ILOPERIDONE
FANAPT® TABLETS
WARNING
INCREASED MORTALITY IN ELDERLY PATIENTS WITH
DEMENTIA-RELATED PSYCHOSIS ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS TREATED WITH ANTIPSYCHOTIC DRUGS ARE AT AN INCREASED RISK OF DEATH. FANAPT IS NOT APPROVED FOR THE TREATMENT OF PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS [SEE WARNINGS AND PRECAUTIONS ].
DESCRIPTION
FANAPT IS AN ATYPICAL ANTIPSYCHOTIC BELONGING TO THE CHEMICAL CLASS OF PIPERIDINYL-BENZISOXAZOLE DERIVATIVES. ITS CHEMICAL NAME IS 4'-[3-[4-(6-FLUORO-1,2-BENZISOXAZOL-3-YL)PIPERIDINO]PROPOXY]-3'-METHOXYACETOPHENONE. ITS MOLECULAR FORMULA IS C24H27FN2O4 AND ITS MOLECULAR WEIGHT IS 426.48. ILOPERIDONE IS A WHITE TO OFF-WHITE FINELY CRYSTALLINE POWDER. IT IS PRACTICALLY INSOLUBLE IN WATER, VERY SLIGHTLY SOLUBLE IN 0.1 N HCL AND FREELY SOLUBLE IN CHLOROFORM , ETHANOL, METHANOL, AND ACETONITRILE.
FANAPT TABLETS ARE INTENDED FOR ORAL ADMINISTRATION ONLY. EACH ROUND, UNCOATED TABLET CONTAINS 1 MG, 2 MG, 4 MG, 6 MG, 8 MG, 10 MG, OR 12 MG OF ILOPERIDONE. INACTIVE INGREDIENTS ARE: LACTOSE MONOHYDRATE, MICROCRYSTALLINE CELLULOSE, HYDROXYPROPYLMETHYLCELLULOSE, CROSPOVIDONE, MAGNESIUM STEARATE, COLLOIDAL SILICON DIOXIDE, AND PURIFIED WATER (REMOVED DURING PROCESSING). THE TABLETS ARE WHITE, ROUND, FLAT, BEVELED-EDGED AND IDENTIFIED WITH A LOGO “ ” DEBOSSED ON ONE SIDE AND TABLET STRENGTH “1”, “2”, “4”, “6”, “8”, “10”, OR “12” DEBOSSED ON THE OTHER SIDE.
INDICATIONS
INDICATIONS
FANAPT® IS INDICATED FOR THE TREATMENT OF SCHIZOPHRENIA IN ADULTS.
WHEN DECIDING AMONG THE ALTERNATIVE TREATMENTS AVAILABLE FOR THIS CONDITION, THE PRESCRIBER SHOULD CONSIDER THE FINDING THAT FANAPT IS ASSOCIATED WITH PROLONGATION OF THE QTC INTERVAL [SEE WARNINGS AND PRECAUTIONS ]. PROLONGATION OF THE QTC INTERVAL IS ASSOCIATED IN SOME OTHER DRUGS WITH THE ABILITY TO CAUSE TORSADE DE POINTESTYPE ARRHYTHMIA , A POTENTIALLY FATAL POLYMORPHIC VENTRICULAR TACHYCARDIA WHICH CAN RESULT IN SUDDEN DEATH. IN MANY CASES THIS WOULD LEAD TO THE CONCLUSION THAT OTHER DRUGS SHOULD BE TRIED FIRST. WHETHER FANAPT WILL CAUSE TORSADE DE POINTES OR INCREASE THE RATE OF SUDDEN DEATH IS NOT YET KNOWN.
PATIENTS MUST BE TITRATED TO AN EFFECTIVE DOSE OF FANAPT. THUS, CONTROL OF SYMPTOMS MAY BE DELAYED DURING THE FIRST 1 TO 2 WEEKS OF TREATMENT COMPARED TO SOME OTHER ANTIPSYCHOTIC DRUGS THAT DO NOT REQUIRE A SIMILAR TITRATION. PRESCRIBERS SHOULD BE MINDFUL OF THIS DELAY WHEN SELECTING AN ANTIPSYCHOTIC DRUG FOR THE TREATMENT OF SCHIZOPHRENIA [SEE DOSAGE AND ADMINISTRATION AND CLINICAL STUDIES ].
DOSAGE
DOSAGE AND ADMINISTRATION
USUAL DOSE
FANAPT MUST BE TITRATED SLOWLY FROM A LOW STARTING DOSE TO AVOID ORTHOSTATIC HYPOTENSION DUE TO ITS ALPHAADRENERGIC BLOCKING PROPERTIES. THE RECOMMENDED STARTING DOSE FOR FANAPT TABLETS IS 1 MG ORALLY TWICE DAILY. DOSE INCREASES TO REACH THE TARGET RANGE OF 6-12 MG TWICE DAILY (12_24 MG/DAY) MAY BE MADE WITH DAILY DOSAGE ADJUSTMENTS NOT TO EXCEED 2 MG TWICE DAILY (4 MG/DAY). THE MAXIMUM RECOMMENDED DOSE IS 12 MG TWICE DAILY (24 MG/DAY). FANAPT DOSES ABOVE 24 MG/DAY HAVE NOT BEEN SYSTEMATICALLY EVALUATED IN THE CLINICAL TRIALS. EFFICACY WAS DEMONSTRATED WITH FANAPT IN A DOSE RANGE OF 6 TO 12 MG TWICE DAILY. PRESCRIBERS SHOULD BE MINDFUL OF THE FACT THAT PATIENTS NEED TO BE TITRATED TO AN EFFECTIVE DOSE OF FANAPT. THUS, CONTROL OF SYMPTOMS MAY BE DELAYED DURING THE FIRST 1 TO 2 WEEKS OF TREATMENT COMPARED TO SOME OTHER ANTIPSYCHOTIC DRUGS THAT DO NOT REQUIRE SIMILAR TITRATION. PRESCRIBERS SHOULD ALSO BE AWARE THAT SOME ADVERSE EFFECTS ASSOCIATED WITH FANAPT USE ARE DOSE RELATED [SEE ADVERSE REACTIONS ].
FANAPT CAN BE ADMINISTERED WITHOUT REGARD TO MEALS.
DOSAGE IN SPECIAL POPULATIONS
DOSAGE ADJUSTMENT FOR PATIENTS TAKING FANAPT CONCOMITANTLY WITH POTENTIAL CYP2D6 INHIBITORS: FANAPT DOSE SHOULD BE REDUCED BY ONE-HALF WHEN ADMINISTERED CONCOMITANTLY WITH STRONG CYP2D6 INHIBITORS SUCH AS FLUOXETINE OR PAROXETINE. WHEN THE CYP2D6 INHIBITOR IS WITHDRAWN FROM THE COMBINATION THERAPY, FANAPT DOSE SHOULD THEN BE INCREASED TO WHERE IT WAS BEFORE [SEE DRUG INTERACTIONS ].
