PDR*
`56
`ZT2
`
`EDITION
`
`www.PDR.net
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`YSIOANS'
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`Mylan v. Janssen (IPR2020-00440) Ex. 1047 p. 001
`
`

`

`EDITION
`
`HATTEN MUCHIN RCSENMAN LLP
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`RECEIVED BY LIBRARY
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`MAY 2 3 2018
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`PDIZ
`56
`2002
`HYSj CANS'
`ttSK
`It kt■PENCE
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`Mylan v. Janssen (IPR2020-00440) Ex. 1047 p. 002
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`

`k
`
`liver function and/or jaundice have
`
`Chronic or Resistant Patients
`
`■mm•& ’-.at fine vermicular movement of the
`■th--.... mbt . sign of tardive dyskinesia and if the
`k that time the full syndrome may
`BiKe.-~ Tirdive dystonia, not associated with
`Kmrs- 'as also been reported. Tardive dysto-
`gji*?-- delayed onset of choreic or dystonic
`- ^rsistent, and has the potential of be-
`
`■■» — '-^mnia, restlessness, anxiety, eupho-
`depression, lethargy, headache,
`■B mal seizures, exacerbation of psy-
`■B - .ding hallucinations, and catatonic-
`B * which may be responsive to drug
`1’ment with anticholinergic drugs.
`M|hM* Neuroleptic malignant syndrome
`- and heat stroke have been reported
`& WARNINGS for further information
`
`Tachycardia, hypotension, hyper-
`■fcAsn^es including prolongation of the Q-T
`HBE : sttern changes compatible with the
`j|fe«ert^-~A*ion of torsade de pointes.
`■Bnb» Reports have appeared citing the oc-
`■k ■ ; -?ually transient leukopenia and leu-
`Bttau wcreaseB in red blood cell counts, ane-
`■mK* . ward lymphomonocvtosis. Agranulocy-
`-eported to have occurred with the use
`- cnly in association with other medi-
`
`■'ct ©ns: Maculopapular and acneiform
`k - • ■--Lited cases of photosensitivity and
`
`MMMrs Lactation, breast engorgement, mas-
`■qk ~r^ularities, gynecomastia, impotence,
`B. x-wrg’ycemia, hypoglycemia and hypona-
`
`h* Anorexia, constipation, dianhea,
`B ; >jpsia, nausea and vomiting.
`■RKSesAs. Dry mouth, blurred vision, urinary
`BiBNri s and priapism.
`■Mss Liryngospasm, bronchospasm and in-
`fe vf - --.nrion.
`■■ tracts, retinopathy and visual dis-
`
`* I ■ d unexpected death have been
`-.n with the administration of HAL-
`k evidence makes it impossible to de-
`3n*.- * hat role, if any, HALDOL played in
`Ste -? ported cases. The possibility that HAL-
`ItaKx atnnot, of course, be excluded, but it is to
`at’ - »udden and unexpected death may oc-
`|*m tats when they go untreated or when
`fes ■» ’ “ other antipsychotic drugs.
`*,
`Hyperammonemia has been re-
`•*.v aid child with dtrullinemia, an inher-
`«Ejuonia excretion, following treatment
`
`»-“--xptans of overdosage would be an exag-
`M*' ■..’.rmacologic effects and adverse rcac-
`— ment of which would be: 1) severe ex-
`■s&~jous. 2) hypotension, or 3) sedation. The
`matose with respiratory depression
`r wfcxh could be severe enough to produce a
`fiK- The extrapyramidal reaction would be
`tawriiar weakness or rigidity and a general-
`B5£ ’.'-“mor as demonstrated by the akinetic or
`> t**?•a ctively. With accidental overdosage, hy-
`ter- than hypotension occurred in a two-year
`« :f ECG changes associated with torsades
`considered. (For further information
`!■ de pointes, please refer to ADVERSE
`
`1 sr mduction of emesis should be carried out
`i<*ed bv dministration of activated char-
`Bific antidote, treatment is primar-
`irway must be established by use
`ty or endotracheal tube or, in pro-
`racheostomy. Respiratory depres-
`by artificial respiration and me-
`otension and circulatory collapse
`C ADMINISTRATION
`ise of intravenous fluids, plasma,
`Mrrable variation from patient to patient in
`and vasopressor agents such as
`£ medication required for treatment. As with
`ne and norepinephrine. Epineph-
`»r. se used. In case of severe extrapyramidal
`K^iririnson medication should be adminis-
`k* ■ital signs should be monitored especially
`►T rmlongation or dysrhythmias and monitor-
`et mue until the ECG is normal. Severe ar-
`jMad be treated with appropriate anti-arrhyth-
`
`tic control.
