Gout Pharmacotherapy Flashcards
When assessing a gout attack, what are the first two questions you should ask a patient in determining treatment?
(1) How severe is the pain? scale of 1-10
(2) How many joints are affected?
the answer to these will determine monotherapy or combo therapy
Three FDA approved NSAIDs for acute gout management are:
Indomethacin
Sulindac
Naproxen
How are NSAIDs dosed for an acute gout attack?
initiated at the highest recommended dose and continued until 24 hours after symptoms resolve
contraindications for NSAID use
(1) hypersensitivity
(2) decompensated HF
(3) active GI bleed or peptic ulcer
(4) severe or acute renal impairment
Use NSAIDs with caution when:
(1) CrCl <50mL/min
(2) in combination with anticoagulant
(3) history of HF
(4) history of GI bleed or peptic ulcer
(5) uncontrolled hypertension
dosing for Indomethacin
one 50mg tablet TID
dosing for naproxen
750mg loading dose followed by 250mg every 8 hours
dosing for Sulindac
200mg BID
Adverse effects associated with NSAID use involve which body systems?
renal, CV, CNS, GI
What additional pharmacotherapy should be considered in patients that require NSAID use but have a history of peptic ulcer, alcoholism, or concomitant anticoagulation therapy?
PPI
For maximum efficacy, colchicine therapy must be initiated within ___ hours of an acute flare up.
24
colchicine dosing (normal renal function)
1.2mg loading dose, followed by 0.6mg one hour later, then 0.6mg QD or BID for the remainder of the attack
colchicine dosing (CrCl <30mL/min)
treatment: no dose adjustment necessary, but cannot repeat tx within 14 days of end
prophylaxis: 0.3mg QD
colchicine dosing (dialysis)
treatment: 0.6mg as a single dose
prophylaxis: 0.3mg twice weekly
colchicine adverse effects
GI, musculoskeletal, bone marrow suppression (aplastic anemia, thrombocytopenia)
corticosteroid options for gout flare-up treatment
(1) prednisone or prednisolone
(2) methylprednisolone
(3) triamcinolone
When are oral and intraarticular corticosteroids indicated for gout flare-ups?
oral: all cases
intraarticular: cases involving 1-2 large joints
corticosteroid adverse effects
(1) hyperglycemia
(2) fluid retention/weight gain
(3) N/V/D
(4) incr. appetite –> weight gain
(5) CNS (HA, insomnia)
Corticosteroid use is usually reserved for which kind of gout flare-ups?
(1) NSAID/colchicine intolerance
(2) polyarticular involvement
(3) resistant cases
Use corticosteroids with caution in patients who:
(1) have diabetes
(2) CHF
(3) immunosuppression
(4) psychiatric disorder
(5) peptic ulcer or GI bleed
An inadequate response to treatment for an acute gout attack is defined as:
either <20% reduction of pain within 24 hours or more than 24 hours have passed with <50% reduction of pain
Name 3 combination therapies that would be acceptable for treatment of a gout attack (if combo therapy warranted).
(1) NSAIDs + colchicine
(2) oral CS + colchicine
(3) intraairticular CS + all other modalities
One of the goals of urate-lowering therapy is a serum urate concentration of ______.
6 mg/dL or less
Serum urate is monitored every ______ weeks during initiation, then every ______ once serum urate reaches a level of ______.
2-5, 6 months, <6 mg/dL
Which class of medications are first-line for irate-lowering therapy? second-line? third-line?
xanthine oxidase inhibitors (allopurinol, febuxostat)
uricosurics (Probenecid)
Uricase agents (Pegloticase)
starting dose of allopurinol (Zyloprim)
100 mg PO QD
starting dose of allopurinol (Zyloprim) for CKD stage IV
50 mg PO QD
Titration of Zyloprim is done every _____ weeks, and has a max dose of ______ QD.
2-4, 800 mg
Common adverse effects of allopurinol
skin rash, pruritus, leukopenia, thrombocytopenia, GI intolerance
allopurinol drug interactions
warfarin, antacids, mercaptopurine, azathioprine
febuxostat starting and max dose
40 mg PO QD up to 80 mg PO QD
The largest limitation of Uloric use is:
price
True or false: dose adjustments for mild to moderate renal and hepatic impairment are necessary during febuxostat therapy.
false (however, use caution if CrCl <30 mL/min
febuxostat adverse effects
(1) rash
(2) nausea
(3) abnormal LFTs
take precaution for CV thromboembolitic events
main monitoring parameter for Uloric
LFTs (baseline, 2 mos, 4 mos)
Uloric contraindications
concomitant use of azathioprine, mercaptopurine, or theophylline
MOA of uricosurics
inhibit the reabsorption of filtered uric acid
Probenecid (Benemid) is indicated for patients who:
(1) have documented underexcretion of uric acid
(2) have not reached target urate levels with XOI monotherapy
(3) cannot tolerate allopurinol (though it can be used in combo)
dosing of Benemid
250 mg PO BID for 7 days, then increase to 500 mg PO BID for 14 days
may titrate by 500 mg q2weeks
max dose: 2g PO QD
Why is it important to start with low doses of probenecid?
to avoid uricosuria and renal stone formation
Probenecid adverse effects
flushing, pruritus, GI upset, stone formation, aplastic anemia/leukopenia
Give one example of a uricase agent and its MOA.
Pegloticase, converts uric acid into allantoin, which is water soluble
Krystexxa is indicated for ________ ________ _____.
refractory chronic gout (It’s a last case agent for those refractory despite tx with XOI, uricosuric)
Krystexxa dosing
8 mg IV every 2 weeks administered over 120 minutes
Patients using pegloticase should be pretreated with what two things?
antihistamines and corticosteroids
Adverse effect of pegloticase.
infusion reactions, anaphylaxis, nephrolithiasis, arthralgia, HF exacerbations, nausea
Precautions for Krystexxa therapy
HF, contraindicated in G6PD deficiency
This drug is a URAT1 (urate transporter) inhibitor that enhances uric acid secretion.
Lesinurad (Zurampic)
Lesinurad (Zurampic) dosing
200 mg PO QD
Lesinurad is approved for use in combination with _______.
XOI
Zurampic adverse effects
HA, GERD, black box warning in acute renal failure
This class of drugs is under investigation for potential use in gout treatment.
IL-1 inhibitors (anakinra, canakinumab)
Which ARB has the unique property of reducing uric acid reabsorption?
Losartan
What is first line therapy for gout prophylaxis?
low dose colchicine (0.6 mg PO QD or BID)
second line therapy for gout prophylaxis
low dose NSAID such as naproxen 250 mg PO BID (and PPI where indicated)
If first and second line therapy fail to prevent gout attacks as desired, what other option is there?
low dose oral CS (prednisone <10 mg/day)