DOSAGE ADJUSTMENT FOR PATIENTS TAKING FANAPT CONCOMITANTLY WITH POTENTIAL CYP3A4 INHIBITORS: FANAPT DOSE SHOULD BE REDUCED BY ONE-HALF WHEN ADMINISTERED CONCOMITANTLY WITH STRONG CYP3A4 INHIBITORS SUCH AS KETOCONAZOLE OR CLARITHROMYCIN. WHEN THE CYP3A4 INHIBITOR IS WITHDRAWN FROM THE COMBINATION THERAPY, FANAPT DOSE SHOULD BE INCREASED TO WHERE IT WAS BEFORE [SEE DRUG INTERACTIONS ].
DOSAGE ADJUSTMENT FOR PATIENTS TAKING FANAPT WHO ARE POOR METABOLIZERS OF CYP2D6: FANAPT DOSE SHOULD BE REDUCED BY ONE-HALF FOR POOR METABOLIZERS OF CYP2D6 [SEE CLINICAL PHARMACOLOGY ].
HEPATIC IMPAIRMENT: NO DOSE ADJUSTMENT TO FANAPT IS NEEDED IN PATIENTS WITH MILD HEPATIC IMPAIRMENT. PATIENTS WITH MODERATE HEPATIC IMPAIRMENT MAY REQUIRE DOSE REDUCTION, IF CLINICALLY INDICATED. FANAPT IS NOT RECOMMENDED FOR PATIENTS WITH SEVERE HEPATIC IMPAIRMENT [SEE USE IN SPECIFIC POPULATIONS ].
MAINTENANCE TREATMENT
IN A LONGER-TERM STUDY, FANAPT WAS EFFECTIVE IN DELAYING TIME TO RELAPSE IN PATIENTS WITH SCHIZOPHRENIA WHO WERE STABILIZED ON FANAPT UP TO 24 MG/DAY [SEE CLINICAL STUDIES ]. PATIENTS SHOULD BE PERIODICALLY REASSESSED TO DETERMINE THE NEED FOR MAINTENANCE TREATMENT.
REINITIATION OF TREATMENT IN PATIENTS PREVIOUSLY DISCONTINUED
ALTHOUGH THERE ARE NO DATA TO SPECIFICALLY ADDRESS REINITIATION OF TREATMENT, IT IS RECOMMENDED THAT THE INITIATION TITRATION SCHEDULE BE FOLLOWED WHENEVER PATIENTS HAVE HAD AN INTERVAL OFF FANAPT OF MORE THAN 3 DAYS.
HOW SUPPLIED
DOSAGE FORMS AND STRENGTHS
FANAPT TABLETS ARE AVAILABLE IN THE FOLLOWING STRENGTHS: 1 MG, 2 MG, 4 MG, 6 MG, 8 MG, 10 MG, AND 12 MG. THE TABLETS ARE WHITE, ROUND, FLAT, BEVELED-EDGED AND IDENTIFIED WITH A LOGO “ ” DEBOSSED ON ONE SIDE AND TABLET STRENGTH “1”, “2”, “4”, “6”, “8”, “10”, OR “12” DEBOSSED ON THE OTHER SIDE.
STORAGE AND HANDLING
FANAPT TABLETS ARE WHITE, ROUND AND IDENTIFIED WITH A LOGO “ ” DEBOSSED ON ONE SIDE AND TABLET STRENGTH “1”, “2”, “4”, “6”, “8”, “10”, OR “12” DEBOSSED ON THE OTHER SIDE. TABLETS ARE SUPPLIED IN THE FOLLOWING STRENGTHS AND PACKAGE CONFIGURATIONS:
PACKAGE CONFIGURATION TABLET STRENGTH (MG) NDC CODE
BOTTLES OF 60 1 MG 43068-101-02
BOTTLES OF 60 2 MG 43068-102-02
BOTTLES OF 60 4 MG 43068-104-02
BOTTLES OF 60 6 MG 43068-106-02
BOTTLES OF 60 8 MG 43068-108-02
BOTTLES OF 60 10 MG 43068-110-02
BOTTLES OF 60 12 MG 43068-112-02
TITRATION PACK 2X1 MG, 2X2 MG, 2X4 MG, 2X6 MG (TOTAL OF 8 TABLETS) 43068-113-04
STORAGE
STORE FANAPT TABLETS AT CONTROLLED ROOM TEMPERATURE, 25°C (77°F); EXCURSIONS PERMITTED TO 15°TO 30 °C (59° TO 86°F) [SEE USP CONTROLLED ROOM TEMPERATURE]. PROTECT FANAPT TABLETS FROM EXPOSURE TO LIGHT AND MOISTURE.
DISTRIBUTED BY: VANDA PHARMACEUTICALS INC. WASHINGTON, D.C. 20037 USA. REVISED: FEB 2017
SIDE EFFECTS
SIDE EFFECTS
CLINICAL STUDIES EXPERIENCE
BECAUSE CLINICAL TRIALS ARE CONDUCTED UNDER WIDELY VARYING CONDITIONS, ADVERSE REACTION RATES OBSERVED IN THE CLINICAL TRIAL OF A DRUG CANNOT BE DIRECTLY COMPARED TO RATES IN THE CLINICAL TRIALS OF ANOTHER DRUG AND MAY NOT REFLECT THE RATES OBSERVED IN CLINICAL PRACTICE. THE INFORMATION BELOW IS DERIVED FROM A CLINICAL TRIAL DATABASE FOR FANAPT CONSISTING OF 3229 PATIENTS EXPOSED TO FANAPT AT DOSES OF 10 MG/DAY OR GREATER, FOR THE TREATMENT OF SCHIZOPHRENIA . OF THESE, 999 RECEIVED FANAPT FOR AT LEAST 6 MONTHS, WITH 657 EXPOSED TO FANAPT FOR AT LEAST 12 MONTHS. ALL OF THESE PATIENTS WHO RECEIVED FANAPT WERE PARTICIPATING IN MULTIPLE-DOSE CLINICAL TRIALS. THE CONDITIONS AND DURATION OF TREATMENT WITH FANAPT VARIED GREATLY AND INCLUDED (IN OVERLAPPING CATEGORIES), OPEN-LABEL AND DOUBLE-BLIND PHASES OF STUDIES, INPATIENTS AND OUTPATIENTS, FIXED-DOSE AND FLEXIBLE-DOSE STUDIES, AND SHORT-TERM AND LONGER-TERM EXPOSURE.
