Naproxen Evolan 500 mg Tablett

Sverige - svenska - Läkemedelsverket (Medical Products Agency)

Bipacksedel Bipacksedel (PIL)

28-10-2020

Produktens egenskaper Produktens egenskaper (SPC)

28-10-2020

Aktiva substanser:
naproxen
Tillgänglig från:
Evolan Pharma AB
ATC-kod:
M01AE02
INN (International namn):
naproxen
Dos:
500 mg
Läkemedelsform:
Tablett
Sammansättning:
naproxen 500 mg Aktiv substans; laktosmonohydrat Hjälpämne
Receptbelagda typ:
Receptbelagt
Produktsammanfattning:
Förpacknings: Blister, 10 tabletter; Blister, 20 tabletter; Blister, 30 tabletter; Blister, 40 tabletter; Blister, 50 tabletter; Blister, 100 tabletter; Blister, 105 tabletter; Blister, 200 tabletter; Blister, 300 tabletter; Blister, 400 tabletter; Blister, 500 tabletter
Bemyndigande status:
Godkänd
Godkännandenummer:
54455
Tillstånd datum:
2017-02-21

Dokument på andra språk

Bipacksedel Bipacksedel - engelska

25-02-2021

Produktens egenskaper Produktens egenskaper - engelska

25-02-2021

Offentlig bedömningsrapport Offentlig bedömningsrapport - engelska

21-02-2017

Läs hela dokumentet

Package Leaflet: Information for the user

Naproxen Evolan 500 mg tablets

naproxen

Read all of this leaflet carefully before you start using this medicine. It contains information that

is important for you.

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

If you have any further questions, ask your doctor, pharmacist or nurse.

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 side effects, talk to your doctor, pharmacist or nurse. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet:

What Naproxen Evolan is and what it is used for

What you need to know before you use Naproxen Evolan

How to use Naproxen Evolan

Possible side effects

How to store Naproxen Evolan

Contents of the pack and other information

1.

What Naproxen Evolan is and what it is used for

Naproxen Evolan is an anti-inflammatory and analgesic drug. Naproxen Evolan belongs to a group of

medicine called NSAIDs (non-steroidal anti-inflammatory drugs). These work by reducing the

formation of so-called prostaglandins, which cause pain and inflammation in the body.

Naproxen Evolan is used for rheumatic diseases, menstrual pains, acute migraine attacks and for mild

to moderate acute pain.

2.

What you need to know before you use Naproxen Evolan

Do not use Naproxen Evolan

if you allergic to naproxen or any of the other ingredients in this medicine (listed in section 6).

if you have had allergic reactions such as asthma, runny nose or rash after taking analgesics

containing acetylsalicylic acid or other anti-pain or inflammation medicines in the NSAID

group.

if you tend to bleed easily

if you have or have had recurrent stomach or intestinal ulcers

if you have had a stomach ulcer or intestinal ulcer during treatment with naproxen or similar

medicines

if you have severe liver or kidney disease

if you have severe heart failure

during the last trimester of pregnancy.

Special warnings and precautions for use

Talk to your doctor or pharmacist before using Naproxen Evolan.

Never use several different kinds of pain medications at the same time without consulting a doctor or

pharmacist.

Always aim for using the lowest dose possible, and for the shortest duration to reduce the risk of side

effects. Higher than recommended doses generally entail risks. This also means that taking a

combination of several NSAIDs medicinal products at the same time must be avoided.

Talk to your doctor before using Naproxen Evolan if you have or have had any of the following

diseases:

inflammatory bowel diseases (such as ulcerative colitis, Crohn's disease)

conditions causing an increased tendency to bleed

SLE (connective tissue disease)

asthma

impaired kidney or liver function

heart failure

high blood pressure

stomach or intestinal ulcer

Caution should be taken by elderly, as there is an increased risk of side effects due to high age.

Patients who have previously had gastrointestinal tract problems, particularly the elderly, must inform

their doctor if they have abdominal symptoms, especially at the beginning of treatment.

Naproxen Evolan may in rare cases affect the white blood cells and impair the immune system. If you

get an infection with symptoms such as fever and severely reduced general condition, or fever with

local infection symptoms such as soreness in the throat, pharynx or mouth, or urinary problems you

should immediately see a doctor to rule out a lack of white blood cells (agranulocytosis) via blood

tests. It is important to inform the doctor about your medication.

In very rare cases, serious skin reactions have been reported after use of NSAIDs. Stop taking

Naproxen Evolan and contact a doctor if you develop a rash or mucosal damage.

Do not take this medicine if you have chickenpox.

Use of naproxen can temporarily make it difficult to become pregnant. Consult a doctor if you are

planning a pregnancy or if you have problem getting pregnant (see Pregnancy, breast-feeding and

fertility).

