Generic Name: Paliperidone
Class: Atypical Antipsychotics
VA Class: CN709
Chemical Name: (±) - 3 - [2 - [4 - (6 - fluoro - 1,2 - benzisoxazol - 3 - yl) - 1 - piperidyl]ethyl] - 6,7,8,9 - tetrahydro - 9 - hydroxy - 2 - methyl - 4H - pyrido[1,2 - a]pyrimidin - 4 - one
Molecular Formula: C23H27FN4O3
CAS Number: 144598-75-4

Warning(s)

Special Alerts:

[Posted 02/22/2011] ISSUE: FDA notified healthcare professionals that the Pregnancy section of drug labels for the entire class of antipsychotic drugs has been updated. The new drug labels now contain more and consistent information about the potential risk for abnormal muscle movements (extrapyramidal signs or EPS) and withdrawal symptoms in newborns whose mothers were treated with these drugs during the third trimester of pregnancy.

The symptoms of EPS and withdrawal in newborns may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty in feeding. In some newborns, the symptoms subside within hours or days and do not require specific treatment; other newborns may require longer hospital stays.

BACKGROUND: Antipsychotic drugs are used to treat symptoms of psychiatric disorders such as schizophrenia and bipolar disorder.

RECOMMENDATION: Healthcare professionals should be aware of the effects of antipsychotic medications on newborns when the medications are used during pregnancy. Patients should not stop taking these medications if they become pregnant without talking to their healthcare professional, as abruptly stopping antipsychotic medications can cause significant complications for treatment. For more information visit the FDA website at: and .

Warning(s)

  • Increased Mortality in Geriatric Patients
  • Substantially higher mortality rate (4.5%) in geriatric patients with dementia-related psychosis† receiving atypical antipsychotic agents (e.g., risperidone, aripiprazole, olanzapine, quetiapine) compared with those receiving placebo (2.6%).1 11

  • Most fatalities resulted from cardiac-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).1 11

  • Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.1 11 (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)

Introduction

Atypical or second-generation antipsychotic agent.1 2 3 4 5 6 7 8 12 39 41

Uses for Invega

Schizophrenia

Acute and maintenance treatment of schizophrenia.1 3 4 6 7 8 39 41

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

The American Psychiatric Association (APA) considers most atypical antipsychotic agents first-line drugs for the management of the acute phase of schizophrenia (including first psychotic episodes).2

Invega Dosage and Administration

Administration

Oral Administration

Administer orally once daily in the morning without regard to meals.1 12 39 41

Paliperidone extended-release tablets should be swallowed whole, with fluids; do not chew, divide, or crush.1 12

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Adults

Schizophrenia
Oral

6 mg once daily; dosage titration is not required.1 5 41

If required, may increase dosage in increments of 3 mg daily at intervals of >5 days to a maximum dosage of 12 mg once daily; increase dosage only after clinical reassessment.1

Maximal efficacy generally observed at dosage of 6 mg daily; dosages >6 mg trended toward greater clinical effects; however, weigh potential increased clinical efficacy against the potential for increased adverse effects.1 3 6 7 8

Optimum duration of therapy is not known, but maintenance therapy with antipsychotics is well established.1 4 In responsive patients, continue as long as clinically necessary and tolerated, but at lowest possible effective dosage; periodically reassess need for continued therapy.1 2

In patients with remitted first or multiple episodes, the APA recommends either indefinite maintenance therapy or gradual discontinuance of the antipsychotic with close follow-up and a plan to reinstitute treatment upon symptom recurrence.2 Consider antipsychotic therapy discontinuance only after ≥1 year of symptom remission or optimal response while taking antipsychotic.2 Indefinite maintenance treatment is recommended if multiple previous psychotic episodes or 2 episodes within 5 years.2

Prescribing Limits

Adults

Schizophrenia
Oral

Maximum 12 mg once daily.1

Special Populations

Hepatic Impairment

No dosage adjustment required in patients with mild to moderate hepatic impairment (Child-Pugh class A and B); not studied in patients with severe hepatic impairment.1 39 41 (See Distribution: Special Populations under Pharmacokinetics.)

Renal Impairment

Mild renal impairment (Clcr 50–79 mL/minute): Maximum 6 mg once daily.1 39

Moderate to severe renal impairment (Clcr 10–49 mL/minute): Maximum 3 mg once daily.1 39 (See Elimination: Special Populations under Pharmacokinetics.)

