Etoricoxib 60mg tablets

United Kingdom - English - eMC (Electronic Medicines Compendium)

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Active ingredient:
Etoricoxib
Available from:
Zentiva
ATC code:
M01AH05
INN (International Name):
Etoricoxib
Dosage:
60mg
Pharmaceutical form:
Tablet
Administration route:
Oral
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: 10010100; GTIN: 5000283658733
Authorization number:
PL 17780/0725

Package leaflet: Information for the patient

Etoricoxib 30 mg film-coated tablets

Etoricoxib 60 mg film-coated tablets

Etoricoxib 90 mg film-coated tablets

Etoricoxib 120 mg film-coated tablets

Read all of this leaflet carefully before you start taking

this medicine because it contains important information

for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or

pharmacist.

This medicine has been prescribed for you only. Do not

pass it on to others. It may harm them, even if their signs

of illness are the same as yours.

If you get any side effects, talk to your doctor or

pharmacist. This includes any possible side effects not

listed in this leaflet. See section 4.

What is in this leaflet

1. What etoricoxib is and what it is used for

2. What you need to know before you take etoricoxib

3. How to take etoricoxib

4. Possible side effects

5. How to store etoricoxib

6. Contents of the pack and other information

1. What Etoricoxib is and what it is used for

The name of your medicine is Etoricoxib film-coated tablets

(referred to as etoricoxib throughout this leaflet). The active

substance etoricoxib belongs to a group of medicines called

selective COX-2 inhibitors. These belong to a family of

medicines called non-steroidal anti-inflammatory drugs

(NSAIDs).

Etoricoxib helps to reduce the pain and swelling

(inflammation) in the joints and muscles of people 16 years

of age and older with osteoarthritis, rheumatoid arthritis,

ankylosing spondylitis and gout.

Etoricoxib is also used for the short term treatment of

moderate pain after dental surgery in people 16 years of

age and older.

What is osteoarthritis?

Osteoarthritis is a disease of the joints. It results from the

gradual breakdown of cartilage that cushions the ends of

the bones. This causes swelling (inflammation), pain,

tenderness, stiffness and disability.

What is rheumatoid arthritis?

Rheumatoid arthritis is a long term inflammatory disease of

the joints. It causes pain, stiffness, swelling, and increasing

loss of movement in the joints it affects. It may also cause

inflammation in other areas of the body.

What is gout?

Gout is a disease of sudden, recurring attacks of very painful

inflammation and redness in the joints. It is caused by

deposits of mineral crystals in the joint.

What is ankylosing spondylitis?

Ankylosing spondylitis is an inflammatory disease of the

spine and large joints.

2. What you need to know before you take etoricoxib

Do not take etoricoxib:

- if you are allergic to etoricoxib or any of the other

ingredients of this medicine (listed in section 6).

- if you are allergic to non-steroidal anti-inflammatory drugs

(NSAIDs), including acetylsalicylic acid and COX-2

inhibitors (see Possible Side Effects, section 4).

- if you have a current stomach ulcer or bleeding in your

stomach or intestines.

- if you have serious liver disease.

- if you have serious kidney disease.

- if you are or could be pregnant or are breast-feeding (see

'Pregnancy, breast-feeding and fertility').

- if you are under 16 years of age.

- if you have inflammatory bowel disease, such as Crohn's

Disease, ulcerative colitis, or colitis.

- if you have high blood pressure that has not been

controlled by treatment (check with your doctor or nurse if

you are not sure whether your blood pressure is

adequately controlled).

- if your doctor has diagnosed you with heart problems

including heart failure (moderate or severe types), angina

(chest pain).

- if you have had a heart attack, bypass surgery, peripheral

arterial disease (poor circulation in legs or feet due to

narrow or blocked arteries).

- if you have had any kind of stroke (including mini-stroke,

transient ischaemic attack or TIA). Etoricoxib may slightly

increase your risk of heart attack and stroke and this is why

it should not be used in those who have already had heart

problems or stroke.

If you think any of these are relevant to you, do not take the

tablets until you have consulted your doctor.

Warnings and precautions

Talk to your doctor or pharmacist before taking etoricoxib if:

- you have a history of stomach bleeding or ulcers.

- you are dehydrated, for example by a prolonged bout of

vomiting or diarrhoea.

