Skip to Content

NAPROXEN 50MG/ML ORAL SUSPENSION

Active substance(s): NAPROXEN / NAPROXEN

View full screen / Print PDF » Download PDF ⇩
Transcript
SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Naproxen 50mg/mL Oral Suspension

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
1mL of oral suspension contains 50mg naproxen.
Excipients with known effect
300mg/mL sucrose, 128.6mg/mL sorbitol 70 % solution, 0.5mg/mL methylparahydroxybenzoate, 9.2mg/mL sodium.
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Oral suspension
White to yellowish-white oral suspension with orange and pineapple flavour

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Adults
Naproxen Oral Suspension is indicated for the symptomatic treatment of
-

-

pain and inflammation in:


rheumatoid arthritis, ankylosing spondylitis and acute attacks of
osteoarthrosis and spondylarthrosis



acute gout



inflammatory rheumatic diseases of soft tissues



painful swelling or inflammation after musculoskeletal injuries

pain in primary dysmenorrhoea

Paediatric population

Naproxen is indicated for juvenile rheumatoid arthritis in children from 2 years of age
and older.

4.2

Posology and method of administration
Posology
Undesirable effects may be minimised by using the lowest effective dose for the
shortest duration necessary to control the symptoms.
The medicinal product contains a 8mL graduated oral syringe with graduations of
0.1mL.
Adults up to 65 years of age
The recommended dose range is from 500mg to not more than 1,000mg naproxen per
day (10–20mL).
Dosage should be individually adjusted to the clinical condition. A single dose of
1,000mg naproxen (20mL) should not be exceeded.
Symptomatic treatment of painful swelling or inflammation after musculoskeletal
injuries
The recommended initial dose is 500mg (10mL); additional doses of 250mg (5mL)
may be taken every 6–8 hours as needed. The daily dose should not exceed 1,000mg
(20mL).
Symptomatic treatment of pain and inflammation in rheumatoid arthritis, ankylosing
spondylitis and acute attacks of osteoarthrosis and spondylarthrosis as well as in
inflammatory rheumatic diseases of soft tissues
The daily dose is usually 10–15mL of Naproxen Oral Suspension (equivalent to 500–
750 mg naproxen).
At the start of therapy, during phases of acute inflammation or when switching from
another high-dose NSAID to Naproxen, the recommended daily dose is 15mL
(equivalent to 750mg naproxen), administered as two divided doses per day (10mL of
Naproxen Oral Suspension in the morning and 5mL in the evening, or vice versa) or
as a single dose (either in the morning or in the evening).
In individual cases, the daily dose may be increased to 20mL (equivalent to 1,000mg
naproxen).
The maintenance dose is 10mL of Naproxen Oral Suspension (equivalent to 500mg
naproxen) per day, which may be administered either in two divided doses (5mL in
the morning and 5mL in the evening) or as a single dose (either in the morning or in
the evening).
Symptomatic treatment of pain and inflammation in acute gout

The recommended initial dose is 750mg (15mL), followed by 250mg (5mL) every 8
hours – until the attack is over. (In this case, exceeding the maximum daily dose of
1,000mg is justified on this single occasion.)

Symptomatic treatment of pain in primary dysmenorrhoea
The recommended initial dose is 500mg (10mL); additional doses of 250mg (5mL)
may be taken every 6–8 hours. A daily dose of 1,000mg (20mL) should not be
exceeded.
Paediatric population (from 2 years of age and older)
For juvenile rheumatoid arthritis: 10mg naproxen/kg of body weight per day which
corresponds to a daily dose of 0.2mL Naproxen Oral Suspension per kilogram of
body weight, administered in two divided doses (single dose 0.1mL/kg of body
weight). The daily dose for adolescents should not exceed 20mL (1,000mg).
Naproxen is not recommended in children under 2 years of age because there is no
adequate experience.
Naproxen is not recommended for use in any indication other than juvenile
rheumatoid arthritis in children and adolescents under 18 years of age.