THE INFORMATION PRESENTED IN THESE SECTIONS WAS DERIVED FROM POOLED DATA FROM 4 PLACEBO-CONTROLLED, 4- OR 6WEEK, FIXED- OR FLEXIBLE-DOSE STUDIES IN PATIENTS WHO RECEIVED FANAPT AT DAILY DOSES WITHIN A RANGE OF 10 TO 24 MG (N=874).
ADVERSE REACTIONS OCCURRING AT AN INCIDENCE OF 2% OR MORE AMONG FANAPT-TREATED PATIENTS AND MORE FREQUENT THAN PLACEBO
TABLE 7 ENUMERATES THE POOLED INCIDENCES OF ADVERSE REACTIONS THAT WERE SPONTANEOUSLY REPORTED IN FOUR PLACEBO-CONTROLLED, 4- OR 6-WEEK, FIXED- OR FLEXIBLE-DOSE STUDIES, LISTING THOSE REACTIONS THAT OCCURRED IN 2% OR MORE OF PATIENTS TREATED WITH FANAPT IN ANY OF THE DOSE GROUPS, AND FOR WHICH THE INCIDENCE IN FANAPT-TREATED PATIENTS IN ANY DOSE GROUP WAS GREATER THAN THE INCIDENCE IN PATIENTS TREATED WITH PLACEBO.
TABLE 7: PERCENTAGE OF ADVERSE REACTIONS IN SHORT-TERM, FIXED- OR FLEXIBLE-DOSE, PLACEBO-CONTROLLED TRIALS IN ADULT PATIENTS*
BODY SYSTEM OR ORGAN CLASS DICTIONARY-DERIVED TERM PLACEBO % (N=587) FANAPT 10-16 MG/DAY % (N=483) FANAPT 20-24 MG/DAY % (N=391)
BODY AS A WHOLE
ARTHRALGIA 233
FATIGUE 3 4 6
MUSCULOSKELETAL STIFFNESS 1 1 3
WEIGHT INCREASED 1 1 9
CARDIAC DISORDERS
TACHYCARDIA 1312
EYE DISORDERS
VISION BLURRED 2 3 1
GASTROINTESTINAL DISORDERS
NAUSEA 8 7 10
DRY MOUTH 1810
DIARRHEA 4 5 7
ABDOMINAL DISCOMFORT 1 1 3
INFECTIONS
NASOPHARYNGITIS 3 4 3
UPPER RESPIRATORY TRACT INFECTION 1 2 3
NERVOUS SYSTEM DISORDERS
DIZZINESS 7 10 20
SOMNOLENCE 5915
EXTRAPYRAMIDAL DISORDER 4 5 4
TREMOR 233
LETHARGY 131
REPRODUCTIVE SYSTEM
EJACULATION FAILURE< 122
RESPIRATORY
NASAL CONGESTION 258
DYSPNEA < 122
SKIN
RASH 2 3 2
VASCULAR DISORDERS
ORTHOSTATIC HYPOTENSION 135
HYPOTENSION < 1 < 1 3
* TABLE INCLUDES ADVERSE REACTIONS THAT WERE REPORTED IN 2% OR MORE OF PATIENTS IN ANY OF THE FANAPT DOSE GROUPS AND WHICH OCCURRED AT GREATER INCIDENCE THAN IN THE PLACEBO GROUP. FIGURES ROUNDED TO THE NEAREST INTEGER.
DOSE-RELATED ADVERSE REACTIONS IN CLINICAL TRIALS
BASED ON THE POOLED DATA FROM 4 PLACEBO-CONTROLLED, 4- OR 6-WEEK, FIXED- OR FLEXIBLE-DOSE STUDIES, ADVERSE REACTIONS THAT OCCURRED WITH A GREATER THAN 2% INCIDENCE IN THE PATIENTS TREATED WITH FANAPT, AND FOR WHICH THE INCIDENCE IN PATIENTS TREATED WITH FANAPT 20-24 MG/DAY WERE TWICE THAN THE INCIDENCE IN PATIENTS TREATED WITH FANAPT 10-16 MG/DAY WERE: ABDOMINAL DISCOMFORT, DIZZINESS, HYPOTENSION, MUSCULOSKELETAL STIFFNESS, TACHYCARDIA, AND WEIGHT INCREASED.
COMMON AND DRUG-RELATED ADVERSE REACTIONS IN CLINICAL TRIALS
BASED ON THE POOLED DATA FROM 4 PLACEBO-CONTROLLED, 4- OR 6-WEEK, FIXED- OR FLEXIBLE-DOSE STUDIES, THE FOLLOWING ADVERSE REACTIONS OCCURRED IN ? 5% INCIDENCE IN THE PATIENTS TREATED WITH FANAPT AND AT LEAST TWICE THE PLACEBO RATE FOR AT LEAST 1 DOSE: DIZZINESS, DRY MOUTH, FATIGUE, NASAL CONGESTION, SOMNOLENCE, TACHYCARDIA, ORTHOSTATIC HYPOTENSION , AND WEIGHT INCREASED. DIZZINESS, TACHYCARDIA, AND WEIGHT INCREASED WERE AT LEAST TWICE AS COMMON ON 20-24 MG/DAY AS ON 10-16 MG/DAY.
EXTRAPYRAMIDAL SYMPTOMS (EPS) IN CLINICAL TRIALS
POOLED DATA FROM THE 4 PLACEBO-CONTROLLED, 4- OR 6-WEEK, FIXED- OR FLEXIBLE-DOSE STUDIES PROVIDED INFORMATION REGARDING EPS . ADVERSE EVENT DATA COLLECTED FROM THOSE TRIALS SHOWED THE FOLLOWING RATES OF EPS-RELATED ADVERSE EVENTS AS SHOWN IN TABLE 8 .
TABLE 8: PERCENTAGE OF EPS COMPARED TO PLACEBO
ADVERSE EVENT TERM PLACEBO (%) (N=587) FANAPT 10-16 MG/DAY (%) (N=483) FANAPT 20-24 MG/DAY (%) (N=391)
ALL EPS EVENTS 11.6 13.5 15.1
AKATHISIA 2.71.72.3
BRADYKINESIA 00.60.5
DYSKINESIA 1.51.71.0
DYSTONIA 0.71.00.8
PARKINSONISM 00.20.3
TREMOR 1.9 2.5 3.1
ADVERSE REACTIONS ASSOCIATED WITH DISCONTINUATION OF TREATMENT IN CLINICAL TRIALS
BASED ON THE POOLED DATA FROM 4 PLACEBO-CONTROLLED, 4- OR 6-WEEK, FIXED- OR FLEXIBLE-DOSE STUDIES, THERE WAS NO DIFFERENCE IN THE INCIDENCE OF DISCONTINUATION DUE TO ADVERSE EVENTS BETWEEN FANAPT-TREATED (5%) AND PLACEBO-TREATED (5%) PATIENTS. THE TYPES OF ADVERSE EVENTS THAT LED TO DISCONTINUATION WERE SIMILAR FOR THE FANAPT- AND PLACEBO-TREATED PATIENTS.
