ARCOXIA 90MG TABLET

Malaysia - English - NPRA (National Pharmaceutical Regulatory Agency, Bahagian Regulatori Farmasi Negara)

Buy It Now

Active ingredient:
ETORICOXIB
Available from:
MERCK SHARP & DOHME (MALAYSIA) SDN BHD
INN (International Name):
ETORICOXIB
Units in package:
10tablet Tablets; 30tablet Tablets; 100tablet Tablets
Manufactured by:
Rovi Pharma Industrial Services S.A
Authorization number:
MAL12065065ACRZ

Documents in other languages

Patient Information leaflet Patient Information leaflet - Malay

17-09-2020

ARCOXIA

®

TABLET

Etoricoxib (30 mg, 60 mg, 90 mg, 120 mg)

Consumer Medication Information Leaflet (RiMUP)

What is in this leaflet

What Arcoxia tablet is used for

How Arcoxia tablet works

Before you take Arcoxia tablet

How to take Arcoxia tablet

While you are taking Arcoxia

tablet

Side effects

Storage and Disposal of

Arcoxia tablet

Product description

Manufacturer and Product

Registration Holder

Date of Revision

What Arcoxia tablet is used for

Your doctor has prescribed

Arcoxia tablet for:

treatment of osteoarthritis

treatment of rheumatoid

arthritis

treatment of ankylosing

spondylitis

treatment of acute pain after

minor dental procedures

treatment of menstrual pain

treatment of gout attacks

Osteoarthritis is a joint disease.

It results from the gradual

breakdown of the cartilage that

cushions the ends of the bones,

resulting in pain, inflammation,

tenderness, stiffness, and

physical disability.

Rheumatoid arthritis is a

chronic disease that causes pain,

stiffness, swelling and loss of

function in the joints and

inflammation in other body

organs.

Ankylosing spondylitis is an

inflammatory disease of the

spine and large joints.

Gout is a disorder characterized

by sudden, recurring attacks of

pain and inflammation in one or

more joints.

You may obtain further

information from your doctor or

pharmacist, who have more

detailed information.

How Arcoxia tablet works

Arcoxia tablet is a member of a

group of medicines called

selective COX-2 inhibitors that

are used to reduce pain and

inflammation. Arcoxia tablet is not

a narcotic.

Before you take Arcoxia tablet

-

When you must not take it

Do not take Arcoxia tablet if you:

are allergic to any of its

ingredients

have had heart failure, a

heart attack, bypass surgery,

chest pain, narrow or

blocked arteries of the

extremities, a stroke or mini

stroke

have high blood pressure that

has not been controlled by

treatment

-

Before you start to take it

Tell your doctor about any

medical problems or allergies you

have now or have had, including:

history of angina, heart

attack or a blocked artery in

your heart

narrow or blocked arteries of

the extremities

kidney disease

liver disease

dehydration, for example by a

prolonged bout of vomiting or

diarrhea.

have or have had ulceration,

bleeding or perforation of

your stomach or intestines

heart failure

high blood pressure

swelling due to fluid retention

an allergic reaction to aspirin

or other anti-inflammatory

medicines (commonly known

as NSAIDs).

a history of stroke or mini

stroke

conditions which increase

your risk of coronary artery

disease or atherosclerosis

such as high blood pressure,

diabetes, high cholesterol or

smoking.

being treated for an infection.

Arcoxia tablet can mask or

hide a fever, which is a sign

of infection.

have had asthma, nasal

inflammation, and/or itching

or hives caused by Aspirin or

NSAIDs.

suffering from dyspepsia

(indigestion).

Etoricoxib may cause severe skin

reactions. Symptoms may include

skin rash, blisters and peeling of

the skin. These could be signs of a

serious condition. If these

reactions occur, stop use and seek

medical assistance right away.

Use in children

Arcoxia tablet has not been

adequately studied in children.

Therefore, Arcoxia tablet should

not be given to children.

Use in the elderly

Arcoxia tablet works equally well

in older and younger adult

patients. Adverse experiences

may occur at a higher incidence in

older patients compared to

younger patients. If you are

elderly (i.e., over 65 years of age),

your doctor will want to

appropriately keep a check on

you. No dosage adjustment is

necessary for older patients.

Consumer Medication Information Leaflet (RiMUP)

Use in pregnancy and

breastfeeding

Tell your doctor if you are:

Arcoxia tablet may cause fetal

harm and should not be used

by a woman who is

attempting to become

pregnant or becomes pregnant

during treatment.

Breastfeeding or plan to

breastfeed.

-

Taking other medicines

You should always tell your

doctor about all medicines that

you are taking or plan to take,

including those obtained without a

prescription.

Your doctor may want to check

that your medicines are working

properly if you are taking:

warfarin (a blood thinner)

rifampin (an antibiotic)

diuretics (water tablets)

ACE inhibitors and

angiotensin receptor blockers

(medicines used for high

blood pressure and heart

failure)

lithium (a medicine used to

treat a certain type of

depression)

birth control pills

hormone replacement therapy

methotrexate (a medicine

used for suppressing the

immune system).

Arcoxia tablet can be taken with

low-dose aspirin. If you are

currently taking low-dose aspirin

for prevention of heart attack or

stroke, you should not discontinue

without consulting your doctor

because Arcoxia tablet cannot

substitute for aspirin for this

purpose.