Duration of treatment
The duration of use is decided by the treating physician.
For rheumatic diseases, it may be necessary to take Naproxen over a prolonged
period.
In primary dysmenorrhoea the treatment duration depends on the respective
symptomology. However, the treatment with Naproxen should not exceed a few days.
Special patient populations
Elderly (over 65 years of age)
Older patients are at increased risk of the serious consequences of adverse reactions.
If an NSAID is considered necessary, the lowest effective dose should be used and
for the shortest possible duration. The patient should be monitored regularly for GI
bleeding during NSAID therapy. Older patients require particularly careful medical
monitoring: Overdose as a result of reduced elimination and an increased proportion
of free – not bound to plasma protein – drug should be expected (see section 4.4).
Hepatic impairment

Patients with liver disease and hypoproteinaemia are also at risk of naproxen
overdose as a result of an increased proportion of free – not bound to plasma protein –
drug. These patients should be given the lowest dose that is still effective and be
monitored. Naproxen is contraindicated in patients with severe hepatic impairment
(see sections 4.3 and 4.4).

Renal impairment
Dose reduction should be considered in patients with renal impairment whose
creatinine clearance is greater than 30mL per minute in order to avoid accumulation
of metabolites.
Naproxen should not be administered to patients whose creatinine clearance is less
than 30mL per minute (see sections 4.3 and 4.4).

Method of administration
For oral use.
Naproxen should be taken with sufficient liquid.
Shake the bottle vigorously before use.
In acute pain, naproxen starts to act earlier when taken on an empty stomach.
Patients with sensitive stomach should take Naproxen during meals.

4.3

Contraindications
Naproxen must not be taken in any of the following conditions:


hypersensitivity to the active substance or to any of the excipients listed in section
6.1



history of asthma attacks, angioedema, skin reactions or acute rhinitis after taking
acetylsalicylic acid or any other non-steroidal anti-inflammatory drugs (NSAIDs).



blood-formation disturbances



severe cardiac insufficiency



active peptic ulcer or bleeding



active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct
episodes of proven ulceration or bleeding)



history of gastrointestinal bleeding or perforation, related to previous NSAID
therapy



cerebral haemorrhage (cerebrovascular bleeding)



acute haemorrhage



severe hepatic impairment

4.4



severe renal impairment (creatinine clearance less than 30mL/min)



Last trimester of pregnancy (see section 4.6)

Special warnings and precautions for use
Undesirable effects may be minimised by using the lowest effective dose for the
shortest duration necessary to control the symptoms (see section 4.2, and GI and
cardiovascular risks below).
Co-administration of naproxen with other non-steroidal anti-inflammatory drugs
(NSAIDs) including COX-2-selective inhibitors should be avoided.
Naproxen must be stopped immediately in case of gastrointestinal bleeding or visual
disturbances or hearing impairment.
Cardiovascular and cerebrovascular effects
Appropriate monitoring and advice are required for patients with a history of
hypertension and/or mild to moderate congestive heart failure because fluid retention
and oedema have been reported in association with NSAID therapy.
Clinical studies and epidemiological data suggest that the use of some NSAIDs,
particularly at high doses and during long-term treatment, may be associated with a
small increased risk of arterial thrombotic events (e.g. myocardial infarction or
stroke). Although data from epidemiological studies suggest that naproxen
(1,000mg/day) may be associated with a lower risk, some of such risk can, however,
not be completely excluded.
Patients with uncontrolled hypertension, congestive heart failure, established
ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease
should only be treated with naproxen after careful consideration. Similar
consideration should also be made before initiating longer-term treatment of patients
with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia,
diabetes mellitus, smoking).
Respiratory tract
Particular caution (careful risk/benefit assessment) is necessary in patients with
asthma and allergic diseases such as hay fever, chronic swelling of the nasal mucosa,
angioedema, urticaria (including a history thereof) or chronic obstructive airway
disease because bronchospasm (asthma attack) may be triggered. This applies
especially if other NSAIDs have previously caused this reaction. If this is the case,
Naproxen must not be administered (see section 4.3).
Gastrointestinal tract
Gastrointestinal bleeding, ulceration or perforation, which can be fatal, has been
reported with all NSAIDs at any time during treatment, with or without warning
symptoms or a previous history of serious GI events.