`lb determine the initial dosage, consideration should be
`given to the patient’s age, severity of illness, previous re­
`sponse to other antipsychotic drugs, and any concomitant
`medication or disease state. Children, debilitated or geriat­
`ric patients, as well as those with a history of adverse reac­
`tions to antipsychotic drugs, may require less HALDOL hal­
`operidol. The optimal response in such patients is usually
`obtained with more gradual dosage adjustments and at
`lower dosage levels, as recommended below.
`Clinical experience suggests the following recommenda­
`tions:
`Oral Administration
`Initial Dosage Range
`Adults
`
`Moderate Symptomatology
`
`Severe Symptomatology
`
`0.5 mg to 2.0 mg
`b.i.d. or t.i.d.
`
`3.0 mg to 5.0 mg
`b.i.d. or tid.
`
`Tb achieve prompt control, higher doses may be required in
`some cases.
`
`Geriatric or Debilitated Patients
`
`0.5 mg to 2.0 mg
`b.i.d. or tid.
`
`3.0 mg to 5.0 mg
`bid. or tid.
`
`Patients who remain severly disturbed or inadequately
`controlled may require dosage adjustment. Daily
`dosages up to 100 mg may be necessary in some
`cases to achieve an optimal response. Infrequently,
`HALDOL has been used in doses above 100 mg for
`severely resistant patients; however, the limited
`clinical usage has not demonstrated the safety of
`prolonged administration of such doses.
`
`Children
`The following recommendations apply to children between
`the ages of 3 and 12 years (weight range 15 to 40 kg). HAL­
`DOL is not intended for children under 3 years old. Therapy
`should begin at the lowest dose possible (0.5 mg per day}. If
`required, the dose should be increased by an increment of
`0.5 mg at 5 to 7 day intervals until the desired therapeutic
`effect is obtained. (See chart below).
`The total dose may be divided, to be given b.i.d. or ti.d.
`
`Psychotic Disorders
`
`Non-Psychotic Behavior
`Disorders and Iburette’s
`Disorder
`
`0.05 mg/kg/day to
`0.15 mg/kg/day
`
`0.05 mg/kg/day to
`0.075 mg/kg/day
`
`Severely disturbed psychotic children may require
`higher doses. In severely disturbed, non-psychotic
`children or in hyperactive children with accompanying
`conduct disorders, who have failed to respond to
`psychotherapy or medications other than anti­
`psychotics, it should be noted that since these
`behaviors may be short-lived, short-term admin­
`istration of HALDOL may suffice. There is no evidence
`establishing a maximum effective dosage. There is
`little evidence that behavior improvement is further
`enhanced in dosages beyond 6 mg per day.
`
`Maintenance Dosage
`Upon achieving a satisfactory therapeutic response, dosage
`should then be gradually reduced to the lowest effective
`maintenance level.
`Intramuscular Administration
`; Adults
`; Parenteral medication, administered intramuscularly in
`■ doses of 2 to 5 mg. is utilized for prompt control of the
`I acutely agitated patient with moderately severe to very se­
`vere symptoms. Depending on the response of the patient,
`subsequent doses may be given, administered as often as
`every hour, although 4 to 8 hour intervals may be satisfac-
`! tory.