- you have swelling due to fluid retention.

- you have a history of heart failure, or any other form of

heart disease.

- you have a history of high blood pressure. Etoricoxib can

increase blood pressure in some people, especially in high

doses, and your doctor will want to check your blood

pressure from time to time.

- you have any history of liver or kidney disease.

- you are being treated for an infection. Etoricoxib can mask

or hide a fever, which is a sign of infection.

- you have diabetes, high cholesterol, or are a smoker. These

can increase your risk of heart disease.

- you are a woman trying to become pregnant.

- you are over 65 years of age.

If you are not sure if any of the above apply to you, talk to

your doctor before taking etoricoxib to see if this

medicine is suitable for you.

Etoricoxib works equally well in older and younger adult

patients. If you are over 65 years of age, your doctor will

want to appropriately keep a check on you. No dosage

adjustment is necessary for patients over 65 years of age.

Children and adolescents

Do not give this medicine to children and adolescents

under 16 years of age.

Other medicines and etoricoxib

Tell your doctor or pharmacist if you are taking, have

recently taken or might take any other medicines.

In particular if you are taking any of the following

medicines, your doctor may want to monitor you to check

that your medicines are working properly, once you start

taking Etoricoxib:

- medicines that thin your blood (anticoagulants), such as

warfarin

- rifampicin (an antibiotic)

- methotrexate (a drug used for suppressing the immune

system, and often used in rheumatoid arthritis)

- ciclosporin or tacrolimus (drugs used for suppressing the

immune system)

- lithium (a medicine used to treat some types of

depression)

- medicines used to help control high blood pressure and

heart failure called ACE inhibitors and angiotensin

receptor blockers, examples include enalapril and ramipril,

and losartan and valsartan

- diuretics (water tablets)

- digoxin (a medicine for heart failure and irregular heart

rhythm)

- minoxidil (a drug used to treat high blood pressure)

- salbutamol tablets or oral solution (a medicine for asthma)

- birth control pills (the combination may increase your risk

of side effects)

- hormone replacement therapy (the combination may

increase your risk of side effects)

- acetylsalicylic acid, the risk of stomach ulcers is greater if

you take etoricoxib with acetylsalicylic acid.

- acetylsalicylic acid for prevention of heart attacks or

stroke:

Etoricoxib can be taken with low-dose acetylsalicylic acid.

If you are currently taking low-dose acetylsalicylic acid to

prevent heart attacks or stroke, you should not stop taking

acetylsalicylic acid until you talk to your doctor

- acetylsalicylic acid and other non-steroidal anti-

inflammatory drugs (NSAIDs):

do not take high dose acetylsalicylic acid or other anti-

inflammatory medicines while taking etoricoxib.

Etoricoxib with food and drink

The onset of the effect of etoricoxib may be faster when

taken without food.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be

pregnant or are planning to have a baby, ask your doctor or

pharmacist for advice before taking this medicine.

Pregnancy

Etoricoxib must not be taken during pregnancy. If you are

pregnant or think you may be pregnant or are planning to

have a baby, do not take the tablets. If you become

pregnant, stop taking the tablets and consult your doctor.

Consult your doctor if you are unsure or need more advice.

Breast-feeding

It is not known if etoricoxib is excreted in human milk. If

you are breast-feeding, or planning to breast-feed, consult

your doctor before taking etoricoxib. If you are taking

etoricoxib, you must not breast-feed.

Fertility

Etoricoxib is not recommended in women attempting to

become pregnant.

Driving and using machines

Dizziness and sleepiness have been reported in some

patients taking etoricoxib.

Do not drive if you experience dizziness or sleepiness.

Do not use any tools or machines if you experience

dizziness or sleepiness.

3. How to take etoricoxib

Always take this medicine exactly as your doctor has told

you. Check with your doctor or pharmacist if you are not

sure.

Do not take more than the recommended dose for your

condition. Your doctor will want to discuss your treatment

from time to time. It is important that you use the lowest

dose that controls your pain and you should not take

etoricoxib for longer than necessary. This is because the risk

of heart attacks and strokes might increase after prolonged

treatment, especially with high doses.

There are different strengths available for this medicinal

product and depending on your disease your doctor will

prescribe the tablet strength that is appropriate for you.