The risk of gastrointestinal bleeding, ulceration or perforation is higher with
increasing NSAID doses, in patients with a history of ulcer, particularly if
complicated with haemorrhage or perforation (see section 4.3), and in older patients.
These patient groups should commence treatment with the lowest dose available (see
section 4.2).
Combination therapy with protective agents (e.g. misoprostol or proton pump
inhibitors) should be considered for these patients and also for patients requiring
concomitant treatment with low-dose acetylsalicylic acid or with other drugs that may
increase gastrointestinal risk (see below and section 4.5).
Patients with a history of gastrointestinal toxicity – particularly when older – should
report any unusual abdominal symptoms (especially gastrointestinal bleeding)
particularly in the initial stages of treatment.
When gastrointestinal bleeding or ulceration occurs during naproxen therapy, the
treatment must be stopped.
Particular caution should be exercised in patients receiving concomitant medication
that might increase the risk of ulceration and bleeding, such as oral corticosteroids,
anticoagulants such as warfarin, selective serotonin re-uptake inhibitors or antiplatelet
agents such as acetylsalicylic acid (see section 4.5).
NSAIDs should only be given with caution to patients with a history of
gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be
exacerbated (see section 4.8).
Haematological
Patients who have coagulation disorders or are receiving drug therapy that interferes
with haemostasis should be carefully observed if naproxen-containing products are
administered.
Patients at high risk of bleeding or those on full anti-coagulation therapy (e.g.
dicoumarol derivatives) may be at increased risk of bleeding if given naproxen
containing products concurrently.
Kidney, urogenital tract
There have been reports of impaired renal function, renal failure, acute interstitial
nephritis, haematuria, proteinuria, renal papillary necrosis and occasionally nephrotic
syndrome associated with naproxen.
The administration of an NSAID may cause a dose dependent reduction in
prostaglandin formation and precipitate renal failure. Patients at greatest risk of this
reaction are those with impaired renal function, cardiac impairment, liver
dysfunction, those taking diuretics, angiotensin converting enzyme inhibitors,
angiotensin-II receptor antagonists and the older patients. Renal function should be
monitored in these patients (see also section 4.3).
As naproxen and its metabolites are excreted to a large extent (95%) in the urine via
glomerular filtration, naproxen should be used with great caution in patients with

renal impairment (whose creatinine clearance is greater than 30mL per minute). In
addition, monitoring of serum creatinine and/or creatinine clearance is advised in
these patients.
Certain patients, specifically those with compromised renal blood flow, such as in
extracellular fluid volume depletion, liver disease, sodium retention, congestive heart
failure and pre-existing renal disease, should have their renal function assessed before
and during naproxen therapy.
Older patients with presumably impaired renal function would fall within this
category, as would patients receiving diuretic therapy. A reduction in the daily dose
should be considered to avoid the possibility of excessive accumulation of naproxen
metabolites in these patients.
Careful monitoring is recommended also because of possible changes in the water
and electrolyte balance immediately after major surgery.
Skin
Serious skin reactions, some of them with a fatal outcome, including exfoliative
dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been
reported very rarely in association with the use of NSAIDs (see section 4.8). Patients
appear to be at highest risk for these reactions early in the course of therapy – the
onset of such reactions occurred in the majority of cases within the first month of
treatment. Naproxen must be discontinued at the first appearance of skin rash,
mucosal lesions or any other sign of hypersensitivity.
Anaphylactic (anaphylactoid) reactions
Hypersensitivity reactions may occur in susceptible individuals. Anaphylactic
(anaphylactoid) reactions may occur both in patients with and without a history of
hypersensitivity or prior exposure to acetylsalicylic acid, other NSAIDs or naproxencontaining medicinal products putting them at risk of such reactions. They may also
occur in patients with a history of angioedema, bronchospastic reactions (e.g.
asthma), rhinitis or nasal polyps. Anaphylactoid reactions, like anaphylaxis, may have
a fatal outcome. Bronchospasm may be precipitated in patients suffering from or with
a history of asthma, allergic diseases or hypersensitivity to acetylsalicylic acid (see
section 4.3).
Eyes
Studies have not shown any ocular changes attributable to naproxen administration.
In rare cases, ocular side effects such as papillitis, retrobulbar optic neuritis and
papilloedema have been reported in users of NSAIDs including naproxen, although a
causal relationship could not be established. Therefore, patients who develop visual
disturbances during treatment with naproxen should have an ophthalmological
examination.
Uterus
Caution should be exercised in women with abnormally heavy menstrual bleeding
(e.g. menorrhagia, metrorrhagia).