Medicines such as Naproxen Evolan can entail a small increased risk of heart attack or stroke. Such a

risk is more likely with high doses and long-term treatment. Do not exceed the recommended dose or

duration of treatment (see How to take Naproxen Evolan).

Ask your doctor or pharmacist about your treatment if you have heart problems, if you previously have

had a stroke or if you think you are at risk of these conditions (for example if you have high blood

pressure, diabetes, high cholesterol or if you smoke).

Children and adolescents

Children under 50 kg should not be treated with Naproxen Evolan, since doses less than 250 mg are

not possible. Naproxen Evolan is not recommended for children under 12 years experiencing acute

pain.

Other medicines and Naproxen Evolan

Tell the doctor or pharmacist if you are taking or have recently taken other medicines, including non-

prescription. Never use several different kinds of pain killers at the same time without consulting a

doctor or pharmacist.

Some medicines may affect or be affected by treatment with Naproxen Evolan, such as medicines for:

blood clots (e.g. ticlopidine, warfarin, clopidogrel, aspirin)

bipolar disorder (lithium)

cancer and immune system disturbances (methotrexate)

hypertension and heart failure (so-called beta-blockers, ACE inhibitors, angiotensin II

antagonists, diuretics)

rejection of organs after transplantation (immunosuppressants, such as cyclosporine, tacrolimus)

gout (probenecid)

depression (so-called SSRIs, e.g. fluoxetine, sertraline, paroxetine, escitalopram, citalopram)

pain, such as acetylsalicylic acid, ibuprofen and diclofenac

swelling and inflammation, such as prednisolone and dexamethasone

Naproxen Evolan with food and drink

If taking Naproxen Evolan with food, the effect will be the same but possibly delayed

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or planning to have a baby, ask your

doctor or pharmacist before taking this medicine.

Naproxen Evolan should not be used during any stage of pregnancy unless prescribed by a doctor.

Pregnant women must not use Naproxen Evolan during the third trimester of pregnancy. Taking

Naproxen Evolan should be avoided by women who are planning to have a baby or are pregnant.

Naproxen can make it harder to get pregnant. You should inform your doctor if you are planning to

become pregnant or if you are having problem getting pregnant.

Naproxen passes into breast milk and should therefore not be used during breastfeeding.

Driving and using machines

During treatment with Naproxen Evolan, reaction time may be reduced in some people. This should be

considered when sharpened attentiveness is required, for example when operating motor vehicles.

Naproxen Evolan contains lactose monohydrate and sodium

The medicine contains lactose monohydrate. If you do not tolerate some types of sugars, you should

talk with your doctor before you take this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-

free’.

3.

How you use Naproxen Evolan

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or

pharmacist if you are not sure.

Your dose will be determined by your doctor and it will be adjusted by your individual needs. Do not

exceed the prescribed dose, as the risk of side effects increases.

Recommended dose:

The usual dose for adults

with

rheumatic disorders and acute pain

is 250–500 mg in the morning and

evening, with a maximum dose of 1000 mg/day. If your symptoms are most acute in the early morning

or when getting out of bed in the morning, it is best to take the 500-mg dose in the evening. Some

patients, however, can take 750–1000 mg once a day to achieve best effect. In these cases, it is

recommended that the tablets are taken in the evening.

For menstrual pain

250–500 mg as needed to a maximum of 1250 mg/day. Start treatment at the first

sign of menstruation.

acute migraine

750 mg at the first sign of a migraine attack. Then take 250 mg as needed, but not

more than 1250 mg/day.

The tablet can be divided in two equal doses.

Use in children:

Children over 50 kg should be given the adult dose. Must not be given to children below 50 kg since

doses below 250 mg is not possible. Naproxen Evolan is not recommended for children under 12 years

experiencing acute pain.

The elderly and people with liver and/or kidney problems

A lower dose is recommended because of the increased risk of side effects. Your doctor will decide the

dose for you.

If you sense that the effect of Naproxen Evolan is too strong or too weak, talk to your doctor or

pharmacist.

If you take more Naproxen Evolan than you should

If you or an adolescent has taken more medicine than you should or, if a child has taken the medicine

accidentally, talk to a doctor or go to a hospital straight away.

If you forget to take Naproxen Evolan

Do not take a double dose to make up for the forgotten tablet.

If you have any further questions about this medicine, ask your doctor or pharmacist.

4.

Possible side effects

Like all medicines, this medicine may cause side effects, although not everybody gets them.

Stop taking Naproxen Evolan and immediately seek a doctor or emergency room if you

experience the following symptoms:

such swelling of the face, tongue or throat, difficulty in swallowing, hives and difficulties in

breathing.

extremely severe allergic reaction with rash usually in the form of blisters or ulcers of in the

mouth and eyes and other mucous membranes such as the genitalia.

fever and severe deterioration of your general condition, or fever with local infection such as

pain in the neck, throat or mouth, or difficulty in urinating.