DEMOGRAPHIC DIFFERENCES IN ADVERSE REACTIONS IN CLINICAL TRIALS
AN EXAMINATION OF POPULATION SUBGROUPS IN THE 4 PLACEBO-CONTROLLED, 4- OR 6-WEEK, FIXED- OR FLEXIBLE-DOSE STUDIES DID NOT REVEAL ANY EVIDENCE OF DIFFERENCES IN SAFETY ON THE BASIS OF AGE, GENDER OR RACE.
LABORATORY TEST ABNORMALITIES IN CLINICAL TRIALS
THERE WERE NO DIFFERENCES BETWEEN FANAPT AND PLACEBO IN THE INCIDENCE OF DISCONTINUATION DUE TO CHANGES IN HEMATOLOGY , URINALYSIS , OR SERUM CHEMISTRY.
IN SHORT-TERM PLACEBO-CONTROLLED TRIALS (4- TO 6-WEEKS), THERE WERE 1.0% (13/1342) ILOPERIDONE-TREATED PATIENTS WITH HEMATOCRIT AT LEAST ONE TIME BELOW THE EXTENDED NORMAL RANGE DURING POST-RANDOMIZATION TREATMENT, COMPARED TO 0.3% (2/585) ON PLACEBO. THE EXTENDED NORMAL RANGE FOR LOWERED HEMATOCRIT WAS DEFINED IN EACH OF THESE TRIALS AS THE VALUE 15% BELOW THE NORMAL RANGE FOR THE CENTRALIZED LABORATORY THAT WAS USED IN THE TRIAL.
OTHER REACTIONS DURING THE PRE-MARKETING EVALUATION OF FANAPT
THE FOLLOWING IS A LIST OF MEDDRA TERMS THAT REFLECT ADVERSE REACTIONS IN PATIENTS TREATED WITH FANAPT AT MULTIPLE DOSES ? 4 MG/DAY DURING ANY PHASE OF A TRIAL WITH THE DATABASE OF 3210 FANAPT-TREATED PATIENTS. ALL REPORTED REACTIONS ARE INCLUDED EXCEPT THOSE ALREADY LISTED IN TABLE 7, OR OTHER PARTS OF THE ADVERSE REACTIONS (6), THOSE CONSIDERED IN THE WARNINGS AND PRECAUTIONS (5), THOSE REACTION TERMS WHICH WERE SO GENERAL AS TO BE UNINFORMATIVE, REACTIONS REPORTED IN FEWER THAN 3 PATIENTS AND WHICH WERE NEITHER SERIOUS NOR LIFE-THREATENING, REACTIONS THAT ARE OTHERWISE COMMON AS BACKGROUND REACTIONS, AND REACTIONS CONSIDERED UNLIKELY TO BE DRUG RELATED.
REACTIONS ARE FURTHER CATEGORIZED BY MEDDRA SYSTEM ORGAN CLASS AND LISTED IN ORDER OF DECREASING FREQUENCY ACCORDING TO THE FOLLOWING DEFINITIONS: FREQUENT ADVERSE EVENTS ARE THOSE OCCURRING IN AT LEAST 1/100 PATIENTS (ONLY THOSE NOT LISTED IN TABLE 7 APPEAR IN THIS LISTING); INFREQUENT ADVERSE REACTIONS ARE THOSE OCCURRING IN 1/100 TO 1/1000 PATIENTS; RARE EVENTS ARE THOSE OCCURRING IN FEWER THAN 1/1000 PATIENTS.
BLOOD AND LYMPHATIC DISORDERS: INFREQUENT - ANEMIA , IRON DEFICIENCY ANEMIA ; RARE - LEUKOPENIA
CARDIAC DISORDERS: FREQUENT - PALPITATIONS ; RARE - ARRHYTHMIA , ATRIOVENTRICULAR BLOCK FIRST DEGREE, CARDIAC FAILURE (INCLUDING CONGESTIVE AND ACUTE)
EAR AND LABYRINTH DISORDERS: INFREQUENT - VERTIGO , TINNITUS
ENDOCRINE DISORDERS: INFREQUENT - HYPOTHYROIDISM
EYE DISORDERS: FREQUENT - CONJUNCTIVITIS (INCLUDING ALLERGIC); INFREQUENT - DRY EYE , BLEPHARITIS , EYELID EDEMA, EYE SWELLING, LENTICULAR OPACITIES, CATARACT , HYPEREMIA (INCLUDING CONJUNCTIVAL )
GASTROINTESTINAL DISORDERS: INFREQUENT - GASTRITIS , SALIVARY HYPERSECRETION, FECAL INCONTINENCE , MOUTH ULCERATION ; RARE - APHTHOUS STOMATITIS, DUODENAL ULCER , HIATUS HERNIA , HYPERCHLORHYDRIA, LIP ULCERATION, REFLUX ESOPHAGITIS , STOMATITIS
GENERAL DISORDERS AND ADMINISTRATIVE SITE CONDITIONS: INFREQUENT - EDEMA (GENERAL, PITTING, DUE TO CARDIAC DISEASE), DIFFICULTY IN WALKING, THIRST; RARE - HYPERTHERMIA
HEPATOBILIARY DISORDERS: INFREQUENT - CHOLELITHIASIS
INVESTIGATIONS: FREQUENT: WEIGHT DECREASED; INFREQUENT - HEMOGLOBIN DECREASED, NEUTROPHIL COUNT INCREASED, HEMATOCRIT DECREASED
METABOLISM AND NUTRITION DISORDERS: INFREQUENT - INCREASED APPETITE, DEHYDRATION, HYPOKALEMIA , FLUID RETENTION
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS: FREQUENT - MYALGIA , MUSCLE SPASMS; RARE - TORTICOLLIS
NERVOUS SYSTEM DISORDERS: INFREQUENT - PARESTHESIA , PSYCHOMOTOR HYPERACTIVITY , RESTLESSNESS, AMNESIA , NYSTAGMUS ; RARE - RESTLESS LEGS SYNDROME
PSYCHIATRIC DISORDERS: FREQUENT - RESTLESSNESS, AGGRESSION, DELUSION ; INFREQUENT - HOSTILITY, LIBIDO DECREASED, PARANOIA, ANORGASMIA , CONFUSIONAL STATE, MANIA , CATATONIA, MOOD SWINGS, PANIC ATTACK, OBSESSIVE-COMPULSIVE DISORDER , BULIMIA NERVOSA , DELIRIUM , POLYDIPSIA PSYCHOGENIC , IMPULSE-CONTROL DISORDER, MAJOR DEPRESSION
RENAL AND URINARY DISORDERS: FREQUENT - URINARY INCONTINENCE ; INFREQUENT - DYSURIA , POLLAKIURIA, ENURESIS , NEPHROLITHIASIS ; RARE - URINARY RETENTION, RENAL FAILURE ACUTE
REPRODUCTIVE SYSTEM AND BREAST DISORDERS: FREQUENT - ERECTILE DYSFUNCTION ; INFREQUENT - TESTICULAR PAIN, AMENORRHEA , BREAST PAIN ; RARE - MENSTRUATION IRREGULAR, GYNECOMASTIA , MENORRHAGIA , METRORRHAGIA , POSTMENOPAUSAL HEMORRHAGE , PROSTATITIS .
