Gout Pharmacotherapy

Question 1

When assessing a gout attack, what are the first two questions you should ask a patient in determining treatment?

Answer 1

(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

Question 2

Three FDA approved NSAIDs for acute gout management are:

Answer 2

Indomethacin
Sulindac
Naproxen

Question 3

How are NSAIDs dosed for an acute gout attack?

Answer 3

initiated at the highest recommended dose and continued until 24 hours after symptoms resolve

Question 4

contraindications for NSAID use

Answer 4

(1) hypersensitivity
(2) decompensated HF
(3) active GI bleed or peptic ulcer
(4) severe or acute renal impairment

Question 5

Use NSAIDs with caution when:

Answer 5

(1) CrCl <50mL/min
(2) in combination with anticoagulant
(3) history of HF
(4) history of GI bleed or peptic ulcer
(5) uncontrolled hypertension

Question 6

dosing for Indomethacin

Answer 6

one 50mg tablet TID

Question 7

dosing for naproxen

Answer 7

750mg loading dose followed by 250mg every 8 hours

Question 8

dosing for Sulindac

Answer 8

200mg BID

Question 9

Adverse effects associated with NSAID use involve which body systems?

Answer 9

renal, CV, CNS, GI

Question 10

What additional pharmacotherapy should be considered in patients that require NSAID use but have a history of peptic ulcer, alcoholism, or concomitant anticoagulation therapy?

Answer 10

PPI

Question 11

For maximum efficacy, colchicine therapy must be initiated within ___ hours of an acute flare up.

Answer 11

24

Question 12

colchicine dosing (normal renal function)

Answer 12

1.2mg loading dose, followed by 0.6mg one hour later, then 0.6mg QD or BID for the remainder of the attack

Question 13

colchicine dosing (CrCl <30mL/min)

Answer 13

treatment: no dose adjustment necessary, but cannot repeat tx within 14 days of end
prophylaxis: 0.3mg QD

Question 14

colchicine dosing (dialysis)

Answer 14

treatment: 0.6mg as a single dose
prophylaxis: 0.3mg twice weekly

Question 15

colchicine adverse effects

Answer 15

GI, musculoskeletal, bone marrow suppression (aplastic anemia, thrombocytopenia)

Question 16

corticosteroid options for gout flare-up treatment

Answer 16

(1) prednisone or prednisolone
(2) methylprednisolone
(3) triamcinolone

Question 17

When are oral and intraarticular corticosteroids indicated for gout flare-ups?

Answer 17

oral: all cases
intraarticular: cases involving 1-2 large joints

Question 18

corticosteroid adverse effects

Answer 18

(1) hyperglycemia
(2) fluid retention/weight gain
(3) N/V/D
(4) incr. appetite –> weight gain
(5) CNS (HA, insomnia)

Question 19

Corticosteroid use is usually reserved for which kind of gout flare-ups?

Answer 19

(1) NSAID/colchicine intolerance
(2) polyarticular involvement
(3) resistant cases

Question 20

Use corticosteroids with caution in patients who:

Answer 20

(1) have diabetes
(2) CHF
(3) immunosuppression
(4) psychiatric disorder
(5) peptic ulcer or GI bleed

Question 21

An inadequate response to treatment for an acute gout attack is defined as:

Answer 21

either <20% reduction of pain within 24 hours or more than 24 hours have passed with <50% reduction of pain

Question 22

Name 3 combination therapies that would be acceptable for treatment of a gout attack (if combo therapy warranted).

Answer 22

(1) NSAIDs + colchicine
(2) oral CS + colchicine
(3) intraairticular CS + all other modalities

Question 23

One of the goals of urate-lowering therapy is a serum urate concentration of ______.

Answer 23

6 mg/dL or less

Question 24

Serum urate is monitored every ______ weeks during initiation, then every ______ once serum urate reaches a level of ______.

Answer 24

2-5, 6 months, <6 mg/dL

Question 25

Which class of medications are first-line for irate-lowering therapy? second-line? third-line?

