Nsai Ds, Dmar Ds & Antigout1

Nonsteroidal Anti-inflammatory Drugs, Disease-Modifying Antirheumatic

Drugs, Nonopioid Analgesics, & Drugs Used in Gout

Florencia D. Munsayac, MD, MBA, RMT

The Inflammatory Response

3 Phases of Inflammation:- Acute Inflammation/acute phase

- The Immune Response/sub-acute or delayed phase

- Chronic Inflammation/chronic proliferative phase

Some of the mediators of acute inflammation & their effects

Mediators Vasodilation

Vascular Permeabilit

y

Chemotaxis

Pain

Histamine ++ - -Serotonin +/- - -Bradykini

n+++ - +++

Prostaglandins +++ +++ +Leukotrien

es- +++ -

Some of the Mediators of Chronic Inflammation

Mediators Sources Primary EffectsInterleukins-1, -2, and -3

Macrophages, T lymphocytes

Lymphocyte activation, PG production

GM-CSF T lymphocytes, endothelial cells, fibroblast

Macrophage & granulocyte activation

TNF-alpha Macrophages PG production

Interferons Macrophages, endothelial cells, T lymphocytes

Many

PDGF Macrophages, endothelial cells, fibroblasts, platelets

Fibroblast chemotaxis, proliferation

Rheumatoid arthritis

Chronic inflammation → pain & destruction of bone & cartilage

An autoimmune disease

Goals of Therapy

- Relief of pain

- Reduction of inflammation

- Protection of articular structures

- Maintenance of function

- Control of systemic involvement

5 General Approaches

NSAIDs and simple analgesics – to control the s/s of local inflammatory process– Minimal effect on the progression of the disease

Groups of NSAIDs- Salicylic acid derivatives (Aspirin, Na salicylate, choline Mg+

+ trisalicylate, salsalate, diflunisal, sulfasalazine)- Para-chlorobenzoic acid derivatives or indoles

(Indomethacin, Sulindac)- Pyrazolone derivatives (Phenylbutazone)- Arylpropionic acid (Ibuprofen, Flurbiprofen, Ketoprofen,

Fenoprofen, Naproxen, Oxaprozin)

5 General Approaches

NSAIDs and simple analgesics – to control the s/s of local inflammatory process– Minimal effect on the progression of the disease

Groups of NSAIDs- Fenamates/Anthranilic acids (Mefenamic Acid,

Meclofenamic acid)- Enolic acids/Oxicams (Piroxicam)- Heteroaryl/Penylacetic acids (Diclofenac Sodium,

Tolmetin, ketorolac)- Alkalones (Nabumetone)- Selective COX-2 inhibitors (Celecoxib, Rofecoxib,

Meloxicam)- Para-aminophenol (Acetaminophen)

5 General Approaches

Glucocorticoids– To suppress s/s of inflammation– Retard the development & progression of bone

erosions

DMARDs– Methotrexate, sulfasalazin, hydroxychloroquine,

gold salts, or D-penicillamine– Have the capacity to decrease elevated levels of

acute phase reactants → modify inflammatory component & its destructive capacity

5 General Approaches

Biologics – TNF-neutralizing agents: infliximab, etanercept,

& adalimumab– IL-1 neutralizing agents: anakinra– Depletes B cells: rituximab– Interferes T cell activation: abatacept

Immunosuppressive & Cytotoxic agents– Leflunomide, cyclosporine, azathioprine,

cyclophosphamide Shown to ameliorate the disease process

Types of Cyclooxygenases / Prostaglandin G/H synthase

COX 1 - involved in tissue hemeostasis

COX 2 - responsible for the production of the prostanoid mediators of inflammation (IL-1 and TNF-)

COX 3

Three major types of effects of NSAIDs

Anti-inflammatory

Analgesic

Antipyretic– related to their

primary action: inhibition of arachidonate cyclooxygenase, → inhibition of prostaglandin and thromboxanes.