These are rare side effects, but can affect up to 1 in 10,000 users:

Common: (may affect up to 1 in 10 users)

stomach pains

heartburn

nausea

diarrhoea

constipation

inflammation in your mouth

skin rash

superficial skin lesions

drowsiness, headache

dizziness

thirst

sweating

buzzing in one’s ears (tinnitus)

visual disturbances

fluid retention in the body (oedema)

palpitations

Uncommon: (may affect up to 1 in 100 users)

difficulty breathing

asthma

nettle rash

skin changes (increased pigmentation or blisters) due to an increased sensitivity to light

inflammation and ulcers in the mouth

inflammation in the stomach’s lining

gastric bleeding and ulcers

fever

loss of hair

abnormal liver function

abnormal kidney function

hearing impairment

difficulty falling asleep

difficulty in concentration

Rare: (may affect up to 1 in 10,000 users)

seizures

muscular weakness.

changes in blood test results

“burst” gastric ulcer

inflammation of the colon

vomiting

inflammation of the oesophagus

wind

inflammation of the pancreas

severe skin reactions with inflammation and high fever

pneumonia

inflammation of the liver

blood in urine or stools

memory loss

depression

nightmares

muscle pain

minor anxiety

meningitis

vasculitis

heart failure

increase in blood pressure

water in the lungs

elevated amounts of potassium in the blood

worsening of colitis and Chron's disease

A few isolated cases of elevated liver enzymes are known.

Naproxen Evolan prolongs bleeding time.

In rare cases, severe skin infections appear in association with chickenpox.

Medicines such as Naproxen Evolan can entail a small increased risk of heart attack or stroke.

Reporting of suspected adverse reactions

If you get any side effects, talk to your doctor, or pharmacist. This includes any possible side effects

not listed in this leaflet. You can also report side effects directly via the national reporting system

listed in Appendix V*. By reporting side effects you can help provide more information on the safety

of this medicine.

5.

How to store Naproxen Evolan

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

No special storage conditions.

Use before the expiry date which is stated on the outer carton after “Exp. date” or “EXP” on the blister

card. The expiry date is the last day of the stated month.

Do not throw away the medicine in wastewater or in 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 Naproxen Evolan contains

The active ingredient is naproxen. Each tablet contains 500 mg.

The other ingredients are hydroxypropylcellulose; cellulose, microcrystalline; magnesium

trisilicate; croscarmellose sodium; silica, colloidal anhydrous; lactose monohydrate; magnesium

stearate and iron oxide yellow (E172).

What Naproxen Evolan looks like and package sizes

Capsular shaped, biconvex, yellow tablet, 18 mm in length, embossed with “500” on one side and with

a score line on the other side. The tablet can be divided in two equal doses.

Pack sizes: 10, 20, 30, 40, 50, 100, 105, 200, 300, 400 and 500 tablets (blister packs).

Not all pack sizes may be marketed.

Market Authorisation Holder and Manufacturer

[to be completed nationally]

This leaflet was last revised in

2021-02-24

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S

UMMARY OF PRODUCT CHARACTERISTICS

1

N

AME OF THE MEDICINAL PRODUCT

Naproxen Evolan 500 mg tablets

2

Q

UALITATIVE AND

Q

UANTITATIVE

C

OMPOSITION

Each tablet contains 500 mg naproxen

Excipient with known effect: Lactose monohydrate 34 mg

For the full list of excipients, see section 6.1.

3

P

HARMACEUTICAL FORM

Tablet

Capsular, biconvex, yellow tablet, 18 mm, embossed with “500” on one side and with a score

line on the other side. The tablet can be divided in two equal doses.

4

C

LINICAL

P

ARTICULARS

4.1

Therapeutic indications

Rheumatoid arthritis. Juvenile rheumatoid arthritis. Osteoarthritis. Ankylosing spondylitis.

Dysmenorrhoea without organic cause. Acute attacks of migraine. Acute pain of mild to

moderate intensity.

4.2

Posology and method of administration

Posology

Treatment should be initiated at the lowest expected effective dose, enabling later adjustment

in response to therapy and possible adverse reactions. During long-term treatment, a low

maintenance dose is desired. The risk of adverse events can be minimized by using the lowest

effective dose for the shortest duration needed to control the symptoms (see section 4.4).

Rheumatic diseases and acute mild to moderate pain:

Adults:

250–500 mg in the morning and evening, to a maximum of 1000 mg/day. Patients

with pronounced morning stiffness and/or night pain should take 500 mg at bedtime. For

patients on a 1000 mg maintenance dose, the recommended intake is one 500 mg tablet in the

morning and one in the evening. Some patients can, however, take 750–1000 mg once a day.