`Controlled trials to establish the safety and effectiveness of
`intramuscular administration in children have not been
`conducted.
`Parenteral drug products should be inspected visually for
`particulate matter and discoloration prior to administra­
`tion, whenever solution and container permit.
`Switchover Procedure
`An oral form should supplant the injectable as soon as prac­
`ticable. In the absence of bioavailability studies establishing
`bioequivalence between these two dosage forms the follow­
`ing guidelines for dosage are suggested. For an initial ap­
`proximation of the total daily dose required , the parenteral
`dose administered in the preceding 24 hours may be used.
`Since this dose is only an initial estimate, it is recom-
`
`U* QlliVVAiWIV,. Ill LAUO v»
`WAAK.
`I
`I adjustments, either upward or downward, can be quickly
`: accomplished. Depending on the patient’s clinical status,
`the first oral dose should be given within 12-24 hours fol­
`lowing the last parenteral dose.
`HOW SUPPLIED
`HALDOL® brand of haloperidol Tablets with a cut-out ‘‘H”
`design, Scored, Imprinted “McNeil” and “HALDOL" with
`the mg strength of the tablet:
`
`V2 mg. white
`1 mg, yellow
`2 mg, pink
`5 mg. green
`10 mg. aqua
`20 mg, salmon
`
`NDC 0045-0240-60
`NDC 0045-0241-60
`NDC. 0045-0242-60
`NDC 0045-0245-60
`NDC 0045-0246-60
`NDC 0045-0248-60
`
`Bottles
`Containing
`100
`X
`X
`X
`X
`X
`X
`
`HALDOL® brand of haloperidol Concentrate 2 mg per mL
`(as the lactate) Colorless, Odorless, and Tasteless Solu­
`tion—NDC 0045-0250-15, bottles of 15 mL and NDC 0045-
`0250-04, bottles of 120 mL.
`HALDOL® brand of haloperidol Injection (For Immediate
`Release) 5 mg per mL (as the lactate)—NDC 0045-0255-01,
`units of 10 x 1 mL ampuls and NDC 0045-0255-49, 10 mL
`multiple-dose vial.
`Store HALDOL® haloperidol Tablets at controlled room
`temperature (15°-30aC, 59O-86°F). Protect from light.
`Store HALDOL® haloperidol Concentrate at controlled
`room temperature (15o-30°C, 59“-86°F). Protect from light.
`Do not freeze.
`Store HALDOL® haloperidol Injection at controlled room
`temperature (15o-30°C, SS’-Sfl’F). Protect from light. Do not
`freeze.
`Dispense the HALDOL haloperidol tablets and concentrate
`in a tight, light-resistent container as defined in the official
`compendium.
`
`OMP DIVISION
`ORTHO-McNEIL PHARMACEUTICAL, INC.
`Raritan, NJ 08869
`Revised August 2000
`643-94-066-5
`Shown in Product Identification Guide, page 329
`
`HALDOL® Decanoate 50 (haloperidol) R
`HALDOL® Decanoate 100 (haloperidol)
`[hal 'dawl dek "ah-nG '6t ]
`For IM Injection Only
`
`DESCRIPTION
`Haloperidol decanoate is the decanoate ester of the buty­
`rophenone, HALDOL (haloperidol). It has a markedly ex­
`tended duration of effect. It is available in sesame oil in
`sterile form for intramuscular (IM) injection. The structural
`formula of haloperidol decanoate, 4-(4-chlorophenyl)-l-[4-
`(4-fluorophenyl)-4-oxobutyl]-4 piperidinyl decanoate, is:
`
`Haloperidol decanoate is almost insoluble in water (0.01
`mg/mL), but is soluble in most organic solvents.
