Transcript Rheumatoid Arthritis/Osteoarthiris

Rheumatoid Arthritis/Osteoarthritis
Sarah Daoud
Florida A&M University
College of Pharmacy and Pharmaceutical Sciences
10/02/13
Seminar: Disease Presentation
Objectives
 Discuss the prevalence, epidemiology, risk factors, and
pathophysiology of RA/OA.
 Discuss the signs and symptoms, diagnosis, and treatment of
RA/OA.
 Assess treatment of disease states in special populations.
 Evaluate the role of the pharmacist in the overall approach
of these conditions.
 Discuss key components of RA/OA which would serve as
educational points for patients and healthcare practitioners.
RHEUMATOID ARTHRITIS
Prevalence
 RA is the most common form of autoimmune arthritis
affecting more than 1.3 million Americans.
 Women encompass 75% of individuals diagnosed with
this disease.
 1-3% of women may get RA in their lifetime.
 Usual occurrence is in individuals between 40-60 years of
age.
Epidemiology
 RA does not have any racial inclination and can occur at
any age.
 Research has shown, this disease has a genetic
predisposition and diagnosis may be necessitated by
certain unknown environmental exposures.
 Major histocompatibility complex (MHC) molecules located
on T-lymphocytes play a major role in patients with RA.
 Human lymphocyte antigen (HLA) typing can characterize
these molecules and assess the risk of RA in those with
presence of antigens on MHC molecules.
Risk Factors
 Sex (Female)
 Family history
 Older age
 Silicate exposure
 Smoking
 Consuming 3 or more cups of coffee/day (esp.
decaffeinated coffee)
Pathophysiology
Signs and Symptoms
 Morning stiffness lasting hours (sometimes whole day)
 Fatigue
 Weakness
 Low-grade fever
 Loss of appetite
 Joint pain
 Firm lumps
***Joint involvement tends to be symmetrical
Diagnosis
Non-pharmacological Treatment
 Rest
 Occupational therapy
 Physical therapy
 Use of assistive devices
 Weight reduction
 Surgery
Pharmacological Treatment
Pharmacological Treatment
 Agents used for pain and inflammation
Drug
Dosage
Adverse Effects
Warnings/Contraindications
Notes
Ibuprofen (Motrin,
Advil)
->200-400mg Q6-8H
(mild to moderate pain)
->600-800mg Q6-8H;
max 3.2g/d (moderate
pain or inflammation)
-Dyspepsia
-Heartburn
-Increase BP
-GI bleeding
-NSAIDS have BBW of increased
risk of adverse CV thrombotic
events; contraindicated for
CABG perioperative pain;
increased GI adverse events
(ulceration, bleeding,
perforation)
-Contraindicated in pregnancy
3rd trimester.
-Avoid use in
advanced
renal disease.
Celecoxib (Celebrex)
->100-200mg BID
-Diarrhea
-Nausea
-Warnings are the same as
NSAIDS.
-Contraindicated with sulfa
allergy.
-Lower risk of
GI
complications.
-Max 400mg
Prednisone (Rayos,
Prednisone Intenson)
->Initial 5-60mg daily
indicated for acute
inflammation
->Can use twice daily
dose every other day to
decrease adrenal
-Fluid retention
-Stomach upset
-Increase
appetite.
-Hyperglycemia
-Osteoporosis
-Contraindicated with live
vaccines, systemic lung
infections.
-Must assess
bone density if
used longterm.
-Must taper
dose off.
Pharmacological Treatment
 Non-biologic Disease-modifying anti-rheumatic drugs (DMARDS)
Drug
Dosage
Adverse Effects
Warnings/Contraindications
Notes
Methotrexate
(Rheumatrex, Trexall)
->7.5-22.5mg/week
-N&V
-Diarrhea
-GI upset
-Anorexia
-Reddening of skin
-BBW: fetal death or
congenital abn.;
hepatotoxicity; BMS;
malignant lymphomas; acute
renal failure.