How to take Arcoxia tablet

-

How much to take

Arcoxia tablet should be taken

once a day. You may take

Arcoxia tablet with or without

food.

Your doctor will decide what dose

of Arcoxia tablet you should take

and how long you should take it.

For treatment of osteoarthritis:

The recommended dose is 30

mg or 60 mg once a day.

For treatment of rheumatoid

arthritis:

The recommended dose is 90

mg once a day.

For treatment of ankylosing

spondylitis:

The recommended dose is 90

mg once a day.

Acute pain conditions

The recommended dose is 90mg

or 120mg once daily. Arcoxia

should be used only for the acute

period limited to a maximum of 8

days.

For the relief of gout attacks and

the treatment of menstrual pain:

The recommended dose is

120 mg once a day which

should only be used for the

acute painful period.

For the relief of pain after minor

dental procedures

The recommended dose is

90mg once a day.

Doses greater than those

recommended for each condition

have either not demonstrated

additional efficacy or have not

been studied. Therefore, the daily

doses stated above for

each condition should not be

exceeded.

If you have mild or moderate liver

disease, your doctor might

prescribe you a lower dose or

recommend that you do not take

Arcoxia.

-

When to take it

Use as directed by your doctor or

pharmacist.

-

How long to take it

Continue taking Arcoxia tablet for

as long as your doctor

recommends.

-

If you forget to take it

Try to take Arcoxia tablet as

prescribed. However, if you miss a

dose, do not take an extra dose.

Just resume your usual schedule

the following day.

-

If you take too much (overdose)

If you take more than the

prescribed dosage, contact your

doctor immediately.

While you are taking Arcoxia

tablet

-

Things you must do

Consult your doctor if:

Any of the following

symptoms appear or worsen:

shortness of breath, chest

pains or ankle swelling

.

Stop

your treatment with Arcoxia

tablet and consult a doctor,

as soon as is practical.

You have kidney, liver or

heart disease, your doctor

will want to appropriately

keep a check on you.

You develop any symptoms

that could indicate a severe

allergic reaction such as

inability to breath or a serious

skin reaction, you must

consult a doctor on an urgent

basis.

Your doctor will want to discuss

your treatment from time to time.

It is important that you use the

Consumer Medication Information Leaflet (RiMUP)

lowest dose that controls your

pain.

Arcoxia tablet can increase blood

pressure in some people,

especially in high doses, and this

could increase the risk of heart

attacks and strokes. Your doctor

will want to check your blood

pressure from time to time, to

make sure that it is safe to

continue treatment.

-

Things you must not do

Do not share Arcoxia tablet with

anyone else; it was prescribed

only for you.

Do not take Arcoxia tablet for

longer than necessary. This is

because the risk of heart attacks

and strokes might increase after

prolonged treatment, especially

with high doses.

-

Things to be careful of

Be careful driving or operating

machinery until you know how

Arcoxia affects you.

Arcoxia contains lactose

If you have been told by your

doctor that you are unable to

tolerate some sugars, contact your

doctor before taking this

medicinal product.

Side effects

Any medicine may have

unintended or undesirable effects,

so-called side effects.

Like all prescription medicines,

Arcoxia tablet may cause side

effects.

Some of the side effects reported

in the studies included:

dizziness,

swelling of the legs and/or

feet,

weakness and fatigue,

high blood pressure,

nausea,

heartburn,

upset stomach,

headache

dry socket (inflammation and

pain after a tooth extraction)

Additionally, the following have

been reported:

allergic reactions (which may

be serious enough to require

immediate medical attention)

including swelling of the face,

lips, tongue, and/or throat

which may cause difficulty in

breathing or swallowing,

wheezing, rash, itching and

hives;

redness of the skin,

severe skin reactions which

may occur without warning;

taste alteration,

abnormal rhythm of the heart,

heart failure,

palpitations,

feeling of tightness, pressure

or heaviness in the chest,

stomach pain,

stomach ulcers that may

become serious and may

bleed and may occur at any

time during use and without

warning,

vomiting,

liver problems including liver

failure, yellowing of the skin

and eyes (jaundice),

serious kidney problems,

high levels of potassium in

your blood,

insomnia,

anxiety,

depression,

restlessness,

drowsiness,

mouth ulcers,

diarrhea,

severe increase in blood

pressure,

confusion,

hallucinations,

platelets decreased,

blurred vision.

In clinical studies, the risk of

developing ulcers while taking

Arcoxia tablet was lower than with

NSAIDs.

Other side effects may also occur

rarely, and as with any

prescription medicine, some side

effects may be serious. Ask your

doctor or pharmacist for more

information. Both have a more

complete list of side effects. Tell

your doctor or pharmacist

promptly about these or any other

unusual symptoms.

You may report any side effects or

adverse drug reactions directly to

the National Centre for Adverse

Drug Reaction Monitoring by

calling Tel: 03-78835490 or

visiting the website npra.gov.my

[Consumers

Reporting Side

Effects to Medicines (ConSERF)

or Vaccines (AEFI)].

Storage and Disposal

-

Storage

Store at 30

C (86

F). Store in the

original package. Protect from

moisture and light.

Keep Arcoxia tablet and all

medicines safely away from

children.

Do not use this medicine after the

month and year shown by the four

numbers following EX (or EXP)

on the container. The first two

numbers indicate the month; the

last two numbers indicate the year.