Other Effects of NSAIDs

Strong O2-radical scavenging effects decrease tissue damage

Inhibit platelet aggregation except COX 2 selective inhibitors

Gastric irritants

Nephrotoxicity

Hypertensive complications

hepatotoxicity

NSAIDs: Pharmacokinetics

Weak organic acid, except Nabumetone

Well absorbed

food does not change their bioavailability, except Fenoprofen & Piroxicam

Highly metabolized: CYP3A or CYP2C

Renal excretion: most important route of final elimination

Biliary excretion & reabsorption (enterohepatic circulation)

Highly protein bound (~ 98%): albumin

Found in synovial fluid

Aspirin or Acetylsalicylic Acid (ASA)

– Comes from the family of salicylates derived from salicylic acid

– Prototype drug

– Developed in 1899 by Adolph Bayer

– The oldest anti-inflammatory agent

– Rarely used as an anti-inflammatory medication

Aspirin or Acetylsalicylic Acid (ASA)Pharmacokinetics

Rapidly absorbed from the stomach & upper small intestine

Peak plasma level: 1-2 hrs

80-90% protein bound

t1/2: 15 minutes

Cross BBB & placental barrier

Undergoes hepatic metabolism

Excretion: kidneys

Aspirin or Acetylsalicylic Acid (ASA)Mechanisms of Action

- Inhibits prostaglandin synthesis- Irreversibly blocks the enzyme cyclooxygenase (PG synthase)

. Pharmacological Properties & Therapeutic indications: - anti-inflammatory effects- analgesic effects - antipyretic effects- Platelet effects- Uricosuric effects

. Dosage: children: 50-75mg/kg/day adult: 325-650mg p.o. q 4 hrs

Aspirin or Acetylsalicylic Acid (ASA)Adverse Effects

Gastric upset Salicylism vomiting, tinnitus, decreased

hearing, & vertigo Hyperpnea Respiratory alkalosis later acidosis supervenes Glucose intolerance Cardiotoxicity Increases uric acid levels Elevation of liver enzymes, hepatitis, decreased

renal function, bleeding, rashes, asthma Reye’s syndrome

Aspirin or Acetylsalicylic Acid (ASA)Contraindications

Pregnancy Severe hepatic damage Vitamin K deficiency Hypoprothrombinemia Hemophilia PUD Viral (chickenpox & influenza)

Aspirin or Acetylsalicylic Acid (ASA)Drug Interactions

Indomethacin, Naproxen Ketoprofen, Fenoprofen Warfarin Sulfonylureas, Methotrexate Spironolactone Penicillin

COX-2 Selective Inhibitors

Were developed in an attempt to inhibit PG synthesis by the COX-2 iso-enzyme without affecting the action of COX-1 found in the GIT, kidneys & platelets

At usual dose: no impact on platelet aggregation

Do not offer cardio-protective effects

Suggested a higher incidence of CV thrombotic events: rofecoxib & valdecoxib

COX-2 Selective inhibitors

Drugs Celecoxib Etoricoxib

Meloxicam

Valdecoxib/Rofecoxib

Parecoxib

Lumiracoxib

Absorption 20-30%(affected by food)

83% Slowly absorb

1-2 hours 15 minutes (IV, IM)

Rapid & well absorbed

Half-life 11 hrs 20-26% 20% 8-11 hours 24 hrs

Protein binding

high

Peak Plasma concentration

1-3 hrs

Metabolism CYP2C9 liver

Excretion Affected by hepatic impairment

kidney 40% decreased in elderly

Side Effects dyspepsia Slightly less ulcerogenic

MI, CVA/HTN, CHF, Stevens-Johnson syndrome

Inc BP, MI, inc transaminases

Non-selective COX inhibitors (Heteroacyl/Phenylacetic acid derivative)

Drugs Diclofenac Etodolac KetorolacAbsorption rapid Rapid, well absorbed Rapid (oral, IM), IV,

oral rinse, topical

Half-life 1-2 hours 7 hours 4-6 hours

Protein-binding 99% 99% 99%

Peak Plasma Concentration

30-50 min.

Bioavailability 30-70% 80% 80%

Metabolism CYP3A4 & CYP2C9

Excretion Biliary (30%) & urine (65%)

Urine (90%)

Side effects GI distress, Occult GI bleeding, Gastric ulceration, amino-transferases

Somnolence, dizziness, HA, dyspepsia, nausea pain at injection site

Non-selective COX inhibitors (Salicylic acid derivative)Diflunisal

Derived from salicylic acid

Not metabolized to salicylic acid or salicylate

Undergoes enterohepatic cycle with reabsorption of its glucoronide metabolite

T1/2: 13 hours

Uses: cancer pain with bone metastases & pain control in dental (3rd molar) surgery

