PSYCHIATRIC SERVICE S

November

1995

PSYCHIATRIC SERVICE S A Journal American Association Formerl (;ornnlilnitv

When Learning Mistakes

Less

Is Less:

From of the

the Past

#{149} Best

Practices:

Mental the

Health

Primary

Keeping Care Care

in Setting

of the Psychiatric

Hospital

afld

Psychiatry

#{149} Impact

and

a VA

Program

Homeless

Cost for Veterans

of

Decanoate 100

HALDOL#{174}

(HALOPERIDOL)

Offer

INJECTION

your

patients

100 mg/mL

the

most

consistent

relapse

protection

Establish a safe, effective oral haloperidol dose

How Much?

Patients

1o

who are stabilized

mg/day,

Initial month’s

who are elderly,

on oral doses or who are debilitated2

Patients

who are maintained

>10 mg/day,

who are tolerant or who are at risk for reIapse

dose is 10 to 15 times patient’s daily oral dose*2

on oral doses to oral medication, (

Initial month’s dose is 20 times patient’s daily oral dose*2

How Often?

#{149} Once a month . Since the first injection should not exceed 100 mg, the balance of the first month’s dosage can be administered 3 to 7 days later

How

U

High?

Maintenance

*Supplemcntatin

U

Total monthly dose should not exceed 450 mg Maximum volume per injection site should not exceed 3 mL