The recommended dose is:

Osteoarthritis

The recommended dose is 30 mg once a day, increased to a

maximum of 60 mg once a day if needed.

Rheumatoid arthritis

The recommended dose is 60 mg once a day, increased to a

maximum of 90 mg once a day if needed.

Ankylosing spondylitis

The recommended dose is 60 mg once a day, increased to a

maximum of 90 mg once a day if needed.

Acute pain conditions

Etoricoxib should be used only for the acute painful period.

Gout

The recommended dose is 120 mg once a day which should

only be used for the acute painful period, limited to a

maximum of 8 days treatment.

Postoperative dental surgery pain

The recommended dose is 90 mg once daily, limited to a

maximum of 3 days treatment.

People with liver problems

If you have mild liver disease, you should not take more

than 60 mg a day.

If you have moderate liver disease, you should not take

more than 30 mg a day.

Use in children and adolescents

Etoricoxib should not be taken by children or adolescents

under 16 years of age.

Elderly

No dose adjustment is necessary for elderly patients.

Caution should be exercised in elderly patients.

Method of administration

Etoricoxib is for oral use. Take the tablets once a day.

Etoricoxib can be taken with or without food.

If you take more etoricoxib than you should

You should never take more tablets than the doctor

recommends. If you do take too many

etoricoxib tablets, you should seek medical attention

immediately.

If you forget to take etoricoxib

It is important to take etoricoxib as your doctor has

prescribed. If you miss a dose, just resume your usual

schedule the following day. Do not take a double dose to

make up for a forgotten tablet.

If you have any further questions on the use of this

medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects,

although not everybody gets them.

If you develop any of these signs you should stop

etoricoxib and talk to your doctor immediately (see

What you need to know before you take etoricoxib

section 2):

- shortness of breath, chest pain, or ankle swelling appear

or if they get worse,

- yellowing of the skin and eyes (jaundice) – these are

signs of liver problems,

- severe or continual stomach pain or your stools become

black,

- an allergic reaction- which can include skin problems

such as ulcers or blistering, or swelling of the face, lips,

tongue, or throat which may cause difficulty in breathing.

The following side effects can occur during treatment with

etoricoxib:

Very common (may affect more than 1 in 10 people)

- stomach pain.

Common (may affect up to 1 in 10 people)

- dry socket (inflammation and pain after a tooth

extraction),

- swelling of the legs and/or feet due to fluid retention

(oedema),

- dizziness, headache,

- palpitations (fast or irregular heartbeat), irregular heart

rhythm (arrhythmia),

- increased blood pressure,

- wheezing or shortness of breath (bronchospasms),

- constipation, wind (excessive gas), gastritis (inflammation

of the lining of the stomach), heartburn, diarrhoea,

indigestion (dyspepsia)/stomach discomfort, nausea,

being sick (vomiting), inflammation of the oesophagus,

mouth ulcers,

- changes in blood tests related to your liver,

- bruising,

- weakness and fatigue, flu-like illness.

Uncommon (may affect up to 1 in 100 people)

- gastroenteritis (inflammation of the gastrointestinal tract

that involves both the stomach and small

intestine/stomach flu), upper respiratory infection,

urinary tract infection,

- changes in laboratory values (decreased number of red

blood cells, decreased number of white blood cells,

platelets decreased),

- hypersensitivity (an allergic reaction including hives

which may be serious enough to require immediate

medical attention),

- appetite increases or decreases, weight gain,

- anxiety, depression, decreases in mental sharpness;

seeing, feeling or hearing things that are not there

(hallucinations),

- taste alteration, inability to sleep, numbness or tingling,

sleepiness,

- blurred vision, eye irritation and redness,

- ringing in the ears, vertigo (sensation of spinning while

remaining still),

- abnormal heart rhythm (atrial fibrillation), fast heart rate,

heart failure, non-specific ECG changes, feeling of

tightness, pressure or heaviness in the chest (angina

pectoris), heart attack,

- flushing, stroke, mini-stroke (transient ischaemic attack),

severe increase in blood pressure,

- inflammation of the blood vessels,

- cough, breathlessness, nose bleed,

- stomach or bowel bloating, changes in your bowel habits,

dry mouth, stomach ulcer, inflammation of the stomach

lining that can become serious and may lead to bleeding,

irritable bowel syndrome, inflammation of the pancreas,

- swelling of the face, skin rash or itchy skin, redness of the

skin,

- muscle cramp/spasm, muscle pain/stiffness,

- high levels of potassium in your blood, changes in blood

or urine tests relating to your kidney, serious kidney

problems, increased levels of uric acid and creatine

phosphokinase,

- chest pain.