Preparation: 2% oral ointment

dosage: 500-1000mg daily in 2 divided doses

Non-selective COX inhibitors (Propionic acid derivative)

Drugs Fenoprofen Flurbiprofen

Ibuprofen Ketoprofen

Absorption Rapid, incomplete Well absorbed

Half-life 2-4 hours 0.5-4 hours 1-2 hours 1-3 hours

Protein-binding 99% 99% 99%

Peak Plasma Concentration

2 hours 1-2 hours 1-2 hours

Metabolism Extensive hepatic Extensive hepatic CYP2C8 & CYP2C9

Excretion urine urine

Side effects Interstitial nephritis, GI irritation, tinnitus, rash pruritus

GI irritation & bleeding

GIT & CNS (30%)

Drug Interactions

Probenecid

Non-selective COX inhibitors (Propionic acid derivative)

Drugs Naproxen Tiaprofen Caprofen OxaprozinAbsorption

Half-life 12 hours 1-2 hours, 2-4 hours (elderly)

10-16 hours 50-60 hours

Protein-binding high

Peak Plasma Concentration

Bioavailability

Metabolism CYP2C9, less in CYP1A2 & CYP2C8

Excretion

Side effects UGIB, allergic pneumonitis, leukocytoclastic vasculitis, pseudoporphyria

Non-selective COX inhibitors (Para-chlorobenzoic acid derivative or indole)Indomethacin

Introduced in 1963

A more potent analgesic, antipyretic & anti-inflammatory agent than ASA

May also inhibit phospholipase A & C

Reduce PMN migration

Decrease T & B cells proliferation

Non-selective COX inhibitors (Para-chlorobenzoic acid derivative or indole)

Drugs Indomethacin SulindacAbsorption Rapid & almost

complete90% absorption

Peak concentration 2 hours 1 hour, t1/2: 7 hours

Metabolism Liver First pass hepatic, sulfide, active metabolite

Excretion Urine, bile, feces Urine, bile, feces

Side effects GIT, CNS, hematologic, psychosis w/ hallucination

GIT, CNS, hematologic, renal, allergic reactions

Drug interaction Furosemide, thiazide, beta blockers, ACEI, probenecid

Non-selective COX inhibitors (Fenamates/Anthranilic Acid)Meclofenamate & Mefenamic acid

Inhibit both COX & phospholipase A2

Peak plasma level: 30-60 min

t1/2: 1-3 hrs

SE: LBM, abdominal pain (meclofenamate)

CI: pregnancy, children

DI: oral anticoagulants

Indications: Primary Dysmenorrhea

Non-selective COX inhibitors (Alkalones) Nabumetone

The only nonacid NSAID, causes less gastric damage

Converted to the active metabolites in the liver, 6-methoxy-2 naphthylacetic acid

Given as a ketone prodrug

Dose: 1000 mg

t1/2: > 24 hrs

Does not undergo enterohepatic circulation

Causes pseudoporphyria & photosensitivity

Non-selective COX inhibitors (Pyrazolone derivative)

Drugs Phenylbutazone Azapropazone

Properties Withdrawn from the market

Structurally related to phenylbutazone

Half-life 12-16 hours

Toxicities aplastic anemia, agranulocytosis

Non-selective COX inhibitors (Oxicams/Enolic acid)19. Piroxicam

Inhibits PMN leukocyte migration, decreases O2 radical production, & inhibits lymphocyte function

Inhibits proteoglycanase & collagenase

Mean t1/2: 50-60 hrs

Dosing: o.d. or every other day

Non-selective COX inhibitors (Oxicams/Enolic acid)19. Piroxicam

Pharmacokinetics:– Rapidly absorbed from the stomach & upper intestine

– Peak plasma concentration: 1 hr

– Extensively metabolized to inactive metabolites

– 99% protein bound

– Elimination: renal – 5% unchanged

– Toxicity: GI symptoms, dizziness, tinnitus, HA & rash, increased incidence of PUD and bleeding

