Chronic Pelvic Pain in Women (1 of 16)

1 Patient presents w/ symptoms suggestive of chronic pelvic pain (CPP)

2 3 COMMON EVALUATION Yes CAUSES OF CPP Do symptoms point to a • Treat according speciﬁc disease? to speciﬁ c disease

4 CHRONIC PELVIC PAIN SYNDROME CPPS EVALUATE & TREAT FOR SPECIFIC CONDITIONS: • Gastrointestinal Are • Gynecological symptoms organ Yes • Musculoskeletal speciﬁ c? • Neurological • Psychological • Sexual No • Urological

A MultidisciplinaryMIMS treatment CONSIDER GENERAL ANALGESIC TREATMENT OF CPP

GENERAL ANALGESIC © TREATMENT OF CPP See next page

B1 © MIMS 2019 CHRONIC PELVIC PAIN B 1 REFER TO PAINREFER SPECIALIST Please see Neuropathic Pain disease management information. Neuropathic for further chart Paindisease see Please • • Pharmacological therapy Pharmacological • • • agents: Alternative • • agents: 1st-line trial 1STLINE AGENT ROTATE AGENTS ROTATE DIFFERENT ADDING CONSIDER Topical Capsaicin Pregabalin Nortriptyline Gabapentin or Amitriptyline Is pain relief relief Is pain Is pain relief relief Is pain adequate? adequate? Yes ©No No Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Chronic Pelvic Pain inWomen (2of16) GENERAL ANALGESIC TREATMENT OF CPP TREATMENT ANALGESIC GENERAL Yes Yes • • REFER BACK TO BACK REFER REDUCTION DOSE CONSIDER TREATMENT CONTINUE PRIMARY CARE CARE PRIMARY neuropathic PHYSICIAN Is the pain Is thepain MIMS nature? B2 1 in in Yes Yes B Pharmacological therapy Pharmacological • • W/ NEUROPATHIC CONSIDER TRIAL TRIAL CONSIDER NSAIDs Paracetamol Is pain relief relief Is pain relief Is pain adequate? adequate? AGENTS No No No © MIMS 2019 CHRONIC PELVIC PAIN • • • • • Examination Physical • • • • • • • • History - - are identifi tohelp specifi guide ed c therapy are to diff structures then pelvic examined Individual of tenderness erentiate areas sources of pain & localized ofpain cause anintraperitoneal indicates test onthe head-raise Painlessening - - pressure avigorouspainresponse) elicits where light localized (areas ortrigger points around scars, hypersensitivity forskinlesions, checking includes exam Abdominal sacroiliac tenderness asymmetry, pelvic theCheck back fortrigger points, forgeneral demeanor,Observe mobility, when patient into &posture the clinic walks physical contributors able toreproducebe the paintoidentify If pain is intermittent, while for pathological in conditionspain in order patient to look & to examined is best tools symptom-based usingother validated comorbidities detected Psychological may be also - the from International &PEforms Pelvic ofthe May makeuse history PainSociety - problems) sleep dysfunction, sexual &physical (tiredness, use), &medication ofactivity control (level behavioral ordepression), perception), ofanxiety emotional (symptoms pain problems), isolation, family cognitive including (painassessment, environmental, (social to CPP social more than has one component often is CPP to investigate & goal of assessment contributing related factors - eff onquality oflife ect activity, sexual trigger situation, urination, defection, relation w/menses, tomovement association &posture, painaccordingCharacterize quality, toits intensity, duration, location, factors, aggravating oralleviating timing, - pelvic pain syndrome (those without obvious pathology) obvious without (those painsyndrome pelvic into specifi subdivided may be CPP pain(conditions w/well-defic disease-associated &chronic pathology) ned &mechanisms responses & cognitive, emotional, behavioral, &sexual involving the CNS, include acutepainthat mechanisms involving visceral orsomatic tissue,chronic isin progress CPP pain A complex problem that &multidimensional multifactorial isboth - understood pathophysiology iscomplex ¬well ¬adiagnosis; It factors w/anumber ofcontributory isasymptom w/pregnancy tointercourse isnotrestricted ormenstruation &isnotassociated Inwomen, CPP - care medical disability orneed functional enough tocause &issevere orthe buttocks; back, lumbosacral the the at umbilicus, anterior orbelow wall abdominal tothe pelvis, cyclically, localized orsituationally; painof>6-month &severe duration; occurs intermittently, distressing, isapersistent, pain(CPP) Chronic pelvic - disorders &sexual psychiatric endocrine, of infectious, ofsystems including athorough symptoms &neurologic review musculoskeletal, urologic shouldinclude organ-specifi history A complete &detailed gynecologic, ongastroenterologic, c inquiries & a rectal exam to check for nodularity, masses, or point tenderness tenderness orpoint fornodularity, to check exam & arectal masses, abimanual by exam, followed one-handexam examinations w/asingle-digit genitalia pelvic exam, External component indicating may amyofascial trigger show points floor &pelvic outer pelvis, Palpation ofthe back, off legs both ofthe cause pain amyofascial inpainindicates the table) w/anincrease Carnett’s (examiner’sA positive sign finger onthe tender ofthe area patient’s abdomen whilepatient raises orparesthesia-like electrical, stabbing, burning, be Visceral &neuropathic somaticdullorsharp, painmay painisdull,crampy, painmay be localized, orpoorly ofage >40years bleeding vaginal menopause, irregular pain after new ofage,years bleeding, postcoital at symptoms >50 bowel suicidalideation, new weight loss, mass, pelvic noting“red fl by diseases systemic orother severe Rule outmalignancy bleeding, rectal eg symptoms ag” infl &chemical &hormones mediators ammatory thatIt isaff inthe system development isassumed ofchronic