Autoimmune disorders
Caution should also be exercised in patients with systemic lupus erythematosus and
other autoimmune disorders – there have been reports of aseptic meningitis and renal
impairment.
Porphyria
In patients with inducible porphyria, naproxen should only be used after very careful
risk/benefit assessment.
Elderly (over 65 years of age)
Elderly patients show an increased incidence of adverse reactions to NSAIDs,
particularly of gastrointestinal bleeding and perforation, which may have a fatal
outcome (see sections 4.2 and 4.8).
Liver
As with other NSAIDs, one or more liver function tests may show elevated readings,
which would be the result of hypersensitivity rather than toxicity. Severe hepatic
reactions including jaundice and hepatitis – some cases have been fatal – have been
reported with naproxen as with other NSAIDs. Cross-reactions have been reported.

General precautions
Persistence of underlying disease
As a result of its pharmacodynamic properties, naproxen – like other NSAIDs – might
mask an underlying disease by its analgesic, anti-pyretic and anti-inflammatory
effects. Patients should be instructed to seek medical advice immediately in case of
persistence or worsening of symptoms such as pain or other signs of inflammation,
e.g. in case of worsening of overall well-being or development of fever during
therapy.
Analgesic-induced headache
Inappropriate prolonged high-dose use of analgesics may give rise to headaches that
must not be treated with increased doses of this medicinal product. Patients should be
informed accordingly as appropriate.
Analgesic nephropathy
Habitual use of analgesics may – especially if multiple analgesic drugs are used in
combination – lead to permanent kidney damage with the risk of renal failure.
Patients should be informed accordingly as appropriate.
Clinical monitoring
All patients receiving long-term and/or high-dose treatment should have periodic
blood counts, as well as hepatic and renal function tests. This applies particularly to
patients with hepatic impairment, cardiac insufficiency, high blood pressure or kidney
damage.

When diabetics treated with hypoglycaemic sulphonylurea derivatives are
additionally given naproxen, blood glucose should be monitored particularly carefully
to avoid missing possibly increased blood glucose reduction.
Patients receiving concomitant anticoagulant therapy are also recommended to have
their clotting status monitored; the potassium concentration should be monitored (in
patients taking potassium-sparing diuretics); patients taking lithium should have their
lithium levels monitored, and those taking cardiac glycosides should have cardiac
glycoside concentrations monitored (see section 4.5).
Interference with laboratory tests


Increase in transaminases, alkaline phosphatase, serum potassium, urea



Decrease in haemoglobin, haematocrit, serum calcium, creatinine clearance



Bleeding time: It should be kept in mind that naproxen reversibly decreases
platelet aggregation and prolongs bleeding time during treatment with naproxen
and for up to 4 days thereafter.



Possible interferences with 17-ketogenic steroids in adrenal function tests and 5hydroxyindoleacetic acid in urine tests: It is recommended that naproxen be
temporarily discontinued at least 72 hours before such tests are performed.

Information on excipients
Sucrose
1mL of Naproxen Oral Suspension contains 300mg sucrose (sugar), equivalent to
approximately 0.03 carbohydrate exchanges. This should be taken into account in
patients with diabetes mellitus.
Patients with rare hereditary problems of fructose intolerance, glucose-galactose
malabsorption or sucrase-isomaltase insufficiency should not take this medicine. May
be harmful to the teeth.
Sorbitol
1mL of Naproxen Oral Suspension contains 128.6mg sorbitol 70 % solution. Patients
with rare hereditary problems of fructose intolerance should not take this medicinal
product.
Sodium
1mL of Naproxen Oral Suspension contains 0.4 mmol (9.2mg) sodium. To be taken
into consideration by patients on a controlled sodium diet.
Methyl-parahydroxybenzoate
May cause allergic reactions (possibly delayed).