Geriatric Patients

No dosage adjustments except those related to renal impairment.1 39 41 (See Renal Impairment under Dosage and Administration.)

Gender, Race, or Smoking Status

No dosage adjustment required.1 39

Cautions for Invega

Contraindications

  • Known hypersensitivity to paliperidone, risperidone, or any ingredient in the formulation.1 12

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Increased Mortality in Geriatric Patients with Dementia-related Psychosis

Possible increased risk of death with use of atypical antipsychotics in geriatric patients with dementia-related psychosis.1

Atypical antipsychotics, including paliperidone, are not approved for the treatment of dementia-related psychosis.1 (See Increased Mortality in Geriatric Patients in Boxed Warning and see Geriatric Use under Cautions.)

Prolongation of QT Interval

Paliperidone causes a modest increase in the corrected QT (QTc) interval.1 7 44

Avoid use in patients with congenital prolonged QT interval, bradycardia, uncorrected electrolyte disorders (e.g., hypokalemia, hypomagnesemia), or a history of cardiac arrhythmias.1 Also avoid use in those receiving other drugs known to prolong the QTc interval.1 (See Drugs that Prolong QT Interval and also Specific Drugs under Interactions.)

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome requiring immediate discontinuance of the drug and intensive symptomatic treatment, reported in patients receiving antipsychotic agents, including paliperidone.1 2 4

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary dyskinetic movements, reported.1 2 The APA recommends assessing patients receiving second-generation antipsychotic agents for abnormal involuntary movements every 12 months; for patients at increased risk for tardive dyskinesia, assess every 6 months.2 Consider discontinuance of paliperidone if signs and symptoms of tardive dyskinesia appear.1

Hyperglycemia and Diabetes Mellitus

Severe hyperglycemia, sometimes associated with ketoacidosis, hyperosmolar coma, or death, reported in patients receiving atypical antipsychotic agents.1 2 13 14 15 16 17 18 19 24 25 26 27 28 29 30 31 32 33 34 35 36 39

Closely monitor patients with preexisting diabetes mellitus for worsening of glucose control and perform fasting glucose tests at baseline and periodically for patients with risk factors for diabetes (e.g., obesity, family history of diabetes).1 24 25 26 27 28 29 30 31 32 33 34 35 36 If manifestations of hyperglycemia occur, perform fasting blood glucose testing.1 24 25 26 27 28 29 30 31 32 33 34 35 36

GI Effects

Extended-release paliperidone tablets are a nondeformable material that does not appreciably change shape in the GI tract.1 Rare cases reported of obstructive symptoms in patients with known strictures in association with nondeformable, controlled-release formulations.1 Avoid administration to patients with severe, preexisting GI narrowing (either pathologic or iatrogenic).1

Esophageal dysmotility and aspiration possible; use caution in patients at risk for aspiration pneumonia (e.g., those with advanced Alzheimer’s dementia).1

General Precautions

Orthostatic Hypotension

Orthostatic hypotension and syncope reported.1 2 4 Use with caution in geriatric patients and in patients with known cardiovascular (e.g., heart failure, history of MI or ischemia, conduction abnormalities) or cerebrovascular disease or other conditions (e.g., dehydration, hypovolemia, concomitant antihypertensive therapy) that would predispose them to hypotension.1 Consider monitoring orthostatic vital signs in patients vulnerable to hypotension.1 2 (See Geriatric Use under Cautions.)

Nervous System Effects

Seizures may occur; use with caution in patients with a history of seizures or other conditions that may lower the seizure threshold (e.g., dementia of the Alzheimer’s type, geriatric patients).1 36 (See Geriatric Use under Cautions.)