pain,the nervous amongothers by ected use of IUD, history of physical or sexual abuse, history ofalcohol abuse &drug abuse, history ofphysical orsexual ofIUD,use history or orinfections surgery treatment, recent ofpelvic radiation ormedical pregnancy, forprevious history Ask - Inspect also forenlargement, also prolapse, discoloration, sequelae distortion, orinfectious Inspect - - © patientwhich makes CPP vulnerable todeveloping achild orsomatization may tothe abuse as anxiety lead development ofsexual ofdepression, A history Chronic Pelvic Pain inWomen (3of16) 1 CHRONIC PELVIC PAIN 2 MIMS EVALUATION B3 © MIMS 2019 CHRONIC PELVIC PAIN Proctitis Anal fissure* Hemorrhoids* Chronic intermittent bowel lesions Neoplastic Diverticulitis* Constipation* Chronic appendicitis Abscess Infl disease* bowel ammatory syndrome* bowel Irritable Gastrointestinal: • • • • Laparoscopy • • • • Imaging • • • TestsLab *Please refer to the corresponding disease management refer formore chart information disease tothe*Please corresponding obstruction Treatment the specifi towards isdirected c condition &according specifi toits c guidelines are the common ofCPP efollowing causes treatment inwomen &surgical emainstay diagnosis ofboth ofCPP orboth) adhesions, conditions (endometriosis, toconfi laparoscopy isperformed abnormality issuspected, If apelvic &totreat contributing diagnosis rm disease orrectovaginal inthe pelvis palpable nodules inassessing used may MRI be - onexamination ofpatient notelicited forpainwas cause ifaclear helpful may MRI be - fi ultrasound are notroutinely help scans donebutcan evaluate &CT MRI ndings masses pelvic inevaluating Useful - of aspecific diagnosis are &physical unrevealing exam workup ofthe ifhistory initialdiagnostic ispart Transvaginal ultrasound pelvic when indicated clinically performed Should only be scan CT MRI, Eg Ultrasound, - aspecifi &PEmay toward point ehistory indicated may testing be forwhich special c diagnosis - appropriateCancer screening topatient’s done age shouldbe &related factors risk Off activepatients tosexually w/CPP infections transmitted forsexually er screening - culture stool & swabs, &endocervical vaginal culture, w/urine beta-hCG, urinalysis ESR, Initial workup aCBC, includes © the workup routine diagnostic forspecifi are reserved ormethods tools diagnostic Other special in included butshouldnotbe c questions orfrequency urgency pain,urinary pelvic bloating, month: per occur >12times satiety, Early symptoms ifthe following measured shouldbe CA-125 A serum Chronic Pelvic Pain inWomen (4of16) 3 Fibroids orLeiomyomas* Pelvic congestion syndrome Post-hysterectomy pain remnant syndrome Ovarian syndrome ovary Residual cysts Ovarian Deformities/Prolapse malignancies Gynecologic Adenomyosis Chronic endometritis Vulvodynia Pelvic infl disease* ammatory Pelvic adhesions Dysmenorrhea* Endometriosis* Gynecological: 2 COMMON CAUSES OF CPP MIMS (CONT’D) EVALUATION B4 Musculoskeletal &connective Musculoskeletal Hernias anisyndrome Levator disease Disc Chronic back pain Stress fractures Coccygodynia Pelvic pain girdle Pelvic fl &spasms/ myalgia oor pain(trigger points) Myofascial Musculoskeletal: tissue malignancies prolapse © MIMS 2019 CHRONIC PELVIC PAIN Schizophrenia*, schizotypal & Schizophrenia*, schizotypal paindisorders Somatoform Neuropathic pain* dysfunction Neurologic Substance abuse stress Psychological entrapmentNerve syndrome disturbanceSleep oforcurrent physical or History Depression* Psychiatric/Neurological: • • Aspect Gynecological • • • • • Proctalgia) (Chronic AnalPain Syndrome Chronic Aspect Gastrointestinal • • • • • • 1 management refer formore chart information disease tothe*Please corresponding Urinary TractUrinary inWomen Infection Tract orUrinary –Complicated management –Uncomplicated Infection charts disease - carefully assessed must symptoms be &urinary w/gastrointestinal Pain associated cause Pain that islikely tohave ispredominantly agynecological cyclical May consider Salbutamol forintermittent inhaled sacralneuromodulation; analpainsyndrome - eff(less stimulation tibialnerve percutaneous than biofeedback), ective Treatment: stimulation is the treatment,preferred electrogalvanic toxin Botulinum A injection, Biofeedback testing Workup: defecography, MRI Endoscopy, expulsiontest, manometry, balloon anorectal fl rectal pelvic muscle oor - pain syndromes considered may ofthe asubgroup be chronic anal Intermittent fugax) (proctalgia chronic analpainsyndrome muscle tractionofthe puborectalis onposterior tenderness demonstrates severe Also abscess &fissure, ischemia infl hemorrhoids, cryptitis, painare coccygodynia, intramuscular excludedrectal eg disease, bowel ammatory 20 at least lasting other of episodes causes minutes, Chronic painoraching, orrecurrent rectal diagnosis: 3 for the met past should be criteria 6 efollowing atmonths of symptoms least w/ onset months before forthe the Study by recommended International ofPain(IASP) system Association onthe axis Based - ifw/adequate evidences (EAU) ofUrology European Association onthe classifi based according phenotype corresponding toits subdivided Should be the by cation proposed &neuropathic include neuroplasticity painmechanisms Mechanisms relationship dynamics &family changes inthepain isnotconsistent are present, ofdepression &signs w/tissuedamage, offunction loss incomplete therapies, months, prior from pain reduction Pain persistence the by following: >6 suggested Also dysfunction orsexual gynecological, tract, that