Rare (may affect up to 1 in 1,000 people)

- angioedema (an allergic reaction with swelling of the

face, lips, tongue and/or throat which may cause difficulty

in breathing or swallowing, which may be serious enough

to require immediate medical

attention)/anaphylactic/anaphylactoid reactions

including shock (a serious allergic reaction that requires

immediate medical attention),

- confusion, restlessness,

- liver problems (hepatitis),

- low blood levels of sodium,

- liver failure, yellowing of the skin and/or eyes (jaundice),

- severe skin reactions (these reactions can involve ulcers

of the mouth, throat, nose and genitals; the rash may

progress to widespread blistering and peeling of the

skin).

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist

or nurse. This includes any possible side effects not listed in

this leaflet. You can also report side effects directly via the

Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By

reporting side effects you can help provide more

information on the safety of this medicine.

5. How to store etoricoxib

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is

stated on the pack after EXP. The expiry date refers to the

last day of that month.

This medicine does not require any special storage

conditions.

Do not throw away any medicines via wastewater or

household waste. Ask your pharmacist how to throw away

medicines you no longer use. These measures will help

protect the environment.

6. Contents of the pack and other information

What Etoricoxib film-coated tablets contain

The active substance is etoricoxib.

Each film-coated tablet contains 30, 60, 90 or 120 mg of

etoricoxib.

The other ingredients are:

Tablet core: Calcium hydrogen phosphate, anhydrous;

Cellulose microcrystalline; Croscarmellose

sodium; Silica colloidal anhydrous; Talc;

Magnesium stearate

Film coat:

Hypromellose; Hydroxypropylcellulose;

Macrogol 6000; Talc; Titanium dioxide E171

The 60 mg tablets also contain brown ferric oxide E172,

the 90 mg tablets also contain yellow ferric oxide E172 and

120 mg tablets also contain red ferric oxide E172.

What Etoricoxib film-coated tablets look like and

contents of the pack

Etoricoxib 30 mg film-coated tablets:

White to off white round biconvex film-coated tablets,

approx. 6 mm in diameter.

Etoricoxib 60 mg film-coated tablets:

Light brown round biconvex film-coated tablets, approx.

8 mm in diameter.

Etoricoxib 90 mg film-coated tablets:

Light yellow round biconvex film-coated tablets, approx.

9 mm in diameter.

Etoricoxib 120 mg film-coated tablets:

Light pink round biconvex film-coated tablets, approx.

10 mm in diameter.

Pack sizes:

Etoricoxib 30 mg film-coated tablets

7, 20, 28, 50, 98 and 100 film-coated tablets

Etoricoxib 60 and 90 mg film-coated tablets

7, 14, 20, 28, 50 and100 film-coated tablets

Etoricoxib 120 mg film-coated tablets

5, 7, 14, 20, 28, 50 and 100 film-coated tablets

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Zentiva Pharma UK Limited, 12 New Fetter Lane, London,

EC4A 1JP, United Kingdom

Manufacturer

Zentiva, k.s., U kabelovny 130,

, Praha 10 - Dolní

102 37

Mĕcholupy, Czech Republic

Pharmadox Healthcare Ltd, KW20A Kordin Industrial Park,

Paola PLA 3000, Malta

This leaflet was last revised in February 2020

'Zentiva' is a registerd trademark © 2017 Zentiva

[547182] [1065016069]

ZENG-01111519-3tt-UK-EX

Etoricoxib Tablets-UK

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

Etoricoxib

60 mg film-coated tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 60 mg of etoricoxib.

Excipient with known effect: Also contains 1.68 mg of lactose monohydrate

For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

Film-coated tablet

60 mg: Green, round, biconvex, film-coated tablets debossed with ‘444’ on

one side and ‘L’ on other side. The tablet diameter is 8.00 mm.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Etoricoxib is indicated in adults and adolescents 16 years of age and older for

the symptomatic relief of osteoarthritis (OA), rheumatoid arthritis (RA),

ankylosing spondylitis, and the pain and signs of inflammation associated with

acute gouty arthritis.