Disruption of ability to regulate core body temperature possible.1 Use caution in patients exposed to conditions that may contribute to an elevation in core body temperature (e.g., dehydration, extreme heat, strenuous exercise, concomitant use of anticholinergic agents.)1

Somnolence reported; potential impairment of judgment, thinking, or motor skills.1 7

Antiemetic effect demonstrated in animals; also may occur in humans and mask manifestations of overdosage with certain drugs or of underlying conditions (e.g., intestinal obstruction, Reye’s syndrome, brain tumor).1

Hematologic Effects

Thrombotic thrombocytopenic purpura reported in association with risperidone therapy; however, currently no reports of this effect with paliperidone.1

Suicide

Attendant risk with psychotic illnesses; closely supervise high-risk patients.1 Prescribe in the smallest quantity consistent with good patient management to reduce the risk of overdosage.1

Hyperprolactinemia

Elevated prolactin concentrations possible; may persist during chronic administration.1 2 4 6 37 38 39 41 42

Concomitant Illnesses

Experience in patients with certain concomitant diseases is limited.1

Possible increased risk of NMS and increased sensitivity to antipsychotic agents in patients with parkinsonian syndrome or dementia with Lewy bodies; manifestations of sensitivity may include confusion, obtundation, postural instability with more frequent falling, or extrapyramidal adverse effects.1 (See Geriatric Use under Cautions.)

Specific Populations

Pregnancy

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Category C.1

Lactation

Distributed into milk.1 39 40 Caution if used in nursing women.a

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 12

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults; however, manufacturer states greater sensitivity of some older individuals cannot be ruled out.1 Use with caution due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in elderly patients.1 (See Concomitant Illnesses and also Nervous System Effects under Cautions and see Renal Impairment under Dosage and Administration.)

Consider monitoring orthostatic vital signs and renal function in geriatric patients.1 41 (See Orthostatic Hypotension under Cautions.)

Possible increased risk of death in geriatric patients with dementia-related psychosis.1 Substantial (1.6- to 1.7-fold) increase in mortality rate reported in geriatric patients with dementia who received atypical antipsychotic agents (i.e., risperidone, aripiprazole, olanzapine, quetiapine) for treatment of behavioral disorders; most fatalities resulted from cardiac-related events (e.g., heart failure, sudden death) or infections (e.g., pneumonia).1 In addition, adverse cerebrovascular effects, sometimes fatal, reported in geriatric patients with dementia-related psychosis receiving atypical antipsychotic agents (i.e., risperidone, aripiprazole, olanzapine).1 Paliperidone is not approved for the treatment of dementia-related psychosis.1 (See Increased Mortality in Geriatric Patients in Boxed Warning and see Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Warnings in Cautions.)

Common Adverse Effects

Tremor,4 headache,1 4 7 39 41 44 orthostatic hypotension,1 4 44 tachycardia,1 4 7 39 41 44 somnolence,1 7 39 41 44 akathisia,1 6 39 44 insomnia,4 7 39 41 anxiety,1 7 39 41 extrapyramidal reaction,1 4 7 39 41 dizziness,1 7 39 41 44 dystonia,1 6 39 QTc interval prolongation,1 7 39 44 nausea,1 7 39 dyspepsia,1 7 39 44 weight gain.4 7 39 41

Interactions for Invega

In vivo results indicate that CYP2D6 and CYP3A4 play a limited role in overall elimination of paliperidone.1

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors or inducers of CYP isoenzymes 2D6, 3A4, 1A2, 2A6, 2C9, and 2C19: Pharmacokinetic interaction unlikely.1 9 41

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP isoenzymes 1A2, 2A6, 2C8/9/10, 2D6, 2E1, 3A4, or 3A5: Pharmacokinetic interaction unlikely.1 9 41

Drugs Inhibiting P-glycoprotein Transport System

Does not inhibit P-glycoprotein; clinically relevant interactions unlikely.1

Drugs that Prolong QT Interval

Potential pharmacologic interaction (additive effect on QT-interval prolongation); avoid concomitant use with drugs known to prolong the QT interval.1 (See Prolongation of QT Interval under Cautions.)

Protein-bound Drugs

Pharmacokinetic interactions unlikely.1 41

Specific Drugs

Drug

Interaction

Comments

Alcohol

Possible additive CNS effects1

Avoid concomitant use1 12

Amiodarone

Possible additive QT prolongation effects1

Avoid concomitant use1

Antiarrhythmics (e.g., procainamide, quinidine, sotalol)

Possible additive QT prolongation effects1

Avoid concomitant use1

Chlorpromazine

Possible additive QT prolongation effects1

Avoid concomitant use1

CNS agents

Additive CNS effects1

Use with caution1

Dopamine agonists (e.g., levodopa)

Potential antagonistic effects1 12

Fluoroquinolones (e.g., moxifloxacin, gatifloxacin)