-

Disposal

Medicines should not be disposed

of via wastewater or household

waste. Ask your pharmacist how

to dispose of medicines no longer

Consumer Medication Information Leaflet (RiMUP)

required. These measures will help

to protect the environment.

Product Description

-

What it looks like

Arcoxia 30mg: Blue-green

apple-shape biconvex film

coated tablets debossed ACX

30 on one side and 101 on the

other side

Arcoxia 60mg: Dark green

apple-shape biconvex film

coated tablets debossed

Arcoxia 60 on one side and

200 on the other side

Arcoxia 90mg: White apple-

shape biconvex film coated

tablets debossed

ARCOXIA

90 on one side and 202 on the

other side

Arcoxia 120mg: Pale green

apple-shape biconvex film

coated tablets debossed

Arcoxia 120 on one side and

204 on the other side

-

Ingredients

Active ingredient:

Etoricoxib

Inactive ingredients:

Calcium hydrogen phosphate

anhydrous; microcrystalline

cellulose; croscarmellose sodium;

hypromellose; magnesium

stearate; lactose monohydrate;

titanium dioxide; glycerol

triacetate and carnauba wax. The

30 mg, 60 mg and 120 mg tablets

also contain yellow ferric oxide

and FD&C Blue #2 (indigo

carmine lake).

-

MAL number

Arcoxia 30 mg tablet:

MAL12065063ACRZ

Arcoxia 60 mg tablet:

MAL12065082ACRZ

Arcoxia 90 mg tablet:

MAL12065065ACRZ

Arcoxia 120 mg tablet:

MAL12065084ACRZ

Product Manufacturer

Rovi Pharma Industrial Services, S.A.

Vía Complutense, 140

28805 Alcalá de Henares

Madrid, Spain

Product Registration Holder

Merck Sharp & Dohme (Malaysia)

Sdn. Bhd.

Lot No. B-22-1 & B-22-2,

Level 22

The Ascent, Paradigm No.1

Jalan SS 7/26A, Kelana Jaya

47301 Petaling Jaya,

Selangor, Malaysia

Date of revision

25/08/2020 (version 062015c)

Serial number

NPRA (R1/2) 14092020/157

LPC-MK0663-T-062015c-Malaysia

LOCAL PRODUCT CIRCULAR

Tablets

ARCOXIA®

(etoricoxib)

I. THERAPEUTIC CLASS

ARCOXIA

(etoricoxib) is a member of a class of arthritis/analgesia medications called Coxibs.

ARCOXIA is a highly selective inhibitor of cyclooxygenase-2 (COX-2).

II. COMPOSITION

IIa. Active Ingredients

Each tablet of ARCOXIA for oral administration contains either 30, 60, 90 or 120 mg of

etoricoxib.

IIb. Inactive Ingredients

Each tablet contains calcium hydrogen phosphate (anhydrous), carnauba wax, croscarmellose

sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose,

titanium dioxide, and glycerol triacetate. The 30 mg, 60 mg and 120 mg tablets also contain

yellow ferric oxide and FD&C Blue #2 (indigo carmine lake).

III. CLINICAL PHARMACOLOGY

IIIa. Mechanism of Action

ARCOXIA is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory,

analgesic, and antipyretic activities in animal models. ARCOXIA is a potent, orally active, highly

selective cyclooxygenase-2 (COX-2) inhibitor within and above the clinical dose range. Two

isoforms of cyclooxygenase have been identified: cyclooxygenase-1 (COX-1) and

cyclooxygenase-2 (COX-2). COX-1 is responsible for prostaglandin-mediated normal physiologic

functions such as gastric cytoprotection and platelet aggregation. Inhibition of COX-1 by

nonselective NSAIDs has been associated with gastric damage and platelet inhibition. COX-2

has been shown to be primarily responsible for the synthesis of prostanoid mediators of pain,

inflammation, and fever. Selective inhibition of COX-2 by etoricoxib decreases these clinical

signs and symptoms with decreased GI toxicity and without effects on platelet function.

Across clinical pharmacology studies, ARCOXIA produced dose-dependent inhibition of COX-2

without inhibition of COX-1 at doses up to 150 mg daily.

The influence on gastroprotective COX-1 activity was also assessed in a clinical study where

prostaglandin synthesis was measured in gastric biopsy samples from subjects administered

either ARCOXIA 120 mg daily, naproxen 500 mg twice daily, or placebo. ARCOXIA did not

inhibit gastric prostaglandin synthesis as compared to placebo. In contrast, naproxen inhibited

gastric prostaglandin synthesis by approximately 80% compared with placebo. These data

further support the COX-2 selectivity of ARCOXIA.

Platelet Function

Multiple doses of ARCOXIA up to 150 mg administered daily up to nine days had no effect on

bleeding time relative to placebo. Similarly, bleeding time was not altered in a single dose study

with ARCOXIA 250 or 500 mg. There was no inhibition of

ex vivo

arachidonic acid- or collagen-

induced platelet aggregation at steady state with doses of ARCOXIA up to 150 mg. These

findings are consistent with the COX-2 selectivity of etoricoxib.

IIIb. Pharmacokinetics

IIIb-1. Absorption

In studies specifically designated to measure the onset of action of etoricoxib, the onset of action

occurred as early as 24 minutes after dosing.

Orally administered etoricoxib is well absorbed. The mean oral bioavailability is approximately

100%. Following 120 mg once-daily dosing to steady state, the peak plasma concentration

(geometric mean C

= 3.6 mcg/mL) was observed at approximately 1 hour (T

) after

administration to fasted adults. The geometric mean AUC

0-24hr

was 37.8 mcghr/mL. The

pharmacokinetics of etoricoxib are linear across the clinical dose range.