U

10 to 15 times daily oral dose depending on clinical response2

with oral haloperidol

Decanoate

HALDOL

can be used during periods ofdose

50 I HALDOL

Decanoate

adjustments

100

(h.IodoI) T lIsuIg

a

ammsiy oily. lusts

pmaIb,

compk. ,scdbEn iuIsrmaon in HALDOLs

HkD

Dscaaoa

-4 tONTRAIICAT1ONI Smce the pharmacog and cmc xo of KkDOI Decanoate 50 and NALDOLDecanoate 1 are attflbuted to H*iDO1 hatopefld the xtM medcabon, CONTRAINOATIONS,WARNINGS,and addon Utormabon are those of HALOOLmodified to reflect tt prolonQedtioit HkD o controddicated in severe toot ceatod nervotmsm premoon or comatose states from any causeand in#{241})divduais whoare hypersensitiveto did drug orhave Parkmsoos disease. WARIIPIG$:TIrdM DysEkissla: Tardivedysisnesi a syndrome consot ot potenhafly rreveodbl involuntary,dysisnodc mements may deodop in patodts tread edth anflpsychohc dmgs. Althoughthe preodence ofthe syndmme appears to be isghest among the isdedy, aspe dertywomen, d o enposmb to retyupon preodence bmatas to predict attt ncepfionotanfipsychofictreatment wflfl pahents am hedlyto developthe nymdrome.Whether anfipsychoficdnig products differin then potented to cause tard dysidnena is unknown. Bothfl osk of deodopisg ta(dM dysisneod ami the kkethood that dwdl become irreversdi are ved to ncrease as the dumfion oftreatment and tt ted cumisatiea dose of anfitmychote:drofisadministered to the it nn:rease.Hnr, the syndmmo can dendop, aJthoih much edo commordy, aften reedvely brief treatment penods at w doses. There o no known treatment for essafifished cases of tard dyskasesia aIthotfl the syndrome may mmd. mty oncompletely, danfihOI trement is withdmon. Mtipsychoeictreatment, died, howeesr, may suppress (an rtiay sopp(ess)ttm signs and symptonm of the sysdmme and thereby may possibty mask the underlyingpross. Tfn effect fled nymptomat soppressmn Z upon the konQ1ermcourse of fl syrismme o unedn. Gwenthese consiserahons, anhpsychotc dni shoskt ed prescisbed is a manner fled is most Iy to nenmoze the xcurrence of rthes dysiosesa Chmn anfipsychot treatment shoukt enery be reserved tor edo sofferfrom acflroni itkresstfoat1)o kno to respond to anflpsychoeicdni, and 2)torntrorn atternafl equallyeffectsie, but tess harmfultreatments am no avadaise or appropisate. In patatnts who do requne chmmc treatment the snodtest dose and the shortest durahonof treatment producm9a sahstactory dinis responseshosidbenaught TheneedforcondonedtreatmeisthouI he reassessedafty. Usons andsymptomsoftardsiedysknessiappearina paflenton aohpsychohcdrog disconfinuahon shoukt he considered. Hovec, somo patients may requne treatment despde the presence of the syndrome. (Fortorther flrformahonabotdttn descispIon cdtarderedystenesiaaod ff5deheat detechon, ptease referto ADVERSERETIONS.) Nsc $s (N A potenhaflyheat symptom com#{216}eo somehmes referred to as Neurisepti Matoaot Syndrome (NMS)f been reported tnassociahnn edth asflpshot( dregs. Ghnicatmandestahoes at NMSam hyperpyreis&muscat rdy, attend menstus(inctudir coseon sigtro)aat esidence ofautonom nrstty(irregular puise or isood pressum tachycardi diaphoresis,and condiec dysrh1hnoas). Adddionatsrm may urctudeatevaedtcreatho phosphisunase, mysgteisnuho(rhabdomyisysm)aod ute rend The diagnostc evatuationof pahents edththis symirome o conyatcated fl arrivv at a diagnosis, d o impoflantto isenhfy cases wherethe choecat presentation includesboth seflous medat iNness(e.g,pneumonasystemi erlechon, etc.)aod untreatedor inadequatelytreated eotrapyramidat ogro and sym (EPS). Other impodant consideratmns inthe ddlerentnddiagnosis Uododecentrat anhchohoerg toiscdy, heat stroke, dregteesr and pismarycerflratnermo system(CNS)pathotogy. The maoement of NMSshouh inchide 1) immediatedisconhnuahon of anhpsychoflc dregs and other drugs not essenthe to concurrent therapy, 2) ntensree symptomafic treatment and method monftoisng,and 3)treatment ofanyconcomdant seflous method proteenroforwhch specifictreatmentsareavadibk. Thereis nogeneris reemerdabout stecific pharmacologacattreatment remerm for uncnmphcated filMS.fi a patient requires anflyshot dreg treatment after recoveryfrom NMS, the patented odntrodoctisnofdnig therystroukt