`Each mL of HALDOL Decanoate 50 for IM injection con­
`tains 50 mg haloperidol (present as haloperidol decanoate
`70.52 mg) in a sesame oil vehicle, with 1.2% (w/v) benzyl
`alcohol as a preservative.
`I Each mL of HALDOL Decanoate 100 for IM injection con­
`tains 100 mg haloperidol (present as haloperidol decanoate
`141.04 mg) in a sesame oil vehicle, with 1.2% (wAr) benzyl
`alcohol as a preservative.
`CLINICAL PHARMACOLOGY
`HALDOL Decanoate 50 and HALDOL Decanoate 100 are
`the long-acting forms of HALDOL (haloperidol). The basic
`effects of haloperidol decanoate are no different from those
`of HALDOL with the exception of duration of action. Halo­
`peridol blocks the effects of dopamine and increases its
`turnover rate; however, the precise mechanism of action is
`unknown.
`Administration of haloperidol decanoate in sesame oil re­
`sults in slow and sustained release of haloperidol. The
`plasma concentrations of haloperidol gradually rise, reach­
`ing a peak at about 6 days after the injection, and falling
`thereafter, with an apparent half-life of about 3 weeks.
`Steady state plasma concentrations are achieved after the
`third or fourth dose. The relationship between dose of hal-
`
`Continued on next page
`
`Consult 2002 PDR supplements and future editions for revisions
`
`Mylan v. Janssen (IPR2020-00440) Ex. 1047 p. 003
`
`

`

`2536/ORTHO-MCNEIL
`
`Haldol Decanoate—Cont.
`
`operidol decanoate and plasma haloperidol concentration is
`roughly linear for doses below 450 mg. It should be noted,
`however, that the pharmacokinetics of haloperidol de­
`canoate following intramuscular injections can be quite
`variable between subjects.
`INDICATIONS AND USAGE
`HALDOL Decanoate 50 and HALDOL Decanoate 100 are
`long-acting parenteral antipsychotic drugs intended for use
`in the management of patients requiring prolonged paren­
`teral antipsychotic therapy (e.g., patients with chronic
`schizophrenia).
`CONTRAINDICATIONS
`Since the pharmacologic and clinical actions of HALDOL
`Decanoate 50 and HALDOL Decanoate 100 are attributed
`to HALDOL (haloperidol) as the active medication, Contra­
`indications, Warnings, and additional information are those
`of HALDOL, modified only to reflect the prolonged action.
`HALDOL is contraindicated in severe toxic central nervous
`system depression or comatose states from any cause and in
`individuals who are hypersensitive to this drug or have Par­
`kinson’s disease.
`WARNINGS
`Tardive Dyskinesia
`A syndrome consisting of potentially irreversible, involun­
`tary, dyskinetic movements may develop in patients treated
`with antipsychotic drugs. Although the prevalence of the
`syndrome appears to be highest among the elderly, espe­
`cially elderly women, it is impossible to rely upon preva­
`lence estimates to predict, at the inception of antipsychotic
`treatment, which patients are likely to develop the syn­
`drome. Whether antipsychotic drug products differ in then-
`potential to cause tardive dyskinesia is unknown.
`Both the risk of developing tardive dyskinesia and the like­
`lihood that it will become irreversible are believed to in­
`crease as the duration of treatment and the total cumula­
`tive dose of antipsychotic drugs administered to the patient
`increase. However, the syndrome can develop, although
`much less commonly, after relatively brief treatment peri­
`ods at low doses.
`There is no known treatment for established cases of tar­
`dive dyskinesia, although the syndrome may remit, par­
`tially or completely, if antipsychotic treatment is with­
`drawn. Antipsychotic treatment, itself, however, may sup­
`press (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, antipsychotic drugs 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 re­
`assessed periodically.
`If signs and symptoms of tardive dyskinesia appear in a pa­
`tient on antipsychotics, drug discontinuation should be con­
`sidered. However, some patients may require treatment de­
`spite the presence of the syndrome. (For further information
`about the description of tardive dyskinesia and its clinical
`detection, please refer to ADVERSE REACTIONS.)