4.5

Interaction with other medicinal products and other forms of interaction
Combinations that are not recommended:

Combination of naproxen
with
Other NSAIDs including
salicylates and COX-2
inhibitors
Corticosteroids
Antiplatelet drugs
Anticoagulants
Lithium
Tacrolimus
Alcohol

Mifepristone

Possible reactions
Increased risk of side effects, particularly
gastrointestinal bleeding risk (combination is not
recommended, see section 4.4)
Increased risk of gastrointestinal ulceration or
bleeding (combination is not recommended)
Increased risk of gastrointestinal bleeding
(combination is not recommended)
NSAIDs may increase the effect of anticoagulants −
increased bleeding risk is possible (monitoring of
clotting status is recommended as appropriate)
Increase in lithium blood level (monitoring and, if
necessary, dose adjustment is recommended)
Renal failure (combination should be avoided)
Increased risk of occurrence and exacerbation of
gastrointestinal bleeding (combination should be
avoided)
Concomitant use of naproxen with mifepristone
should be avoided because of a theoretical risk that
prostaglandin synthetase inhibitors may decrease
the efficacy of mifepristone.

Combinations where caution should be exercised:

Combination of naproxen
with
Cardiac glycosides
Quinolones
Sulphonamides
Zidovudine
Phenytoin
Selective serotonin re-uptake
inhibitors
Probenecid
Sulphinpyrazone
Triamterene
Diuretics
Potassium-sparing diuretics

Possible reactions
Increase in their blood levels (appropriate
monitoring and, if necessary, dose adjustment is
recommended)
Convulsions have been reported (very rarely)
Affect naproxen plasma levels
Increased risk of haematotoxicity as a result of
increased plasma levels of zidovudine
Possible increase in phenytoin blood level
(appropriate monitoring and, if necessary, dose
adjustment is recommended)
Increased risk of gastrointestinal bleeding
Delayed excretion of naproxen (dose reduction of
naproxen and special monitoring recommended)
Renal failure
Decrease in their blood pressure lowering effect,
increased risk of kidney damage (blood pressure
and renal function monitoring recommended, and
adequate hydration should be ensured)
Effect may be increased (potassium level

Combination of naproxen
with
Antihypertensives

ACE inhibitors
Angiotensin II antagonists

Methotrexate

Ciclosporin

Oral antidiabetic agents
Antacids

Possible reactions
monitoring recommended)
Decrease in their blood pressure lowering effect
(blood pressure monitoring recommended)
Increased risk of nephrotoxicity as a result of
inhibition of cyclooxygenase (acute renal failure is
possible, especially in older and dehydrated
individuals) and increased risk of hyperkalaemia
(renal function and potassium level monitoring
recommended, and adequate hydration should be
ensured)
Administration of naproxen within 24 hours before
or after treatment with methotrexate may lead to an
increase in methotrexate blood levels and, therefore,
increase the toxicity of the latter (either this
combination should be avoided, or blood counts,
hepatic and renal function should be monitored very
closely)
Increased risk of gastrointestinal injuries,
nephrotoxicity (avoid combination or use lower
dose of naproxen; renal function monitoring
recommended)
Blood glucose fluctuations are possible
(more frequent blood glucose monitoring
recommended)
Decreased absorption of naproxen

Paediatric population
Interaction studies have mostly been performed in adults. There is sporadic evidence
to suggest that similar interactions are likely in children.

4.6

Fertility, pregnancy and lactation
Pregnancy
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or
embryo/foetal development. Data from epidemiological studies suggest an increased
risk of miscarriage and of cardiac malformations and gastroschisis after use of a
prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for
cardiovascular malformation was increased from less than 1%, up to approximately
1.5%. The risk is believed to increase with dose and duration of therapy.
In animals, administration of a prostaglandin synthesis inhibitor has been shown to
result in increased pre- and post-implantation loss and embryo-foetal lethality. In
addition, increased incidences of various malformations, including cardiovascular,
have been reported in animals given a prostaglandin synthesis inhibitor during the
organogenetic period.

During the first and second trimester of pregnancy, naproxen should not be given
unless clearly necessary. If naproxen is used by a woman attempting to conceive, or
during the first and second trimester of pregnancy, the dose should be kept as low and
the duration of treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may:
-

-

expose the foetus to:


cardiopulmonary toxicity (with premature closure of the ductus arteriosus and
pulmonary hypertension)



renal dysfunction, which may progress to renal failure with
oligohydramniosis

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


possible prolongation of bleeding time, an anti-platelet aggregating effect,
which may occur even at very low doses



inhibition of uterine contractions resulting in delayed or prolonged labour

Consequently, naproxen is contraindicated during the third trimester of pregnancy.
Naproxen should not be used post-partum because it may delay involution of the
uterus.
Breast-feeding
Small amounts of naproxen pass into breast-milk. Use of Naproxen during breastfeeding should be avoided as a precautionary measure.
Fertility
The use of naproxen may impair female fertility and is not recommended in women
attempting to conceive. In women who have difficulties conceiving or who are
undergoing investigation of infertility, withdrawal of naproxen should be considered.