A standard meal had no clinically meaningful effect on the extent or rate of absorption of a dose

of etoricoxib 120 mg. In clinical trials, etoricoxib was administered without regard to food.

The pharmacokinetics of etoricoxib in 12 healthy subjects were similar (comparable AUC, C

within approximately 20%) when administered alone, with a magnesium/aluminium hydroxide

antacid, or a calcium carbonate antacid (approximately 50 mEq acid-neutralizing capacity).

IIIb-2. Distribution

Etoricoxib is approximately 92% bound to human plasma protein over the range of

concentrations of 0.05 to 5 mcg/mL. The volume of distribution at steady state (V

) is

approximately 120 L in humans.

Etoricoxib crosses the placenta in rats and rabbits, and the blood-brain barrier in rats.

IIIb-3. Metabolism

Etoricoxib is extensively metabolized with <1% of a dose recovered in urine as the parent drug.

The major route of metabolism to form the 6’-hydroxymethyl derivative is catalyzed by

cytochrome P450 (CYP) enzymes.

Five metabolites have been identified in man. The principal metabolite is the 6’-carboxylic acid

derivative of etoricoxib formed by further oxidation of the 6’-hydroxymethyl derivative. These

principal metabolites either demonstrate no measurable activity or are only weakly active as

COX-2 inhibitors. None of these metabolites inhibit COX-1.

IIIb-4. Elimination

Following administration of a single 25 mg radiolabeled intravenous dose of etoricoxib to healthy

subjects, 70% of radioactivity was recovered in urine and 20% in feces, mostly as metabolites.

Less than 2% was recovered as unchanged drug.

Elimination of etoricoxib occurs almost exclusively through metabolism followed by renal

excretion. Steady state concentrations of etoricoxib are reached within seven days of once-daily

administration of 120 mg, with an accumulation ratio of approximately 2, corresponding to an

accumulation half-life of approximately 22 hours. The plasma clearance is estimated to be

approximately 50 mL/min.

IV. INDICATIONS

ARCOXIA is indicated for:

Acute and chronic treatment of the signs and symptoms of osteoarthritis (OA) and

rheumatoid arthritis (RA)

Treatment of ankylosing spondylitis (AS)

Treatment of acute gouty arthritis

Treatment of acute pain, including that related to primary dysmenorrhoea and minor dental

procedures.

The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of the

individual patient's overall risks (see PRECAUTIONS).

V. DOSAGE AND ADMINISTRATION

ARCOXIA is administered orally. ARCOXIA may be taken with or without food. ARCOXIA should

be administered for the shortest duration possible and the lowest effective daily dose should be

used.

Osteoarthritis

The recommended dose is 30 mg or 60 mg once daily.

Rheumatoid Arthritis

The recommended dose is 60 mg or 90 mg once daily. The minimum effective daily dose is

60 mg once daily. In some patients, 90 mg once daily may provide increased therapeutic benefit.

Ankylosing Spondylitis

The recommended dose is 60 mg or 90 mg once daily. The minimum effective daily dose is

60 mg once daily. In some patients, 90 mg once daily may provide increased therapeutic benefit.

Acute Pain

In the following acute painful conditions, ARCOXIA should be used only for the acute

symptomatic period, limited to a maximum of 8 days treatment:

Acute Gouty Arthritis

The recommended dose is 120 mg once daily.

Primary Dysmenorrhea

The recommended dose is 120 mg once daily.

Minor Dental Procedures

The recommended dose is 90 mg once daily.

Doses greater than those recommended for each indication have either not demonstrated

additional efficacy or have not been studied. Therefore:

The dose for OA should not exceed 60 mg daily.

The dose for RA should not exceed 90 mg daily.

The dose for ankylosing spondylitis should not exceed 90 mg daily.

VI. CONTRAINDICATIONS

The dose for acute gout should not exceed 120 mg daily.

The dose for acute pain and primary dysmenorrhea should not exceed 120 mg daily.

The dose for minor dental procedures should not exceed 90 mg daily.

As the cardiovascular risks of selective COX-2 inhibitors may increase with dose and duration of

exposure, the shortest duration possible and the lowest effective daily dose should be used. The

patient's need for symptomatic relief and response to therapy should be re-evaluated

periodically (see PRECAUTIONS).

Elderly, Gender, Race

No dosage adjustment in ARCOXIA is necessary for the elderly or based on gender or race.

Hepatic Insufficiency

In patients with mild hepatic insufficiency (Child-Pugh score 5-6), a dose of 60 mg once daily

should not be exceeded. In patients with moderate hepatic insufficiency (Child-Pugh score 7-9),

the dose should be reduced; a dose of 60 mg

every other day

should not be exceeded,

administration of 30 mg once daily can also be considered. There are no clinical or

pharmacokinetic data in patients with severe hepatic insufficiency (Child-Pugh score >9). (see

PRECAUTIONS).

Renal Insufficiency

In patients with advanced renal disease (creatinine clearance <30 mL/min), treatment with

ARCOXIA is not recommended. No dosage adjustment is necessary for patients with lesser

degrees of renal insufficiency (creatinine clearance ≥30 mL/min). (see PRECAUTIONS).