The single 1000 mg dose is recommended to take it in the evening.

Acute attacks of migraine:

750 mg, initially and then 250 mg as needed. The maximum daily dose is 1250 mg. It is

substantial that Naproxen Evolan is taken at the first sign of the migraine attack.

Dysmenorrhoea:

250–500 mg as needed to a maximum of 1250 mg/day. Begin treatment at the first sign of

menstrual pain.

Paediatric population

Naproxen Evolan 500 mg tablet can be divided in two equal doses, but a titration to lower

doses than 250 is not possible. Naproxen Evolan should, therefore, not be used in children

under 50 kg. For this patient population other products are recommended. Children over 50 kg

should be given the adult dose. Naproxen Evolan is not recommended for children under 12

years experiencing acute pain.

Elderly patients

A lower dose is recommended (see section 4.4). Naproxen Evolan 500 mg tablet can be

divided in two equal doses, which makes a dose of 250 mg possible. A titration of lower

doses than 250 mg is not possible.

Impaired renal function:

Naproxen should be administered at the lowest effective dose for patients with mild renal

impairment, and renal function must be carefully monitored. If possible, naproxen should be

avoided in patients with moderate renal impairment and is contraindicated in patients with

severe renal impairment (see sections 4.3 and 4.4). A Naproxen Evolan 500 mg tablet can be

divided in two equal doses, which makes a dose of 250 mg possible. A titration of lower

doses than 250 mg is not possible.

Impaired hepatic function:

Naproxen should be used with caution in patients with hepatic impairment (see section 4.4). If

possible, naproxen should be avoided in patients with severe hepatic impairment and is

contraindicated to patients with cirrhotic liver disease (see section 4.3). A Naproxen Evolan

500 mg tablet can be divided in two equal doses, which makes dose of 250 mg possible. A

titration of lower doses than 250 mg is not possible.

Route of administration:

Naproxen Evolan: oral administration

4.3

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in Section 6.1.

Due to cross-reaction, Naproxen Evolan must not be administered to patients who have

exhibited symptoms of asthma, rhinitis or urticaria when taking acetylsalicylic acid or other

nonsteroidal anti-inflammatory drugs (NSAID). Conditions with increased haemorrhagic

tendencies. History of gastrointestinal bleeding or perforation related to previous NSAID

therapy. Active or prior repeated occurrence of peptic ulcer/bleeding (two or more distinct

episodes of proven ulceration or bleeding). Liver cirrhosis. Severe heart failure and severe

renal disease (glomerulus filtration < 30 ml/min.). Third trimester of pregnancy.

4.4

Special warnings and precautions for use

Concurrent use of Naproxen Evolan and other NSAIDs, including selective cyclooxygenase-2

(COX 2) inhibitors, should be avoided.

The risk of undesirable effects can be minimised by using the lowest effective dose for the

shortest possible time needed to control the symptoms (see section 4.2 and the effects on the

gastrointestinal tract and heart/blood vessels below).

Caution should be taken when treating patients with history of asthma, gastrointestinal

disorders, SLE, haematological disorders, coagulation disorders, or inflammatory bowel

diseases.

When treating patients with mild to moderate heart failure, kidney or liver disease the risk for

fluid retention and impaired renal function must be observed, especially when they are on

concurrent diuretic therapy. Naproxen should be avoided, if possible, in patients with

moderate to severe renal impairment or severe hepatic impairment. Caution should be

exercised when initiating treatment with naproxen in patients with considerable dehydration.

As with other NSAIDs, long-term treatment with naproxen has caused papillary renal necrosis

and other pathological renal changes. Renal toxicity has also been seen in patients in whom

renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these

patients, administration of NSAIDs may cause a dose-dependent reduction of prostaglandin

synthesis and, secondarily, reduce renal blood flow, which may induce renal decompensation.

The patients at greatest risk of this reaction are those with impaired renal function, heart

failure, liver dysfunction, those treated with diuretics and ACE inhibitors, and the elderly.

Discontinuation of NSAID therapy usually provides recovery to the state that existed before

treatment began. Naproxen may increase the risk of renal dysfunction associated with

treatment with ACE inhibitors.

Elderly patients have an increased risk of undesired effects when treated with NSAIDs, such

as gastrointestinal haemorrhage and perforation, which may be fatal. One study suggests that

the amount of free naproxen in serum increases in elderly even though the total serum

concentration is unchanged. The consequences (gastrointestinal bleeding and/or perforation)

often becomes more serious and may occur at any time during treatment without warning

symptoms, and without any history of such disorders. It is also more likely that elderly

patients have impaired renal, cardiac or hepatic function.

Gastrointestinal bleeding, ulceration or perforation, which can be fatal, has been reported with

all sorts of NSAIDs and has occurred regardless of treatment duration, with or without

warning symptoms or a previous history of serious gastrointestinal events.