Possible additive QT prolongation effects1

Avoid concomitant use1

Hypotensive agents

Additive hypotensive effects1 12

Use with caution; monitor for orthostatic hypotension in susceptible patients1

Paroxetine

Possible increased paliperidone AUC in CYP2D6 extensive metabolizersa

Clinical importance unknowna

Risperidone

Paliperidone is principal active metabolite of risperidone; possible additive paliperidone exposure1 39

Thioridazine

Possible additive QT prolongation effects1

Avoid concomitant use1

Invega Pharmacokinetics

Absorption

Bioavailability

Absolute oral bioavailability is 28%; single-dose peak plasma concentrations attained approximately 24 hours after dosing.1

Food

Food increases rate and extent of absorption, and possible increase in exposure.1

Special Populations

Decreased bioavailability in patients with decreased GI transit time (e.g., diarrhea); increased bioavailability in patients with increased GI transit time (e.g., GI neuropathy, diabetic gastroparesis).1 Changes in bioavailability more likely when transit time changes occur in the upper GI tract.1 (See GI Effects under Cautions.)

Distribution

Extent

Not known whether paliperidone crosses the placenta.1 Risperidone (the parent drug of paliperidone) crosses the placenta in rats.1 Paliperidone is distributed into human milk.a

Plasma Protein Binding

74%.1

Special Populations

In mild to moderate hepatic impairment (Child-Pugh class B); decreased total paliperidone exposure due to decreased protein binding.1 (See Hepatic Impairment under Dosage and Administration.)

Elimination

Metabolism

In vitro studies suggested a role for CYP2D6 and CYP3A4; however, in vivo results suggest a limited role.1 39

Elimination Route

Paliperidone and its metabolites excreted in urine (80%), mainly as unchanged drug, and in the feces (11%).1 39

Half-life

Terminal half-life is approximately 23 hours.1 39 41

Special Populations

In patients with renal impairment, mean plasma terminal half-life is 24, 40, and 51 hours in individuals with mild, moderate, and severe renal impairment, respectively.1 (See Renal Impairment under Dosage and Administration.)

No difference in exposure or clearance of paliperidone between extensive metabolizers and poor metabolizers of CYP2D6.1

Stability

Storage

Oral

Extended-release Tablets

25°C (may be exposed to 15–30°C); protect from moisture.1

Actions

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Benzisoxazole derivative; major active metabolite of risperidone.1 2 3 4 5 6 7 8 12 39 41

  • Exact mechanism of antipsychotic action has not been fully elucidated; may involve antagonism of central dopamine type 2 (D2) receptors and serotonin type 2 (5-hydroxytryptamine [5-HT2A]) receptors.1 39 41

  • Antagonism at other receptors (e.g., α1- and α2-adrenergic receptors, histamine H1 receptors) may contribute to other therapeutic and adverse effects.1 2 39

  • Paliperidone possesses no affinity for cholinergic, muscarinic, or β1- and β2-adrenergic receptors.1 39

Advice to Patients

  • Risk of orthostatic hypotension.1 12 Importance of using nonpharmacologic methods (e.g., sitting on edge of bed for several minutes upon waking, slowly rising from sitting to standing position) to minimize effects.12

  • Risk of somnolence.1 Importance of avoiding driving, operating machinery, or performing hazardous tasks until the patient gains experience with the drug’s effects.1 12

  • Importance of avoiding alcohol during paliperidone therapy.1 12

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, dietary supplements, and/or herbal products, as well as any concomitant illnesses (e.g., cardiovascular disease, diabetes mellitus, seizures).1 12

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 12

  • Importance of avoiding overheating or dehydration.1 12

  • Importance of swallowing paliperidone tablets whole with the aid of liquids; do not chew, divide, or crush tablets.1 12 Patients should not be concerned if they notice a tablet-like substance in their stool.1 12

  • Importance of informing patients of other important precautionary information.1 12 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Paliperidone

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release

3 mg

Invega (with povidone and propylene glycol)

Janssen

6 mg

Invega (with povidone and propylene glycol)

Janssen

9 mg

Invega (with povidone and propylene glycol)

Janssen

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Invega 3MG 24-hr Tablets (JANSSEN): 100/$1,688.96 or 200/$3,376.01

Invega 6MG 24-hr Tablets (JANSSEN): 100/$1,879.48 or 200/$3,734.95

Invega 9MG 24-hr Tablets (JANSSEN): 100/$2,461.97 or 200/$4,817.05

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 15, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Janssen, L.P. Invega (paliperidone) extended-release tablets prescribing information. Titusville, NJ; 2007 Apr.

