy risk factor: C Lactation: Enters breast milk/not recommended Preparations: Injection 100mg/2 mL (acetate), 200 mg/mL (decanoate) ED(K)

• ZIPRASIDONE Indication: Management of schizophrenia and other psychotic disorders . Unlabeled/investigation indication: TouretteT s syndrome Usual Dose: Oral: Initial: 20 mg twice daily Adverse Reactions: - Cardiovascular: Chest pain, postural hypotension, hypertension, bradycardia, tachycardia - Central nervous system: Extrapyramidal symptoms, somnolence, headache, dizziness

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- 69 - CENTRAL NERVOUS SYSTEM DRUGS - Dermatologic: Rash, fungal dermatitis - Endocrine & metabolic: Dysmenorrhea - Gastrointestinal: Nausea, weight gain, constipation, dyspepsia, diarrhea, vomiting, salivation increased - Genitourinary: Priapism - Neuromuscular & skeletal: Weakness, hypoesthesia, myalgia, paresthesia, dysarthria, dyskinesia, hyper-/hypokinesia, hypotonia, neuropathy, tremor - Ocular: Vision abnormal, diplopia - Respiratory: Infection, rhinitis, cough, pharyngitis , dyspnea Pregnancy risk factor: C Lactation: Excretion in breast milk unknown/not recommended Preparations: Capsules 20, 60, 80 mg NED

7.6.3 ANTIMANIC • LITHIUM CARBONATE Indication: Management of bipolar disorders, mania in individuals with bipolar disorder. Unlabeled/investigation indication: Potential augmenting agent for antidepressants, aggression, post- traumatic stress disorder and conduct disorder in children. Usual Dose: Oral: 900-2400 mg/day in 3-4 divided doses Adverse Reactions: - Cardiovascular: Cardiac arrhythmia, hypotension, sinus node dysfunction, flattened or inverted T waves (reversible), edema, bradycardia, syncope - Central nervous system: Dizziness, vertigo, slurred speech,seizure, sedation, restlessness, confusion, psychomotor retardation, stupor, coma, dystonia, fatigue, lethargy, headache, pseudotumor cerebri, slowed intellectual functioning, tics - Dermatologic: Dry or thinning of hair, folliculitis, alopecia, exacerbation of psoriasis, rash - Endocrine & metabolic: Euthyroid goiter and/or hypo/hyperthyroidism, hyperglycemia, diabetes insipidus - Gastrointestinal: Polydipsia, anorexia, nausea, vomiting, diarrhea, xerostomia, metallic taste, weight gain, salivary gland swelling, excessive salivation - Genitourinary: Incontinence, polyuria, glycosuria, oliguria, albuminuria - Hematologic: Leukocytosis - Neuromuscular & skeletal: Tremor, muscle hyperirritability, ataxia, hyperactive deep tendon reflexes - Ocular: Nystagmus, blurred vision, transient scotoma - Miscellaneous: Coldness and painful discoloration of fingers and toes Pregnancy risk factor: D Lactation: Enters breast milk/contraindicated Preparations: Capsules 300 mg. ED(C)

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- 70 - CENTRAL NERVOUS SYSTEM DRUGS 7.7 RESPIRATORY AND CEREBRAL STIMULANT • Indication: Treatment of attention deficit/hyperactivity disorder (ADHD). Unlabeled/investigation indication: N/A Usual Dose: Adult: Oral: Initial 40 mg/day, increased after minimum of 3 days to 80 mg/day, may increase to 100 mg in 2-4 additional weeks to achieve optimal response. Children and Adolescents 70 kg : Oral: Initial: 0.5 mg/kg/day, increase after minimum of 3 days to 1.2 mg/kg/day. Maximum daily dose: 1.4 mg/kg or 100 mg Adverse Reactions: - Cardiovascular: Palpitations, diastolic/ systolic pressure increased, orthostatic hypotension, tachycardia - Central nervous system: Headache, insomnia, fatigue/lethargy, irritability, somnolence - Dermatologic: Dermatitis - Endocrine & metabolic: Dysmenorrhea, libido decreased, menstruation disturbance, hot flashes - Gastrointestinal: Xerostomia, abdominal pain, vomiting, appetite decreased, nausea - Genitourinary: Urinary hesitation/retention, erectile disturbance, ejaculatory disturbance, prostatitis, impotence - Neuromuscular & skeletal: Paresthesia, myalgia - Ocular: Mydriasis - Otic: Ear infection - Respiratory: Cough, sinusitis, rhinorrhea, sinus headache Pregnancy risk factor: C Lactation: Excretion in breast milk unknown/use caution Preparations: Capsule 25 mg, 40 mg NED