urinary lower are suggestive ofabowel, cognitive, consequences behavioral, emotional w/negative orsexual inadditiontosymptoms associated that process account can It ongoing disease isthe anobvious forthe without occurrence pain,often ofCPP orspecifi localized painispoorly when pelvic used may be also CPPS eterm isunidentific pathology ed Patients may perceive coming symptoms the 1organ systemic painas from orfrom - ofCPP,A subdivision to>1 organ site ispainlocalized CPPS delusional disorders marital) (work, abuse sexual dysfunction ofCPP dysfunction eff oracomponent cause orasecondary ofCPP primary brought theect by eff about erent neurological a may &these be areSymptoms inwomen frequently w/CPP orinterstitial suggestive seen ofIBS cystitis © episodes tomin,absence painbetween ofanorectal sec several from lasting to the anus episodes orrectum, lower of pain localized episodes Recurring diagnosis: before months 6 atmonths ofsymptoms least w/onset 3 forthe met past shouldbe criteria diagnostic efollowing 4 Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not CHRONIC PELVIC PAIN SYNDROME (CPPS) SYNDROME PAIN PELVIC CHRONIC Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing 3 Chronic Pelvic Pain inWomen (5of16) COMMON CAUSES OF CPP (CONT’D) Chronic urinary tractinfection* Chronic urinary Urethral syndrome Interstitial cystitis Urological: MIMS malignancies Urological Urolithiasis* ordysfunction stones Bladder B5 1 Heavy metal poisoning metal Heavy zoster Herpes Hyperparathyroidism* Porphyria Sickle cell disease infection Mesh Chronic painsyndromes diseases Infectious Others: © MIMS 2019 CHRONIC PELVIC PAIN • • Aspect Psychological • • • • • • Neuralgia Pudendal Aspect Neurological • • • • Pain Syndrome Muscle Pelvic Floor • • • • (Coccygodynia) Pain Syndrome Coccyx Aspect Musculoskeletal • • • • Vaginal &Vulvar Pain Syndrome • Pain Syndrome Endometriosis-associated • Dysmenorrhea (Cont’d) Aspect Gynecological an existing psychopathologic condition psychopathologic an existing may aff also painperception &encourageect the development ofchronic pain isdiffi &CPP diseases Evaluating psychiatric the link between whilechronic inapsychopathology, result paincan cult; problems oremotional confl w/psychosocial associated ict forapersistent paindisorder inwhich somatoform pain is criteria the ofpatients diagnostic Majority meet Treat available utilize toneuropathic standard regimens painmanagement forany injury; as other nerve - problemTreatment: issuspected nerve ifaperipheral Refer toaspecialist injection anesthetic local locator-guided standard isanimage &nerve Gold - Workup: butinvestigations normal are often may &neurophysiology aidinthe Imaging diagnosis, Patient’s muscular immobility&disability &painthat aches develop toinvolvement lead ofthe musculoskeletalsystem cancer, falls), fractures, (eg trauma, birth orcycling surgery, older &postmenopausal women; ofpelvic rarely intrauma sitting, prolonged w/history Associated (pins&needles) paresthesia stimulus), (heightened & apainful hyperalgesia painperception after duetoprovocation), but notnecessarily perceptions usually (unpleasant (painonlight sensory Related features touch), include dysesthesia allodynia the from anus painperceived inthe toclitoris perineum orelectric crushing Burning, Management involve ofpainwill aphysiotherapist, apaindoctor, &apsychologist - fl May consider &pelvic fortrigger Atoxin Botulinum injection points muscle overactivity oor - Treatment trigger points formyofascial isrecommended pressure orneedling by - adjuvant tomuscle as exercises Use biofeedback - Treatment: First-line treatment fl ispelvic muscle therapyoor inpatients w/CPPS Workup: Test fl forpelvic fl pelvic trigger points, &myofascial function oor muscle EMG oor involved may be trigger also points fl ofthe due tomisuse pelvic of myalgia a form be can CPP fl pelvic muscles; oor &myofascial overactivity oor evacuation w/incomplete &isfrequentlyA dullpressure orache that associated down w/sitting worsens orlying isunstable ifcoccyx injection Consider local - Treatment: Anti-infl physical therapy, drugs, neuroablation massage, ammatory Workup: painrelief produces injection anesthetic Local orintercourse defecation, sitting, bending, Usually related arising, sittingby toprolonged ortrauma &isworsened manipulation that its fl by elicited isduetopelvic Pain at the coccyx mobility coccyx &reduced hypertonicity oor - fortreatable Laparoscopy causes - innature cyclical considered forpainthat to be should be seems orDanazol) Treatment: agonists, GnRH treatments Hormonal (combined progestins, oralcontraceptives, Workup: laparoscopy examination, ultrasound, Complete gynecological abnormal infl totrauma orinfection response ammatory or allergies to chemicalsinfections or other or muscle, to yeast tosubstances, the irritation hypersensitivity nerve or injury ofchronic changes, abuse, hormonal antibiotic orsexual use include history ofvulvodynia Causes vulvodynia entrance) called also cause; &vaginal w/noknown clitoris, for>6 Pain persisting months which orthe the includes inthe female labia, genitalia external vagina (vulva dysfunction bowel cognitive behavioral, oremotional w/negative eff &associated strategies apeutic or urological orsexual, ects, Patients w/laparoscopically-confi w/chronic appropriate orrecurrent endometriosis paindespite ther-rmed effemotional orsexual ects cognitive, behavioral, w/ negative if persistent a chronic considered & associated May pain syndrome as be refractory chronic vulvar pain chronic vulvar refractory treatment for &psychological approachOther therapies forpersistent include amultidisciplinary diseases 4