Etoricoxib is indicated in adults and adolescents 16 years of age and older for

the short-term treatment of moderate pain associated with dental surgery.

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

assessment of the individual patient's overall risks (see sections 4.3, 4.4).

4.2

Posology and method of administration

Posology

As the cardiovascular risks of etoricoxib 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, especially in patients with

osteoarthritis (see sections 4.3, 4.4, 4.8 and 5.1).

Osteoarthritis

The recommended dose is 30 mg once daily. In some patients with insufficient

relief from symptoms, an increased dose of 60 mg once daily may increase

efficacy. In the absence of an increase in therapeutic benefit, other therapeutic

options should be considered.

Rheumatoid arthritis

The recommended dose is 60 mg once daily.

In some patients with insufficient

relief from symptoms, an increased dose of 90 mg once daily may increase

efficacy. Once the patient is clinically stabilised, down-titration to a 60 mg

once daily dose may be appropriate. In the absence of an increase in

therapeutic benefit, other therapeutic options should be considered.

Ankylosing spondylitis

The recommended dose is 60 mg once daily.

In some patients with insufficient

relief from symptoms, an increased dose of 90 mg once daily may increase

efficacy. Once the patient is clinically stabilised, down-titration to a 60 mg

once daily dose may be appropriate. In the absence of an increase in

therapeutic benefit, other therapeutic options should be considered.

Acute pain conditions

For acute pain conditions, etoricoxib should be used only for the acute

symptomatic period.

Acute gouty arthritis

The recommended dose is 120 mg once daily. In clinical trials for acute gouty

arthritis, etoricoxib was given for 8 days.

Postoperative dental surgery pain

The recommended dose is 90 mg once daily, limited to a maximum of 3 days.

Some patients may require other postoperative analgesia in addition to

etoricoxib during the three day treatment period.

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 and ankylosing spondylitis should not exceed 90 mg daily.

The dose for acute gout should not exceed 120 mg daily, limited to a

maximum of 8 days treatment.

The dose for postoperative acute dental surgery pain should not exceed 90 mg

daily, limited to a maximum of 3 days.

Special populations

Elderly patients

No dosage adjustment is necessary for elderly patients. As with other drugs,

caution should be exercised in elderly patients (see section 4.4).

Patients with hepatic impairment

Regardless of indication, in patients with mild hepatic dysfunction (Child-

Pugh score 5-6) a dose of 60 mg once daily should not be exceeded. In

patients with moderate hepatic dysfunction (Child-Pugh score 7-9), regardless

of indication, the dose of 30 mg once daily should not be exceeded.

Clinical experience is limited particularly in patients with moderate hepatic

dysfunction and caution is advised. There is no clinical experience in patients

with severe hepatic dysfunction (Child-Pugh score

10); therefore, its use is

contra-indicated in these patients (see sections 4.3, 4.4 and 5.2).

Patients with renal impairment

No dosage adjustment is necessary for patients with creatinine clearance

ml/min (see section 5.2). The use of etoricoxib in patients with creatinine

clearance <30 ml/min is contra-indicated (see sections 4.3 and 4.4).

Paediatric population

Etoricoxib is contra-indicated in children and adolescents under 16 years of

age (see section 4.3).

Method of administration

Etoricoxib is administered orally and may be taken with or without food. The

onset of the effect of the medicinal product may be faster when Etoricoxib is

administered without food. This should be considered when rapid

symptomatic relief is needed.

4.3

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed

in section 6.1.

Active peptic ulceration or active gastro-intestinal (GI) bleeding.

Patients who, after taking acetylsalicylic acid or NSAIDs including COX-

2 (cyclooxygenase-2) inhibitors, experience bronchospasm, acute rhinitis,

nasal polyps, angioneurotic oedema, urticaria, or allergic-type reactions.

Pregnancy and lactation (see sections 4.6 and 5.3).

Severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score

10).

Estimated renal creatinine clearance <30 ml/min.

Children and adolescents under 16 years of age.

Inflammatory bowel disease.

Congestive heart failure (NYHA II-IV).