• METHYLPHENIDATE HCL Indication: Treatment of attention-deficit/hyperactivity disorder (ADHD), narcolepsy. Unlabeled/investigation indication: Depression (especially elderly or medically ill) Usual Dose: Narcolepsy (adult): Oral: 10 mg 2-3 times/day, maximum dose: 60 mg/day . ADHD - Immediate release product: Children 6 years: Initial: 0.3 mg/kg/dose or 2.5-5 mg/dose given before breakfast and lunch, increase by 0.1 mg/kg/dose or by 5-10 mg/day at weekly intervals, usual dose: 0.3-1 mg/kg/day; maximum dose: 2 mg/kg/day or 60 mg/day . - Sustained release and extended release product: Children > 6 years and Adults: Initial 18 mg once daily. Maximum dose in children 6-12 years: 54 mg/day, adolescent and adults: 72 mg/day , do not exceed 2 mg/kg/day . Adverse Reactions: - Central nervous system: Insomnia (13%), tic, emotional instability - Endocrine & metabolic: Appetite decreased (26%)      .. 2553            !

- 71 - CENTRAL NERVOUS SYSTEM DRUGS - Gastrointestinal: Nausea, vomiting, anorexia - Respiratory: Nasal congestion, nasopharyngitis - Endocrine & metabolic: Weight loss Pregnancy risk factor: C Lactation: Enters breast milk/use caution Preparations: Tablet 10 mg, 18, 36 mg (sustained release) ED(>)

7.8 ANXIOLYTICS, SEDATIVES AND HYPNOTICS GROUP • AMOBARBITAL+CHLORPROMAZINE Indication: For psychoneurosis, anxiety and tension. Unlabeled/investigation indication: N/A Usual Dose: 1 tablet at bedtime. Adverse Reactions: - Cardiovascular: Tachycardia, postural hypotension - Central nervous system: Drowsiness, dependence, insomnia, depression, convulsion, agitation - Gastrointestinal: Nausea, vomiting, constipation - Respiratory: Respiratory depression, apnea, hypoventilation, circulatory collapse. - Skin: Rash, , exfoliative dermatitis Pregnancy risk factor: C (chlorpromazine), D (amobatbital) Lactation: Not recommended Preparations: Tablet (chlorpromazine 25 mg+ amobarbital 50 mg) NED

• PHENOBARBITAL (See in section 7 page 51)

BENZODIAZEPINE GROUP (ALPRAZOLAM, CLORAZEPATE DIPOTASSIUM, CLORAZEPATE DIPOTASSIUM, , ) Adverse Reactions: >10%: - Central nervous system: Abnormal coordination, cognitive disorder, depression, drowsiness, fatigue, irritability, lightheadedness, memory impairment, sedation, somnolence - Gastrointestinal: Appetite increased/decreased, constipation, salivation decreased, weight gain/loss, xerostomia - Genitourinary: Micturition difficulty - Neuromuscular & skeletal: Dysarthria 1% to 10%: - Cardiovascular: Hypotension - Central nervous system: Agitation, attention disturbance, confusion, depersonalization,

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- 72 - CENTRAL NERVOUS SYSTEM DRUGS derealization, disorientation, dizziness, dream abnormalities, fear, hallucinations,seizure, - Dermatologic: Dermatitis, pruritus, rash - Endocrine & metabolic: Libido decreased/increased, menstrual disorders - Gastrointestinal: Salivation increased - Genitourinary: Incontinence - Hepatic: Bilirubin increased, jaundice, liver enzymes increased - Neuromuscular & skeletal: Arthralgia, ataxia, myalgia, paresthesia - Ocular: Diplopia - Respiratory: Allergic rhinitis, dyspnea

• ALPRAZOLAM Indication: Treatment of anxiety disorder (GAD), panic disorder, with or without agoraphobia, anxiety associated with depression. Unlabeled/investigation indication: Anxiety in children Usual Dose: Anxiety : Oral: 0.5-4 mg/day in divided doses, maximum dose 4 mg/day . Panic disorder : Oral Initial 0.5 mg 3 times/day, mean effective dosage 5-6 mg/day, maximum dose 10 mg/day . Pregnancy risk factor: D Lactation: Enters breast milk/not recommended (AAP rates "of concern") Preparations: Tablet 0.25, 1 mg ED(K)

• CLORAZEPATE DIPOTASSIUM Indication: Treatment of generalized anxiety disorder, management of ethanol withdrawal, adjunct anticonvulsant in management of partial seizures. Unlabeled/investigation indication: N/A Usual Dose: Anxiety: 7.5-15 mg 2-4 times/day. Ethanol withdrawal : Oral Initial 30 mg, then 15 mg 2-4 times/day on first day ; maximum dose 90 mg/day . Seizures (anticonvulsant): Oral Initial 7.5 mg/dose 2-3 times/day; maximum dose 90 mg/day . Pregnancy risk factor: D Lactation: Enters breast milk/not recommended (AAP rates "of concern") Preparations: Capsules 25 mg ED(G)