Non-selective COX inhibitors (Oxicams/Enolic acid)20. Tenoxicam

Half-life: 72 hours

Similar to piroxicam

Other analgesics ACETAMINOPHEN

– Active metabolite of phenacetine

– A weak PG inhibitor

– No significant anti-inflammatory effect

– For the treatment of mild to moderate pain

– Antipyretic effect

Other analgesics ACETAMINOPHEN

Pharmacokinetics:– Administered orally– Absorption: related to rate of gastric emptying– Peak blood concentration: 30-60 min– Slightly protein bound– Partially metabolized by hepatic microsomal enzyme

acetaminophen SO4 & glucuronide– Excretion: unchanged < 5%– A minor but highly active metabolite (N-acetyl-p-

benzoquinone) is important liver & kidney toxicity– t1/2: 2-3 hrs

Other analgesics ACETAMINOPHEN

Adverse effects:– Mild increase in hepatic enzymes– Dizziness, excitement & disorientation– Ingestion of 15gm: fatal death caused by

hepatotoxicity with centrilobular necrosis & sometimes with acute renal tubular necrosis

– Symptoms of early hepatic damage: N/V, diarrhea, abdominal pain

Antidote: N-acetylcysteine (sulfhydryl groups)

Caution: liver disease

Dosage: 325-500mg q.i.d.

CORTICOSTEROID DRUGS

Capable of slowing the appearance of new bone erosions

Known to inhibit phospholipase A2

Shown to selectively inhibit the expression of COX-2

SE: fracture, infections, cataracts

Prep: oral, intra-articular

DISEASE-MODIFYING ANTIRHEUMATIC DRUGS (DMARDS)

Might arrest or at least slow the progression of bone & cartilage destruction

Effects may take 6 weeks to 6 months to become evident

Exert minimal direct nonspecific anti-inflammatory or analgesic effects

Frequent improvement in serologic evidence of disease activity, titers of RF & CRP and ESR decline

METHOTREXATE

MOA: inhibition of aminoimidazolecarboxamide ribonucleotide (AICAR) transformylase & thymidylate synthase, with secondary effects on PMN chemotaxis plus enhanced adenosine release

Absorption: 70% after oral administration

Excretion: urine & bile

Dose: 7.5 - 25mg/wk (oral, SC or IM)

Toxicities: nausea, mucosal ulcers, dose-related hepatotoxicity, “hypersensitivity” lung reaction, pseudolymphomatous reaction

Folic acid & leucovorin

SULFASALAZINE

Consists of sulfapyridine & 5-amino-salicylic acid connected by diazo bond

Metabolized by bacteria in the colon

Have some anti-inflammatory action by O2 radical scavenging & inhibition of prostanoids and inhibit immune reactivity

t1/2: 6-17 hrs

Dose: 2-3g/d

Uses: RA, juvenile arthritis & ankylosing spondylitis

CHLOROQUINE, HYDROXYCHLOROQUINE

Used for the treatment of RA & SLE

MOA: unclear– They suppress the responsiveness of T lymphocytes to

nitrogens– decrease leukocyte chemotaxis– stabilize lysosomal membranes– inhibit DNA & RNA synthesis and trap free radicals

Effects are seen after 12-24 weeks

Other indications: juvenile chronic arthritis, Sjogren’s syndrome

Toxicity: ocular, dyspepsia, N/V, abdominal pain, rashes, nightmares

GOLD

Prep: auranofin – oral aurothiomalate & aurothioglucose – parenteral

95% protein-bound

Concentrate in synovial membrane, liver, kidney, spleen, adrenal glands, LN, & BM

Peak serum level: 2-6 hrs

Excretion: 40% within a week = 2/3-urine; 1/3-feces

Total body t1/2 (IM) – 1 year

GOLD

Mechanisms of action:– alters the morphology and functional capabilities of human

macrophages

– inhibition of lysosomal enzyme activity

– reduction of histamine release from mast cells

– suppression of phagocytic activity of the PMN leukocytes

– Aurothiomalate reduces the number of circulating lymphocytes

– Auranofin inhibits the release of PGE2 from synovial cells and the release of leukotrienes B4 & C4 from PMN leukocytes

GOLD

Indications:– Active RA– Active inflammation & erosive changes– RA with Sjogren’s syndrome – Juvenile RA

CI: history of previous toxicity from the drug, pregnancy, serious liver & renal impairment & blood dyscrasia

GOLD

Adverse effects:– Dermatitis - 15-20% (most common)

– Thrombocytopenia, leukopenia, pancytopenia – 1-10%

– Aplastic anemia – rare but fatal

– Proteinuria nephrotic syn – 8-10%

– Stomatitis, metallic taste, skin pigmentation, enterocolitis, cholestatic jaundice, peripheral neuropathy, pulmonary infiltrates, & corneal deposition of gold

