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Prepared by : Tamara OdehDiana Jawhari
Supervised by : Dr. Ola Ayesh
ULORIC® (febuxostat)
DNA
Adenine Guanine
Purine group
Cytosine Thymine
Pyrimidine group
Purines degradation
Adenine&Guanine (Purines)
Hypoxanthine
Xanthine
Uric acid
Xanthine Oxidese
Xanthene Oxidase
Uric acid in blood
Monosodium Urate Crystals deposition in joints and may be also in soft tissues
Inflammatory response to the crystals
Gout , Uric acid stones in kidney
Causes of blood uric acid
Excretion
Excretory
defect in
kidney
Drugs Ex ;
thiazide diuretic
s
Production
Idiopathic
(mutations )
Cell turn over
(chemotherapy)
Consuming
ethanol,types of
food
1)Nonpharmacological
Reduce intake of foods with high purines Exp: organ meats Avoid alcohol Loose Wt if obese
2)Pharmacological
Using drugs for acute & chronic gout
Treatment
Drugs used in gout
Acute
NSAIDs (Indomethacin)
Corticosteroids
Colchicine
Chronic
Xanthine oxidase
inh. Allopurinol
Target : Inflammation & pain
Drugs : NSAIDs inflammatory
Corticosteroids mediators
Colchicine
neutrophils movement
to the affected
area
Acute Gout
Drug of choice if there is no C/I Exp: Indomethacin It is as effective as colchicine but it is
preferred because it has less GIT toxicity Begin with dose (Exp: 75mg ) First 24-48hr Then 50mg/6hr for 1day, then 50mg/8hr for
1-2days.
Cont…
NSAIDs
S/E : headache , dizziness .
Use in caution in pt with :
Peptic ulcer HF Chronic kidney disease Coronary artery disease
Cont…
PO dose 1mg initially , then 0.5mg/2hr S/E of PO colchicine is GIT toxicity so IV
dose is used 2mg initially, if no relief then
additional 1mg/6-12hr to total dose of 4mg. S/E of Iv colchicine: inflammation and
necrosis of surrounding tissue.
Cont…
Colchicine
Colchicine should be diluted with 20ml normal saline to minimize sclerosis of
vein.
C/I Of IV colchicine :
Neutropenia Sever renal impairment Combined renal and hepatic insufficiency
Cont…
Colchicine should be discontinued within 7days after Iv or PO therapy to reduce the risk of bone marrow toxicity
Used for resistant cases or Pt with C/I to NSAIDs & colchicine
For multiple joint involvement: 1) Prednisone 30-60mg PO once daily for 3-
5 days
Cont…
Corticosteroids
The dose should be decreased gradually to prevent rebound
attacks
2) Adrenocorticotropic hormone (ASTH) gel
40-80 USP units given IM/6-8hr for2-3 days.
For limited 1-2 joint involvement ;
Triamcinolone hexacetonide 20-40mg given intra-articularly.
Cont…
Target : Treat the cause Drugs : 1) Colchicine
Chronic GoutChronic Gout
2) Uricosurics : Probenecid Uric acid Sulfinopyrazone excretion
2) Xanthene oxidase Inh. : Allopurinol : converted to Oxypurinol Febuxostat
Chronic GoutCont….
Allopurinol Febuxostat
Inh. Xanthine oxidase
Inh. Uric acid production
PO 0.5mg twice daily during the first 6-12 months of uric acid lowering therapy to minimize the risk of acute attacks that may occur during initiation of this therapy.
Cont…
Colchicine
Probenecid 250mg twice daily for 1-2weeks then 500mg twice daily for 2 weeks, then increase until control is achieved or a maximum dose of 2g/day is reached .
Sulfinpyrazone 50mg twice daily for 3-4 days then100mg twice daily,increasing the daily dose by 100mg each week up to 800mg/day.
Cont…
Uricosurics
S/E :
GI Irritation Rash & hypersensitivity Precipitation of acute gouty arthritis Stone formation
Cont…
C/I :
Pt allergic to these drugs. Impaired renal function. History of renal calculi. Over producers of uric acid.
Cont…
Allopurinol is converted to oxypurinol It has long half –life so given once daily Po daily dose is usually 300mg 600-800mg/day may be necessary
Cont…
Xanthine oxidase inh.
Allopurinol is DOC in Pt with :
History of urinary stones Impaired renal function Over producers of uric acid
Cont…
Before initiation of cytotoxic therapy pretreatment with
allopurinol is needed to prevent acute uric acid nephropathy.
1) Skin rash .2) Leukopenia.3) GI toxicity.4) Increase frequency of gouty attacks with
the initiation of therapy.5) Allopurinol hypersensitivity syndrom: Fever. Dermatitis. Vasculitis. Renal & hepatic dysfunction.
S/E
ULORIC® (febuxostat)
Company : Takeda
Approval Status : Approved February 2009
Treatment for : hyperuricemia
Cont… Once-daily oral medication.
Available in : 40-mg and 80-mg tablets.
It is the first new treatment option for hyperuricemia in patients with gout.
Cont…
Recommended initial dose 40 mg once daily.
For patients who do not achieve a serum uric acid less than 6 mg per dL after 2 weeks with 40 mg
80 mg is recommended
Mechanism of action
Adenine&Guanine (Purines)
Hypoxanthine
Xanthine
Uric acid
Xanthine Oxidese
Xanthene Oxidase
Clinical studies
ULORIC was studied and evaluated in multiple clinical trials
CONFIRMS which was the largest phase 3 clinical trial shows that ULORIC 80 mg was better than
ULORIC 40 mg and allopurinol 300/200 mg
at achieving serum uric acid levels of less than 6.0 mg/dL
A higher rate of cardiovascular thromboembolic events was observed in
Pt treated with Uloric than Pt with Allopurinol
Uloric Allopurinol
0.60 per 100 Pt
every year
0.74 per 100 Pt every year
Side Effects
Nausea
Arthralgia
Rash
Dizziness
Contraindications
ULORIC is contraindicated in patients being treated with :
Azathioprine
Mercaptopurine
Theophylline
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