4.7

Effects on ability to drive and use machines
Naproxen has minor to moderate influence on the ability to drive and use machines.
If side effects such as visual disturbances, dizziness, fatigue or other CNS
disturbances occur, patients should refrain from activities requiring increased
alertness – e.g. participating in road traffic or operating machines. Patients should be
informed as appropriate.

4.8

Undesirable effects
The most commonly observed adverse events have been gastrointestinal in nature.
Peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal, may occur –
particularly in older patients (see section 4.4). Nausea, vomiting, diarrhoea, bloating,
constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative
stomatitis and exacerbation of colitis and Crohn's disease have been reported after use
of the product. Less frequently, gastritis has been observed.
Oedema, hypertension and cardiac insufficiency have been reported in association
with NSAID therapy.
Clinical studies and epidemiological data suggest that the use of some NSAIDs,
particularly at high doses and during long-term treatment, may be associated with a
small increased risk of arterial thrombotic events (e.g. myocardial infarction or
stroke).
The reported frequencies of undesirable effects are based on the following categories:
Very common (≥ 1/10)
Common

(≥ 1/100 to <1/10)

Uncommon

(≥ 1/1,000 to <1/100)

Rare

(≥ 1/10,000 to <1/1,000)

Very rare

(< 1/10,000)

Not known

(cannot be estimated from the available data)

Like other NSAIDs, naproxen may cause the following side effects:
Blood and lymphatic system disorders


Uncommon:

Blood count changes
Eosinophilia



Very rare:

Aplastic or haemolytic anaemia, thrombocytopenia,
leukopenia, pancytopenia, agranulocytosis
The following prodromes might occur: fever, sore throat,
superficial inflammation of the oral mucosa, flu-like
symptoms such as fatigue, nosebleeds and skin bleeding.
Periodic blood counts should be done during long-term use.



Not known:

Neutropenia

Immune system disorders


Common:

Rash, pruritus



Very rare:

Anaphylactic or anaphylactoid systemic reactions – severe
and sudden hypotension, acceleration or slowing of the heart
rate, unusual tiredness or weakness, anxiety, agitation,

unconsciousness, difficulty breathing or swallowing, itching,
urticaria with or without angioedema, skin redness, nausea,
vomiting, spasmodic abdominal pain or diarrhoea to the point
of life-threatening shock
Metabolism and nutrition disorders


Not known:

Hyperkalaemia

Psychiatric disorders


Common:

Depression, dream abnormalities, insomnia

Nervous system disorders
• Common:



Very rare:

Headache, dizziness, CNS disorders such as agitation,
irritability, sleep disorders, tiredness, perceptual disorders,
cognitive dysfunction
Seizures
Aseptic meningitis in patients with autoimmune disorders
(SLE, mixed connective tissue disease), neuritis



Not known:

Paraesthesia

Eye disorders


Very rare:

Visual disturbances



Not known:

Lens swelling and papilloedema, corneal opacity, papillitis

Ear and labyrinth disorders


Common:

Tinnitus, hearing impaired, vertigo

Cardiac disorders


Very rare:

Hypertension, tachycardia, palpitations, cardiac insufficiency

Vascular disorders


Very rare:

Vasculitis

Respiratory, thoracic and mediastinal disorders


Common:

Dyspnoea



Uncommon:

Bronchospasm, asthma attacks (with and without drop in
blood pressure), eosinophilic pneumonia



Not known:

Pulmonary oedema

Gastrointestinal disorders


Very common:

Nausea, vomiting, heartburn, gastric pain, fullness,
constipation or diarrhoea and minor blood loss in the
gastrointestinal tract which, in exceptional cases, may cause
anaemia.