The risk of gastrointestinal haemorrhage, ulceration or perforation is higher at elevated doses

of NSAIDs in patients with a history of gastric ulcers, particularly when complicated by

haemorrhage or perforation (see section 4.3, Contraindications) and in elderly patients.

Patients with identified risk factors should commence treatment on lowest possible dose.

Treatment with mucosa-protective preparations (e.g. misoprostol or proton pump inhibitors)

should be considered for these patients, as well as for patients treated with low-dose

acetylsalicylic acid or other medicines that may increase the risk of undesirable

gastrointestinal effects (see below and section 4.5).

Patients, particularly elderly, with a history of adverse gastrointestinal effects should be

advised to be alert of any unusual abdominal symptoms (especially gastrointestinal bleeding),

especially in early treatment and to contact health care if it occur.

Caution is needed in patients who are concomitantly treated with medicinal products which

may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants

such as warfarin, selective serotonin reuptake inhibitors or products that counteract the

platelet aggregation, such as acetylsalicylic acid (see section 4.5).

When gastro-intestinal bleeding or ulceration occurs in patients who are receiving naproxen,

the treatment should be discontinued.

NSAIDs should be used with caution in patients with a history of gastro-intestinal diseases

(e.g. ulcerative colitis, Crohn’s disease) as these conditions may worsen (see section 4.8).

Pending further clinical documentation, Naproxen Evolan is not recommended in children

under 5 years of age.

Naproxen may reduce fertility (temporarily and during ongoing use) and is not recommended

for women who wish to become pregnant. Discontinuation of naproxen should be considered

for women with problems conceiving or who are undergoing fertility investigation.

Naproxen may affect tests for 17-ketogenic steroids and 5-HIAA in urine and should be

temporarily withdrawn 48 hours before sampling.

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

Johnson’s syndrome and toxic epidermal necrolysis have been reported very rarely in

connection with the use of NSAIDs (see section 4.8). The risk for this type of reactions is

increased in the beginning of the treatment: in the majority of the cases the reaction started

within the first month of treatment. Treatment with naproxen must be discontinued with the

first symptoms of a skin rash, mucosal lesions or any other signs of hypersensitivity.

In rare cases, serious skin and soft tissue infections may originate from chickenpox. To date, a

contributing role of NSAIDs in the worsening of these infections cannot be ruled out. The

recommendation is therefore to avoid use of Naproxen Evolan in patients having chickenpox.

Adequate monitoring and information is required to patients with a history of hypertension

and/or mild to moderate heart failure since fluid retention and oedema have been reported in

connection to NSAID treatment.

Clinical trials and epidemiological data suggest that use of coxibs and some NSAIDs,

(particularly at high doses and in long-term treatment), may be associated with a small

increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). Data

indicate that use of naproxen (1000 mg daily) have a lower risk then described above, even if

a small risk cannot be ruled out.

Caution should be exercised in patients with a history of uncontrolled hypertension, heart

failure, established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular

disease prior treatment with naproxen. Similar consideration should be given prior initiation

of long-term treatment in patients with risk factors for cardiovascular events (e.g.

hypertension, hyperlipidemia, diabetes mellitus, smoking).

Patients with any of the following rare, heritable conditions should not use this drug:

galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially

‘sodium-free’.

4.5

Interaction with other medicinal products and other forms of interaction

The following combinations should be avoided with Naproxen Evolan:

Warfarin

NSAIDs inhibit thrombocyte aggregation and damage the mucosal lining of the

gastrointestinal tract, which would increase the risk of gastrointestinal bleeding in patients

taking anticoagulants. Recent epidemiological studies indicate that the risk of bleeding

gastrointestinal ulcers is especially high during concomitant use of NSAIDs and warfarin.

Concomitant use should therefore be avoided. It has recently been shown that this interaction

also may have a metabolic component, in that NSAIDs and warfarin are metabolised by the

same enzyme, CYP2C9. NSAIDs inhibit the metabolism of anticoagulants

in vitro

. The

interaction potential is greatest for phenylbutazone followed by diclofenac and ibuprofen.

Other drugs have not been investigated (see section 4.4).

Methotrexate, high dose

Organic acids such as NSAIDs may reduce the clearance of methotrexate as a result of tubular

secretion of methotrexate being inhibited, and some metabolic interaction. During

high-dose

methotrexate treatment

, concomitant prescription of NSAIDs should therefore always be

avoided.

Ticlopidine

NSAIDs should not be combined with ticlopidine due to additive inhibition of thrombocyte

function.

NSAIDs and ASA

Naproxen in combination with other NSAIDs is not recommended due to an increased

cumulative risk of serious NSAID-related adverse events.