-Contraindications:
pregnancy; alcoholism;
chronic liver disease; blood
dyscrasias
-Never dose daily
for RA (dose can be
split into smaller
doses taken over
12-36 hours)
-Pregnancy
category X
Hydroxychloroquine
(Plaquenil)
->Initial: 400600mg/day
->Maintain: 200400mg/day
-Decreased visual
acuity
-Photophobia
-Blurred vision
-Corneal deposits
-Can cause neuromyopathy
with long-term use; SJS;
alopecia; pigmentation of
skin and hair (bleaching)
-Used in mild RA
-Take with food or
milk
-Mainly eliminated
by the kidney
Sulfasalazine
(Azulfidine,
Sulfazine)
->500-1,000mg BID;
max 3g/day
-Headache
-Anorexia
-Dyspepsia
-GI upset
-Contraindications: pts with a
sulfa or salicylate allergy, GI
or GU obstruction
-Can cause reversible
oligospermia; folate
-Take with food and
8oz of water to
prevent crytalluria
-Can cause yelloworange
-folate
antimetaboline that
inhibits DNA
synthesis
-5-aminosalicyclic
Pharmacological Treatment
 Non-biologic DMARDS cont.
Drug
Dosage
Adverse
Effects
Warnings/Contraindications
Notes
Minocycline
(Dynacin,
Minocin,
Solodyn)
->100mg BID
-GI upset
-N&V
-May cause SJS and decreased
LFTs
-Used in mild RA
-Pregnancy Cat. D
-Do not use in children 8 yoa or
younger.
Leflunomide
(Arava)
-> 100mg
x3days, then
20mg daily
-Diarrhea
-URTIs
-Rash
-Alopecia
-BBW: women of childbearing
potential should not use age until
pregnancy is excluded;
hepatotoxicity
-Must have negative pregnancy
test before starting and use 2
forms of birth control.
-If pregnancy wanted, must wait
2 yrs after discontinuation or give
cholestyramine.
-Can use with or without
methotrexate
-Pregnancy Cat. X
Pharmacological Treatment
 Biologic agents- TNFalpha inhibitors
 BBW: serious infxs; lymphomas; malignancies; perform test for latent
TB before initial therapy.
 Contraindication: sepsis
 Can cause worsening or new onset Heart Failure; hep. B
reactivation; demyelinating disease.
 Do not give with other biologics or live vaccines
 SE: infections and injection site reactions
 Administration: do not shake; require refrigeration; allow to reach
room temp. before injecting
 These agents are usually add-on therapy to methotrexate
Pharmacological Treatment
 Biologic DMARD agents- TNFalpha inhibitors
Drug
Dosage
Notes
Etanercept (Enbrel)
->50mg SC once/week
Adalimumab (Humira)
->40mg SC every other week
-If not taking MTX, can increase dose to 40mg
SC weekly
Infliximab (Remicade)
->3mg/kg IV at weeks 0,2,6 and then
Q8W can increase to 10mg/kg
-Higher dose=increase infx risk
-Infusion reaction: hypotension, fever, chills,
pruritis (benefit from APAP/ antihistamine/
steroids as pre-treatment)
-Delayed hypersensitivity rxn 3-10d after admin
(fever, rash, myalgia, HA, sore throat)
Certolizumab pegol (Cimzia)
->400mg SC at weeks 0,2,4 and then
400mg Q4W
-Can maintain at 200mg every other week
Golimumab (Simponi)
->50mg SC once/month
-Give with MTX
Pharmacological Treatment
 Biologic response modifiers
Drug
Dosage
Adverse Effects
Warnings/Contraindication
s
Notes
Rituximab (Rituxan)
-depletes CD20+ B
cells
->1g IV day 1 and 15
@50mg/hr (can
increase to 400mg/hr
if no rxn)
-Fever
-Chills
-Angioedema
-BMS
-Abdominal pain
-BBW: severe and fatal
infusion related reactions;
PML due to JC virus
infection; tumor lysis
syndrome leading to acute
renal failure and dialysis;
SJS, TEN can occur
-Warnings: serious infxs
-Pre-medicate with a
steroid
-Used with MTX
-Do not give with live
vaccines or other
biologics
-Screen for latent TB
before initiating
Anakinra (Kineret)
-IL-1 receptor
antagonist
->100mg SC daily
-Headache
-Infections
-BMS
-Injection site rxn
-Warnings: serious infxs
-Do not give with live
vaccines or other
biologics
-Screen for latent TB
before initiating
Abatacept (Orencia)
-Selective T cell
costimulation blocker
->500mg-1,000mg IV
based on body wt;
given over 30min
-Headache
-Infections
-Injection site rxn
-Warnings: serious infxs
-Do not give with live
vaccines or other
biologics
-Screen for latent TB
before initiating
Pharmacological Treatment
Kinase Inhibitors
Drug
Dosage
Adverse
Effects
Warnings/ Contraindications
Notes
Tofacitinib
(Xeljanz)
->5mg PO BID
-URTIs
-Diarrhea
-Headache
-BBW: can cause serious
infections, lymphomas and other
malignancies; screen for latent TB
-Can cause GI perforation
-Not recommended in severe
hepatic impairment
-Do not give with live vaccines
-Do not use with potent 450
inducers; reduce dose to 5mg
daily w/ potent 3A4 and 2C19
inhibitor.