© (CONT’D) (CPPS) SYNDROME PAIN PELVIC CHRONIC Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing A Chronic Pelvic Pain inWomen (7of16) MULTIDISCIPLINARY TREATMENT MIMS B7 © MIMS 2019 CHRONIC PELVIC PAIN • • Surgery Open • • &Laser) (Coagulation Transurethral Resection • • • • • Neuromodulation • • • Neuroablation • • • TreatmentsSurgical/Invasive • • • (TENS) Stimulation Transcutaneous Nerve Acupressure, Acupuncture, • • Biofeedback • • • • Psychotherapy • • • Physical erapy • Exercise augmentation may relief provide bladder from pain w/bladder conduit w/ileal formation orsupratrigonal suggest that cystectomy cystectomy reports Some considered allotherShould forpatients onlybe after therapies w/bladder painsyndrome have failed ofpain& urgency alleviation inprolonged suggest that results transurethral laser Reports 3Cifconventional consideredMay inpatients be type w/bladder painsyndrome treatments are ineff ective isrequired research More detailed stimulationstimulation, nerve orperipheral spinal cord eg stimulation, in the stimulation, modulation sacral CNS root consecutive ganglion dorsal root information w/ Gabaminergic stimulated toanexaggerated leading sensory interneurons are electrically &chronic analpainsyndrome considered pudendal neuralgia May forbladder be painsyndrome, management pain inpelvic forchronic considered painrelief, specialists method by itshouldonlybe A possible stimulation stimulation, pudendal stimulation, nerve tibialnerve Eg percutaneous Sacralnerve recommended this be before can More studies are needed conduction tissueoralters neural neural destroys itdirectly neuralgia, floor orpelvic wall forabdominal Used cryoneurolysis radiofrequency, orcooled thermocoagulation, pulsed Eg neuroablation, Chemical radiofrequency the stage clinical successful ifarelatedOften pathological fi at even ofthe cause symptoms the possible tobe nding isbelieved paintransmission neural esymptomaticeff relies onthe orinterruptionofthe modulation pelvic forCPP procedures ofsurgical ect hysterectomy,Eg Adhesiolysis, neurectomy forchronic approved painreliefAcupressure patients hadbeen inoncology - pain pain&visceral-peritoneal Acupuncture pelvic inpatients helpful may w/myofascial be pain helps reduce somatic myofascial TENS muscle tension decreasing which painby control &decrease &general quieting w/physiological are relaxation taught pain Biofeedback pelvic topatients w/myofascial training tobiofeedback sources ofpainareMusculoskeletal responsive &that Patients causes itispossible come tounderstand &psychological that theirphysical, social painhas - the empiric most support &has used widely Most - therapies areCognitive-behavioral eff forcoping forpatients w/pain strategies ective indeveloping Psychotherapy into integrated the treatment shouldbe planat stage anearly treatment alone medical over tohave treatmentAddition response appears animproved ofpsychotherapy tothe medical ofCPP therapy,Eg Cognitive modifi behavioral cation, operant conditioning pain referred decreases Also Beneficial inwomen w/bladder painsyndrome - oftrigger inactivation Helps points component by treat the painsyndrome myofascial ofpelvic stimulation, heat &ice high-voltagegalvanic treatment ultrasound, eg ofCPP atreatment consideredShould diff as be optionas erent tohelp inthe appear physical therapy modalities &spasms tightness, muscle weakness, Corrects - w/ahomestretching managed may &exercise be program dysfunction duetomyofascial CPP © alteration ofsympathetic tone Benefi cial eff of endogenous release opioid,& gate control from may be ect increased ofpain pathways, to reduce painthrough their eff treatment orsurgical &w/medical orts A MULTIDISCIPLINARY TREATMENT (CONT’D) MIMS Chronic Pelvic Pain inWomen (8of16) B8 © MIMS 2019 CHRONIC PELVIC PAIN • • • • Anticonvulsants • • Inhibitors (SSRIs) Reuptake Serotonin Selective • • Inhibitors (SNRIs) Reuptake &Norepinephrine Serotonin • (TCAs) Tricyclic Antidepressants • • Antidepressants • • • Analgesics Neuropathic • • • • Anti-inflNonsteroidal (NSAIDs) Drugs ammatory • • (Acetaminophen) Paracetamol • Analgesics • • • • • Common sideeffCommon patients tolerated by butare often edema &peripheral dizziness, include drowsiness, ects w/ CPP A study that suggests Gabapentin signifi provides cant pain relief alone in womenor w/ Amitriptyline when used treatment ofneuropathic pain Gabapentin excessive inhibits stimulation ofthe spinal cord’s inthe &iscommonly neurons used secondary Eg Gabapentin, Pregabalin sideeffHave fewer their butstudies toshow benefiects painare insuffit inpelvic cient Eg Paroxetine, Sertraline Venlafaxine ofbenefi evidence has t forchronic w/caution disease inpatients pain;use w/heart Eg Duloxetine, Venlafaxine &Imipramine include Alternatives Nortriptyline - is the commonlyAmitriptyline most used outcomesclinical Treatment therapies &other may medical improve support w/antidepressants together w/psychological totreat concomitantUsed depression Side eff usuallylimittheir use ects quality oflife in combination, are benefiagainst titrated used doses Often t & side eff w/ the goal of improving patient’sects Agents that centrally modulate painwhich are required taken than regularly mediated as than pain isbetter another that forpelvic toshow oneNSAID evidence ere isnogood fi are mostly as recommended NSAIDs rst-line empiric