Lecture 7.1 - Gout 2 Flashcards
Allopurinol Hypersensitivity Syndrome Manifestation
Rash, chills, fever, leukopenia, leukocytosis, eosinophilia, and pruritus
Maybe severe and fatal ( hepatotoxicity, vasculitis, SJS and TEN)
AHS prevention
HLA-B*5801 screening
only in high risk, and those who are positive we won’t use allopurinol
AHS management
Discontinue allopurinol at 1st sign of rash
Supportive care
AHS mortality rate
~ 25%
Rare tho
Allopurinol CI
Allopurinol sensitivity
concurrent didanosine use
Allopurinol DI
Didanosine
Azathioprine + 6-mercaptourine (MUST reduce dose of both when used in combo with Allopurinol)
Theophylline
Pegloticase
Loop/thiazide diuretics
Allopurinol monitoring
Efficacy: SUA every few weeks till goal
Safety: HLA-B*5801 test prior to start in high risk pops
High risk pops for HLA-B*5801
Han chinese
Korean
Thai
AA
Allopurinol patient education
Signs and symptoms of allergic reaction
HLA testing
How to use
Febuxostat (Uric) MOA
non-purine inhib of XAI leading to reduced production of uric acid
Febuxostat ADR
Hepatic: abnormal LFTs
GI: nausea
Rheumatologic: Gout flares
Rash, Arthralgia
Febuxostat CI
concomitant use of Azathioprine or 6-mercaptopurine
Febuxostat Precuations
Acute gout flare
CVD events
Hepatoxicity
Serious skin reactions
Febuxostat DI
Azathioprine or 6-mercaptourine
Theophylline
pegloticase
didanosine
Febuxostat Monitoring
Efficacy: SUA after 2 weeks of treatment + periodically
Safety: LFTs at BL and if signs of hepatic injury
Febuxostat Pt education
use
ADR
dont use with azathioprine or 6-MP
Study that chose Allopurinol > Febuxostat in CV patients?
CARES Trial
Febuxastat as Black Box warning due to study
Uricosurics
Probenecid
Sulfinpyrzone
Benzbromerone
Losartan
Probenecid MOA (Benamid)
Competitively inhibits the postsecretory renal proximal tubular reabsorption of uric acid
When to avoid Probenecid?
CrCl < 50
Probenecid SE
Most common = GI, uric acid nephrolithiasis (Uric Acid kidney stones)
Hemolytic Anemia (in G6PD deficiency in Mediterranean & AA)
Probenecid CI
HX of urolithiasis Overproducer of uric acid Hypersensitivity to it Small & Large dose salicylate therapy Blood dyscrasias < 2 yrs old initiation during acute gout attack
Probenecid Precautions
Disease related: G6PD, PUD, Renal impairment
Drug-related: Methotrexate, penicillin, salicylate
Probenecid DI
Salicylates
Penicillins/Cephalosporins/Carbapenems
Methotrexate
Pegloticase
Probenecid Pt education
inc fluid intake
Probenecid place in therapy?
Add on therapy to XOI in patients not controlled on single agent
XOI is preferred over probenecid for those with > Stage 3 CKD
Losartan place in therapy?
Add on in patients with HTN who are already on XOI and not controlled
Is probenecid for Overproducers or Underexcretors?
Under excreters
Pegloticase (Krystexxa) MOA
pealed recombination modified mammalian rate oxidase (Uricase)
What to know about Krystexxa infusion?
Premeditate with corticosteroid and antihistamine pre-medication
Pegloticase (Krystexxa) SE
Gout flares Infusion reactions Nausea Vomiting Bruising Nasopharyngitis Constipation Chest pain Anaphylaxis (Black Box for this)
Pegloticase (Krystexxa) CI
G6PD deficiency
Pegloticase (Krystexxa) Precautions
Anaphylaxis
Infusion reactions
Gout Flares
CHF
When should you stop Krystexxa?
When SUA above 6mg/dL for 2 infusion in a row
Place of use for Krystexxa
used in patients who continue to have elevated SUA > 6mg/dL, and either frequent flares (> 2/yr) or non resolving subcutaneous tophi
Chronic ULT Medication selection
- Depends on response to therapy, tolerability
- Genetics
- Co-morbid conditions
- DI
- Cost of therapy
ULT guidelines
- Allopurinol is preferred to all other ULT. should be imitated at low doses, and intesified to SUA < 6 mg/dL
- If pt is not responding to XOI at max tolerated or FDA approved dose, change to another OXI over adding on a uricosuric agent
- Swapping ULT to pegloticase strongly recommended for those in whom interventions have been unable to achieve SUA target and continue to have frequent flares or subcu top
- continue ULT indefinitely
Gout self Care
can reduce SUA ~ 10-18%
- consider alone or in combo with pharm therapy
- smoking cessation
- patient ed
- Hydration
- exercise
- weight loss
- avoidance of risk factors (dietary/meds)
Medication Risk factors gout
HCTZ = swap to alternative hypertensive if possible
Losartan = preferred anti hyper when possible
Low dose aspirin= dont stop if recommended in pt
Fenofibrate = dont swap to or add in pts with gout