Answer 25

xanthine oxidase inhibitors (allopurinol, febuxostat) uricosurics (Probenecid) Uricase agents (Pegloticase)

Question 26

starting dose of allopurinol (Zyloprim)

Answer 26

100 mg PO QD

Question 27

starting dose of allopurinol (Zyloprim) for CKD stage IV

Answer 27

50 mg PO QD

Question 28

Titration of Zyloprim is done every _____ weeks, and has a max dose of ______ QD.

Answer 28

2-4, 800 mg

Question 29

Common adverse effects of allopurinol

Answer 29

skin rash, pruritus, leukopenia, thrombocytopenia, GI intolerance

Question 30

allopurinol drug interactions

Answer 30

warfarin, antacids, mercaptopurine, azathioprine

Question 31

febuxostat starting and max dose

Answer 31

40 mg PO QD up to 80 mg PO QD

Question 32

The largest limitation of Uloric use is:

Answer 32

price

Question 33

True or false: dose adjustments for mild to moderate renal and hepatic impairment are necessary during febuxostat therapy.

Answer 33

false (however, use caution if CrCl <30 mL/min

Question 34

febuxostat adverse effects

Answer 34

(1) rash (2) nausea (3) abnormal LFTs take precaution for CV thromboembolitic events

Question 35

main monitoring parameter for Uloric

Answer 35

LFTs (baseline, 2 mos, 4 mos)

Question 36

Uloric contraindications

Answer 36

concomitant use of azathioprine, mercaptopurine, or theophylline

Question 37

MOA of uricosurics

Answer 37

inhibit the reabsorption of filtered uric acid

Question 38

Probenecid (Benemid) is indicated for patients who:

Answer 38

(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)

Question 39

dosing of Benemid

Answer 39

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

Question 40

Why is it important to start with low doses of probenecid?

Answer 40

to avoid uricosuria and renal stone formation

Question 41

Probenecid adverse effects

Answer 41

flushing, pruritus, GI upset, stone formation, aplastic anemia/leukopenia

Question 42

Give one example of a uricase agent and its MOA.

Answer 42

Pegloticase, converts uric acid into allantoin, which is water soluble

Question 43

Krystexxa is indicated for ________ ________ _____.

Answer 43

refractory chronic gout (It's a last case agent for those refractory despite tx with XOI, uricosuric)

Question 44

Krystexxa dosing

Answer 44

8 mg IV every 2 weeks administered over 120 minutes

Question 45

Patients using pegloticase should be pretreated with what two things?

Answer 45

antihistamines and corticosteroids

Question 46

Adverse effect of pegloticase.

Answer 46

infusion reactions, anaphylaxis, nephrolithiasis, arthralgia, HF exacerbations, nausea

Question 47

Precautions for Krystexxa therapy

Answer 47

HF, contraindicated in G6PD deficiency

Question 48

This drug is a URAT1 (urate transporter) inhibitor that enhances uric acid secretion.

Answer 48

Lesinurad (Zurampic)

Question 49

Lesinurad (Zurampic) dosing

Answer 49

200 mg PO QD

Question 50

Lesinurad is approved for use in combination with _______.

Answer 50

XOI

Question 51

Zurampic adverse effects

Answer 51

HA, GERD, black box warning in acute renal failure

Question 52

This class of drugs is under investigation for potential use in gout treatment.

Answer 52

IL-1 inhibitors (anakinra, canakinumab)

Question 53

Which ARB has the unique property of reducing uric acid reabsorption?

Answer 53

Losartan

Question 54

What is first line therapy for gout prophylaxis?

Answer 54

low dose colchicine (0.6 mg PO QD or BID)

Question 55

second line therapy for gout prophylaxis

Answer 55

low dose NSAID such as naproxen 250 mg PO BID (and PPI where indicated)

Question 56

If first and second line therapy fail to prevent gout attacks as desired, what other option is there?

Answer 56

low dose oral CS (prednisone <10 mg/day)