therapy - considered formildtomoderate pain should be NSAIDs conditions orinfl related inpainful Useful toperipheral mechanisms ammatory Anti-infl enzyme that analgesics &antipyretic inhibitthe cyclooxygenase ammatory tried little considered inthe treatmentHas ifnotpreviously evidence butshouldbe ofCPP w/acentral analgesic An antipyretic ofaction mechanism oftime period foraprolonged used shouldnotbe forCPP Analgesics Ifthere isstillnoimprovement, consider referral toapainspecialist - initiallythenSimple neuropathic adequate painrelief are used toprovide analgesics agents ifthe failed former eff Lowest ifbenefi used shouldbe dose ective sideeff- by t islimited ects thus the sideeff minimizing ects agreater benefiCombination therapy gives often forusage doses oflower t than aloneallowing agents used components &social psychological biological, are general below inamanagement treatmentsListed that used planw/aholisticapproach shouldbe including inchronic painmanagement physiciansConsider involving w/expertise trained at this stage complicated the treatment least Aimtoprovide that capacity improve can functional - - initiated been Patients off shouldbe paincontrolered iftherapeutic have maneuvers w/appropriate notyet even analgesia © initially explained Attempts made to empirically treat a management the should be pain & develop be if pain cannot plan even Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Chronic Pelvic Pain inWomen (9of16) B MIMS PHARMACOLOGICAL THERAPY B9 © MIMS 2019 CHRONIC PELVIC PAIN • Antibiotics • • • • ToxinBotulinum Type A Other erapies • • Injection Anesthetic Local • • • • Opioids • Antipsychotics • Topical Capsaicin • Agents Other • • Adjuvant therapy w/ antibiotics can be of supporting help inspecifiAdjuvant therapy ofsupporting be w/antibiotics can c conditions Data onoptimum dosage, &eff technique duration areect lacking eff ofits because successful oftrigger ininactivation points been Has onmuscle contractionect reduce the itcan pressure resting amuscle inthe fl muscles relaxant, ofthe As pelvic oor - intoInjections the fl muscles ofthe pelvic have demonstratedoor benefi t of acetylcholine eff release atInhibits the aparalyzing neuromuscular junction & has muscles on the striated ect eff to be reported been Has pain pelvic formyofascial ective of CPP relief toprovide anesthetic Trigger w/alocal injected may &sacrum be vagina ofthe wall, abdominal points Tramadol ofactionw/eff adualmode has &serotonin onopioidreceptors release ects - visceral pain states eg inhyperalgesic than better Morphine may Oxycodone be - Transdermal Fentanyl considered may iforalpreparations be are restricted - isthe fi Morphine rst-line opioid - & Hydromorphone Weak Dihydrocodeine, opioidsare &Tramadol; Codeine, Fentanyl, strong Oxycodone, opioidsare Morphine, - - function non-narcotic therapieswhen &ifpersistent previous painisthe have major limitation failed toimproved eff adverse toits Due maintenance as &potential forabuse,given opioidsmay only be therapy ects forCPP specialist ofatrained under the adequate supervision used Should only be non-malignant pain act onthe of the dorsal horns spinalcordOpioids causing central totreat chronic inhibition of pain; &isused antipsychotics onatypical research further suggests review butasystematic used previously Have been tolerated More convenient application well may topical than though other notbe duetoits skinsensitivity medications inpainmanagement tospecialists limited &are best tried standard optionshave after been Considered Consider available painmanagement w/appropriate staff facilities - complex &cognitive behavioral Provide medical interventions eg - topatients care w/complex needs &secondary support specialized Provide - - inpatientsFollow-up longterm may w/complex be conditions ifpainisstillinadequately controlled Consider referral toaspecialist - oftreatment &revision May dore-evaluation - of treatment failure to the nature multifactorial Due of CPP, to for check cases & treatment reviewed diagnosis be should always w/ an opioid is given anotherw/ anopioidisgiven agent that tolerated better may be rotationOpioid donewherein may be apatient signifi experiencing cant sideeff &inadequate painrelief ects stimuli thus use limitingits may hyperalgesia happen wherein Opioid-induced patients more topainful sensitive onopioidsbecome ©multispecialized management painassessment, &rehabilitation togive that &Pain specialists are interdisciplinary B Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing PHARMACOLOGICAL THERAPY (CONT’D) Chronic Pelvic Pain inWomen (10of16) FOLLOW-UP

B10 MIMS © MIMS 2019 CHRONIC PELVIC PAIN 1 Combination w/Tramadol the forspecifi latest MIMS see isavailable. Please information. c prescribing Morphine sulfate Morphine Alkaloids Natural Opium (Acetaminophen) Paracetamol Preparation Anilide Floctafenine 400-600 mg PO 400-600mgPO Floctafenine Analgesic Other Capsaicin Anesthetic Local as Agent Used Other All dosage recommendations are for non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults non-elderly for are recommendations dosage All Drug Drug Products listed above may not be mentioned in the disease management chart but have been been have but chart management disease the in mentioned be not may above listed Products 1 placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed 1000 mg PO 12hrly 1000 mgPO relief 12-hrpain achieve days to following Titrate dosage over 12 hrly Initially 20-30mgPO opioids: weaker by Pain