IS THIS SEAT TAKEN?

A Review of TRAMADOL in Pain Management

Jamie Falk, Pharm M!FP Ann"al S#ientifi# A$$em%l& A'ril ((, ()*)

!ommon +"e$tion$
How ,oe$ trama,ol work? -hi#h 'atient$ might it %enefit? I$ it %etter tolerate, than other analge$i#$? oe$ it have a%"$e 'otential?

-here ,oe$ it fit in the analge$i# #ontin""m?

How ,oe$ it work?

-eak .o'ioi, re#e'tor effe#t$
Str"#t"rall& relate, to mor'hine an, #o,eine /*).fol, le$$ affinit& for re#e'tor than #o,eine an, 0))).fol, le$$ than mor'hine "' to

Meta%oli1e, to highl& a#tive M* 2)).fol, greater affinit& than 'arent #om'o"n, Analge$ia onl& 'artiall& %lo#ke, %& nalo3one 4/2256

Serotonin an, nore'ine'hrine re"'take inhi%ition

Effe#t re,"#e, %& 7 8 %& a,renergi# re#e'tor antagoni$t 9e$$ than that with imi'ramine
:ron, S, et al; Clin Pharmacokin ())<=<2>?@A.A(2; Raffa RB; J Clin Pharm Therap ())?=22>*)*.?;

Kineti#C &nami# S'e#$

Dn$et of a#tion> / 2) min"te$ Peak a#tion> ( E 2 ho"r$ "ration of a#tion> < E 0 ho"r$ E3ten$ive he'ati# meta%oli$m
Meta%oli1e, to M* %& !FP( 0 o$e re,"#tion reG"ire, for #irrho$i$

Hrinar& elimination
2)5 a$ "n#hange,= 0)5 of M* e3#rete, o$e re,"#tion reG"ire, for $evere renal im'airment
:ron, S, et al; Clin Pharmacokin ())<=<2>?@A.A(2;

Effi#a#&
D$teoarthriti$ Ne"ro'athi# Pain 9ow %a#k 'ain A#"te Pain !hroni# Pain

A#"te Pain
Man& $mall $t",ie$ v$; o'ioi,$
9ikle& I mor'hine in eG"i.analge$i# ,o$e$ 4T>M I /*)>*6 "' to <)) E 0))mgC,a& ma3im"m NNT 4J)5 re,"#tion in 'ain v$; 'la#e%o6 I <;? for trama,ol *))mg I 2;0 for #o,eine 0)mg K ASA

Man& $mall $t",ie$ v$; non.o'ioi,$

Similar analge$ia #om'are, to NSAI $ 'o$t.o'erativel& in a variet& of ,o$e$

:ron, S, et al; Clin Pharmacokin ())<=<2>?@A.A(2;

D$teoarthriti$
!o#hrane Review of Trama,ol in DA
** R!T$ 4nI*A2A with $&m'tomati# DA of knee or hi'6 Trama,ol 4KC. a#etamino'hen6 v$; 'la#e%o 40 $t",ie$6, or a#tive #ontrol 4J $t",ie$ E a#etamino'hen, ,i#lofena#, ,ih&,ro#o,eine, 'ro'o3&'hene, 'enta1o#ine6 average n I *)?

Mean ,ail& trama,ol ,o$e I ()*;<mg KC. J);*J Average length of fC" I 2J ,a&$ A#tive #ontrol 4non.'la#e%o6 I *@ ,a&$
!e'e,a MS, et al; CDSR ())A;

D$teoarthriti$
Intervention Pain intensity (0100)

Functional improvement
(WOMA 0-10)

(##T $or reportin% mo&erate improvement)

!lo"al improvement

Trama,ol v$; 'la#e%o

.?;J

Se'arate MA> D'ioi, NNH = 19

.);2<

Se'arate MA> Se'arate MA$> Minor Se'arate MA> Mo$t #ommon AE$> Intervention Ma(or D'ioi, = -0.7 events A#etamino'hen NNT I 6 Na"$ea, vomiting, NSAI I .*) Se'arate MA> a&verse event a&verse ,i11ine$$, #on$ti'ation, D'ioi, NNH D'ioi, = 12 = -9 (##') (##') $omnolen#e, tire,ne$$, A#etamino'hen =-4 Trama,ol v$; hea,a#he J ? 'la#e%o
!e'e,a MS, et al; CDSR ())A;

!hroni# 9ow Ba#k Pain

In$"ffi#ient evi,en#e availa%le to #om'are trama,ol to tra,itional o'ioi,$ Two 'arallel $t",ie$ #om'aring #ele#o3i% to trama,ol !o#hrane Review of D'ioi,$ in !hroni# 9BP
2 R!T$ 4nIA*<6 Trama,ol v$; 'la#e%o 42 $t",ie$6 Mean trama,ol ,o$e I *J) E (<)mgC,a& "ration of fC" I < wk$ E 2 month$

!ho" R, et al; Ann Intern Med ())@=*<@>J)J.*<; DL onnell J , et al; J Int Med Res ())A=2@>*@?A.*?)(; e$h'an,e A, et al; CDSR ())?;

!hroni# 9ow Ba#k Pain

Intervention Pain intensity
(0-100)

Functional )mprovement (RD* 0-+, ) .*;)

A,ver$e event$ na"$ea $omnolen#e ,i11ine$$ #on$ti'ation ,r& mo"th hea,a#he

R 456 A5 A5 ?5 ?5 @5 25

Trama,ol v$; 'la#e%o Intervention

.*);?
-0. Pain )mprovement (.) J( 02

Wit/&ra0al &ue to tolera"ility (.) *2;< *);0

Trama,ol J)mg +I #ele#o3i% ())mg BI

M all ,ifferen#e$ $tati$ti#all& $ignifi#ant

e$h'an,e A, et al; CDSR ())?; DL onnell J , et al; J Int Med Res ())A=2@>*@?A.*?)(;