Patients with hypertension whose blood pressure is persistently elevated

above 140/90mmHg and has not been adequately controlled.

Established ischaemic heart disease, peripheral arterial disease, and/or

cerebrovascular disease.

4.4

Special warnings and precautions for use

Gastrointestinal effects

Upper gastrointestinal complications [perforations, ulcers or bleedings

(PUBs)], some of them resulting in fatal outcome, have occurred in patients

treated with etoricoxib.

Caution is advised with treatment of patients most at risk of developing a

gastrointestinal complication with NSAIDs; the elderly, patients using any

other NSAID or acetylsalicylic acid concomitantly or patients with a prior

history of gastrointestinal disease, such as ulceration and GI bleeding.

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

(gastrointestinal ulceration or other gastrointestinal complications) when

etoricoxib is taken concomitantly with acetylsalicylic acid (even at low doses).

A significant difference in GI safety between selective COX-2 inhibitors +

acetylsalicylic acid vs. NSAIDs + acetylsalicylic acid has not been

demonstrated in long-term clinical trials (see section 5.1).

Cardiovascular effects

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

associated with a risk of thrombotic events (especially myocardial infarction

(MI) and stroke), relative to placebo and some NSAIDs. As the cardiovascular

risks of etoricoxib 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, especially in patients with osteoarthritis (see sections

4.2, 4.3, 4.8 and 5.1).

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

hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be

treated with etoricoxib after careful consideration (see section 5.1).

COX-2 selective inhibitors are not a substitute for acetylsalicylic acid for

prophylaxis of cardiovascular thrombo-embolic diseases because of their lack

of antiplatelet effect. Therefore antiplatelet therapies should not be

discontinued (see sections above, 4.5 and 5.1.).

Renal effects

Renal prostaglandins may play a compensatory role in the maintenance of

renal perfusion. Therefore, under conditions of compromised renal perfusion,

administration of etoricoxib 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.

Fluid retention, oedema and hypertension

As with other medicinal products known to inhibit prostaglandin synthesis,

fluid retention, oedema and hypertension have been observed in patients

taking etoricoxib. All Nonsteroidal Anti-inflammatory Drugs (NSAIDs),

including etoricoxib, can be associated with new onset or recurrent congestive

heart failure. For information regarding a dose related response for etoricoxib

see section 5.1. Caution should be exercised in patients with a history of

cardiac failure, left ventricular dysfunction, or hypertension and in patients

with pre-existing oedema from any other reason. If there is clinical evidence of

deterioration in the condition of these patients, appropriate measures including

discontinuation of etoricoxib should be taken.

Etoricoxib may be associated with more frequent and severe hypertension than

some other NSAIDs and selective COX-2 inhibitors, particularly at high

doses. Therefore, hypertension should be controlled before treatment with

etoricoxib (see section 4.3) and special attention should be paid to blood

pressure monitoring during treatment with etoricoxib. Blood pressure should

be monitored within two weeks after initiation of treatment and periodically

thereafter. If blood pressure rises significantly, alternative treatment should be

considered.

Hepatic effects

Elevations of alanine aminotransferase (ALT) and/or aspartate

aminotransferase (AST) (approximately three or more times the upper limit of

normal) have been reported in approximately 1% of patients in clinical trials

treated for up to one year with etoricoxib 30, 60 and 90 mg daily.

Any patients with symptoms and/or signs suggesting liver dysfunction, or in

whom an abnormal liver function test has occurred, should be monitored. If

signs of hepatic insufficiency occur, or if persistently abnormal liver function

tests (three times the upper limit of normal) are detected, etoricoxib should be

discontinued.

General

If during treatment, patients deteriorate in any of the organ system functions

described above, appropriate measures should be taken and discontinuation of

etoricoxib therapy should be considered. Medically appropriate supervision

should be maintained when using etoricoxib in the elderly and in patients with

renal, hepatic, or cardiac dysfunction.

Caution should be used when initiating treatment with etoricoxib in patients

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

with etoricoxib.

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 use of NSAIDs and some selective

COX-2 inhibitors during post-marketing surveillance (see section 4.8).

Patients appear to be at highest risk for these reactions early in the course of

therapy with 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 section 4.8). 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.

Etoricoxib may mask fever and other signs of inflammation.