hecarehiftycOns$dered.Thepaflentshouid hecarefuffymoistored, once recurrences of NMS have been reported.ttyperpflleolaand heat stroke, rotassociated withtheabove symom compIe havealso been reported withHALDOL heap Pmpacy(sea PRECAUTKtNS - Usain Pregnancy) camI UN W U1um:(sea PRECAU11ONS-DrUg Interachons) GsNra Bronchopneumnni snmehmes tat has ho am of anfiterychoficdregs.incsidir odognodotProm remededtherapyshonAt he rosfitotedd dehydration, hemoconcentratmo or reducedpulmonaryntntdahonoccur,especiodyn theteddy. Decreasedserumcholesterd andisr cutasenes and acsiar changes kent been reported eath them-rekeed drugn, atthough not eath hatopefldoi See PRECAUTtONS tnlormabon for Pahents for intormafionon mend andierphyncat atethesand on concoodtent usewdh othersobstences. PRECAUTiONS:Mmsnister cauhousty to patents: 1) wrth severe cardiovascuko thsorder due to the possthuldyof transrent hypotenoon and/or preapitahon olaogAratn)davasopressor is required,nnephnneshosid not he used since HALOOImay blockttsvasopressorachvdyand paradoiscatfurther Hweflngof blood pressure may occur metararnino),phenylephflseor norepmephflre shouH he used); 2) recer anficonvuisardmodcokons, edth a hotory at seizures or who EEGahnormatdies, because HALDOImay isrfl convokevethreshoot. fluidceded,ateqUateWbCOnVOISant theryshOUH be concomHArttynskntaaned;(3)w*h knownateogno ora historyof atterg( machorn to dregs; )4) recerving articoagulants. since or notated instance of interferenceoccurred with the effects of one anticoagulant )phenindione). Concomdantanhpattdnson medafion, Hrequired,mayhaveto he confinuedafter HALDOLn disconhmed because of ddterent excrefionrates; d both are disconhnued snouIneousiy, extrryrantttA synrorrm may occor. Intraocolarpressure may iscrease when antichotnergic drugs, wrdodnrganflgsrtonson drugs, am odrmootered concormtanffyeath HALOOLWhen HAW is used for owes in tepoter disorders, there may be a repel mood swmg to depression. Severe nesratoocfly may occur in pahents wok thyrotoiscoso receromganhpsychofic meduiotuir mctudingHALDOL. Wsi*Iu ed PIsutr Mentis ardor physicat abdfiinsreqiared for hazardoes tasire or drerug may be impaned Aicohidshount he avoided dueto pOSSdeeoddOiVeefteCtS and hypotension Drip hdsmchout Pahents receskng kthium pbs hatopendis shosid he monoored cuisidyfor eady evidence of seuhoogat toiscfiyand treatmont disconhnued prornpttyfisuch sigosappear. As edth otheranhpsychohc agents, 0 shount he noted that HALDOLmay he capabteof patesflaflogtNS depressants such asanesthefics, opotes, aodaicohid caicio . ipakusW ii Feff No matageho potentid of hatopendcdwas found in the Ames Satmoneta n*rooonot achvaiion assay. Negafiveor erconsistent posdon fodugs have keen obeaned ir a, wOnid re ides studies of effects at hatopeisdcdon chromosome structure and number The available cytogeoetic evidence is considered too inconsistent to he conctusive at this fime. Carcisogencty stunted orat odopefidis were conducted n Wntar rats)dosed at up to 5 mgthg dy for 24 months)and mAJtenoSatss nice )desed up to 5 mgliQ HA ton 18 months).tr the rat study surevat was edo than openrot is ott dose groups reductug 9 number at ratsat flsktor developingtumors. Hor, atihotigha relaMy greater nundrer at rats sinvoed to fl tint atthe study n hh dose node aid temate gmup these aismals did nat havea greater incidenceattomors then contris aimats. Therefore,altho4 not opfimat,this study does suggest the ahsence at a fndopefldcdrotatedincrease ui the iscotence at neoptesia ii rats at doses up to 20 horns the usuat doty human dose terchrononresotaotpienes. trtemmisett5and2Oflmesffrehflestnded dadydosehothrooicor resished patients, therewasastahshcaffysignthcant nicrease in mammary gtand neo#{216}asis and tent tumor rocidence;at 20 tidies the same dady dose there was a stahshcoty sniflrant increase In pdufiarygtend neoptasia In male m no stahstlcaflysigrdficantdifferencesin inddences at totat tumors or specthc tumor pes were noted. Anhpshot dregs idevatepnntactn veis; theetevahon porsots duflng chmoiodminitraflon Issue cuflureeopeflmeeds indatn that ugproism&y one-druidat human breast cancers am prolacbn dependent is idtro,a factor at potenhat Unportanceif the