`Neuroleptic Malignant Syndrome (NMS)
`A potentially fatal symptom complex sometimes referred to
`as Neuroleptic Malignant Syndrome (NMS) has been re­
`ported in association with antipsychotic drugs. Clinical
`manifestations of NMS are hyperpyrexia, muscle rigidity,
`altered mental status (including catatonic signs) and evi­
`dence of autonomic instability (irregular pulse or blood
`pressure, tachycardia, diaphoresis, and cardiac dysrhyth­
`mias). Additional signs may include elevated creatine phos­
`phokinase, 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 where 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 ner­
`vous system (CNS) pathology.
`The management of NMS should include 1) immediate dis­
`continuation of antipsychotic drugs and other drugs not es­
`sential 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 un­
`complicated NMS.
`If a patient requires antipsychotic drug treatment after re­
`covery from NMS. the potential rointroduction of drug ther-
`
`Hyperpyrexia and heat stroke, not associated with the
`above svmptom complex, have also been reported with
`HALDOL.
`General
`A number of cases of bronchopneumonia, some fatal, have
`followed the use of antipsychotic drugs, including HALDOL
`(haloperidol). It has been postulated that lethargy and de­
`creased sensation of thirst due to central inhibition may
`lead to dehydration, hemoconcentration and reduced pulmo­
`nary ventilation. Therefore, if the above signs and symp­
`toms appear, es])ecially in the elderly, the physician should
`institute remedial therapy promptly.
`Although not reported with HALDOL, decreased serum cho­
`lesterol and/or cutaneous and ocular changes have been re­
`ported in patients receiving chemically-related drugs.
`PRECAUTIONS
`HALDOL Decanoate 50 and HALDOL Decanoate 100
`should be administered cautiously to patients:
`— with severe cardiovascular disorders, because of the pos­
`sibility of transient hypotension and/or precipitation of
`anginal pain. Should hypotension occur and a vasopres­
`sor be required, epinephrine should not be used since
`HALDOL (haloperidol) may block its vasopressor activ­
`ity, and paradoxical further lowering of the blood pres­
`sure may occur. Instead, metaraminol, phenylephrine or
`norepinephrine should be used.
`— receiving anticonvulsant medications, with a history of
`seizures, or with EEG abnormalities, because HALDOL
`may lower the convulsive threshold. If indicated, ade­
`quate anticonvulsant therapy should be concomitantly
`maintained.
`— with known allergies, or with a history of allergic reac­
`tions to drugs.
`— receiving anticoagulants, since an isolated instance of in­
`terference occurred with the effects of one anticoagulant
`(phenindione).
`If concomitant antiparkinson medication is required, it may
`have to be continued after HALDOL Decanoate 50 or
`HALDOL Decanoate 100 is discontinued because of the pro­
`longed action of haloperidol decanoate. If both drugs are dis­
`continued simultaneously, extrapyramidal symptoms may
`occur. The physician should keep in mind the possible in­
`crease in intraocular pressure when anticholinergic drugs,
`including antiparkinson agents, are administered concomi­
`tantly with haloperidol decanoate.
`In patients with thyrotoxicosis who are also receiving anti­
`psychotic medication, including haloperidol decanoate, se­
`vere neurotoxicity (rigidity, inability to walk or talk) may
`occur.
`When HALDOL is used to control mania in bipolar disor­
`ders, there may be a rapid mood swing to depression.
`Information for Patients
`Haloperidol decanoate may impair the mental and/or phys­
`ical abilities required for the performance of hazardous
`tasks such as operating machinery or driving a motor vehi­
`cle. The ambulatory patient should be warned accordingly.
`The use of alcohol with this drug should be avoided due to
`possible additive effects and hypotension.