2. American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2004; 161(Suppl):1-56.

3. Kane J, Canas F, Kramer M et al. Treatment of schizophrenia with paliperidone extended-release tablets: a 6-week placebo-controlled trial. Schizophr Res. 2007; 90:147-61. [PubMed 17092691]

4. Kramer M, Simpson G, Maciulis V et al. Paliperidone extended-release tablets for prevention of symptom recurrence in patients with schizophrenia: a randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol. 2007; 27:6-14. [PubMed 17224706]

5. Conley R, Gupta SK, Sathyan G. Clinical spectrum of the osmotic-controlled release oral delivery system (OROS), an advanced oral delivery form. Curr Med Res Opin. 2006; 22:1879-92. [PubMed 17022845]

6. Davidson M, Emsley R, Kramer M et al. Efficacy, safety and early response of paliperidone extended-release tablets (paliperidone ER): results of a 6-week, randomized, placebo-controlled study. Schizophren Res. 2007; 93:117-30.

7. Marder SR, Kramer M, Ford L et al. Efficacy and safety of paliperidone extended-release tablets: results of a 6-week, randomized, placebo-controlled study. Biol Psychiatry. 2007; (in press).:.

8. Meltzer H, Kramer M, Gassmann-Mayer C et al. Efficacy and tolerability of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 6-week placebo-controlled studies. Poster presented at Collegium Internationale NeuroPsychopharmacologium 2006 Congress. Chicago, IL: 2006 July 9-13. Poster PO2.226.

9. Berwaerts J, Cleton A, Van de Vliet I et al. A randomized, open-label, single-center, crossover study of the potential effects of paroxetine on the pharmacokinetics of a single dose of paliperidone extended-releease tablets in healthy subjects. Poster presented at the American Psychiatric Association 160th Annual Meeting. San Diego, CA: 2007 May 19-24.

10. American Psychiatric Association. DSM-IV: diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994:273-86.

11. Food and Drug Administration. Public health advisory: deaths with antipsychotics in elderly patients with behavioral disturbances. Rockville, MD; 2005 Apr 11. From the FDA website.

12. Food and Drug Administration. Paliperidone (marketed as Invega) patient information sheet. 2007 Mar 30.

13. American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004; 27:596-601. [PubMed 14747245]

14. Koller EA, Weber J, Doraiswamy PM et al. A survey of reports of quetiapine-associated hyperglycemia and diabetes mellitus. J Clin Psychiatry. 2004; 65:857-63. [IDIS 518849] [PubMed 15291665]

15. Ananth J, Johnson KM, Levander EM et al. Diabetic ketoacidosis, neuroleptic malignant syndrome, and myocardial infarction in a patient taking risperidone and lithium carbonate. J Clin Psychiatry. 2004; 65:724. [IDIS 516345] [PubMed 15163265]

16. Torrey EF, Swalwell CI. Fatal olanzapine-induced ketoacidosis. Am J Psychiatry. 2003; 160:2241. [IDIS 516756] [PubMed 14638601]

17. Wehring HJ, Kelly DL, Love RC et al. Deaths from diabetic ketoacidosis after long-term clozapine treatment. Am J Psychiatry. 2003; 160:2241-2. [IDIS 516757] [PubMed 14638600]

18. Anon. Atypical antipsychotics and hyperglycaemia. Aust Adv Drug React Bull. 2004; 23:11-2.

19. Citrome L, Jaffe A, Levine J et al. Relationship between antipsychotic medication treatment and new cases of diabetes among psychiatric inpatients. Psychiatr Serv. 2004; 55:1006-13 [PubMed 15345760]

20. Cunningham F, Lambert B, Miller DR et al. Antipsychotic induced diabetes in veteran schizophrenic patients. In: Abstracts of the 1st International Conference on Therapeutic Risk Management and 19th International Conference on Pharmacoepidemiology, Philadelphia, PA, 2003 Aug 21-24. Pharmacoepidemiol Drug Saf. 2003; 12(Suppl 1): S154-5.