-Do not use with biological
DMARDs or potent
immunosuppressants
-Monitor neutrophil count,
hemoglobin, and lymphocyte
count
-inhibitor of
Janus kinase
(JAKs)
OSTEOARTHRITIS
(AKA: Degenerative Joint Disease)
Prevalence
 An estimated 15.8 million adults display symptoms of OA
 Prevalence increased with age
 E.g. Those aged 75-79 years, 85% have OA of the hands,
whereas those 45 year and younger, only 1/5th have OA of
the hands.
 Severity also increases with age
 Women are more affected
 Knee OA twice as prevalent in black opposed to white
women
Epidemiology
 Most prevalent of the rheumatic diseases
 Responsible for disability and loss of productivity
 OA at some skeletal sites occurs in nearly everyone 75
years and older
 ½ million symptomatic cases of idiopathic OA occur
yearly in the US white population
Risk Factors
 Obesity
 Repetitive motion (constant stress on hand, knee, etc.)
 Joint injury
 Genetics
 Type and intensity of physical activity
Pathophysiology
Signs and Symptoms
 Pain with motion
 Joint stiffness lasting <30min (usually in the morning)
 Joint:
 Tenderness
 Crepitus
 Enlargement
Diagnosis
 3 Goals:
 Differentiate between
primary or secondary OA
 Clarify joints involved
 Assess prior therapies
 Diagnostic Parameters:
 OA of knee Refer to signs and
symptoms
 Age >50yo
 OA of hand Heberden’s node (2
or more out of 10)
 OA of hip Normal ESR
 Osteophytes and joint
space narrowing on
on X-ray
Non-pharmacological Treatment
 Exercise programs (aquatic)
 Weight loss
 Patient education for self-management
 Wedged shoe insoles
 Rest
 Braces (symptomatic relief)
Pharmacological Treatment
 Pain Relief (primary indication for pharmacological treatment)
Drug
Dosage
Adverse Effects
Warnings/
Contraindications
Notes
Acetaminophen
(Tylenol)
->650-1000mg PO
Q6H
-Constipation
-Headache
-Vomiting
-Contraindications;
hepatic impairment
-Alcoholism can
increase hepatic
injury
-For mild to
moderate pain
-Max 4g/day
Tramadol (Ultram)
->initial:
25mg/day,
increase by 25mg
increments in
separate doses
every 3 days
->maintain: 50100mg PO Q4-6H
-Flushing
-Constipation
-Headache
-Nausea
-Xerostomia
-Contraindications:
hypercapnia, severe
bronchial asthma,
acute intoxication
with alcohol,
narcotics, etc.
-For moderate to
severe pain
-Max 400mg/day
-Adjust dose for
renal impairment
Pharmacological Treatment
Opioid Analgesics
Drug
Dosage
Adverse Effects
Warnings/
Contraindications
Notes
Codeine sulfate
->15-60mg
PO Q4H
-Somnolence
-Dyspnea
-Hypotension
-Bowel
obstruction
-Pancreatitis
-Contraindications:
bronchial asthma,
hypercarbia
-Has potential for abuse
-May cause diminished
biliary and pancreatic
secretions
-May prolong GI
obstruction
-For mild to
moderate pain
-Max dose:
360mg/day
Oxycodone
hydrochloride
->5-15mg PO
Q4-6H
-Constipation
-Nausea
-Somnolence
-BBW: fatal respiratory
depression
-Contraindications:
bronchial asthma,
hypercarbia
-For moderate to
severe pain
Pharmacological Treatment
NSAIDS
Drug
Dosage
Adverse Effects
Warnings/ Contraindications
Notes
Aspirin
->Up to 3g/day
in divided doses
-GI upset
-Bleeding
-GI ulcer
-Caution with bleeding disorders, renal
or hepatic disease
-May take with food
or milk
Ibuprofen
(Advil)
->1200 to 3200
mg/day PO in
3-4 divided
doses
-Dyspepsia
-Heartburn
-Increase BP
-GI bleeding
-NSAIDS have BBW of increased risk of
adverse CV thrombotic events;
contraindicated for CABG perioperative
pain; increased GI adverse events
(ulceration, bleeding, perforation)
-Contraindicated in pregnancy 3rd
trimester.