uncontrolled or 10-15 mgPO opioid: Without of use prior or 4hrly 10-30 mgPO daily 1200mg dose: Max 24 hrly © aff 6-8hrly areas ected Apply thinly to 0.075% cream 0.025% gel, lotion 0.0125% gel, lotion Available strengths: Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Dosage Dosage Initially Initially Chronic Pelvic Pain inWomen (11of16) ANALGESICS (NON-OPIOIDS) ANALGESICS ANALGESICS (OPIOIDS) ANALGESICS Dosage Guidelines • Instructions Special • Reactions Adverse • • • • Instructions Special • Reactions Adverse • • Instructions Special • Reactions Adverse • • Instructions Special • Reactions Adverse damage. Concomitant w/Warfarin use liver Use w/caution inpatients severe w/renal dysfunction, nephropathy)w/ chronic analgesic overdose, ammonia);Renal eff increased phosphatase, (nephrotoxicity ects Hepatic eff dyscrasias); blood &alkaline bilirubin (increased ects Hematologic eff &Ca); bicarbonate Na, decreased (anemia, ects eff Metabolic Rash; acid&glucose; Cl,uric (increased ects Avoid oradministration abruptwithdrawal ofnarcotic antagonist Tolerance use long-term may upon develop depression resp disease, acuteresp poisoning, by caused diarrhea toopiate narcotichypersensitivity analgesics, concomitant (or 2wkofuse), within w/MAOI use Avoid ileus, paralytic inpatients w/acutehepatic disease, hypothyroidism, anemia depression, CNS ofconvulsions, history insuffi resp conditions, abdominal ciency, shock, hypotension, Use w/ caution inpatients w/renal orhepatic impairment, sweating) shock, arrest, &cardiac resp depression, circulatory Other eff hallucination,confusion, euphoria); & (resp ects GI eff (N/V,ects eff constipation); CNS (somnolence, ects w/ beta-blockers, severe heart failure, CHD failure, heart severe w/ beta-blockers, antrafenine, treatment aloneorincombination, associated Avoid toglafenine or hypersensitivity inpatients w/known administrationAvoid repeated occasional acuterenal insuffi reversible micturition, ciency, drowsiness burning GIdisorders, anaphylactic-like reactions, Allergic-type Treated area should not be exposed to heat or direct sunlightTreated toheat ordirect exposed shouldnot be area membranes skinormucous tobroken applied orirritated Should not be burning temporary irritation, Local

B11 MIMS Remarks Remarks © MIMS 2019 CHRONIC PELVIC PAIN 1 Combination w/ Naloxone HCl is available. Please see the forspecifi latest MIMS Combination w/Naloxone see isavailable. HCl Please information. c prescribing Oxycodone (Cont’d) Alkaloids Natural Opium Fentanyl Derivative Phenylpiperidine All dosage recommendations are for non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults non-elderly for are recommendations dosage All Drug 1 Products listed above may not be mentioned in the disease management chart but have been been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed pain relief if necessary, toachieve frequently once as aday Titrate carefully, dose as 12hrly 5 mgPO impairment: orhepatic Renal 12hrly 10 mgPO patients: Opioid-naive © 25 mcg/hr, ifrequired Titrate at 12or dose 25 mcg/hr ¬exceed initial dose the as dose the lowest Use adult: Opioid-naive application after intervals at regular assessed patient &shouldbe ofthe & opioidhistory status the medical upon based Individualized Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Chronic Pelvic Pain inWomen (12of16) Dosage ANALGESICS (OPIOIDS)(CONT’D) ANALGESICS Dosage Guidelines • • Instructions Special • Reactions Adverse • • • • Instructions Special • Reactions Adverse • •

B12 MIMS increased cerebrospinalincreased orintracranial pressure, renal impairment, acutealcoholism,abdomen, severe surgical suspected ileus, paralytic arrhythmias, Avoid inpatients cardiac depression, w/acuteresp tractdisease intracranial biliary pressure, hypotension, chronic nonmalignant pain,hypothyroidism, raised abuse, fordrug ortendency history hepatic disease, Use w/caution inpatients w/chronic pulmonary, renal/ fever,pruritus, chills) sweating, alteration, rash, orthostatic hypotension, Otherdisturbances; eff voice (pharyngitis, ects effResp GI&CNS dyspnea); (bronchospasm, ects convulsive disorders, concurrent (orconvulsive 2wk) within MAOIs disorders, patches notcutthe Do &supervision. evaluation proper without patch toanother 1transdermal from system not switch patch Do forupto24hrafter removal. monitored be should events adverse Patients serious whoexperienced Notforacuteorpost-op function. pain CNS impaired severely dysrhythmias, pain, bradycardiac short-term states of ileus, ofhaving paralytic suspected patients whohave bronchial or asthma, severe Avoid inpatients w/signifi acute/ cant depression, resp application intracranial pressure. Fever/external heat increased bradyarrhythmias, disease, pulmonary dysfunction, Use w/caution inpatients w/hepatic &renal 72hr Patch every replaced shouldbe hypoventilation) retention, erythema, rash, urinary sweating, (pruritus, eff Other bradycardia); eff (hypotension, ects ects Cardiac hallucination, headache, confusion, euphoria); GI eff (N/V,ects eff constipation); CNS (somnolence, ects Avoid abrupt cessation use ofprolonged Tolerance &physical dependence may develop Remarks © MIMS 2019 CHRONIC PELVIC PAIN 1 Combination w/ Paracetamol is available. Please see the forspecifi latest MIMS Combination see w/Paracetamol isavailable. Please information. c prescribing Tramadol Opioid Other Pregabalin Gabapentin All dosage recommendations are for non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults non-elderly