`Drug Interactions
`An encephalopathic syndrome (characterized by weakness,
`lethargy, fever, tremulousness and confusion, extrapyrami­
`dal symptoms, leukocytosis, elevated serum enzymes, BUN,
`and FBS) followed by irreversible brain damage has oc­
`curred in a few patients treated with lithium plus
`HALDOL. A causal relationship between these events and
`the concomitant administration of lithium and HALDOL
`has not been established; however, patients receiving such
`combined therapy should be monitored closely for early ev­
`idence of neurological toxicity and treatment discontinued
`promptly if such signs appear.
`As with other antipsychotic agents, it should be noted that
`HALDOL may be capable of potentiating CNS depressants
`such as anesthetics, opiates, and alcohol.
`In a study of 12 schizophrenic patients coadministered oral
`haloperidol and rifampin, plasma haloperidol levels were
`decreased by a mean of 70% and mean scores on the Brief
`Psychiatric Rating Scale were increased from baseline. In 5
`other schizophrenic patients treated with oral haloperidol
`and rifampin, discontinuation of rifampin produced a mean
`3.3-fold increase in haloperidol concentrations. Thus, care­
`ful monitoring of clinical status is warranted when rifompin
`is administered or discontinued in haloperidol-treated pa­
`tients.
`Carcinogenesis, Mutagenesis, and Impairment of Fertility
`No mutagenic potential of haloperidol decanoate was found
`in the Ames Salmonella microsomal activation assay. Nega­
`tive or inconsistent positive findings have been obtained in
`in vitro and in vivo studies of effects of short-acting haloper­
`idol on chromosome structure and number. The available
`cytogenetic evidence is considered too inconsistent to be con­
`clusive at this time.
`Carcinogenicity studies using oral haloperidol were con­
`ducted in Wistar rats (dosed at up to 5 mg/kg daily for 24
`months) and in Albino Swiss mice (dosed at up to 5 mg/kg
`daily for 18 months). In the rat study survival was less than
`optimal in all dose groups, reducing the number of rats at
`risk for developing tumors. However, although a relatively
`greater number of rats survived to the end of the studv in
`
`PHYSICIANS' DE!
`
`absence of a haloperidol related incna
`neoplasia in rats at doses up to 2." -j
`human dose for chronic or resistant r .1
`In female mice at 5 and 20 times tr
`dose for chronic or resistant patient?
`cally significant increase in mamm?r
`total tumor incidence: at 20 times th* n
`was a statistically significant incre^ i
`oplasia. In male mice, no statistical."- I
`in incidences of total tumors or spec^
`noted.
`Antipsychotic drugs elevate prolar.^: »
`persists during chronic administrar... ■_
`periments indicate that approxim?.: :
`breast cancers arc prolactin depeni ji
`potential importance if the prescr.:.,
`contemplated in a patient with a pr . •:
`ameer. Although disturbances such as
`orrhea, gynecomastia, and impote; >
`the clinical significance of elevated sr -
`unknown for most patients.
`An increase in mammary neoplasm? :
`dents after dironic administration
`Neither clinical studies nor epidemi i
`to date, however, have shown an
`chronic administration of these drug? s
`igenesis; the available evidence is cca
`be conclusive at this time.
`Usage in Pregnancy
`Pregnancy Category C. Rodents ~
`usual maximum human dose :
`showed an increase in incidence of r .i
`ity, and pup mortality. No fetal 3
`served.
`Cleft palate has been observed in r. a
`dol at 15 times the usual maximum. -
`ate in mice appears to be a non-sp-;::
`nutritional imbalance as well as te ;
`there is no evidence to relate this z
`able human risk for most of these .
`There are no adequate and well-ce^'* .-wi
`nant women. There are reports, h: ■
`malformations observed following
`along with other drugs which hsv* -j
`potential during the first trimester ::
`lationships were not established v.-.-.-
`such experience does not exclude •
`damage due to HALDOL, haloper.z :i
`used during pregnancy or in womer. -;.i
`nant only if the benefit clearly jusc.*: ■ .
