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