Ne"ro'athi# Pain
!ana,ian Pain So#iet& :"i,eline$ 4())@6
Trama,ol an, o'ioi, analge$i#$ #on$i,ere, thir,.line

S#ant evi,en#e on whi#h to ,raw an& #on#l"$ion$ on #om'arative agent$ 4o'ioi,$, T!A$, anti.#onv"l$ant$6 !o#hrane Review of Trama,ol for Ne"ro'athi# Pain
2 R!T$ 4n1-0- 6 of trama,ol v$; 'la#e%o "ration < E 2 wk$ Trama,ol ,o$e I *)) E <))mgC,a&

Mo"lin E, et al; Pain Res Manage ())@=*(>*2.(*; "ehmke RM, et al; CDSR ())A;

Ne"ro'athi# Pain
Intervention 50% Pain )mprovement (##T) 2;? Wit/&ra0al &ue to 3i&e 4$$ects (##') @;@

Trama,ol v$; 'la#e%o

"ehmke RM, et al; CDSR ())A; Finner"' NB, et al; Pain ())J=**?>(?A.2)J;

Si,e Effe#t Profile !om'ari$on$

Na"$ea, #on$ti'ation>
trama,ol N #o,eine an, mor'hine

Re$'irator& ,e're$$ion>
Trama,ol NN mor'hine, o3&#o,one

:I %lee,ing, renal im'airment, !O ri$k>

Non.e3i$tent with trama,ol In#rea$e, ri$k with NSAI $, e$'e#iall& with ri$k fa#tor$

Smith AB, et al; Am J Surg ())<=*?@>J(*.@; :ron, S, et al; Clin Pharmacokin ())<=<2>?@A.A(2;

Dther Serio"$ A,ver$e Event$

Serotonin S&n,rome
Rare with monothera'& In#i,en#e in#rea$e$ with SSRI$, SNRI$, T!A$, et#;

Sei1"re ri$k
In#i,en#e N *5 4'o$$i%l& no greater than other analge$i#$6 Ma& in#rea$e ( . 0.fol, with ri$k fa#tor$ EtDH a%"$e, 'a$t $troke or hea, inP"r&, m"lti'le $ei1"re thre$hol,.re,"#ing ,r"g$, m"lti'le trama,ol r3

In#rea$e, ri$k 'o$$i%le with higher ,o$e$ an, #on#omitant SSRI$, SNRI$, T!A$
:ar,ner JS, et al; Pharmacotherapy ()))=()>*<(2.2*; :ron, S, et al; Clin Pharmacokin ())<=<2>?@A.A(2;

A%"$e Potential
In rat mo,el$>
Peak %rain M* level$ ,ela&e, "ntil ().0) min 'o$t.,o$e A$ ,o$e in#rea$e$, %rain trama,ol>M* in#rea$e$

In h"man$>
Negative re'ort$ %& ,r"g a%"$er$ of ,ela& in $"%Pe#tive !NS effe#t$ Trama,ol ha$ *C*) the 'oten#& of mor'hine for analge$ia, %"t onl& *C() the 'oten#& for $"%Pe#tive !NS effe#t$

Raffa RB; J Clin Pharm Therap ())?=22>*)*.?;

A%"$e Potential
A,am$, et al;
nI**,2J( 'atient$ with #hroni# non.#an#er 'ain Po$itive $#oring on A%"$e In,e3 within *( month$ NSAI $ I (;J5 Trama,ol I (;@5 H&,ro#o,one I <;A5 4'N);)*6

Drtho.M#Neil.f"n,e, $"rveillan#e 'rogram>

<J< #a$e$ of a%"$e over 2 &r$ *.2 #a$e$ 'er *)),))) 't$

Monitoring 'rogram for im'aire, H!P$ 4nI*0)*6

*? #a$e$ 'er *))) 'er$on.&r$
A,am$ EH, et al; J Pain S&m'tom Manage ())0=2*><0J.@0; M# iarmi, T, et al; J Fam Pra#t ())J=J<>@2;

ollar$ Q !ent$
Me,i#ation
Trama#et 4trama,ol 2@;Jmg K
a#etamino'hen 2(Jmg6

A''ro3imate eG"ivalent ,o$e

( ta%$ G<.0h 4?C,a&I2))mg6 2))mg D ())mg BI J))mg BI ( ta%$ G<.0h 4?C,a&I(<)mg6 * ta% G0h 4<C,a&I()mg6 *Jmg G*(h (J.*))mg

/RC2) ,a&$
*?) *)) A) *J () *J (J *)

Trama,ol long.a#ting 4Ralivia,

Tri,"ral, S&tram S96

!ele#o3i% Na'ro3en T&lenol T2 4#o,eine 2)mg K

a#etamino'hen 2(Jmg6

Per#o#et 4o3&#o,one Jmg K

a#etamino'hen 2(Jmg6

Mor'hine SR Amitri't&line

To $"m "'U
A#"te 'ain management D$teoarthriti$ !hroni# low %a#k 'ain Ne"ro'athi# 'ain Minor $i,e effe#t$ 4e;g; na"$ea, #on$ti'ation, $e,ation6 Serio"$ $i,e effe#t$ 4e;g; $1, $erot $&n,, re$' ,e're$$ion6 A%"$e 'otential !o$t

Thank Fo"
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