The following combinations of Naproxen Evolan may require dose adjustment or special

monitoring of the patient:

Methotrexate, low dose

Caution should be exercised if both a NSAID and methotrexate are given within 24 hours, as

the plasma level of methotrexate may increase and cause toxicity. The risk of a potential

interaction between NSAID and methotrexate must therefore be considered even for low

doses of methotrexate. Patients with impaired renal function may be a risk group for this

interaction. Renal function should therefore be monitored during combination therapy.

Lithium

Naproxen decreases the renal clearance of lithium. This causes up to a 40 % increase of the

lithium concentration in serum. Because of lithium’s very low therapeutic index, the

combination of lithium and NSAIDs should be avoided unless frequent monitoring of serum

lithium can be implemented, and a reduction can be made to the lithium dose.

Cyclosporin

The risk of nephrotoxic effect caused by ciclosporin is increased by the co-administration of

certain NSAIDs, due to the reduced synthesis of prostacyclin in the kidneys. Renal function

must therefore be carefully monitored during concomitant treatment.

Probenecid

Probenecid prolongs the half-life of naproxen.

Tacrolimus

Concomitant administration of NSAIDs with tacrolimus may increase the risk of

nephrotoxicity due to decreased synthesis of prostacyclin in the kidneys. Renal function must

therefore be carefully monitored during concomitant treatment.

NSAIDs may reduce the effect of diuretics and antihypertensive medicinal products.

Loop diuretics, thiazides

NSAIDs (propionic acid derivatives) have been shown to counteract the diuretic effect of

furosemide and bumetanide (loop diuretics), possibly through inhibition of prostaglandin

synthesis. NSAIDs may also reduce the antihypertensive effect of thiazide derivatives.

Diuretics can increase the nephrotoxicity caused by NSAIDs.

Beta blockers

NSAIDs counteract the antihypertensive effect of beta-blockers. It is, however, mainly

indomethacin that has been studied.

ACE inhibitors and Angiotensin II antagonists

There is an increased risk of usually reversible acute renal failure in patients with renal

impairment (e.g. dehydrated patients and/or elderly) when ACE inhibitors or angiotensin II

receptor antagonists are combined with NSAIDs, including selective cyclooxygenase-2

inhibitors. The combination should therefore be used with caution in patients with impaired

renal function, especially the elderly. Patients should be adequately hydrated, and monitoring

of renal function should be considered after initiation of concomitant treatment and at regular

intervals throughout treatment (see section 4.4)

Corticosteroids

Concomitant treatment increases the risk of gastrointestinal ulceration or bleeding (see section

4.4).

Aggregation Inhibitors, Platelet

Concomitant treatment increases the risk of gastrointestinal ulceration or bleeding (see section

4.4).

Clopidogrel

Experimental studies have found that clopidrogrel increases naproxen-induced gastrointestinal

blood loss (see section 4.4). This is likely to apply to all NSAIDs.

Selective serotonin re-uptake inhibitors (SSRI)

Both SSRIs and NSAIDs pose an increased risk of bleeding, e.g. from the gastrointestinal

tract. This risk is increased during combination therapy. The mechanism may be associated

with a decreased uptake of serotonin in the thrombocytes.

The clinical significance of the following combination with Naproxen Evolan is yet to be

determined:

Antacids, cholestyramine or food

may delay the absorption of naproxen, without decreasing

the amount absorbed.

Acetylsalicylic acid

Clinical pharmacodynamic data suggest that concomitant naproxen usage for more than one

day consecutively may inhibit the effects of low-dose acetylsalicylic acid on platelet activity.

This inhibition may persist for up to several days after discontinuing naproxen treatment. The

clinical relevance of this interaction is not known.

4.6

Pregnancy, breast-feeding and fertility

Pregnancy

Inhibition of prostaglandin synthesis may negatively affect the pregnancy and/or

embryonic/foetal development. Data from epidemiological studies suggest an increased risk

of miscarriage and of cardiac malformation after use of prostaglandin-synthesis inhibitors in

the early stages of the pregnancy. The absolute risk of cardiovascular malformations was

increased from less than 1 % to approximately 1.5%. It is assumed that the risk increases with

the dose and the duration of the treatment. The administration of prostaglandin synthesis

inhibitors in animals resulted in an increased pre- and post-implantation loss and embryo-

foetal lethality. In addition, an increased incidence of various malformations, including

cardiovascular ones, have been reported in animals who received a prostaglandin synthesis

inhibitor during the period of organogenesis. During the first and second trimesters of

pregnancy, Naproxen Evolan should be used only if absolutely necessary. If Naproxen Evolan

is used by a woman planning to become pregnant or taken during the first and second

trimester, the dose should be as low, and the treatment period as short as possible.

During the third trimester of pregnancy all prostaglandin synthesis inhibitors can expose

the foetus to:

- Cardiopulmonary toxicity (premature closure of the ductus arteriosus and pulmonary

hypertension).