ARCOXIA is contraindicated in patients with:

Hypersensitivity to any component of this product.

Congestive heart failure (NYHA II-IV).

Established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease

(including patients who have recently undergone coronary artery bypass graft surgery or

angioplasty).

Patients with hypertension whose blood pressure has not been adequately controlled.

Pregnancy.

Clinical trials suggest that the selective COX-2 inhibitor class of drugs may be associated with

an increased risk of thrombotic events (especially MI and stroke), relative to placebo and some

NSAIDs (naproxen). As the cardiovascular risks of selective COX-2 inhibitors may increase with

dose and duration of exposure, the shortest duration possible and the lowest effective daily dose

should be used. The patient's need for symptomatic relief and response to therapy should be re-

evaluated periodically.

Patients with significant risk factors for cardiovascular events (e.g. hypertension,

hyperlipidaemia, diabetes mellitus, smoking) should only be treated with etoricoxib after careful

consideration.

Selective COX-2 inhibitors are not a substitute for aspirin for cardiovascular prophylaxis because

of their lack of effect on platelets. Because etoricoxib, a member of this class, does not inhibit

platelet aggregation, antiplatelet therapies should not be discontinued.

There is a further increase in the risk of gastrointestinal adverse effects (gastrointestinal

ulceration or other gastrointestinal complications) for etoricoxib, other selective COX-2 inhibitors

and NSAIDs, when taken concomitantly with acetylsalicylic acid (even at low doses). The

relative difference in gastrointestinal safety between selective COX-2 inhibitors + acetylsalicylic

acid

. NSAIDs + acetylsalicylic acid has not been adequately evaluated in long-term clinical

trials.

VII. PRECAUTIONS

In patients with advanced renal disease, treatment with ARCOXIA is not recommended. Clinical

experience in patients with estimated creatinine clearance of <30 mL/min is very limited. If

therapy with ARCOXIA must be initiated in such patients, close monitoring of the patient’s renal

function is advisable.

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal

injury.

Renal

prostaglandins

play

compensatory

role

maintenance

renal

perfusion.

Therefore,

under

conditions

compromised

renal

perfusion,

administration

ARCOXIA may cause a reduction in prostaglandin formation and, secondarily, in renal blood

flow, and thereby impair renal function. Patients at greatest risk of this response are those with

pre-existing significantly impaired renal function, uncompensated heart failure, or cirrhosis.

Monitoring of renal function in such patients should be considered.

Caution should be used when initiating treatment with ARCOXIA in patients with considerable

dehydration. It is advisable to rehydrate patients prior to starting therapy with ARCOXIA.

As with other drugs known to inhibit prostaglandin synthesis, fluid retention, edema and

hypertension have been observed in some patients taking ARCOXIA. The possibility of fluid

retention, edema or hypertension should be taken into consideration when ARCOXIA is used in

patients

with

pre-existing

edema,

hypertension,

heart

failure.

Nonsteroidal

Antiinflammatory Drugs (NSAIDs), including etoricoxib, can be associated with new onset or

recurrent congestive heart failure. (see SIDE EFFECTS.). Etoricoxib may be associated with

more

frequent

severe

hypertension

than

some

other

NSAIDs

selective

COX-2

inhibitors, particularly at high doses. Therefore, special attention should be paid to blood

pressure monitoring

during

treatment

with

etoricoxib.

blood

pressure

rises

significantly,

alternative treatment should be considered.

Physicians should be aware that individual patients may develop upper gastrointestinal (GI)

ulcers/ulcer complications irrespective of treatment. Although the risk of GI toxicity is not

eliminated with ARCOXIA, the results of the MEDAL Program demonstrate that in patients

treated with ARCOXIA, the risk of GI toxicity with ARCOXIA 60 mg or 90 mg once daily is

significantly less than with diclofenac 150 mg daily. In clinical studies with ibuprofen and

naproxen, the risk of endoscopically detected upper GI ulcers was lower in patients treated with

ARCOXIA 120 mg once daily than in patients treated with the non-selective NSAIDs. While the

risk of endoscopically detected ulcers was low in patients treated with ARCOXIA 120 mg it was

higher than in patients treated with placebo. Upper GI ulcers/ulcer complications have occurred

in patients treated with ARCOXIA. These events can occur at any time during use and without

warning symptoms. Independent of treatment, patients with a prior history of GI perforation,

ulcers and bleeding (PUB) and patients greater than 65 years of age are known to be at a higher

risk for a PUB.

Elevations

alanine

aminotransferase

(ALT)

and/or

aspartate

aminotransferase

(AST)

(approximately

three

more

times

upper

limit

normal)

have

been

reported

approximately 1% of patients in clinical trials treated for up to one year with ARCOXIA 30, 60

and 90 mg daily. In active comparator portions of clinical trials, the incidence of elevated AST

and/or ALT in patients treated with ARCOXIA 60 and 90 mg daily was similar to that of patients

treated with naproxen 1000 mg daily, but notably less than the incidence in the diclofenac 150

mg daily group. These elevations resolved in patients treated with ARCOXIA, with approximately

half resolving while patients remained on therapy. In controlled clinical trials of ARCOXIA 30 mg

daily versus ibuprofen 2400 mg daily or celecoxib 200 mg daily, the incidence of elevations of

ALT or AST was similar.

A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver

function test has occurred, should be evaluated for persistently abnormal liver function tests. If

persistently abnormal liver function tests (three times the upper limit of normal) are detected,

ARCOXIA should be discontinued.