#{149} 10 to 15 times daily oral dose depending on clinical response2 . 1120 times the daily oral dose is used, monthly dose should be reduced based on clinical response (by approximately 25% of the original dose, each month for 2 months) until appropriate maintenance dose is reached3 until steady state has been achieved.

prescnpflon at these dregs o coirteni1ated in a pabent with a preidoustydetected breast cancer. Althoughdisturbances such as gatactorrhet amenorrhea gynecomasb&and kepotence tens been reported,the cbrdcatsnificance at elevatedtenon prokechntends is unknownfor most patients. do increase n mammay rwo#{216}asois has beer found in rodente after chroisc ednuidsOratiOnat anfipoychoficdregs. NidtherctrWcat studies nor epideeneato$ skated conducted to date,hnoer, Poseshownan associahontatweer thmoi odmoristrahOr at these drugs and mammaiytumoisgenesis: theavaitabItevidence iscOns)deredtOOlimied to beconctusiveatthisbnw. Use,. to Pviguoc PregruocyCategory C.Sate use in pregnancyorinwomenOkidytohecomeprnatif has not been estabtehed; useMy if benefitCteaify)UShfieS potentot hazardstothe fetus. N Methenc tnfantsshoute not be nursed duflng drug treatment Petetrfc Use: Controtedtrislsto estabhohthe safetyand effechvenessof intrarnuscuteradminitrahon in chddren havenot been conducted AOVERU REACTiONS:Adverse machoes fotmwmgthe edministrahor of HALDOLDecanoate 50 or HALDOt.Decaooate 1HAare those at HALDOLedopefldot Suice vastexpenence hasaccamufated edth HALDOLtheadveise macboos am reported forthatcoinpourid as t astor hatopeisdo)decanoate. Made at in medicahons, iscatbssoe machoes hans been reported who huopefldd decaooate. csisEIci EThymm Syu#{216}oms($)- EPS doflyp theabniisstrahon at HALDOI(fatopefldot)have teen reported frequenfly,often duisug the first few days of treatment. EPS can be categonzed generafly as Partunson-like symptoms, akethisia,or dystonis (inctioting opisthotonosandacidogyriccrisis).Wtd aftcan occurat refafivety doses, they occar morefreguenttyandwithgreaterseesnityat tegher doses. The synoptonromaybe coiflrofed withdose reductionsor odministrafionat anhparfdnson drugs such as berotropore mesytate USP or thhexyphenid)1hydrochuidde USP. f shotid he noted that persistent EPShans teen reported;fla dreg may have to be disconfimuedin such cases. WftbIrIWII Emst Nsmio,ic& $os - Abrupt disconhnuahon of short-term anh-psyshnhc therapy is generallyunenentful. However,some pahentson matntenance treatment eugeisencetraruterd dystenefic signs after abrupt wifhdrawat.tn certisr cases these am indishnguishabtefreonTarthve Dysuinesia”except for durahon, ft is unknown whethergraduat Wifhdrawatad) reduce the occurrence at these signs, but unfi)further evidence is avistebteHALDOLshouot be graduoty wfthdrawn.TardlvsDystdossia - As who at) anttpsychoficagents ItALDOLhas beenassocatted wifhpersisttmdysidnesias. Tardise dysidnesi&asyndronu consisbog of poterthaflyirreversth1 inviduntary,dys#{149} uinetc monements, maypear insorne pabentson king-termtheryor may occarafterdnig thery has been disconhnoed. The flskappeais to begreater is eldedy patents on h#{231}h-dosetherapy, especaNyfemales. Thesymptomsam persistentand insnow patients appearirreversisle Thesyndromeis charactenzedby rhylhskcatinvotantarymovementsat tongut fain, mouthor w e.g., protrusionat tongue,puffingat cheetu, puckenng at month, chewng moesments). Sometunes these may be accompaised trj iruntaty mmests at erifrenibes and the trunk There o no knowneftecbve treatment for tendon dyshmesia anbpartenson agents usuafty do