- Renal dysfunction, which may develop into renal failure with oligohydramnios.

and at the end of pregnancy expose the mother and neonate to:

- Prolonged bleeding time.

- Inhibition of the contraction of the uterus resulting in a delayed or prolonged delivery.

Based on the above, Naproxen Evolan is contraindicated during the third trimester of

pregnancy.

Breast-feeding

Naproxen is excreted into human milk, but the risk of affecting the infant is considered

unlikely at therapeutic doses.

Fertility

The use of naproxen, as with all drugs that inhibit cyclooxygenase/prostaglandin synthesis,

may impair fertility and is not recommended for women who wish to become pregnant. For

women who have difficulty conceiving or are undergoing investigation of infertility,

withdrawal of Naproxen Evolan should be considered (see section 4.4).

4.7

Effects on ability to drive and use machines

During treatment with naproxen, undesirable effects such as visual disturbances and dizziness

may occur. This should be considered in cases when sharpened attentiveness is required, for

example in operating motor vehicles.

4.8

Undesirable effects

The undesirable effects are mainly linked to the pharmacological effect of naproxen on

prostaglandin synthesis. Undesirable gastrointestinal effects such as dyspepsia, abdominal

pain and nausea are the most frequently reported undesirable effects.

The undesirable effects are compiled in accordance with MedDRA System Organ Class and

frequency. The following frequency categories have been used:

Very common (

1/10), Common (

1/100, <1/10), Uncommon (

1/1 000, <1/100), Rare

1/10 000, <1/1 000).

System Organ Class

Frequency

Undesirable effects

Blood and lymphatic system

disorders

Rare

Thrombocytopaenia,

granulocytopaenia,

leukopenia, aplastic and

haemolytic anaemia,

agranulocytosis

Metabolism

Rare

Hyperkalemia

Uncommon

Difficulty falling asleep,

difficulty concentrating

Psychiatric disorders

Rare

Cognitive disturbances,

depression, nightmares,

minor anxiety, myalgia

Central and peripheral

nervous system disorders

Rare

Aseptic meningitis

Eyes

Common

Visual disturbances

Common

Tinnitus

Ear and labyrinth disorders

Uncommon

Hearing impairment

Vascular disorders

Common

Fluid retention, palpitations,

oedema

Rare

Vasculitis, congestive heart

failure, hypertension,

pulmonary oedema

Uncommon

Asthma, dyspnoea

Respiratory, thoracic and

mediastinal disorders

Rare

Eosinophilic pneumonitis

Gastrointestinal disorders

Common

Dyspepsia, abdominal pain,

nausea, diarrhoea,

constipation, heartburn,

stomatitis

Uncommon

Gastrointestinal bleeding,

gastric ulcers, ulcerative

stomatitis, gastritis

Rare

Colitis, perforation,

vomiting, melaena,

esophagitis, pancreatitis,

haematemesis, flatulence,

exacerbation of ulcerative

colitis, exacerbation of

Crohn's disease

Hepatobiliary disorders

Uncommon

Abnormal liver function

Rare

Toxic hepatitis (in isolated

cases fatal)

Renal and urinary disorders

Uncommon

Abnormal kidney function

Rare

Haematuria

Skin and subcutaneous

tissue disorders

Common

Exanthema, skin erosions

Uncommon

Urticaria, photosensitivity

including pseudoporphyria

Rare

Severe mucocutaneous skin

reactions such as Stevens-

Johnson Syndrome,

angioneurotic oedema,

erythema multiforme, toxic

epidermal necrolysis

Common

Drowsiness, dizziness,

headache, thirst and

sweating

Uncommon

Hair loss, fever

General disorders and/or

administration-site

conditions

Rare

Anaphylaxis, seizures,

muscle weakness

At signs of pseudoporphyria, treatment should be discontinued, and the patient monitored.

Elevated liver function test results have occasionally been reported for non-steroidal anti-

inflammatory drugs.

In rare cases, severe skin and soft tissue infections appear in association with chickenpox.

Sodium retention has not been reported in metabolic studies, but it is possible that patients

with suspected or verified heart failure are at greater risk when treated with Naproxen Evolan.

Naproxen inhibits thrombocyte aggregation and prolongs bleeding time.

Gastroduodenal ulcers, perforation or gastrointestinal bleeding can be fatal, especially in the

elderly (see section 4.4).

Clinical trials and epidemiological data indicate that use of certain NSAIDs, (particularly in

high doses and during long-term treatment), may lead to a small, increased risk of arterial

thrombotic events (e.g. cardiac infarct or stroke, see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is

important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

Healthcare professionals are asked to report any suspected adverse reactions via the national

reporting system listed in Appendix V.*

4.9

Overdose

Toxicity:

1 g to a 7-year-old resulted in no symptoms. 12.5 and 25 g resulted in moderate

intoxication in adults who received gastric lavage. Adults have however developed kidney

problems following 3.75 to 5 g, while one other adult developed moderate intoxication after

6.25 g. Also, 12.5 g to an adult caused severe intoxication.