– Nitritoid reaction (sweating, faintness, flushing, & headache)

– GI disturbances (LBM)

PENICILLAMINE

Pharmacodynamics:– Interact with lymphocytes membrane receptors

– Interfere with the synthesis of DNA, collagen, & mucopolysaccharides

Parmacokinetics:– A metabolite of penicillin– Is an analog of amino acid cysteine– Absorption: half of the orally administered, enhanced

after 1.5 hrs p.c.– Excretion: urine & feces in 24 hrs– Dose: 125-250mg daily for 1-3 months, 1.5 hrs p.c.

PENICILLAMINE

Adverse effects:– Decrease RF titer– Impedes absorption of many drugs– Inhibition of wound healing, muscle & blood vessel damage– Proteinuria – 20%– Immune complex nephritis – 4%– Leukopenia & thrombocytopenia aplastic anemia– Skin & mucosal membrane reactions– Drug fever associated with cutaneous eruption– Any of these maybe seen: myasthenia gravis, hemolytic

anemia, thyroiditis, Goodpasture’s syndrome & SLE– Loss of taste perception or metallic taste, anorexia, N/V– Mammary hyperplasia, alopecia, & psychologic changes

PENICILLAMINE

Contraindications:– Pregnancy– Renal insufficiency

Drug Interactions: – Gold– Cytotoxic drugs– Phenylbutazone

Biologics

Bind & neutralize TNF– Etanercept – a TNF type II receptor fused to IgG1– Infliximab – a chimeric mouse/human antibody to

TNF– Adalimumab – a fully human antibody to TNF

L-1 neutralizing agent– Anakinra

Depletes B cells– rituximab

Interferes with T cell activation– abatacept

Biologics that bind & neutralize TNF

Drugs Etanercept Infliximab Adalimumab

Peak Serum Concentration

72 hour

Route of Administration

25mg SC b.i.d. 3 or 10mg/kg at 0, 2 & 6 weeks I V infusion

40mg every other week SC

Half-life 8-12 days 10-20 days

Side Effects Injection site reactions, activation of latent pulmonary tuberculosis

Upper RTI, nausea, headache, sinusitis, rash & cough with MTX

Opportunistic infections, leukopenia, vasculitis, lupus

Biologics

Drugs Anakinra Rituximab AbataceptMOA A recombinant IL-1

receptor antagonist that competitively blocks the binding of IL-1β & IL-1

A chimeric monoclonal antibody that targets CD20 B lymphoctyes

Inhibits the activation of T cells by inhibiting the binding to CD28 and CD80/86

Route/Dose 2 I V infusions 2 weeks apart

I V infusion, 3 initial dose (day 0, week 2, week 4), then followed by monthly infusion

Half-life/Drug interaction

Not recommended to combined with anti-TNF

May be combined with MTX

13-16 days, May or may not be combined with MTX, but not with anti-TNF

Side Effects injection site reaction

related to transfusion reaction

increased risk of infection, hypersensitivity reactions

Immunosuppressive Therapy

These drugs have been reserve for patients who have clearly failed therapy with DMARDs and biologics

Effective in the treatment of RA

AZATHIOPRINE

Acts through its major metabolite, 6-thioguanine suppresses inosinic acid synthesis and B & T cell functions, immunoglobulin production & IL-2 secretion

Dosage: 2mg/kg/d

Other indications: SLE, Behcet’s syndrome, psoriatic arthritis, reactive arthritis, polymyositis

Toxicities: BM suppression, GI disturbances, increased in risk for infections and malignancy

LEFLUNOMIDE

A77-1726 (active metabolite) inhibits dihydroorotate dehydrogenase decrease de novo RNA synthesis and lower levels of rUMP translocation of p53 to nucleus inhibits autoimmune T cell proliferation & production of autoantibodies by B cells

Increases the mRNA level of IL-10 receptor, decreases IL-8 receptor type A mRNA concentrations & blocks TNF-dependent nuclear factor-kappa B activation

LEFLUNOMIDE

Pharmacokinetics:– Orally active molecule– MW: 270– Absorption: rapidly & nearly 100% – plasma t1/2: 15 days– Strong protein binding– Enterohepatic circulation– Excretion: bile