Common:

Gastrointestinal ulcers (which may be accompanied by
bleeding and perforation)



Uncommon:

Haematemesis, melaena or bloody diarrhoea; lower
abdominal symptoms (e.g. bleeding colitis or exacerbation of
Crohn's disease/ulcerative colitis), stomatitis, oesophageal
lesions, flatulence, gastritis



Not known:

Pancreatitis

Hepatobiliary disorders


Uncommon:

Changes in hepatic function with transaminase elevation



Very rare:

Hepatitis (with or without jaundice, may be fulminant in
isolated cases), liver damage especially after long-term
therapy



Not known:

Jaundice

Skin and subcutaneous tissue disorders


Common:

Sweating, ecchymoses, purpura



Uncommon:

Alopecia (usually reversible), photodermatitis (may include
blistering)



Rare:

Epidermolysis bullosa-like reactions



Very rare:

Hypersensitivity reactions such as skin rash, erythema
multiforme, in isolated cases manifesting as severe forms
such as Stevens-Johnson syndrome or toxic epidermal
necrolysis



Not known:

Erythema nodosum, lichen planus, SLE (systemic lupus
erythematosus), urticaria, pustular reaction

Musculoskeletal and connective tissue disorders


Uncommon:

Myalgia, muscle weakness



Very rare:

worsening of infection-related inflammation (e.g.
development of necrotising fasciitis) has been described in
temporal relationship with the systemic use of NSAIDs.

Renal and urinary disorders


Common:

Peripheral oedema, particularly in patients with hypertension



Uncommon:

Acute renal failure, nephrotic syndrome or interstitial
nephritis



Very rare:

Kidney damage (renal papillary necrosis), especially during
long-term therapy, hyperuricaemia



Not known:

Haematuria, glomerulonephritis

Reproductive system and breast disorders


Not known:

Female infertility

General disorders


Common:

Thirst



Uncommon:

Pyrexia (fever and chills), malaise



Not known:

Oedema

Investigations


Not known:

Serum creatinine increased. Naproxen may interfere with
laboratory tests – see section 4.4.

Other undesirable effects
Methyl-parahydroxybenzoate may cause allergic reactions (possibly delayed).

Patients should be apprised that they must discontinue using this medicinal
product and seek medical advice immediately if they experience any of the
following symptoms:


Breathlessness



Large drop in blood pressure



Clouding of consciousness or severe and/or increasing impairment of overall
well-being



Swelling of the face or throat, difficulty swallowing



(Itchy) skin rash, redness, vesicles or bleeding of the skin



Local tender, warm redness and swelling, which may be accompanied by fever



Severe headache or abdominal pain – especially if onset is sudden



Haematemesis or coffee grounds-like vomit



Bloody or black stools



Heart symptoms (chest pain)



Severe fatigue with anorexia, with or without yellow colouration of the skin and
the sclerae



Stiff neck with headache



Visual disturbances or hearing impairment



Flu-like symptoms, mouth sores, sore throat and nosebleeds.

Paediatric population
The frequency, type and severity of undesirable effects in children and adolescents
are similar to those in adults.
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 Yellow Card scheme at www.mhra.gov.uk/yellowcard.

4.9

Overdose
Symptoms of overdose
Symptoms of overdose may include CNS disturbances including headache, dizziness
or lightheadedness, and epigastric pain and abdominal discomfort, dyspepsia, nausea,
vomiting, transient change in hepatic function, hypoprothrombinaemia, renal
dysfunction, metabolic acidosis, apnoea and disorientation. Naproxen can be
absorbed rapidly. High and early drug concentrations in the blood should be expected.
A few patients have experienced seizures, but it remained unclear whether these were
caused by treatment with naproxen. Gastrointestinal bleeding may also occur.
Hypertension, acute renal failure, respiratory depression and coma may occur, but are
rare. Anaphylactic reactions have been described after treatment with non-steroidal
anti-inflammatory drugs and may also occur following overdose.
Management of overdose
Patients should be treated symptomatically. There is no specific antidote. Preventive
measures to avoid further absorption (e.g. administration of activated charcoal) may
be indicated in patients within four hours after ingestion or because of a large
overdose. Forced diuresis, alkalinisation of urine, haemodialysis or haemoperfusion
are probably unsuitable because of the high protein binding of naproxen.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Anti-inflammatory and antirheumatic products, nonsteroids, propionic acid derivatives, naproxen, ATC code: M01AE02.
Mechanism of action
The anti-inflammatory effect of naproxen has even been shown in adrenalectomised
animals, suggesting that its mechanism of action is not mediated through the
pituitary-adrenal axis. However, the exact mechanism of action is not known.