`the fetus.
`Nursing Mothers
`Since haloperidol is excreted in hue....
`should not be nursed during druc t .
`dol decanoate.
`Pediatric Use
`Safety and effectiveness of halopi r .
`dren have not been established.
`Geriatric Use
`Clinical studies of haloperidol did
`numbers of subjects aged 65 and over •„ a
`they respond differently from your* ' i
`ported clinical experience has not cor - «
`ferences in responses between the e.r •
`tients. However, the prevalence of :< ra
`pears to be highest among the eider
`women (see WARNINGS, Tardive Dysi
`pharmacokinetics of haloperidol in r j
`ally warrants the use of lower doses
`MINISTRATION).
`ADVERSE REACTIONS
`Adverse reactions following the adm .r._ •.
`Decanoate 50 or HALDOL Decan
`HALDOL (haloperidol). Since vast ;
`lated with HALDOL, the adverse reaa ,
`that compound as well as for haloper.r...
`all injectable medications, local tissu. r
`reported with haloperidol decanoate
`CNS Effects:
`Extrapyramidal Symptoms (EPS) —
`istration of HALDOL (haloperidol * hu_- ■ an
`quently, often during the first few day:-
`can be categorized generally as Parkuaaaa
`akathisia, or dystonia (including opu&c -i
`ric crisis). While all can occur at reE: .-
`occur more frequently and with greater »
`doses. The symptoms may be contrc
`tions or administration of antiparkm.<j
`benztropine mesylate USP or trihexyphssj
`USP. It should be noted that persistent E
`ported; the drug may have to be discont r s
`Withdrawal Emergent Neurological —
`tients receiving short term therapy exp
`with abrupt discontinuation of antipsyi
`ever, some patients on maintenance tn
`transient dyskinetic signs after abrupt
`tain of these cases the dyskinetic movei
`guishable from the syndrome described
`dive Dyskinesia’’ except for duration. Al:
`
`Mylan v. Janssen (IPR2020-00440) Ex. 1047 p. 004
`
`

`

`all antipsychotic agents
`b£ with persistent dyskinesias,
`sse consisting of potentially ir-
`ssetic movements, may appear
`- therapy with haloperidol de-
`trjg therapy has been discon-
`t greater in elderly patients on
`5?males. The symptoms are
`eaas appear irreversible. The
`’-.ythmical involuntary move-
`ih. or jaw (e.g., protrusion of
`■. - :kering of mouth, chewing
`me may be accompanied by in-
`• : rntties and the trunk.
`-varment for tardive dyskine-
`c&2y do not alienate the symp-
`2ggested that all antipsychotic
`.... symptoms appear. Should it
`reassneht, or increase the dos-
`. :r5erent antipsychotic agent,
`
`r. • ermicular movement of the
`’.srdive dyskinesia and if the
`time the full syndrome may
`
`- -?$tonia, not associated with
`i been reported. Tardive dysto-
`u- :nset of choreic or dystonic
`i ' t and has the potential of be-
`
`r ..; *-. <lessness, anxiety, eupho-
`:••-session, lethargy, headache,
`- - .rures, exacerbation of psy-
`.. : . . -rinations, and catatonic-
`: may be responsive to drug
`■ anticholinergic drugs,
`mu; malignant syndrome
`- -moke have been reported
`for further information
`
`. irdia, hypotension, hyper-
`- mng prolongation of the Q-T
`:• sr.ges compatible with the
`' ■ rsades de pointes.
`r ■. »ve appeared citing the oc-
`; •-^ient leukopenia and leu-
`-- red blood cell counts, ane-
`s x •■monocytosis. Agranulocy-
`r; : have occurred with the use
`. fsodation with other medi-
`
`- ~_x-rtion and/or jaundice have
`
`: -. ?papular and acneiform
`of photosensitivity and
`
`creast engorgement, mas-
`-•■necomastia, impotence,
`• ypoglycemia and hypona-
`
`’HssrssEa. constipation, diarrhea,
`cssaaei and vomiting.