• DIAZEPAM Indication: Management of anxiety disorders, ethanol withdrawal symptoms, skeletal , treatment of convulsive disorders. Unlabeled/investigation indication: Panic disorders; preoperative sedation, light anesthesia, amnesia Usual Dose: Anxiety/sedation/skeletal muscle relaxation : Oral: 2-10 mg 2-4 times/day, I.M., I.V.: 2-10 mg, may repeat in 3-4 hours if needed. Sedation in the ICU patient : I.V. 0.03-0.1 mg/kg every 30 minutes to 6 hours. Status epilepticus : I.V.: 5-10 mg every 10-20 minutes, up to 30 mg in an 8-hour period; may repeat in

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- 73 - CENTRAL NERVOUS SYSTEM DRUGS 2-4 hours if necessary. Rapid tranquilization of agitated patient (administer every 30-60 minutes): Oral: 5-10 mg; average total dose for tranquilization: 20-60 mg. Adverse Reactions: Frequency not defined. Adverse reactions may vary by route of administration. Pregnancy risk factor: D Lactation: Enters breast milk/contraindicated (AAP rates "of concern") Preparations: Tablets 2, 5 mg ED(C) Injection 10 mg/2 mL ED(C)

• LORAZEPAM Indication: Management of anxiety disorders or short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms. Unlabeled/investigation indication: Ethanol detoxification, insomnia, psychogenic catatonia, partial complex seizures. Usual Dose: Anxiety and sedation : Oral: 1-10 mg/day in 2-3 divided doses. Insomnia : Oral 2-4 mg at bedtime. Pregnancy risk factor: D Lactation: Enters breast milk/contraindicated (AAP rates "of concern") Preparations: Tablets 0.5, 1, 2 mg ED(C)

MISCELLANEOUS • ZOLPIDEM Indication: Short-term treatment of insomnia. Unlabeled/investigation indication: N/A Usual Dose: 10 mg before bedtime, maximum dose 10 mg Adverse Reactions: - Cardiovascular: Blood pressure increased, chest discomfort, palpitation - Central nervous system: Dizziness, headache(>10%), somnolence(>10%), anxiety, apathy, amnesia, ataxia, confusion, depersonalization, depression, disorientation, drowsiness - Dermatologic: Rash, urticaria, wrinkling - Endocrine & metabolic: Menorrhagia - Gastrointestinal: Abdominal discomfort, appetite disorder, constipation, diarrhea, yspepsia, gastroenteritis, gastroesophageal reflux, hiccup, nausea, vomiting, xerostomia - Genitourinary: Urinary tract infection - Neuromuscular & skeletal: Arthralgia, back pain, balance disorder, myalgia, neck pain, paresthesia, psychomotor retardation, tremor, weakness - Ocular: Asthenopia, blurred vision, depth perception altered, diplopia, red eye, visual disturbance - Otic: Labyrinthitis, tinnitus, vertigo - Renal: Dysuria - Respiratory: Pharyngitis, sinusitis, throat irritation, upper respiratory tract infection

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- 74 - CENTRAL NERVOUS SYSTEM DRUGS Pregnancy risk factor: C Lactation: Enters breast milk/not recommended (AAP rates "compatible") Preparations: Tablets 10 mg NED

7.9 ALZHEIMER=S DRUGS • MEMANTINE Indication: Treatment of patients with moderately severe to severe Alzheimer's disease. Unlabeled/investigation indication: Treatment of mild-to-moderate vascular dementia Usual Dose: Oral: Initial: 5 mg/day; increase dose by 5 mg/day to a target dose of 20 mg/day. Adverse Reactions: - Cardiovascular: Hypertension, cardiac failure, syncope, cerebrovascular accident, transient ischemic attack - Central nervous system: Dizziness, confusion, headache, hallucinations, pain, somnolence, fatigue, aggressive reaction, ataxia, vertigo - Dermatologic: Rash - Gastrointestinal: Constipation, vomiting, weight loss - Genitourinary: Micturition - Hematologic: Anemia - Hepatic: Alkaline phosphatase increased - Neuromuscular & skeletal: Back pain, hypokinesia - Ocular: Cataract, conjunctivitis - Respiratory: Cough, dyspnea, pneumonia Pregnancy risk factor: B Lactation: Excretion in breast milk unknown/use caution Preparations: Tablets 10 mg NED

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