Caution should be exercised when co-administering etoricoxib with warfarin

or other oral anticoagulants (see section 4.5).

The use of etoricoxib, as with any medicinal product known to inhibit

cyclooxygenase / prostaglandin synthesis, is not recommended in women

attempting to conceive (see sections 4.6, 5.1, and 5.3).

Important information regarding the ingredients of this medicine

This medicine contains lactose monohydrate. Patients with rare hereditary

problems of galactose intolerance, total lactase deficiency or glucose-galactose

malabsorption should not take this medicinal product.

4.5

Interaction with other medicinal products and other forms of interaction

Pharmacodynamic interactions

Oral anticoagulants: In subjects stabilised on chronic warfarin therapy, the

administration of etoricoxib 120 mg daily was associated with an approximate

13% increase in prothrombin time International Normalised Ratio (INR).

Therefore, patients receiving oral anticoagulants should be closely monitored

for their prothrombin time INR, particularly in the first few days when therapy

with etoricoxib is initiated or the dose of etoricoxib is changed (see section

4.4).

Diuretics, ACE inhibitors and Angiotensin II Antagonists: NSAIDs may

reduce the effect of diuretics and other antihypertensive drugs. In some

patients with compromised renal function (e.g. dehydrated patients or elderly

patients with compromised renal function) the co-administration of an ACE

inhibitor or Angiotensin II antagonist and agents that inhibit cyclo-oxygenase

may result in further deterioration of renal function, including possible acute

renal failure, which is usually reversible. These interactions should be

considered in patients taking etoricoxib concomitantly with ACE inhibitors or

angiotensin II antagonists. Therefore, the combination should be administered

with caution, especially in the elderly. Patients should be adequately hydrated

and consideration should be given to monitoring of renal function after

initiation of concomitant therapy, and periodically thereafter.

Acetylsalicylic Acid: In a study in healthy subjects, at steady state, etoricoxib

120 mg once daily had no effect on the anti-platelet activity of acetylsalicylic

acid (81 mg once daily). Etoricoxib can be used concomitantly with

acetylsalicylic acid at doses used for cardiovascular prophylaxis (low-dose

acetylsalicylic acid). However, concomitant administration of low-dose

acetylsalicylic acid with etoricoxib may result in an increased rate of GI

ulceration or other complications compared to use of etoricoxib alone.

Concomitant administration of etoricoxib with doses of acetylsalicylic acid

above those for cardiovascular prophylaxis or with other NSAIDs is not

recommended (see sections 5.1 and 4.4.).

Ciclosporin and tacrolimus: Although this interaction has not been studied

with etoricoxib, coadministration of ciclosporin or tacrolimus with any

NSAID may increase the nephrotoxic effect of ciclosporin or tacrolimus.

Renal function should be monitored when etoricoxib and either of these drugs

is used in combination.

Pharmacokinetic interactions

The effect of etoricoxib on the pharmacokinetics of other drugs

Lithium: NSAIDs decrease lithium renal excretion and therefore increase

lithium plasma levels. If necessary, monitor blood lithium closely and adjust

the lithium dosage while the combination is being taken and when the NSAID

is withdrawn.

Methotrexate: Two studies investigated the effects of etoricoxib 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. Etoricoxib at 60

and 90 mg had no effect on methotrexate plasma concentrations or renal

clearance. In one study, etoricoxib 120 mg had no effect, but in the other

study, etoricoxib 120 mg increased methotrexate plasma concentrations by

28% and reduced renal clearance of methotrexate by 13%. Adequate

monitoring for methotrexate-related toxicity is recommended when etoricoxib

and methotrexate are administered concomitantly.

Oral contraceptives: Etoricoxib 60 mg given concomitantly with an oral

contraceptive containing 35 micrograms ethinyl estradiol (EE) and 0.5 to 1 mg

norethindrone for 21 days increased the steady state AUC0-24hr of EE by

37%. Etoricoxib 120 mg given with the same oral contraceptive concomitantly

or separated by 12 hours increased the steady state AUC0-24hr of EE by 50 to

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

an oral contraceptive for use with etoricoxib. 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 (HRT): Administration of etoricoxib 120 mg