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS: INFREQUENT - EPISTAXIS , ASTHMA , RHINORRHEA , SINUS CONGESTION, NASAL DRYNESS; RARE - DRY THROAT, SLEEP APNEA SYNDROME, DYSPNEA EXERTIONAL
POSTMARKETING EXPERIENCE
THE FOLLOWING ADVERSE REACTIONS HAVE BEEN IDENTIFIED DURING POST-APPROVAL USE OF FANAPT: RETROGRADE EJACULATION AND HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS ; ANGIOEDEMA ; THROAT TIGHTNESS; OROPHARYNGEAL SWELLING; SWELLING OF THE FACE, LIPS, MOUTH, AND TONGUE; URTICARIA ; RASH; AND PRURITUS ). BECAUSE THESE REACTIONS WERE REPORTED VOLUNTARILY FROM A POPULATION OF UNCERTAIN SIZE, IT IS NOT POSSIBLE TO RELIABLY ESTIMATE THEIR FREQUENCY OR ESTABLISH A CAUSAL RELATIONSHIP TO DRUG EXPOSURE.
DRUG INTERACTIONS
DRUG INTERACTIONS
GIVEN THE PRIMARY CNS EFFECTS OF FANAPT, CAUTION SHOULD BE USED WHEN IT IS TAKEN IN COMBINATION WITH OTHER CENTRALLY ACTING DRUGS AND ALCOHOL. DUE TO ITS - ALPHA1-ADRENERGIC RECEPTOR ANTAGONISM, FANAPT HAS THE POTENTIAL TO ENHANCE THE EFFECT OF CERTAIN ANTIHYPERTENSIVE AGENTS.
POTENTIAL FOR OTHER DRUGS TO AFFECT FANAPT
ILOPERIDONE IS NOT A SUBSTRATE FOR CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, OR CYP2E1 ENZYMES. THIS SUGGESTS THAT AN INTERACTION OF ILOPERIDONE WITH INHIBITORS OR INDUCERS OF THESE ENZYMES, OR OTHER FACTORS, LIKE SMOKING, IS UNLIKELY.
BOTH CYP3A4 AND CYP2D6 ARE RESPONSIBLE FOR ILOPERIDONE METABOLISM . INHIBITORS OF CYP3A4 (E.G., KETOCONAZOLE) OR CYP2D6 (E.G., FLUOXETINE, PAROXETINE) CAN INHIBIT ILOPERIDONE ELIMINATION AND CAUSE INCREASED BLOOD LEVELS.
KETOCONAZOLE: CO-ADMINISTRATION OF KETOCONAZOLE (200 MG TWICE DAILY FOR 4 DAYS), A POTENT INHIBITOR OF CYP3A4, WITH A 3 MG SINGLE DOSE OF ILOPERIDONE TO 19 HEALTHY VOLUNTEERS, AGES 18-45 YEARS, INCREASED THE AREA UNDER THE CURVE (AUC) OF ILOPERIDONE AND ITS METABOLITES P88 AND P95 BY 57%, 55% AND 35%, RESPECTIVELY. ILOPERIDONE DOSES SHOULD BE REDUCED BY ABOUT ONE-HALF WHEN ADMINISTERED WITH KETOCONAZOLE OR OTHER STRONG INHIBITORS OF CYP3A4 (E.G., ITRACONAZOLE). WEAKER INHIBITORS (E.G., ERYTHROMYCIN , GRAPEFRUIT JUICE) HAVE NOT BEEN STUDIED. WHEN THE CYP3A4 INHIBITOR IS WITHDRAWN FROM THE COMBINATION THERAPY, THE ILOPERIDONE DOSE SHOULD BE RETURNED TO THE PREVIOUS LEVEL.
FLUOXETINE: COADMINISTRATION OF FLUOXETINE (20 MG TWICE DAILY FOR 21 DAYS), A POTENT INHIBITOR OF CYP2D6, WITH A SINGLE 3 MG DOSE OF ILOPERIDONE TO 23 HEALTHY VOLUNTEERS, AGES 29-44 YEARS, WHO WERE CLASSIFIED AS CYP2D6 EXTENSIVE METABOLIZERS, INCREASED THE AUC OF ILOPERIDONE AND ITS METABOLITE P88, BY ABOUT 2- TO 3- FOLD, AND DECREASED THE AUC OF ITS METABOLITE P95 BY ONE-HALF. ILOPERIDONE DOSES SHOULD BE REDUCED BY ONE-HALF WHEN ADMINISTERED WITH FLUOXETINE. WHEN FLUOXETINE IS WITHDRAWN FROM THE COMBINATION THERAPY, THE ILOPERIDONE DOSE SHOULD BE RETURNED TO THE PREVIOUS LEVEL. OTHER STRONG INHIBITORS OF CYP2D6 WOULD BE EXPECTED TO HAVE SIMILAR EFFECTS AND WOULD NEED APPROPRIATE DOSE REDUCTIONS. WHEN THE CYP2D6 INHIBITOR IS WITHDRAWN FROM THE COMBINATION THERAPY, ILOPERIDONE DOSE COULD THEN BE INCREASED TO THE PREVIOUS LEVEL.
PAROXETINE: COADMINISTRATION OF PAROXETINE (20 MG/DAY FOR 5-8 DAYS), A POTENT INHIBITOR OF CYP2D6, WITH MULTIPLE DOSES OF ILOPERIDONE (8 OR 12 MG TWICE DAILY) TO PATIENTS WITH SCHIZOPHRENIA AGES 18-65 YEARS RESULTED IN INCREASED MEAN STEADY-STATE PEAK CONCENTRATIONS OF ILOPERIDONE AND ITS METABOLITE P88, BY ABOUT 1.6 FOLD, AND DECREASED MEAN STEADY-STATE PEAK CONCENTRATIONS OF ITS METABOLITE P95 BY ONE-HALF. ILOPERIDONE DOSES SHOULD BE REDUCED BY ONE-HALF WHEN ADMINISTERED WITH PAROXETINE. WHEN PAROXETINE IS WITHDRAWN FROM THE COMBINATION THERAPY, THE ILOPERIDONE DOSE SHOULD BE RETURNED TO THE PREVIOUS LEVEL. OTHER STRONG INHIBITORS OF CYP2D6 WOULD BE EXPECTED TO HAVE SIMILAR EFFECTS AND WOULD NEED APPROPRIATE DOSE REDUCTIONS. WHEN THE CYP2D6 INHIBITOR IS WITHDRAWN FROM THE COMBINATION THERAPY, ILOPERIDONE DOSE COULD THEN BE INCREASED TO PREVIOUS LEVELS.