not aJeidate fla penifonre at that syredrome. fi n suggested that at)anbpsychot agentsbedisconhooedfithesesymptomsappear.Shouhiifbe rwcessatyto rnnstihdetreatnoen or kicrease thedosageof the agent or switchto a differentanhpsychot agent, this syndrome may he masked. ft has been reportedthat floe venrmcutermovementat the tongue may he an earfysign at tardsie dystunesiaand ifthe medicahon is stopped at that how the fat) syndrome may not devetop.Titles Dysloufa - Tandsiedystona not assoaated edth the above syndrome, has aiso been reported. Tardise #{216}ystorila is charactenuedby detayedonset ofchoroc ordystoruc movement is often persistent, and hasthe potenhatat becoming irreversdot fiber NS Efiscis - )nsornn resttessness, anroety, euph* agifahon, drowsiness, depression, )ethargy, headache, contusion, verfigo, grand mat sesiurns, and enacerbatuin of poychof symptoms inchidinghafluctnahons,and catatoioc-)ikebehaidOot states wfoch may he responsive to drug withdrawatand)ortreatmentedth anhchokneypcdrugs. Bodyas a Wsfs: Nesr mahgnant syndrome )NMS),hyperpyreroaand heat stroke have been reported ado HALDOL.Sea WARNINGS forfurther intormahonconcerningNMS.) Csidtevaacalat Bisdi Tzhycard hypotension, hypertension and EcG changes, iscludAigpridongahon of fla O-Tirftervatand EcGpattern cfwngescornpahhte withthe pofymorphotoconfigurahon attorsades do porntes. Nimaite#{231}k Efl.c Reports at mALusuaty transient edhOpemaand teukocytosis,nodmat decreases ot red Hood cef counts, anernj ora tendencytoward monocytosis; agceoidosy1osisrarefyreported and My inassocishonwhoOthesmedahOn. UWEIPIdE tmred fiverfUnctiOnanWorureiice. OsiiiaI AsasDoerMaradopapufarandacneifonn machors,isofatedcasesofphidoserottMty,isss at hur. EndocetueDteoodsnc Lactahon, breast engorgenient, masta menstniat irreguhohes, gynecomas* impotence, increased libido, hypergceini hypogcernisand hyponatrern GastrointeetloalBhctt Anorexj consbpahon, diarrhea hypersatsiahon,dyspepsa nauseaand vomifing AiNomic Rudloos: Drymouth, blurredvision, urinaeyretenhon, diaphoresis and priapism. Rssoiy tecf Laryogospasin,bronchospasm and ircreaseddepth at respirahon. s_I Sins Cataracts,rehhyandidsuat disturbances. mlii,: Cases atsudder and anexpected death bans teen reported inassociatior withthe administrabonat HALDOLThe natureatttw evidence nodies if impossible to determine deflnthvelywhat rote, if any, HALDOLplaynd in the outcome at the reported cases. The possdoldy that HALDOLcoused death cannot at cours he erduded, bid if is to be kept vi mod that sodden and uneopected death may occur vi when theygo untreatedoration theyamtreated wiffiOthenanhpsychObrdrugs. Psaait Eneir Hyperammonema has teen reported ina 5/ year old cfnd with citrolhnemi an inherded disorder at ammonia tomehoe, tidtuedngtreabneeifidth HALDOL. PORTAIIT: Fell dbadieiwtenaeaalmete be read before NALD or NALD Decaneats prodacteats edmtetensd anpnescotbad. Fot*rmatfse ooppmptsssauhoaImudetevseteaap, see tell prsscdbhig hdonoalloa. Theshoif-achug HWDO1inform isuiteodedoisytoracid&yagdated psychohcpahents who moderatidyseoeretovesysevereponp(orns. 1th192 1. DaviiJM, KanCJM. Marder SR.,et al. Dose response oiprophybctk antipsychotics J a: Piyb:a. 1993;54(suppl 3):24-30. 2. HALDOL2 DecanoatePackc risen. McNeil Pharmaceutical. Spring House. PA i94”. Revised 0/13/92. 3. Ereshefsky L. Toney G, Lyman RL Saldad S1 Anderson co, RichardSAL. Halopendoldecanoatc an effective dising strategy. Presented at the American Psychiatric Association 44th Annual Meermg. May 991; New Orleans, La. Rcferc&es;