for are recommendations dosage All Drug Drug 1 Products listed above may not be mentioned in the disease management chart but have been been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed Max dose: 600mg/day dose: Max 7-day interval another after dose max to further May increase interval 300 mg/day a3-7day after to increased May be 8-12 hrly divided 150 mg/day PO dose: Initial 3.6g/day dose: Max of 3600mg/day dose 2-3 days up toamax every increments of300mg/day in dose increase & tolerability, may onpatient response Based 8hrly 3:300mgPO Day 12hrly 2:300mgPO Day 1 Day dose: Initial © 400 mg/day dose: Max 4-6 hrly 2-3min over 50-100 mgIMorIV or 400 mg/day dose: Max 100 mgPO Initially pain: Severe 8-12 hrly 50-100 mgPO : 300 mg PO 24hrly : 300mgPO Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Dosage Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Dosage Chronic Pelvic Pain inWomen (13of16) ANALGESICS (OPIOIDS)(CONT’D) ANALGESICS Dosage Guidelines ANTICONVULSANTS • • • Instructions Special • Reactions Adverse analgesics or psychotropics, narcotic treatment withdrawal orpsychotropics, analgesics hypnotics, tochronic lungdisease, secondary failure heart conditions inwhich intracranial injuries, pressure israised, head acutealcoholism, &excessive bronchial secretions, cyanosis Avoid inpresence of in patients especially depression w/resp long-term use long-term Possibility oftolerance, &physical dependence w/ psychic pressure, patients prone toconvulsive disorders orinshock intracranial hypothyroidism, increased impairment, disorders, resp Use hepatic &renal w/caution inpatients function w/ severe disorder) micturition allergic reactions, fl facial (skin reactions, miosis, hypothermia, sweating, ushing, Other eff orthostatic hypotension); palpitations, (bradycardia, ects eff Cardiac restlessness); muscle weakness, mood, ects changes headache, in fatigue, seizures, hallucinations, confusion, eff changes); CNS appetite heartburn, (drowsiness, ects GI eff (N/V,ects spasm, mouth, biliary constipation, dry • • Instructions Special • Reactions Adverse • • • Instructions Special • Reactions Adverse May aff patient’sect ability or operate machinery todrive renal impairment, DM defilactase malabsorption, orglucose-galactose ciency intolerance,Use w/caution inpatients w/galactose (constipation, fl vomiting, atulence); Other eff (fatigue) ect GI eff libido, irritability); decreased appetite, increased ects mouth, vertigo, dry diplopia, vision, blurred paresthesia, impairment, tremor,coordination, memory dysarthria, attention disturbance, ataxia, abnormal mood, effCNS euphoric confusion, (somnolence, dizziness, ects May aff patient’sect ability oroperate machinery todrive 1wk at over alternative therapy least gradual shouldbe Discontinuation &/oradditionorsubstitution of renal impairment illness, ofpsychotic Use w/ caution inpatients w/history &/orvomiting) nausea (fatigue, tremor,headache, amblyopia);Other eff diplopia, ects effCNS nystagmus, ataxia, (somnolence, dizziness, ects

B13 MIMS Remarks Remarks © MIMS 2019 CHRONIC PELVIC PAIN Nortriptyline Amitriptyline Tricyclic (TCAs) Antidepressants Venlafaxine 24hrly 60mgPO Duloxetine (SNRIs) Inhibitors Reuptake &Norepinephrine Serotonin All dosage recommendations are for non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults non-elderly for are recommendations dosage All Drug Products listed above may not be mentioned in the disease management chart but have been been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed © 12 hrly ordivided dose bedtime single as 75 mgPO : dose Usual interval onawkly dose day tomax 25mg/ by dose Increase at bedtime 10-25 mgPO dose: Initial 150 mg/day : dose Max interval onawkly dose day tomax 25mg/ by dose Increase at bedtime 10-50 mgPO dose: Initial 225 mg/day dose: Max interval 37.5-75 mg/day onawkly by dose Increase 12-24 hrly 37.5mgPO dose: Initial 120 mg/day dose: Max Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Dosage Chronic Pelvic Pain inWomen (14of16) Dosage Guidelines ANTIDEPRESSANTS • • • • Instructions Special • • Reactions Adverse • Administration • • • Instructions Special • • Reactions Adverse Do not stop medication abruptly; taper dose over several wk several over taper dose abruptly; notstopmedication Do disease forelderlyNot recommended patients w/CV &those function ofepilepsy, impaired hepatic DM, history disease, w/ CV constipation, untreated angle-closure patients glaucoma, retention, chronicUse w/ caution inpatients w/urinary response tothe desired upward sideeff tominimize dose w/alow Start &titrate ects gain wt sweating, tachycardia, N/V,older patients, hypotension, irritation, gastric tremor,ataxia, in occur especially confusion/delirium can neuropathy, peripheral headache, insomnia, nervousness, occur, can drowsiness retention, hyperthermia, pressure, intraocular urinary increased vision, blurred mouth, constipation ileus), (mayDry toparalytic lead gradually &increased at dose low ifstarted decreased may be Side eff are mostly duetoantimuscarinic actions & ects Total at given bedtime should be dailydose wk several over taper dose abruptly; notstopmedication Do Use w/caution inrenal &hepatic impairment response tothe desired upward sideeff tominimize dose w/low Start &titrate ects Vasodilation,Dose-related: hypertension sweating) increased vision, Other eff tremor, yawning, (abnormal dreams, blurred ects GIeff anxiety); dysfunction, (constipation,ects diarrhea); sexual anorexia, loss, wt xerostomia, nausea, nervousness, effCNS insomnia, (somnolence, dizziness, ects