PAROXETINE AND KETOCONAZOLE: COADMINISTRATION OF PAROXETINE (20 MG ONCE DAILY FOR 10 DAYS), A CYP2D6 INHIBITOR, AND KETOCONAZOLE (200 MG TWICE DAILY) WITH MULTIPLE DOSES OF ILOPERIDONE (8 OR 12 MG TWICE DAILY) TO PATIENTS WITH SCHIZOPHRENIA AGES 18-65 YEARS RESULTED IN A 1.4 FOLD INCREASE IN STEADY-STATE CONCENTRATIONS OF ILOPERIDONE AND ITS METABOLITE P88 AND A 1.4 FOLD DECREASE IN THE P95 IN THE PRESENCE OF PAROXETINE. SO GIVING ILOPERIDONE WITH INHIBITORS OF BOTH OF ITS METABOLIC PATHWAYS DID NOT ADD TO THE EFFECT OF EITHER INHIBITOR GIVEN ALONE. ILOPERIDONE DOSES SHOULD THEREFORE BE REDUCED BY ABOUT ONE-HALF IF ADMINISTERED CONCOMITANTLY WITH BOTH A CYP2D6 AND CYP3A4 INHIBITOR.
POTENTIAL FOR FANAPT TO AFFECT OTHER DRUGS
IN VITRO STUDIES IN HUMAN LIVER MICROSOMES SHOWED THAT ILOPERIDONE DOES NOT SUBSTANTIALLY INHIBIT THE METABOLISM OF DRUGS METABOLIZED BY THE FOLLOWING CYTOCHROME P450 ISOZYMES: CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, OR CYP2E1. FURTHERMORE, IN VITRO STUDIES IN HUMAN LIVER MICROSOMES SHOWED THAT ILOPERIDONE DOES NOT HAVE ENZYME INDUCING PROPERTIES, SPECIFICALLY FOR THE FOLLOWING CYTOCHROME P450 ISOZYMES: CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP3A4 AND CYP3A5.
DEXTROMETHORPHAN: A STUDY IN HEALTHY VOLUNTEERS SHOWED THAT CHANGES IN THE PHARMACOKINETICS OF DEXTROMETHORPHAN (80 MG DOSE) WHEN A 3 MG DOSE OF ILOPERIDONE WAS CO-ADMINISTERED RESULTED IN A 17% INCREASE IN TOTAL EXPOSURE AND A 26% INCREASE IN THE MAXIMUM PLASMA CONCENTRATIONS CMAX OF DEXTROMETHORPHAN. THUS, AN INTERACTION BETWEEN ILOPERIDONE AND OTHER CYP2D6 SUBSTRATES IS UNLIKELY.
FLUOXETINE: A SINGLE 3 MG DOSE OF ILOPERIDONE HAD NO EFFECT ON THE PHARMACOKINETICS OF FLUOXETINE (20 MG TWICE DAILY).
MIDAZOLAM (A SENSITIVE CYP 3A4 SUBSTRATE): A STUDY IN PATIENTS WITH SCHIZOPHRENIA SHOWED A LESS THAN 50% INCREASE IN MIDAZOLAM TOTAL EXPOSURE AT ILOPERIDONE STEADY STATE (14 DAYS OF ORAL DOSING AT UP TO 10 MG ILOPERIDONE TWICE DAILY) AND NO EFFECT ON MIDAZOLAM CMAX. THUS, AN INTERACTION BETWEEN ILOPERIDONE AND OTHER CYP3A4 SUBSTRATES IS UNLIKELY.
DRUGS THAT PROLONG THE QT INTERVAL
FANAPT SHOULD NOT BE USED WITH ANY OTHER DRUGS THAT PROLONG THE QT INTERVAL [SEE WARNINGS AND PRECAUTIONS ].
DRUG ABUSE AND DEPENDENCE
CONTROLLED SUBSTANCE
FANAPT IS NOT A CONTROLLED SUBSTANCE.
ABUSE
FANAPT HAS NOT BEEN SYSTEMATICALLY STUDIED IN ANIMALS OR HUMANS FOR ITS POTENTIAL FOR ABUSE, TOLERANCE, OR PHYSICAL DEPENDENCE. WHILE THE CLINICAL TRIALS DID NOT REVEAL ANY TENDENCY FOR DRUG-SEEKING BEHAVIOR, THESE OBSERVATIONS WERE NOT SYSTEMATIC AND IT IS NOT POSSIBLE TO PREDICT ON THE BASIS OF THIS EXPERIENCE THE EXTENT TO WHICH A CNS ACTIVE DRUG, FANAPT, WILL BE MISUSED, DIVERTED, AND/OR ABUSED ONCE MARKETED. CONSEQUENTLY, PATIENTS SHOULD BE EVALUATED CAREFULLY FOR A HISTORY OF DRUG ABUSE, AND SUCH PATIENTS SHOULD BE OBSERVED CLOSELY FOR SIGNS OF FANAPT MISUSE OR ABUSE (E.G. DEVELOPMENT OF TOLERANCE, INCREASES IN DOSE, DRUG-SEEKING BEHAVIOR).
WARNINGS & PRECAUTIONS
WARNINGS
INCLUDED AS PART OF THE PRECAUTIONS SECTION.
PRECAUTIONS
INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS
ANTIPSYCHOTIC DRUGS INCREASE THE ALL-CAUSE RISK OF DEATH IN ELDERLY PATIENTS WITH DEMENTIA -RELATED PSYCHOSIS . ANALYSES OF 17 DEMENTIA-RELATED PSYCHOSIS PLACEBO-CONTROLLED TRIALS (MODAL DURATION OF 10 WEEKS AND LARGELY IN PATIENTS TAKING ATYPICAL ANTIPSYCHOTIC DRUGS) REVEALED A RISK OF DEATH IN THE DRUG-TREATED PATIENTS OF BETWEEN 1.6 TO 1.7 TIMES THAT IN PLACEBO-TREATED PATIENTS. OVER THE COURSE OF A TYPICAL 10-WEEK CONTROLLED TRIAL, THE RATE OF DEATH IN DRUG-TREATED PATIENTS WAS ABOUT 4.5%, COMPARED TO A RATE OF ABOUT 2.6% IN PLACEBO-TREATED PATIENTS.