1’

McNEIL PHARMACEUTICAL RARITAN,

08H02978/02-i4-95

NEWJERSEVOSeOG0002

NOVA P0001000UOICALS

I

I

-

HALDOL

/morr/i Provides

the

protection with

no

increased

X T E N 1) 1 N G

consistent

from

relapse...

risk

as compared

E

most

to oral

PROTECTION

of side therapy

Fioi

HALDOL#{174} Decanoate (HALOPERIDOL)

V

\{

i

INJECTION

effects

R

#{128} L A P S E

100

100 rng/mL

%

4’

She’s

anxious.

She’s

agitated.

She can’t sleep.

She’s depressed. Paxil effectively

relieves depression and associated symptoms of anxiety.14 60% to 90% of depressed patients exhibit associated

symptoms of anxiety such as agitation, sleep disorders, weight lossand gastrointestinal problems56 Incidence of agitation with Paxil iscomparable to placebo (2.1% vs 1.9%);incidence of nervousness and of anxiety vs placebo is 5.2% vs 26% and 5.0% vs 2.9%, respectively7 Most common adverse events include: nausea, somnolence, asthenia, dizziness, insomnia, sweating, ejaculatory disturbance and other male genital disorders*7Concomitant use of Paxil in patients taking monoamine oxidase inhibitors (MAOIs) iscontraindicated. ‘Incidence of 5%or greater and incidence for Paxil at least twice that for placebo Please see brief summary of prescnbing information on adjacent page of this advertisement

ONCE-DAILY

20

MG

hC/ LIFTS DEPRESSION. LOWERS ASSOCIATED ANXIETY SYMPTOMS.

3

Sm,thKhne Pharmaceuticals

Philadelphia,

PA 19101

Beecham

_____________________________ © SmithKline

Beecham,

1995

Body as a Whole: headache, asthenia, abdominal pain, fever, chest pain, trauma, back pain. Cardiovaacular: palpitation, vasodilation, postural hypotension. Dermatologic: sweating, rash. Gastrolnteetinal: nausea, dry mouth, constipation, diarrhea, decreased appetite, flatulence, vomiting, oropharynx disorder, dyspepsia, increased appetite. Musculosk&.tal: myopathy, myalgia, myasthenia. Nervous System: somnolence, dizziness, insomnia, tremor, nervousness, anxiety, paresthesia, libido decreased, agitation, drugged feeling, myoclonus, CNS stimulation, confusion. Respiration: respiratory disorder, yawn, pharyngitis. Special Senses: blurred vision, taste perversion. Urogenital System: ejaculatory disturbance, other male genital disorders, urinary frequency, urination disorder, female genital

ONCE-DAILY

IAKL PAROXET/NEHC/

disorders.

Studies show a clear dose dependency for some of the more common adverse events associated with Paxil use. There was evidence of adaptation to some adverse events with continued Paxil therapy (e.g., nausea and dizziness). Significant weight loss may be an undesirable result of Paxil treatment for some patients but. on average, patients in controlled trials had minimal (about 1 Ib) loss. In placebo-controlled clinical trials, Paxi/-treated patients exhibited abnormal values on liver func-

References: 1. Dunbar G, 398. 2. cohn

cohn JB, Fabre LF, et al. BriPsychiatry. 1991;159:394JB, Wilcox J Clln Psychiatry. 1992;53(suppl): 52-56. 3. Feighner JP, Boyer WE JCIIn Psychiatry. 1992;53(suppl):44-47. 4. Fabre LE J Clln Psychiatry 1992;53(suppl):40-43. 5. Sheehan D, Dunbar G, Fuell DL. Psychopharmaco/Bull. 1992;28:139-143. 6. clayton PJ, Grove WM, coryell W, et al. Am JPsychiatry. 1991 ;148: 1512-1517. 7. Paxil (paroxetine HCI) Prescribing Information.

cs.

PAXIL (brand of paroxtine

tion tests

hydrochloride)

See complete

prescribing information In SmithKllne Beecham Pharmaceutior PDR. The following is a brief summary. AND USAGE: Paxil is indicated for the treatment of depression. CONTRAINDICAT1ONS: Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) is contraindicated. (See WARNINGS.) WARNINGS: Interactions with MAOls may occur. Given the fatal intractions reported with concomftant or immediately consecutive administration of MAOls and other SSRIs, do not use Paxllin combination with a MAOI or withIn 2 weeks of discontinuing MAOI treatment. Allow at least 2 weeks after stopping Paxil before starting a MAOI. PRECAUTiONS: As with all antidepressants, use Paxil cautiously in patients with a cal. literature INDICATiONS

history

of mania.