B14 MIMS Remarks © MIMS 2019 CHRONIC PELVIC PAIN eorfn50-100mgIM4hrly uptoa Naproxen Ketoprofen Derivatives Propionic Acid acid 24hrly 60mgPO Mefenamic Fenamic Derivative Acid 24hrly 400mgPO Etoricoxib Coxib Sulindac Acetic Acid Derivative Acetic Acid Tiropramide 100 mg PO 8-12hrly 100mgPO Tiropramide 8hrly 100mgPO Fenoverine All dosage recommendations are for non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults non-elderly for are recommendations dosage All Drug Drug Products listed above may not be mentioned in the disease management chart but have been been have but chart management disease the in mentioned be not may above listed Products NONSTEROIDAL ANTI-INFLAMMATORY DRUGS(NSAIDs) placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed Max dose: 1250-1375mg/day dose: Max 6-8hrly 250-275 mgPO then Initially 500-550mgPO of200mg/24hr max required 6hrly as PO then 250mg initially 500mgPO 8hrly or 250-500 mgPO © 200 mg12hrly upto May increase Dosage Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Chronic Pelvic Pain inWomen (15of16) Dosage Dosage Guidelines • Instructions Special • Reactions Adverse • • Instructions Special • Reactions Adverse ANTISPASMODICS hypersensitivity toTiropramidehypersensitivity failure, megacolon, circulatory tract, gastrointestinal Avoid source in patients ofthe ofmechanical w/stenosis Seldom N/V, constipation, allergic reactions mouth dryness, myopathy,mitochondrial renal insufficiency anesth orphysical eff orafter during ofhyperthermia history ort, Avoid ofchronic liver disease, inpatients w/activeorhistory Use w/caution inpatients or w/multiple therapy >60yr drug upset gastric rhabdomyolysis, reversible Myalgias,

B15 MIMS • • • Instructions Special • • Reactions Adverse - Coxibs should be used w/caution inpatients w/ used shouldbe Coxibs - hepatic orrenal impairment disorders, hemorrhagic orallergic asthma disorders, infections, Use w/ caution inpatients w/hypertension, - other NSAIDs or toAspirin ofallergy history failure, heart severe Avoid ulceration, inpatients use w/activepeptic GIeff todecrease w/food given May be ects have GIeffCoxibs lesser ects retention, photosensitivity, pancreatitis) (hepatotoxicity, nephrotoxicity, fl hematuria, uid Other eff neutropenia); thrombocytopenia, ects occur rarely); Hematologicsyndrome eff (anemia, ects Stevens-Johnson rashes, bronchospasm, (angioedema, reactions Hypersensitivity insomnia); drowsiness, depression, tinnitus, nervousness, vertigo, dizziness, effulceration, CNS GIbleeding); (headache, ects GI eff peptic diarrhea, GIdiscomfort, (nausea, ects failure, w/ risk factors for developing heart disease heart fordeveloping factors w/risk failure, ofcardiac history ventricular edema, failure, left arterial disease, cerebrovascular disease disease, arterial peripheral disease, ischemic heart failure, heart inpatients w/moderate used should not be Coxibs Remarks Remarks © MIMS 2019 CHRONIC PELVIC PAIN sodium polysulfate Pentosan (Dipyrone) sodium Metamizole Preparation Pyrazolone All dosage recommendations are for non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults non-elderly for are recommendations dosage All Drug Drug NONSTEROIDAL ANTI-INFLAMMATORY (CONT’D) DRUGS(NSAIDs) OTHER DRUGS ACTING ON THE GENITO-URINARY SYSTEM OTHER DRUGSACTINGONTHEGENITO-URINARY Products listed above may not be mentioned in the disease management chart but have been been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed © 8hrly 100 mgPO syndrome: pain Bladder 24hrly 1000-2500 mgIM/IV 6-8hrly or 500 mgPO Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Please see the end of this section for the reference list. reference the for section this of end the see Please Chronic Pelvic Pain inWomen (16of16) Dosage Dosage Dosage Guidelines

B16 MIMS • • • Instructions Special • Reactions Adverse • • Instructions Special • Reactions Adverse renal/hepatic impairment Avoid inpatients w/activehemorrhage, serious 3 mth treatment during Monitor patients every post-surgery varices, oresophageal hypertension severe endocarditis, bacterial cerebrovascular disorders, ulcer disease, peptic thrombocytopenia, disorders, blood hemorrhagic disorders, impairment, spleen Use w/ caution inpatients w/renal orhepatic pain) pelvic hyperkalemia, use, w/prolonged (osteoporosis eff Other eff drowsiness); (headache, ects ects effDermatologic CNS skinnecrosis); (alopecia, ects hemorrhage, pain,rectal abdominal dyspepsia); GI eff abnormal LFTs, diarrhea, (nausea, ects patients orunstable w/hypotension hemodynamics Parenterallyintermittent in hepatic porphyria. acute anaphylactoid toanalgesics, reaction orother bronchospasm system, hematopoietic ofthe ordiseases function marrow bone orcongenital G6PDdefiporphyria ciency, impaired Avoid allergy, in patients w/pyrazolone hepatic &intensive Prolonged usage urticaria. renal orhepatic impairment, chronic infections, chronic tract resp bronchial asthma, disorders, coagulation circulation, blood instability ofblood 1wk, forat least immunoallergic lasting origin w/an agranulocytosis Metamizole-induced Use w/caution inpatients w/incidence of at reactions inj site) painorlocal proteinuria, anuria or oliguria, rash, mucosal symptoms, dyscrasia, blood angioedema, severe reactions, Other eff (rarely anaphylactic/anaphylactoidects shock); &circulatory hypotension (cardiac arrhythmia, effResp eff Cardiac bronchospasm); (dyspnea, ects ects Remarks Remarks © MIMS 2019