-Avoid use in
advanced renal
disease
Naproxen
(Aleve)
->250-500mg PO
BID
-Edema
-Abdominal pain
-Tinnitus
-Dyspnea
--NSAIDS have BBW of increased risk of
adverse CV thrombotic events;
contraindicated for CABG perioperative
pain; increased GI adverse events
(ulceration, bleeding, perforation)
-Max 1500mg/day for
up to 6 mo
Celecoxib
(Celebrex)
->100mg BID or
200mg daily
-Diarrhea
-Nausea
-Warnings are the same as NSAIDS.
-Contraindicated with sulfa allergy.
-Max 200mg
Pharmacological Treatment
Topical NSAIDS (preferred over oral NSAIDs for pts >75 yoa)
Drug
Dosage
Adverse Effects
Warnings/
Contraindications
Notes
Diclofenac
sodium 1% gel
(Voltaren)
->4g topically to
lower extremities
4x/day
->2g to upper
extremities 4x/day
-Application
site rxn
-Burning sens.
in eye
-Raised IOP
-Same as NSAIDs BBWs
-NSAID oral therapy not
recommended
concomitantly
-Can cause anaphylaxis
-Max 8g/day to any single joint of
upper extremity; 16g/day for lower
extremity; 32g/day total over all
affected joints
Trolamine
salicylate 10%
cream
(Arthricream)
->Apply topically 34x/day
-Erythema
-Skin irritation
-Contraindications:
hypersensitivity to
salicylates, severe renal
insufficiency
-May cause tinnitus
-Beware of toxicity with over use
-Do not cover area with occlusive
material
Topical Analgesics
Drug
Dosage
Adverse Effects
Warnings/
Contraindications
Notes
Capsaisin 0.025% or
0.075%
->Apply to affected
joints 3-4x/day
-Application site
erythema
-Pruritus
-Nausea
-Hypertension
-May increase risk
of cardiovascular
adverse effects
-Use nitrile gloves for handling
Pharmacological Treatment
Intra-acrticular Glucocorticoids (knee or hip)
Drug
Dosage
Adverse Effects
Warnings/
Contraindications
Notes
Triamcinolone
acetonide (Kenalog,
Aristocrat A, Nasacort)
->initial 2.515mg as single
injection
->Additional
doses can be
adjusted to
20mg or more
-Cushing’s
syndrome
-Headache
-Pharyngitis
-Flu-like
symptoms
-Contraindications:
administration with
live vaccines;
idiopathic
thrombocytopenic
purpura
-Increased risk of
infections
-Impaired skin
healing
-Weight gain
-Hyperglycemia
Triamcinolone
hexacetonide
(Aristospan)
->up to
0.5mg/square
inch of
affected skin
-Hypertension
-Osteoporosis
-Same as above
-Same as above
-Total daily dose
may vary from 248mg/day
Pharmacist Role
 Be aware of certain labs to order for particular agents
 Understand patient populations, which certain
medications should be avoided in
 Counsel patients on the disease state , SE, possible
treatments
 Assess progression of disease and appropriate measures
to take
 Make recommendations to physicians regarding drug
regimen
Clinical Pearls- Based on Guidelines

RA
 Etanercept recommended for
use in patients with hepatitis C.
 No biologics for hepatitis B
 Rituxibam recommended for
pts with malignancy <5yrs,
treated skin melanoma,
treated lymphoproliferative
disease
 TNF inhibitor recommended for
patients with CHF

OA
 Knee
 Acetaminophen
 Oral NSAIDs
 Topical NSAIDs
 Tramadol
 Intraarticular corticosteroid
injections
 Hip
 Same as above without
topical NSAIDs
 Hand
 Topical NSAIDs
 Topical capsaicin
 Oral NSAIDs
Reference
 American College of Rheumatology 2012 Recommendations for the
Use of Nonpharmacologic and Pharmacologic Therapies in
Osteoarthritis of the Hand, Hip, and Knee. American College of
Rheumatology. vol. 64, No. 4, April 2012, pp 465–474

2012 Update of the 2008 American College of Rheumatology
Recommendations for the Use of Disease-Modifying Antirheumatic
Drugs and Biologic Agents in the Treatment of Rheumatoid
ArthritisAmerican College of Rheumatology. vol. 64, No. 5, May 2012, pp
625–639
 Kenneth C Kalunian, MD. Patient information: Osteoarthritis symptoms
and diagnosis (Beyond the Basics). UpToDate August 2013.
 Peter H. Schur, MD. General principles of management of rheumatoid
arthritis in adults. UpToDate August 2013
 Micromedex