ARCOXIA should be used with caution in patients who have previously experienced acute

asthmatic attacks, urticaria, or rhinitis, which were precipitated by salicylates or non-selective

cyclooxygenase inhibitors. Since the pathophysiology of these reactions is unknown, physicians

should weigh the potential benefits of prescribing ARCOXIA versus the potential risks.

When using etoricoxib in the elderly and in patients with renal, hepatic, or cardiac dysfunction,

medically appropriate supervision should be maintained. If these patients deteriorate during

treatment, appropriate measures should be taken, including discontinuation of therapy.

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson

syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the

VIII. WARNINGS

IX. PREGNANCY

use of NSAIDs and some selective COX-2 inhibitors during post-marketing surveillance (see

SIDE EFFECTS). These serious events may occur without warning. Patients appear to be at

highest risk for these reactions early in the course of therapy: the onset of the reaction occurring

in the majority of cases within the first month of treatment. Serious hypersensitivity reactions

(such as anaphylaxis and angioedema) have been reported in patients receiving etoricoxib (see

SIDE EFFECTS). Some selective COX-2 inhibitors have been associated with an increased risk

of skin reactions in patients with a history of any drug allergy. Etoricoxib should be discontinued

at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

ARCOXIA may mask fever, which is a sign of infection. The physician should be aware of this

when using ARCOXIA in patients being treated for infection.

RISK OF GI ULCERATION, BLEEDING AND PERFORATION WITH NSAIDs

Serious GI toxicity such as bleeding, ulceration and perforation can occur at any time, with or

without warning symptoms, in patients treated with NSAIDs therapy. Although minor upper GI

problems (e.g. dyspepsia) are common, usually developing early in therapy, prescribers should

remain alert for ulceration and bleeding in patients treated with NSAIDs even in the absence of

previous GI tract symptoms.

Studies to date have not identified any subset of patients not at risk of developing peptic

ulceration and bleeding. Patients with prior history of serious adverse events and other risk

factors

associated

with

peptic

ulcer

disease

(e.g.

alcoholism,

smoking

corticosteroid

therapy) are at increased risk. Elderly or debilitated patients seem to tolerate ulceration or

bleeding less than other individuals and account for most spontaneous reports for fatal GI

events.

The use of etoricoxib, as with any drug substance known to inhibit COX-2, is not recommended

in women attempting to conceive. No clinical data on exposed pregnancies are available for

etoricoxib. Studies in animals have shown reproductive toxicity. The potential for human risk in

pregnancy is unknown. Etoricoxib, as with other medicinal products inhibiting prostaglandin

synthesis, may cause uterine inertia and premature closure of the ductus arteriosus during the

last trimester. Etoricoxib is contraindicated in pregnancy. If a woman becomes pregnant during

treatment, etoricoxib should be discontinued.

X. NURSING MOTHERS

Etoricoxib is excreted in the milk of lactating rats. It is not known whether this drug is excreted in

human milk. Because many drugs are excreted in human milk and because of the possible

adverse effects of drugs that inhibit prostaglandin synthesis on nursing infants, a decision should

be made whether to discontinue nursing or to discontinue the drug, taking into account the

importance of the drug to the mother.

XI. PEDIATRIC USE

Safety and effectiveness of etoricoxib in pediatric patients have not been established.

XII. USE IN THE ELDERLY

Pharmacokinetics in the elderly (65 years of age and older) are similar to those in the young. In

clinical studies, a higher incidence of adverse experiences was seen in older patients compared

to younger patients; the relative differences between etoricoxib and control groups were similar

in the elderly and the young. Greater sensitivity of some older individuals cannot be ruled out.

XIII. DRUG INTERACTIONS

Warfarin

: In subjects stabilized on chronic warfarin therapy, the administration of ARCOXIA

daily

associated

with

approximate

increase

prothrombin

time

International Normalized Ratio (INR). Standard monitoring of INR values should be conducted

when therapy with ARCOXIA is initiated or changed, particularly in the first few days, in patients

receiving warfarin or similar agents.

Rifampin

: Co-administration of ARCOXIA with rifampin, a potent inducer of hepatic metabolism,

produced a 65% decrease in etoricoxib plasma area under the curve (AUC). This interaction

should be considered when ARCOXIA is co-administered with rifampin.

Methotrexate

: Two studies investigated the effects of ARCOXIA 60, 90 or 120 mg administered

once daily for seven days in patients receiving once-weekly methotrexate doses of 7.5 to 20 mg

for rheumatoid arthritis. ARCOXIA at 60 and 90 mg had no effect on methotrexate plasma

concentrations (as measured by AUC) or renal clearance. In one study, ARCOXIA 120 mg had

no effect on methotrexate plasma concentrations (as measured by AUC) or renal clearance. In

the other study, ARCOXIA 120 mg increased methotrexate plasma concentrations by 28% (as

measured by AUC) and reduced renal clearance of methotrexate by 13%. Monitoring for

methotrexate-related toxicity should be considered when ARCOXIA at doses greater than 90 mg

daily and methotrexate are administered concomitantly.

Diuretics, Angiotensin Converting Enzyme (ACE) Inhibitors and Angiotensin II Antagonists

(AIIAs)

: Reports suggest that NSAIDs including selective COX-2 inhibitors may diminish the

antihypertensive effect of diuretics, ACE inhibitors and AIIAs. This interaction should be given

consideration in patients taking ARCOXIA concomitantly with these products.