ALTHOUGH THE CAUSES OF DEATH WERE VARIED, MOST OF THE DEATHS APPEARED TO BE EITHER CARDIOVASCULAR (E.G., HEART FAILURE , SUDDEN DEATH) OR INFECTIOUS (E.G., PNEUMONIA ) IN NATURE. FANAPT IS NOT APPROVED FOR THE TREATMENT OF PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS [SEE BOXED WARNING , CEREBROVASCULAR ADVERSE REACTIONS, INCLUDING STROKE, IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS].
CEREBROVASCULAR ADVERSE REACTIONS, INCLUDING STROKE, IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS
IN PLACEBO-CONTROLLED TRIALS IN ELDERLY SUBJECTS WITH DEMENTIA, PATIENTS RANDOMIZED TO RISPERIDONE, ARIPIPRAZOLE, AND OLANZAPINE HAD A HIGHER INCIDENCE OF STROKE AND TRANSIENT ISCHEMIC ATTACK , INCLUDING FATAL STROKE. FANAPT IS NOT APPROVED FOR THE TREATMENT OF PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS [SEE BOXED WARNING , INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS].
QT PROLONGATION
IN AN OPEN-LABEL QTC STUDY IN PATIENTS WITH SCHIZOPHRENIA OR SCHIZOAFFECTIVE DISORDER (N=160), FANAPT WAS ASSOCIATED WITH QTC PROLONGATION OF 9 MSEC AT AN ILOPERIDONE DOSE OF 12 MG TWICE DAILY. THE EFFECT OF FANAPT ON THE QT INTERVAL WAS AUGMENTED BY THE PRESENCE OF CYP450 2D6 OR 3A4 METABOLIC INHIBITION (PAROXETINE 20 MG ONCE DAILY AND KETOCONAZOLE 200 MG TWICE DAILY, RESPECTIVELY). UNDER CONDITIONS OF METABOLIC INHIBITION FOR BOTH 2D6 AND 3A4, FANAPT 12 MG TWICE DAILY WAS ASSOCIATED WITH A MEAN QTCF INCREASE FROM BASELINE OF ABOUT 19 MSEC.
NO CASES OF TORSADE DE POINTES OR OTHER SEVERE CARDIAC ARRHYTHMIAS WERE OBSERVED DURING THE PRE-MARKETING CLINICAL PROGRAM.
THE USE OF FANAPT SHOULD BE AVOIDED IN COMBINATION WITH OTHER DRUGS THAT ARE KNOWN TO PROLONG QTC INCLUDING CLASS 1A (E.G., QUINIDINE, PROCAINAMIDE) OR CLASS III (E.G., AMIODARONE, SOTALOL) ANTIARRHYTHMIC MEDICATIONS, ANTIPSYCHOTIC MEDICATIONS (E.G., CHLORPROMAZINE, THIORIDAZINE), ANTIBIOTICS (E.G., GATIFLOXACIN, MOXIFLOXACIN), OR ANY OTHER CLASS OF MEDICATIONS KNOWN TO PROLONG THE QTC INTERVAL (E.G., PENTAMIDINE, LEVOMETHADYL ACETATE, METHADONE ). FANAPT SHOULD ALSO BE AVOIDED IN PATIENTS WITH A KNOWN GENETIC SUSCEPTIBILITY TO CONGENITAL LONG QT SYNDROME AND IN PATIENTS WITH A HISTORY OF CARDIAC ARRHYTHMIAS.
CERTAIN CIRCUMSTANCES MAY INCREASE THE RISK OF TORSADE DE POINTES AND/OR SUDDEN DEATH IN ASSOCIATION WITH THE USE OF DRUGS THAT PROLONG THE QTC INTERVAL, INCLUDING (1) BRADYCARDIA ; (2) HYPOKALEMIA OR HYPOMAGNESEMIA ; (3) CONCOMITANT USE OF OTHER DRUGS THAT PROLONG THE QTC INTERVAL; AND (4) PRESENCE OF CONGENITAL PROLONGATION OF THE QT INTERVAL; (5) RECENT ACUTE MYOCARDIAL INFARCTION ; AND/OR (6) UNCOMPENSATED HEART FAILURE.
CAUTION IS WARRANTED WHEN PRESCRIBING FANAPT WITH DRUGS THAT INHIBIT FANAPT METABOLISM [SEE DRUG INTERACTIONS ], AND IN PATIENTS WITH REDUCED ACTIVITY OF CYP2D6 [SEE CLINICAL PHARMACOLOGY ].
IS RECOMMENDED THAT PATIENTS BEING CONSIDERED FOR FANAPT TREATMENT WHO ARE AT RISK FOR SIGNIFICANT ELECTROLYTE DISTURBANCES HAVE BASELINE SERUM POTASSIUM AND MAGNESIUM MEASUREMENTS WITH PERIODIC MONITORING. HYPOKALEMIA (AND/OR HYPOMAGNESEMIA) MAY INCREASE THE RISK OF QT PROLONGATION AND ARRHYTHMIA . FANAPT SHOULD BE AVOIDED IN PATIENTS WITH HISTORIES OF SIGNIFICANT CARDIOVASCULAR ILLNESS, E.G., QT PROLONGATION, RECENT ACUTE MYOCARDIAL INFARCTION , UNCOMPENSATED HEART FAILURE, OR CARDIAC ARRHYTHMIA. FANAPT SHOULD BE DISCONTINUED IN PATIENTS WHO ARE FOUND TO HAVE PERSISTENT QTC MEASUREMENTS > 500 MSEC.
IF PATIENTS TAKING FANAPT EXPERIENCE SYMPTOMS THAT COULD INDICATE THE OCCURRENCE OF CARDIAC ARRHYTHMIAS, E.G., DIZZINESS, PALPITATIONS , OR SYNCOPE , THE PRESCRIBER SHOULD INITIATE FURTHER EVALUATION, INCLUDING CARDIAC MONITORING.
NEUROLEPTIC MALIGNANT SYNDROME (NMS)
A POTENTIALLY FATAL SYMPTOM COMPLEX SOMETIMES REFERRED TO AS NEUROLEPTIC MALIGNANT SYNDROME (NMS) HAS BEEN REPORTED IN ASSOCIATION WITH ADMINISTRATION OF ANTIPSYCHOTIC DRUGS, INCLUDING FANAPT. CLINICAL MANIFESTATIONS INCLUDE HYPERPYREXIA, MUSCLE RIGIDITY, ALTERED MENTAL STATUS (INCLUDING CATATONIC SIGNS) AND EVIDENCE OF AUTONOMIC INSTABILITY (IRREGULAR PULSE OR BLOOD PRESSURE, TACHYCARDIA , DIAPHORESIS, AND CARDIAC DYSRHYTHMIA). ADDITIONAL SIGNS MAY INCLUDE ELEVATED CREATINE PHOSPHOKINASE, MYOGLOBINURIA (RHABDOMYOLYSIS ), AND ACUTE RENAL FAILURE .