Pharmacodynamic effects
Naproxen reduces prostaglandin synthesis by inhibiting cyclooxygenase.
This is presumably also the basis of its effects including: analgesia (non-narcotic in
nature), anti-inflammatory effect, antipyretic effect, inhibition of platelet aggregation,
stabilisation of the lysosomal membrane, bradykinin inhibition and anti-complement
effect.
Clinical efficacy and safety
The clinical efficacy and safety of naproxen in the indications listed in section 4.1 has
been demonstrated in numerous clinical trials.

Paediatric population
The efficacy and safety of naproxen used in children and adolescents has been
demonstrated in numerous studies.

5.2

Pharmacokinetic properties
Absorption
After oral administration, part of a naproxen dose is absorbed from the stomach and
then the remainder is absorbed completely from the small intestine, with therapeutic
plasma concentrations being reached approximately 2–4 hours post-dose.
Distribution
Patients with renal impairment tend to have lower plasma levels, and those with
hepatic impairment tend to have higher plasma levels.
The half-life in healthy individuals and patients with kidney disease is 10 to 18 hours.
Older individuals showed no change in half-life, whilst those with hepatic impairment
show an increase.
Over 99% of naproxen is reversibly bound to plasma proteins.
Biotransformation and elimination
95% of an administered dose is excreted in the urine both as unchanged drug and as
6-O-desmethylnaproxen either as free drug or in conjugated form.
Linearity/non-linearity
The AUC of naproxen shows linear dose proportionality up to a maximum dose of
500mg. Beyond this dose, the proportion of unbound naproxen in plasma increases,
leading to an increased renal excretion rate of naproxen.

Pharmacokinetic/pharmacodynamic relationships
The required therapeutically effective plasma concentration ranges from 30–
90µg/mL.
Paediatric population
The pharmacokinetic profile of naproxen in children is similar to the profile in adults,
but clearance is higher in this age group compared to adults.

5.3

Preclinical safety data
Chronic toxicity studies showed that naproxen exhibited the toxicological profile
typical of NSAIDs, i.e. gastrointestinal toxicity and – in high doses – kidney damage.
Naproxen had embryotoxic effects in rats and rabbits, but has not been found to have
any teratogenic effects. No adverse effects on male and female fertility were detected
in the rat for daily doses up to 30mg/kg, however, higher doses resulted in an
inhibition of ovulation in rabbits. Naproxen inhibits prostaglandin synthesis and,
therefore, when administered during the last few months of pregnancy, it may delay
parturition and have toxic effects on the foetus.
A two-year study in rats produced no evidence of carcinogenic potential.
Mutagenicity studies of naproxen gave negative results.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Sucrose
Saccharin sodium (E 954)
Sodium cyclamate (E 952)
Sodium chloride
Methyl-parahydroxybenzoate (E 218)
Potassium sorbate (E 202)
Tragacanth (E 413)
Citric acid (E 330)
Sorbitol 70% solution (E 420)
Water
Orange flavour
Pineapple flavour

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
24 months.
After first opening: 3 months.

6.4

Special precautions for storage
Store in the original package in order to protect from light.
After first opening: Store in the original package in order to protect from light.

6.5

Nature and contents of container
Amber glass bottle (type III) with child-resistant screw closure
8mL graduated oral syringe with graduations of 0.1mL
Pack of 100mL

6.6

Special precautions for disposal
The bottle is equipped with a child-resistant screw closure. To open, push down and
turn the closure. Replace the cap firmly after use.
Cleaning of the oral syringe:
Wash the syringe with water. Disassemble the two parts of the syringe and allow to
dry.
Any unused medicinal product or waste material should be disposed of in accordance
with local requirements.

7

MARKETING AUTHORISATION HOLDER
INFECTOPHARM Arzneimittel und Consilium GmbH
Von-Humboldt-Str. 1
64646 Heppenheim
Germany
Distributed by:
Thornton & Ross Ltd.
Linthwaite
Huddersfield
HD7 5QH
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 15011/0020

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
23/06/2016

10

DATE OF REVISION OF THE TEXT
23/06/2016

Expand view ⇕

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

Hide