In some patients with compromised renal function (e.g., elderly patients or patients who are

volume-depleted, including those on diuretic therapy) who are being treated with non-steroidal

anti-inflammatory drugs, including selective COX-2 inhibitors, the co-administration of ACE

inhibitors or AIIAs may result in a further deterioration of renal function, including possible acute

renal failure. These effects are usually reversible. Therefore, the combination should be

administered with caution, especially in the elderly.

Lithium

Reports

suggest

that

non-selective

NSAIDs

selective

COX-2

inhibitors

increase plasma lithium levels. This interaction should be given consideration in patients taking

ARCOXIA concomitantly with lithium.

Aspirin

: ARCOXIA can be used concomitantly with low-dose aspirin at doses for cardiovascular

prophylaxis. At steady state, etoricoxib 120 mg once daily had no effect on the anti-platelet

activity of low-dose aspirin (81 mg once daily). However, concomitant administration of low-dose

XIV. SIDE EFFECTS

aspirin with ARCOXIA increases the rate of GI ulceration or other complications compared to

use of ARCOXIA alone. (see PRECAUTIONS).

Oral Contraceptives

: ARCOXIA 60mg given concomitantly with an oral contraceptive containing

35 mcg ethinyl estradiol (EE) and 0.5 to 1 mg norethindrone for 21 days increased the steady

state AUC

0-24hr

of EE by 37%. ARCOXIA 120 mg given with the same oral contraceptive either

concomitantly or separated by 12 hours, increased the steady state AUC

0-24hr

of EE by 50 to

60%. This increase in EE concentration should be considered when selecting an appropriate

oral contraceptive for use with ARCOXIA. An increase in EE exposure can increase the

incidence of adverse events associated with oral contraceptives (e.g., venous thrombo-embolic

events in women at risk).

Hormone Replacement Therapy

: Administration of ARCOXIA 120 mg with hormone replacement

therapy consisting of conjugated estrogens (0.625 mg PREMARIN

®†

) for 28 days, increased the

mean steady state AUC

0-24hr

of unconjugated estrone (41%), equilin (76%) and 17-ß-estradiol

(22%). The effect of the recommended chronic doses of ARCOXIA (30, 60 and 90 mg) has not

been studied. The effects of ARCOXIA 120mg on the exposure (AUC

0-24hr

) to these estrogenic

components of PREMARIN

®†

were less than half of those observed when PREMARIN

®†

administered alone and the dose was increased from 0.625 to 1.25 mg. The clinical significance

these

increases

unknown,

higher

doses

PREMARIN

®†

were

studied

combination with ARCOXIA. These increases in estrogenic concentration should be taken into

consideration when selecting post-menopausal hormone therapy for use with ARCOXIA.

Other

: In drug-interaction studies, ARCOXIA did not have clinically important effects on the

pharmacokinetics of prednisone/prednisolone or digoxin.

Antacids and ketoconazole (a potent inhibitor of CYP3A4) did not have clinically important

effects on the pharmacokinetics of ARCOXIA.

®†

Registered Trademark

In clinical trials, ARCOXIA was evaluated for safety in 9295 individuals, including 5774 patients

with OA, RA or chronic low back pain (approximately 600 patients with OA or RA were treated

for one year or longer).

The following drug-related adverse experiences were reported in clinical studies in patients with

OA, RA, or chronic low back pain treated for up to 12 weeks. These occurred in ≥1% of patients

treated with ARCOXIA and at an incidence greater than placebo: asthenia/fatigue, dizziness,

lower extremity edema, hypertension, dyspepsia, heartburn, nausea, headache, ALT increased,

AST increased.

The adverse experience profile was similar in patients with OA or RA treated with ARCOXIA for

one year or longer.

In the MEDAL Study, an endpoint driven CV outcomes trial involving 23, 504 patients, the safety

of ARCOXIA 60 or 90 mg daily was compared to diclofenac 150 mg daily in patients with OA or

RA (mean duration of treatment was 20 months). In this large trial, only serious adverse events

and discontinuations due to any adverse events were recorded. The rates of confirmed

thrombotic cardiovascular serious adverse events were similar between ARCOXIA and

diclofenac. The incidence of discontinuations for hypertension-related adverse events was less

than 3% in each treatment group; however, ARCOXIA 60 and 90 mg demonstrated significantly

higher rates of discontinuations for these events than diclofenac. The incidence of congestive

heart failure adverse events (discontinuations and serious events) and the incidence of

discontinuations due to edema occurred at similar rates on ARCOXIA 60 mg compared to

diclofenac, however, the incidences for these events were higher for ARCOXIA 90 mg compared

to diclofenac. The incidence of discontinuations due to atrial fibrillation was higher for etoricoxib

compared to diclofenac.

The EDGE and EDGE II studies compared the GI tolerability of etoricoxib 90 mg daily (1.5 to 3

times the doses recommended for OA) and diclofenac 150 mg daily in 7111 patients with OA

(EDGE Study; mean duration of treatment 9 months) and 4086 patients with RA (EDGE II; mean

duration of treatment 19 months). In each of these studies, the adverse experience profile on

ARCOXIA was generally similar to that reported in the phase IIb/III placebo-controlled clinical

studies; however, hypertension and edema-related adverse experiences occurred at a higher

rate on etoricoxib 90 mg than on diclofenac 150 mg daily. The rate of confirmed thrombotic

cardiovascular serious adverse events occurring in the two treatment groups was similar.