THE DIAGNOSTIC EVALUATION OF PATIENTS WITH THIS SYNDROME IS COMPLICATED. IN ARRIVING AT A DIAGNOSIS, IT IS IMPORTANT TO IDENTIFY CASES IN WHICH THE CLINICAL PRESENTATION INCLUDES BOTH SERIOUS MEDICAL ILLNESS (E.G., PNEUMONIA, SYSTEMIC INFECTION, ETC.) AND UNTREATED OR INADEQUATELY TREATED EXTRAPYRAMIDAL SIGNS AND SYMPTOMS (EPS ). OTHER IMPORTANT CONSIDERATIONS IN THE DIFFERENTIAL DIAGNOSIS INCLUDE CENTRAL ANTICHOLINERGIC TOXICITY, HEAT STROKE , DRUG FEVER, AND PRIMARY CENTRAL NERVOUS SYSTEM (CNS) PATHOLOGY .
THE MANAGEMENT OF THIS SYNDROME SHOULD INCLUDE: (1) IMMEDIATE DISCONTINUATION OF THE ANTIPSYCHOTIC DRUGS AND OTHER DRUGS NOT ESSENTIAL TO CONCURRENT THERAPY, (2) INTENSIVE SYMPTOMATIC TREATMENT AND MEDICAL MONITORING, AND (3) TREATMENT OF ANY CONCOMITANT SERIOUS MEDICAL PROBLEMS FOR WHICH SPECIFIC TREATMENTS ARE AVAILABLE. THERE IS NO GENERAL AGREEMENT ABOUT SPECIFIC PHARMACOLOGICAL TREATMENT REGIMENS FOR NMS.
IF A PATIENT REQUIRES ANTIPSYCHOTIC DRUG TREATMENT AFTER RECOVERY FROM NMS, THE POTENTIAL REINTRODUCTION OF DRUG THERAPY SHOULD BE CAREFULLY CONSIDERED. THE PATIENT SHOULD BE CAREFULLY MONITORED, SINCE RECURRENCES OF NMS HAVE BEEN REPORTED.
TARDIVE DYSKINESIA
TARDIVE DYSKINESIA IS A SYNDROME CONSISTING OF POTENTIALLY IRREVERSIBLE, INVOLUNTARY , DYSKINETIC MOVEMENTS, WHICH MAY DEVELOP IN PATIENTS TREATED WITH ANTIPSYCHOTIC DRUGS. ALTHOUGH THE PREVALENCE OF THE SYNDROME APPEARS TO BE HIGHEST AMONG THE ELDERLY, ESPECIALLY ELDERLY WOMEN, IT IS IMPOSSIBLE TO RELY ON PREVALENCE ESTIMATES TO PREDICT, AT THE INCEPTION OF ANTIPSYCHOTIC TREATMENT, WHICH PATIENTS ARE LIKELY TO DEVELOP THE SYNDROME. WHETHER ANTIPSYCHOTIC DRUG PRODUCTS DIFFER IN THEIR POTENTIAL TO CAUSE TARDIVE DYSKINESIA IS UNKNOWN.
THE RISK OF DEVELOPING TARDIVE DYSKINESIA AND THE LIKELIHOOD THAT IT WILL BECOME IRREVERSIBLE ARE BELIEVED TO INCREASE AS THE DURATION OF TREATMENT AND THE TOTAL CUMULATIVE DOSE OF ANTIPSYCHOTIC ADMINISTERED INCREASES. HOWEVER, THE SYNDROME CAN DEVELOP, ALTHOUGH MUCH LESS COMMONLY, AFTER RELATIVELY BRIEF TREATMENT PERIODS AT LOW DOSES.
THERE IS NO KNOWN TREATMENT FOR ESTABLISHED CASES OF TARDIVE DYSKINESIA, ALTHOUGH THE SYNDROME MAY REMIT, PARTIALLY OR COMPLETELY, IF ANTIPSYCHOTIC TREATMENT IS WITHDRAWN. ANTIPSYCHOTIC TREATMENT ITSELF, HOWEVER, MAY SUPPRESS (OR PARTIALLY SUPPRESS) THE SIGNS AND SYMPTOMS OF THE SYNDROME AND THEREBY MAY POSSIBLY MASK THE UNDERLYING PROCESS. THE EFFECT THAT SYMPTOMATIC SUPPRESSION HAS UPON THE LONG-TERM COURSE OF THE SYNDROME IS UNKNOWN.
GIVEN THESE CONSIDERATIONS, FANAPT SHOULD BE PRESCRIBED IN A MANNER THAT IS MOST LIKELY TO MINIMIZE THE OCCURRENCE OF TARDIVE DYSKINESIA. CHRONIC ANTIPSYCHOTIC TREATMENT SHOULD GENERALLY BE RESERVED FOR PATIENTS WHO SUFFER FROM A CHRONIC ILLNESS THAT (1) IS KNOWN TO RESPOND TO ANTIPSYCHOTIC DRUGS, AND (2) FOR WHOM ALTERNATIVE, EQUALLY EFFECTIVE, BUT POTENTIALLY LESS HARMFUL TREATMENTS ARE NOT AVAILABLE OR APPROPRIATE. IN PATIENTS WHO DO REQUIRE CHRONIC TREATMENT, THE SMALLEST DOSE AND THE SHORTEST DURATION OF TREATMENT PRODUCING A SATISFACTORY CLINICAL RESPONSE SHOULD BE SOUGHT. THE NEED FOR CONTINUED TREATMENT SHOULD BE REASSESSED PERIODICALLY.
IF SIGNS AND SYMPTOMS OF TARDIVE DYSKINESIA APPEAR IN A PATIENT ON FANAPT, DRUG DISCONTINUATION SHOULD BE CONSIDERED. HOWEVER, SOME PATIENTS MAY REQUIRE TREATMENT WITH FANAPT DESPITE THE PRESENCE OF THE SYNDROME.
METABOLIC CHANGES
ATYPICAL ANTIPSYCHOTIC DRUGS HAVE BEEN ASSOCIATED WITH METABOLIC CHANGES THAT MAY INCREASE CARDIOVASCULAR/CEREBROVASCULAR RISK. THESE METABOLIC CHANGES INCLUDE HYPERGLYCEMIA , DYSLIPIDEMIA , AND BODY WEIGHT GAIN. WHILE ALL ATYPICAL ANTIPSYCHOTIC DRUGS HAVE BEEN SHOWN TO PRODUCE SOME METABOLIC CHANGES, EACH DRUG IN THE CLASS HAS ITS OWN SPECIFIC RISK PROFILE.