Symptoms:

Nausea, vomiting, abdominal pain. Headache, dizziness, lethargy, tinnitus.

Tachycardia, palpitations. At high doses, disorientation, hyperkinesia, aggressiveness,

possibly seizures. Kidney disorders, metabolic acidosis. Hypoprothrombinaemia. Possibly

hypokalaemia, leukocytosis.

Treatment:

If justifiable, gastric lavage, charcoal. Antacids as required. Correction of acid-

base and electrolyte imbalance. Ensure good diuresis. In the case of seizures, administer

diazepam. Use general symptomatic treatment.

5

P

HARMACOLOGICAL

P

ROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Non-steroidal anti-inflammatory drugs, NSAID.

ATC code: M01AE02

Naproxen Evolan belongs to the group of non-steroidal antiinflammatory/antirheumatic drugs

(NSAID). Naproxen is a propionic acid derivative with the chemical name (S)-2-(6-methoxy-

2-naphthyl) propionic acid. Naproxen has also analgesic and antipyretic properties.

Naproxen inhibits prostaglandin synthesis. Naproxen affects hypercontractility in the uterus

and reduces elevated basal tone associated with dysmenorrhoea. Naproxen prolongs bleeding

time and inhibits platelet aggregation.

Naproxen suppresses renal prostacyclin synthesis. This effect has no essential significance in

patients with normal renal function. In patients with chronic renal insufficiency, cardiac

insufficiency or hepatic insufficiency, as well as in patients with conditions of changes in

plasma volume, the suppressed prostacyclin synthesis can lead to acute renal insufficiency,

fluid retention and heart failure. See 4.3 Contraindications and 4.4 Special warnings and

precautions.

5.2

Pharmacokinetic properties

Absorption

Naproxen is rapidly and completely absorbed regardless of pharmaceutical form.

The maximal plasma concentration is reached after approximately 2 hours. Steady state is

reached after 4 to 5 doses. The absorption is not affected by simultaneous intake of antacids

food.

Distribution and metabolism

Over 99 % is bound to serum albumin at a therapeutic dose.

The volume of distribution is

small, approximately 0.1 l/kg body weight. Approximately 30 % of naproxen is metabolised

into 6-O-desmethylnaproxen, which is not pharmacologically active.

Elimination

The plasma half-life is 10 to 17 hours. Naproxen is mainly excreted via the urine, and only in

small amounts (1–2 %) in faeces. Mainly intact naproxen is found in the blood in humans.

5.3

Preclinical safety data

Preclinical data reveal no special hazard for humans based on conventional animal studies of

genotoxicity, carcinogenicity, embryo-foetal toxicity and fertility in addition to what is stated

in the Summary of product characteristics.

Naproxen acid has been studied

in vitro

in vivo

for mutagenicity, but no relevant evidence

of a mutagenic potential was observed. No carcinogenic effects from naproxen have been

detected in studies on rats.

Naproxen (20 mg/kg/day) showed no teratogenic effects in studies on rats and rabbits.

The main findings in animal toxicity studies using high oral repeated doses were

gastrointestinal irritation and kidney damage, both of which were attributed to inhibition of

prostaglandin synthesis. Oral administration in peri- and postnatal studies of naproxen (2, 10

and 20 mg/kg/day) given to pregnant rats during the third trimester of pregnancy resulted in

difficult delivery. This is a known effect for this class of compounds.

6

P

HARMACEUTICAL

P

ARTICULARS

6.1

List of excipients

Hydroxypropylcellulose

Cellulose, microcrystalline

Magnesium trisilicate

Croscarmellose sodium

Silica, colloidal anhydrous

Lactose monohydrate

Magnesium stearate

Iron oxide yellow (E172)

6.2

Incompatibilities

Not applicable

6.3

Shelf life

4 years.

6.4

Special precautions for storage

No special storage conditions.

6.5

Nature and contents of container

Al/PVC blisters containing 10, 20, 30, 40, 50, 100, 105, 200, 300, 400 and 500 tablets.

Not all pack sizes may be marketed.

6.6

Special instructions for destruction and other handling

No special requirements.

7

M

ARKET

A

UTHORISATION

H

OLDER

[To be completed nationally]

8

M

ARKETING AUTHORISATION NUMBER

(

S

).

[To be completed nationally]

9

D

ATE OF

F

IRST

A

UTHORISATION

/R

ENEWAL OF

A

UTHORISATION

[To be completed nationally]

10

DATE

OF

REVISION

OF

THE

TEXT

2021-02-24

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