DI: cholestyramine

SE: diarrhea, elevation of liver enzymes

CYCLOSPORINE

Acts through IL-2 & TNF-a suppression, mediated through T cell effects

Absorption: erratic

Bioavailability: 30%, grape fruit juice increases by 62%

Metabolized in the liver

Dosage: 3-5mg/kg/d

Toxicities: nephrotoxicity, HTN, hyperkalemia, hepatotoxicity, gingival hyperplasia, & hirsutism

CYCLOPHOSPHAMIDE

MOA: through it active metabolite, phosphoramide mustard, cross-links DNA & prevents cell replication, it suppresses T & B cell functions by 30-40%

Metabolized in the liver

Given orally at 2mg/kg/d

Toxicities: infertility, BM suppression, hemorrhagic cystitis, bladder Ca acrolein

Other indications: SLE

Mycophenolate mafetil

Active form: mycophenolic acid

Inhibits cytosine monophosphate dehydrogenase Inhibits T-cell lymphocyte proliferation Interferes with leucocyte adhesion to endothelial cells

through inhibition of E-selectin, P-selectin, & IC adhesion molecule1

Indication: SLE, vasculitis, Wagener’s granulomatosis, RA

Dosage: 2 g/day

Adverse effects: GI, hematopoietic & hepatic

IMMUNOADSORPTION APHERESIS

Mechanism of action:– Down-regulation of B cell function through the

release of small amounts of staphylococcal protein A complexed with immunoglobulins

Median duration of response: 6 months

SE: chills – 30%, musculoskeletal pain – 15%, HA & nausea – 20-30%, joint pains & swelling – 30%

DRUGS USED IN GOUT(COLCHICINE)

Dramatically relieves pain, by binding to IC protein tubulin preventing polymerization into microtubules inhibition of leukocyte migration & phagocytosis

Absorption: readily, oral

Peak serum level: 2 hrs

Excretion: intestinal tract & urine

DRUGS USED IN GOUT(COLCHICINE)

Indication: gouty arthritis, acute Mediterranean fever, sarcoid arthritis, hepatic cirrhosis

Dosage: 0.5-1 mg q 2 hrs

SE: LBM, N/V, abdominal pain, hair loss, BM depression, peripheral neuritis, myopathy

Acute intoxication: burning throat pain, bloody LBM, shock, hematuria, oliguria, CNS depression

NSAIDs in GOUT

Inhibit urate crystal phagocytosis

Indomethacin is the agent most often used – 50 mg q 6 hrs reduced to 25mg t.i.d or q.i.d. for 5 days

ASA, salicylates, tolmetin are not effective for gouty episodes

Oxaprozin, lowers serum uric acid, but not given to patients with uric acid stone

URICOSURIC AGENTS(Probenecid & Sulfinpyrazone)

Act at the anionic transport sites of the renal tubule

Employed to decrease the body pool of urates

Reabsorption of uric acid in the proximal tubule is decreased

Probenecid: completely reabsorbed by renal tubules & metabolized slowly

Sulfinpyrazone: rapidly excreted by the kidneys

Probenecid & SulfinpyrazoneAdverse Effects, CI & Cautions

AE: GI irritation, allergic dermatitis, nephrotic syndrome (probenecid), aplastic anemia

CI & C: stone formation

Dosage: probenecid – 0.5 gm orally in divided doses, sulfinpyrazone – 200 mg daily

ALLOPURINOL

Reduce uric acid synthesis by inhibiting xanthine oxidase and increasing uric acid excretion

Absorption: 80%, oral

Given o.d.

Indications: chronic tophaceous gout, uric acid urine (24hrs) > 600-700mg, allergic reactions to probenecid & sulfinyrazone, renal impairment, grossly elevated serum uric acid levels

AE: N/V, diarrhea, peripheral neuritis, necrotizing vasculitis, BM depression, aplastic anemia, hepatic toxicity, interstitial nephritis, allergic skin reaction, cataracts

Febuxostat

First non-purine inhibitor of xanthine oxidase

More than 80% absorbed following oral administration

Maximum concentration: 1 hour

Extensively metabolized in the liver

Excreted in the urine

Febuxostat

Pharmacodynamics:– Potent & selective inhibitor of xanthine

oxidase → reduces the formation of xanthine & uric acid

Dose: 80mg, 120mg, 300mg daily

Adverse effects: liver function abnormalities, diarrhea, headache nausea