21. Melkersson K, Dahl ML. Adverse metabolic effects associated with atypical antipsychotics. Drugs. 2004; 64:701-23. [PubMed 15025545]

22. Citrome LL, Jaffe AB. Relationship of atypical antipsychotics with development of diabetes mellitus. Ann Pharmacother. 2003; 37:1849-57. [IDIS 510453] [PubMed 14632602]

23. Citrome LL. The increase in risk of diabetes mellitus from exposure to second generation antipsychotic agents. Drugs Today (Barc). 2004; 40: 445-64. [PubMed 15319799]

24. Otsuka America Pharmaceutical, Inc. Abilify (aripiprazole) tablets prescribing information. Rockville, MD; 2004 Sep.

25. Novartis Pharmaceuticals. Clozaril (clozapine) prescribing information. East Hanover, NJ; 2003 Dec.

26. Eli Lilly and Company. Zyprexa (olanzapine) tablets and Zyprexa Zydis (olanzapine) orally disintegrating tablets prescribing information. Indianapolis, IN; 2004 Sep 22.

27. Janssen Pharmaceutica. Risperdal (risperidone) tablets and oral solution prescribing information. Titusville, NJ; 2003 Oct.

28. Pfizer Inc. Geodon (ziprasidone) prescribing information. New York, NY; 2004 Aug.

29. Lewis-Hall F. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. Princeton, NJ: Briston-Myers Squibb Company; 2004 Mar 25. From FDA website.

30. Bess AL, Cunningham SR. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2004 Apr 1. From the FDA website.

31. Eli Lilly and Company. Lilly announces FDA notification of class labeling for atypical antipsychotics regarding hyperglycemia and diabetes. Indianapolis, IN; 2003 Sep 17. Press release.

32. Eisenberg P. Dear health care professional letter regarding safety data on Zyprexa (olanzapine) – hyperglycemia and diabetes. Indianapolis, IN: Eli Lilly and Company; 2004 Mar 1. From the FDA website.

33. Macfadden W. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. Wilmington, DE: AstraZeneca Pharmaceuticals; 2004 Apr 22. From the FDA website.

34. Mahmoud RA. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. Titusville, NJ: Janssen Pharmaceutica, Inc; 2004. From the FDA website.

35. Clary CM. Dear health care practitioner letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. New York NY: Pfizer Global Pharmaceuticals; 2004 Aug. From the FDA website.

36. AstraZeneca Pharmaceuticals LP. Seroquel (quetiapine fumarate) tablets prescribing information. Wilmington, DE; 2007 Jul.

37. Haddad PM, Wieck A. Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management. Drugs. 2004; 64:2291-314. [PubMed 15456328]

38. Melkersson K. Differences in prolactin elevation and related symptoms of atypical antipsychotics in schizophrenic patients. J Clin Psychiatry. 2005; 66:761-7. [PubMed 15960571]

39. Yang LPH, Plosker GL. Paliperidone extended release. CNS Drugs. 2007; 21:417-25. [PubMed 17447829]

40. Ilett KF, Hackett LP, Kristensen JH et al. Transfer of risperidone and 9-hydroxyrisperidone into human milk. Ann Pharmacother. 2004; 38:273-6. [PubMed 14742766]

41. Owen RT. Extended-release paliperidone: efficacy, safety and tolerability profile of a new atypical antipsychotic. Drugs Today (Barc). 2007; 43:249-58. [PubMed 17460786]

42. Eerdekens M, Kramer M, Rossenu S et al. Effect of paliperidone extended-release tablets on prolactin exposure in patients with stable schizophrenia. Poster presented at US Psychiatry & Mental Health Congress. New Orleans, LA: 2006 Nov 16-19.

43. Ortho-McNeil Janssen Scientific Affairs, LLC. Titusville, NJ: Personal communication.

44. Hough D, Kramer M, Cleton A et al. A randomized, double-blind, placebo-controlled, parallel-group study evaluating QT/QTC intervals following administration of paliperidone ER and quetiapine in patients with schizophrenia or schizoaffective disorder. Poster presented at 62nd Society of Biological Psychiatry Convention. San Diego, CA; 2007 May 17-19.

a. Janssen, L.P. Invega (paliperidone) extended-release tablets prescribing information. Titusville, NJ; 2007 Dec.

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