Use Paxil cautiously in patients with a history of seizures. Discontinue it in any patient who develops seizures. The possibility of suicide attempt is inherent in depression and may persist until significant remission occurs. Close supervision of high-risk patients should accompany initial drug therapy. Write Paxil prescriptions for the smallest quantity of tablets consistent with good patient management in order to reduce the risk of overdose. Reversible hyponatremia has been reported. mainly in elderly patients, patients taking diuretics or those who were otherwise volume depleted. Clinical experience with Paxil in patients with concomitant systemic illness is limited. Use cautiously in patients with diseases or conditions that could affect metabolism or hemodynamic responses. Observe the usual cautions in cardiac patients. In patients with severe renal impairment Icreatinine clearance placebo at week 6. to treatment was defined as CGI improvement score of I (very much improved)

2 (much improved). In one randomized, on venlafaxine

double-blind,

or imipramine

placebo-controlled

study of depressed

at 75 mg to 2.25 mg daily in divided

The effectiveness of EFFEXOR in long-term cally evaluated in controlled trials.

patients

initiated/maintained

doses (observed

use (>6 weeks)

or

cases at week

6).’

has not been systemati-

EFFEXOR Is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs). EFFEXOR should not be used in combination with an MAOI or within at least 4 days of discontinuing treatmont with an MAOI because of potential for serious adverse reactions. Based on the half-ilk of EFFEXOR, at least 7 days should be allowed after stopping EFFEXOR before starting an MAOI. Treatment with EFFEXOR is associated with sustained increases in blood pressure (BP) in some patients. These appear to be dose dependent and were seen at an incidence of >5% at dosages above 200 mg/day. Regular monitoring of BP is recommended. As with any psychotropic drug, EFFEXOR may impair judgment, thinking, should be advised to exercise caution until they have adapted to therapy. The most common adverse events reported in EFFEXOR placebo) were: nausea, somnolence, dry mouth, dizziness, abnormal ejaculation/orgasm, and anorexia.’ Please see brief summary

or motor

skills, and patients

clinical trials (incidence >10% and 2x that of constipation, nervousness, sweating, asthenia,

of prescribing information on last page of this advertisement.

VENLAFAXINE

HCI

25 mg, 37.5 mg, SO mg, 75 mg, and 100 mg Brief Summary See package need for full prescribing information. Clinical Pharmacology: The antidepressant action of venlafaxine is believed to be associated with potentiation of neurotransmitter activity in the CNS. In preclinical studies, venlafaxine and its active metabolite, 0-desmethylvenlafaxine (ODV). were potent inhibitors of neuronat serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptakeVenlafaxine and ODV have no significant aftinity for muscarinic, histaminergic, or a-i adrenergic receptors in vitro. Pharmacologic activity at these receptors is hypothesized to be associated with the various anticholinergic, sedative, and cardiovascular effects seen with other psychotropic drugs. Venlafaxine and ODV do not possess monoamine oxidase (MAO) inhibitory activity. indications and Usage: Effexor is indicated for the treatment of depression.

Contraindicatlons:

Contraindicated in patients with known hypersensitivity. Concomitant use in

patients taking monoamine oxidase inhibitors (MAOI5) is contraindicated (see “Warnings”). Warnings: POTENTIAL FOR INTERACTION WITH MONOAMINE OXIDASE INHIBITORS (MAOIs)Adverse reactions, some serious, have been reported when veniafaxine therapy is initiated soon after discontinuation of an MAO1 and when an MAO1 Is initiated soon after discontlnuation of veniafaxine. Reactions have Included tremor, myocionus, diaphoresis, nausea, vomlt ing, flushing, dizziness, hyperthermia with features resembling neuroieptic malignant syn drome, seizures, and death. Given these reactions as well as the serious, sometimes fatal