`, blurred vision, urinary
`•
`
`bronchospasm and in-
`
`jpathy and visual dis-
`
`i ..’.-expected death have been
`: the administration of
`■ isace makes it impossible to
`- J any. HALDOL played in
`■- t&ses. The possibility that
`i - ‘: urse. be excluded, but it
`l . a 7 and unexpected death may
`~ "ey go untreated or when
`r-"-motic drugs.
`-. —monemia has been re-
`t 5
`fcic - -j- strullinemia, an inher-
`- following' treatment
`
`7.: 3ccur with a parenteral
`-f-rmation pertaining to
`ffied. modified only to reflect
`:*■ haloperidol decanoate.
`- iymptoms of overdosage
`c.-s-x pharmacologic effects
`;< prominent of which would
`-< i 2»hypotension, or 3)
`i.X73ear comatose with respira-
`es on which could be severe
`; - state. The extrapyramidal
`C : muscular weakness or ri-
`- <i. jEed tremor, as demon-
`acrsxs types, respectively. With
`tessm rather than hypoten-
`■ i child The risk of ECG
`□£4 de pointes should be con-
`• r. regarding torsades de
`SSE REACTIONS '
`saridste. treatment is
`x KTwzy must be established
`
`Patients
`Stabilized on low daily oral doses
`(up to 10 mg/day)
`Debilitated or Elderly
`High Dose
`Risk of relapse
`Tblerant to oral HALDOL®
`
`HALDOL DECANOATE DOSING RECOMMENDATIONS
`Monthly
`1st Month
`10-15 x Daily Oral Dose
`
`Maintenance
`10—15 x Previous Daily Oral Dose
`
`20 x Daily Oral Dose
`
`10-15 x Previous Daily Oral Dose
`
`HOW SUPPLIED
`HALDOL® (haloperidol) Decanoate 50 for IM injection, 50
`mg haloperidol as 70.5 mg per mL haloperidol decanoate—
`NDC 0045-0253, 10 X 1 mL ampuls, 3X1 mL ampuls and
`5 mL multiple dose vials.
`HALDOL® (haloperidol) Decanoate 100 for IM injection,
`100 mg haloperidol as 141.04 mg per mL haloperidol de­
`canoate—NDC 0045-0254, 5 X 1 mL ampuls and 5 mL mul­
`tiple dose vials.
`Store at controlled room temperature (15°-30oC, 59°-868F).
`Do not refrigerate or freeze.
`Protect from light.
`OMP DIVISION
`ORTHO-McNEIL PHARMACEUTICAL, INC.
`RARITAN, NJ 08869
`Revised August 2000
`643-94-253-4
`Shown in Product Identification Guide, page 329
`
`LEVAQUIN® Tablets/lnjectlon
`(levofloxacin tablets/!njection)
`
`Prescribing Information
`DESCRIPTION
`LEVAQUIN (levofloxacin tablets/injection) Tablets/Injection
`are synthetic broad spectrum antibacterial agents for oral
`and intravenous administration. Chemically, levofloxacin, a
`chiral fluorinated carboxyquinolone, is the pure (-)-(S)-enan-
`tiomer of the racemic drug substance ofloxacin. The chemi­
`cal name is (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-
`methyl-l-piperazinyl)-7-oxo-7H-pyrido[l,2,3-de]-l,4-ben-
`zoxazine-6-carboxylic acid hemihydrate.
`The chemical structure is:
`
`by use of an oropharyngeal airway or endotracheal tube or,
`in prolonged cases of coma, by tracheostomy. Respiratory
`depression may be counteracted by artificial respiration and
`mechanical respirators. Hypotension and circulatory col­
`lapse may be counteracted