In a combined analysis of phase IIb to V clinical studies of 4 weeks duration or longer (excluding

the MEDAL PROGRAM Studies), there was no discernible difference in the rate of confirmed

thrombotic cardiovascular serious adverse events between patients receiving etoricoxib ≥30 mg

or non-naproxen NSAIDs. The rate of these events was higher in patients receiving etoricoxib

compared with those receiving naproxen 500 mg twice daily.

In a clinical study for ankylosing spondylitis, patients were treated with ARCOXIA 90 mg once

daily for up to 1 year (N=126). In another clinical study for ankylosing spondylitis (N=857),

patients were treated with ARCOXIA 60 mg or 90 mg once daily for up to 26 weeks. The

adverse experience profile in these studies was generally similar to that reported in chronic

studies in OA, RA and chronic low back pain.

In a clinical study for acute gouty arthritis, patients were treated with ARCOXIA 120 mg once

daily for eight days. The adverse experience profile in this study was generally similar to that

reported in the combined OA, RA, and chronic low back pain studies.

In initial clinical studies for acute analgesia, patients were treated with ARCOXIA 120 mg once

daily for one to seven days. The adverse experience profile in these studies was generally

similar to that reported in the combined OA, RA, and chronic low back pain studies.

In the combined studies for acute post-operative dental pain, the incidence of post-dental

extraction alveolitis (dry socket) reported in patients treated with ARCOXIA was similar to that of

patients treated with active comparators.

Post-marketing experience

The following adverse reactions have been reported in post-marketing experience:

Blood and lymphatic system disorders:

thrombocytopenia.

Immune system disorders

hypersensitivity reactions, anaphylactic/anaphylactoid reactions

including shock.

Metabolism and nutrition disorders:

hyperkalemia.

XVI. AVAILABILITY

Psychiatric disorders:

anxiety, insomnia, confusion, hallucinations, depression, restlessness.

Nervous system disorders

: dysgeusia, somnolence.

Eye disorders:

blurred vision.

Cardiac disorders:

congestive heart failure, palpitations, angina, arrhythmia.

Vascular disorders:

hypertensive crisis.

Respiratory, thoracic and mediastinal disorders

: bronchospasm.

Gastrointestinal disorders:

abdominal pain, oral ulcers, peptic ulcers including perforation and

bleeding (mainly in elderly patients), vomiting, diarrhea.

Hepatobiliary disorders:

hepatitis, jaundice, hepatic failure.

Skin and subcutaneous tissue disorders

: angioedema, pruritus, erythema, rash, Stevens-

Johnson syndrome, toxic epidermal necrolysis, urticaria, fixed drug eruption.

Renal and urinary disorders

: renal insufficiency, including renal failure (see PRECAUTIONS).

XV. OVERDOSAGE

In clinical studies, administration of ARCOXIA at single doses up to 500 mg and multiple doses

up to 150 mg/day for 21 days did not result in significant toxicity. There have been reports of

acute overdosage with etoricoxib, although adverse experiences were not reported in the

majority of cases. The most frequently observed adverse experience were consistent with the

safety profile for etoricoxib. (e.g. gastrointestinal events, renovascular events).

In the event of overdose, it is reasonable to employ the usual supportive measures, e.g., remove

unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute

supportive therapy, if required.

Etoricoxib is not dialyzable by hemodialysis; it is not known whether etoricoxib is dialyzable by

peritoneal dialysis.

ARCOXIA 30mg: Available in blister packs of 10’s, 30's & 100’s per pack

ARCOXIA 60mg: Available in blister packs of 10’s & 100’s per pack

ARCOXIA 90mg: Available in blister packs of 10’s, 30’s & 100’s per pack

XVII. PHYSICAL APPEARANCE

ARCOXIA 120mg: Available in blister packs of 30’s per pack

Not all pack sizes may be marketed

ARCOXIA 30mg: Blue-green apple-shape biconvex film coated tablets debossed ACX 30 on

one side and 101 on the other side

ARCOXIA 60mg: Dark green apple-shape biconvex film coated tablets debossed ARCOXIA 60

on one side and 200 on the other side

ARCOXIA 90mg: White apple-shape biconvex film coated tablets debossed ARCOXIA 90 on

one side and 202 on the other side

ARCOXIA 120mg: Pale green apple-shape biconvex film coated tablets debossed ARCOXIA

120 on one side and 204 on the other side

XVIII. STORAGE

Store at 30 °C (86 °F). Store in the original package. Protect from moisture and light.

XIX. SHELF LIFE

Please refer to the expiry date on the outer carton.

XX. MANUFACTURER

Rovi Pharma Industrial Services, S.A.

Vía Complutense, 140

28805 Alcalá de Henares

Madrid, Spain

XXI. PACKER

PT. Merck Sharp Dohme Pharma Tbk

Jl. Raya Pandaan Km 48, Pandaan,

Pasuruan, Jawa Timur, Indonesia.

XXII. PRODUCT REGISTRATION HOLDER

Merck Sharp & Dohme (Malaysia) Sdn. Bhd.

Lot No. B-22-1 & B-22-2, Level 22

The Ascent, Paradigm No. 1

Jalan SS 7/26A, Kelana Jaya

47301 Petaling Jaya

Selangor, Malaysia.

Date of Revision: August 2020

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