interactions reported with concomitant or immediately consecutive administration

of MAOIs

and other antidepressants with pharmacological properties similar to Effexor, do not use Effexor in combination with an MAOI or within at least 14 days of discontinuing MAOI treatment. Allow at least 7 days after stopping Effexor before starting an MAOI. Hyperthermia, rigidity, myocionus, autonomic instability, mental status changes including extreme agitation progreasing to delirium and coma, and features resembling neuroleptic malignant syndrome have been reported with concomitant selective serotonln reuptake inhlbitor/MAOI therapy. Severe hyperthermia and seizures, sometimes fatal, have been reported with concomitant tricyclic antidepressants/MAOI therapy. SUSTAINED HYPERTENSION-Effexor treatment is associated with dose-related sustained increases in supine diastolic blood pressure. Regular monitoring of blood pressure is recommended, and, when appropriate, consider dose reduction or discontinuation. Precautions: GENERAL-Anxiety and Insomnia: Anxiety, nervousness, and insomnia have been reported in short-term studies. Changes in Appetite/weight: Anorexia has been reported in short-term studies, and a dose-dependent weight loss has been reported in patients taking Effexor for several weeks. Activation of Mania/Hypomania: Hypomania or mania has been reported; as with all antidepressants, use cautiously in patients with a history of mania. Seizures: Seizures were reported in premarketing testing (0.26%). Use cautiously in patients with a history of seizures. Discontinue it in any patient who develops seizures. Suicide: The possibility of suicide attempt is inherent in depression and may persist until significant remission occurs. Closely supervise high-risk patients during initial drug therapy. Write Effexor prescriptions for the smallest quantity consistent with good patient managementto reduce risk of overdose. Use in Patients with Concomitant Illness: Clinical experience with Eflexor in patients with concomitant systemic illness is limited. Use cautiously in patients with diseases or conditions that could affect metabolism or hemodynamic responses. In patients with renal impairment (GFR=1O7OmL/min) or liver cirrhosis, clearance of venlafaxine and its active metabolite were decreased, resulting in prolonged elimination half-lives. A lower dose may be necessary; use with caution in such patients. INFORMATION FOR PATIENTS-Clinical studies revealed no clinically significant impairment of psychomotor, cognitive, or complex behavior performance. However, caution patients about operating hazardous machinery, including automobiles, until they are reasonably sure that Effexor does not adversely affect their ability to engage in such activities. Tell patients to 1) notify their physician if they become pregnant or intend to become pregnant during therapy, or ifthey are nursing; 2) inform physicians about other medications they are taking or plan to take; 3) avoid alcohol while taking Effexor; 4) notify their physicians if they develop a rash, hives, or related allergic phenomena. DRUG INTERACTIONS-Cimetidine: Use caution when administering Effexor with cimetidine to patients with pre-existing hypertension or hepatic dysfunction, and the elderly. Drugs Inhibiting Cytochrome P,IID, Metabolism: In vitro, venlafaxine is metabolized to its active metabolite, 0-desmethylvenlafaxine (ODV), via cytochrome P4,lID,. Therefore drugs inhibiting this isoenzyme could potentially increase plasma concentrations of venlafaxine and decrease concentrations of ODV. Drugs Metabolized by Cytochrome PlID6: In vitro, venlafaxine is a relatively weak inhibitor of this isoenzyme; clinical significance is unknown. Monoamine Oxidase Inhibitors: See Contraindications” and “Warnings.” CNS-Active Drugs: Use of venlafaxine with CNS-active drugs has not been systematically evaluated; therefore, use caution when administering Effexor

with such drugs. CARCINOGENESIS. MUTAGENESIS, IMPAIRMENT OF FERTILITY-Carcinogenesis: In 18-month studies, there was no evidence of carcinogenicity in mice given 120mg/kg/day (16 times the maximum recommended human dose (MRHD)]. In 24-month studies, there was no evidence of carcinogenicity in rats given 120mg/kg/day. Mutagenicity: In male rats receiving 200 times (on a mg/kg basis) the MRHD, chromosomal aberrations were found in the bone marrow in vivo. Impairment ofFertiity: No impaired reproductive function was found in rats given 8 times (mg/kg) the MRHD. PREGNANCY-Teratogenic Effects-Pregnancy Category C. Reproduction studies in rats given 11 times, and rabbits given 12 times the MRHD (on a mg/kg basis) revealed no malformations of offspring. However, in rats given 10 times the MRHD, there was a decrease in pup weight, increase in stillborn pups, and an increase in pup deaths during the first 5 days of lactation when dosing began during pregnancy and continued until weaning. There are no adequate and well-controlled studies in pregnant women; use Effexor during pregnancy only if clearly needed.

LABOR, DELIVERY, NURSING-The effect on labor and delivery in humans is unknown. It is also not known whether Eftexor or its metabolites are excreted in human milk; exercise caution when administering to a nursing woman. PEDIATRIC USE-Safety and effectiveness in children (