with hormone replacement therapy consisting of conjugated estrogens (0.625

mg PREMARINTM) for 28 days, increased the mean steady state AUC0-24hr

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

-estradiol (22%). The

effect of the recommended chronic doses of etoricoxib (30, 60, and 90 mg) has

not been studied. The effects of etoricoxib 120 mg on the exposure (AUC0-

24hr) to these estrogenic components of PREMARIN were less than half of

those observed when PREMARIN was administered alone and the dose was

increased from 0.625 to 1.25 mg. The clinical significance of these increases is

unknown, and higher doses of PREMARIN were not studied in combination

with etoricoxib. These increases in estrogenic concentration should be taken

into consideration when selecting post-menopausal hormone therapy for use

with etoricoxib because the increase in oestrogen exposure might increase the

risk of adverse events associated with HRT.

Prednisone/prednisolone: In drug-interaction studies, etoricoxib did not have

clinically important effects on the pharmacokinetics of prednisone

/prednisolone.

Digoxin: Etoricoxib 120 mg administered once daily for 10 days to healthy

volunteers did not alter the steady-state plasma AUC0-24hr or renal

elimination of digoxin. There was an increase in digoxin Cmax (approximately

33%). This increase is not generally important for most patients. However,

patients at high risk of digoxin toxicity should be monitored for this when

etoricoxib and digoxin are administered concomitantly.

Effect of etoricoxib on drugs metabolised by sulfotransferases

Etoricoxib is an inhibitor of human sulfotransferase activity, particularly

SULT1E1, and has been shown to increase the serum concentrations of ethinyl

estradiol. While knowledge about effects of multiple sulfotransferases is

presently limited and the clinical consequences for many drugs are still being

examined, it may be prudent to exercise care when administering etoricoxib

concurrently with other drugs primarily metabolised by human

sulfotransferases (e.g., oral salbutamol and minoxidil).

Effect of etoricoxib on drugs metabolised by CYP isoenzymes

Based on in vitro studies, etoricoxib is not expected to inhibit cytochromes

P450 (CYP) 1A2, 2C9, 2C19, 2D6, 2E1 or 3A4. In a study in healthy subjects,

daily administration of etoricoxib 120 mg did not alter hepatic CYP3A4

activity as assessed by the erythromycin breath test.

Effects of other drugs on the pharmacokinetics of etoricoxib

The main pathway of etoricoxib metabolism is dependent on CYP enzymes.

CYP3A4 appears to contribute to the metabolism of etoricoxib in vivo. In vitro

studies indicate that CYP2D6, CYP2C9, CYP1A2 and CYP2C19 also can

catalyse the main metabolic pathway, but their quantitative roles have not been

studied in vivo.

Ketoconazole: Ketoconazole, a potent inhibitor of CYP3A4, dosed at 400 mg

once a day for 11 days to healthy volunteers, did not have any clinically

important effect on the single-dose pharmacokinetics of 60 mg etoricoxib

(43% increase in AUC).

Voriconazole and Miconazole: Co-administration of either oral voriconazole

or topical miconazole oral gel, strong CYP3A4 inhibitors, with etoricoxib

caused a slight increase in exposure to etoricoxib, but is not considered to be

clinically meaningful based on published data.

Rifampicin: Co-administration of etoricoxib with rifampicin, a potent inducer

of CYP enzymes, produced a 65% decrease in etoricoxib plasma

concentrations. This interaction may result in recurrence of symptoms when

etoricoxib is co-administered with rifampicin. While this information may

suggest an increase in dose, doses of etoricoxib greater than those listed for

each indication have not been studied in combination with rifampicin and are

therefore not recommended (see section 4.2).

Antacids: Antacids do not affect the pharmacokinetics of etoricoxib to a

clinically relevant extent.

4.6

Fertility, pregnancy and lactation

Pregnancy

No clinical data on exposed pregnancies are available for etoricoxib. Studies

in animals have shown reproductive toxicity (see section 5.3). 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 (see section 4.3). If a woman becomes

pregnant during treatment, etoricoxib must be discontinued.

Breastfeeding

It is not known whether etoricoxib is excreted in human milk. Etoricoxib is

excreted in the milk of lactating rats. Women who use etoricoxib must not

breast feed (see sections 4.3 and 5.3).

Fertility

The use of etoricoxib, as with any drug substance known to inhibit COX-2, is

not recommended in women attempting to conceive.

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