.2009 ‫ ספטמבר‬:‫ עלון מאושר‬.

"‫"פורמט עלון זה נקבע ע"י משרד הבריאות ותוכנו נבדק ואושר‬

2017 ‫ בספטמבר‬:‫העלון עודכן‬
“This leaflet format has been determined by the Ministry of Health and the content thereof has been
checked and approved.” Date of approval: September 2009. Date of revision: September 2017

NAXYN®
TABLETS, SUPPOSITORIES

Naxyn Tablets 500 mg

Each tablet contains:
Active Ingredient
Naproxen 500 mg
Other Ingredients
Lactose monohydrate, starch, povidone, magnesium stearate,
hydroxypropylmethylcellulose, polyethylene glycol 400, polyethylene glycol 6000, D&C
yellow No.10, FD&C yellow No.6
Each tablet contains 138.83 mg lactose.

Mechanism of Action
Naxyn is a nonsteroidal anti-inflammatory agent with analgesic and antipyretic
properties. Naproxen anion inhibits prostaglandin synthesis but beyond this its mode of
action is unknown.
Naproxen appears to be completely absorbed from the gastrointestinal tract. After
administration of naproxen, peak plasma levels of naproxen anion are attained at 2-4
hours, depending on food intake, with steady-state conditions normally achieved after
4-5 doses. The mean biological half-life of the anion in humans is approximately 13
hours, and at therapeutic levels it is greater than 99% albumin bound.
Approximately 95% of the dose is excreted in the urine, primarily as naproxen, 6-0-
desmethyl naproxen or their conjugates. The rate of excretion has been found to
coincide closely with the rate of drug disappearance from the plasma. The drug does
not induce metabolizing enzymes.
By virtue of its prostaglandin synthetase inhibitory activity, naproxen proved valuable
in markedly decreasing uterine contractility in primary dysmenorrhea, thus offering
relief from the associated pain and discomfort.
Naxyn Suppositories are particularly useful when relief of night pain and early
morning stiffness are desired and when the oral medication is not feasible for whatever
reason.

Indications
 Relief of the signs and symptoms of rheumatic diseases including osteoarthritis,
ankylosing spondylitis and of rheumatoid arthritis, both in the treatment of acute
flares and in the long-term management of the disease.
 Juvenile Rheumatoid Arthritis.
 Periarticular and Musculoskeletal Disorders - Relief of pain in bursitis, tendinitis,
synovitis, tenosynovitis and lumbago.
 Relief of pain, swelling, tenderness and fever in acute gouty arthritis.
 Relief of symptoms of primary dysmenorrhea.

Contraindications
Naxyn is contraindicated in patients who have shown hypersensitivity to naproxen or
naproxen sodium.
Because the potential exists for cross-sensitivity reactions, Naxyn is also
contraindicated in patients in whom aspirin or other nonsteroidal anti-inflammatory

NAXYN, 28.09.2017, LK
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agents induce allergic manifestations such as the syndrome of asthma, rhinitis or

nasal polyps. Severe anaphylactic-like reactions to naproxen have been reported in
such patients.
Severe renal, hepatic or heart failure.
Naxyn is contraindicated for the treatment of perioperative pain in the setting of
coronary artery bypass graft (CABG) surgery.
Naxyn Suppositories are contraindicated in patients with a history of proctitis or
recent rectal bleeding.

Warnings
Gastrointestinal (GI) Effects – Risk of GI Ulceration, Bleeding, and Perforation
Naxyn should not be given to patients with active peptic ulcer. In other patients with a
history of gastrointestinal disease, naproxen should be given under close supervision.
Serious gastrointestinal adverse reactions can occur at any time in patients on therapy
with nonsteroidal anti-inflammatory agents (NSAIAs) with or without warning
symptoms. The cumulative incidence of serious gastrointestinal adverse reactions,
including gross bleeding and perforation, increases approximately linearly with duration
of use of naproxen (or other nonsteroidal anti-inflammatory agents ). As with other
nonsteroidal anti-inflammatory agents, there is probably a higher risk of adverse
reactions with use of higher doses of these drugs.
Studies to date have not identified any subset of patients not at risk of developing
peptic ulcer and bleeding. However, elderly and debilitated patients tolerate
gastrointestinal ulceration or bleeding less well than other individuals. Most of fatal
gastrointestinal events associated with nonsteroidal anti-inflammatory agents occurred
in this population of patients. Studies to date are inconclusive concerning the relative
risk of various NSAIAs in causing such reactions.
The utility of periodic laboratory monitoring has not been demonstrated, nor has it
been adequately assessed. Only 1 in 5 patients who develop a serious upper GI
adverse event on NSAIAs therapy is symptomatic. Therefore, physicians and patients
should remain alert for ulceration and bleeding, even in the absence of previous GI
tract symptoms. Patients should be informed about the signs and/or symptoms of
serious GI toxicity and the steps to take if they occur. To minimize the potential risk for
an adverse GI event, the lowest effective dose should be used for the shortest possible
duration. When GI bleeding or ulceration occurs in patients receiving this drug, the
treatment should be withdrawn.
Combination therapy with protective agents (e.g. proton pump inhibitors) should be
considered for these patients, and also for patients requiring concomitant low dose
aspirin, or other drugs likely to increase gastrointestinal risk.
Caution should be advised in patients receiving concomitant medications which could
increase the risk of ulceration or bleeding, such as oral corticosteroid, anticoagulants
such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as
aspirin.
NSAIAs should be given with care to patients with a history of gastrointestinal
disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated.

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 as fluid retention and
oedema have been reported in association with NSAIA therapy.
Clinical trial and epidemiological data suggest that use of COX-2 selective and non-
selective NSAIAs (particularly at high doses and in long term treatment) may be
associated with a small increased risk of arterial thrombotic events (for example
myocardial infarction or stroke). Although data suggest that the use of naproxen
(1000 mg daily) may be associated with a lower risk, some risk cannot be excluded.
NSAIAs, including naproxen, can lead to onset of new hypertension or worsening of
pre-existing hypetension, either of which may contribute to the increased incidence of

NAXYN, 28.09.2017 LK
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cerebrovascular events. Fluid retention, edema, and peripheral edema have been
observed in some patients taking NSAIAs.
Therefore 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 be made before initiating longer-term
treatment of patients with risk factors for cardiovascular events (e.g. hypertension,
hyperlipidaemia, diabetes mellitus, smoking).

Hepatic Effects
As with other nonsteroidal anti-inflammatory drugs, borderline elevations of one or
more liver tests may occur in up to 15% of patients. Hepatic abnormalities may be the
result of hypersensitivity rather than direct toxicity. These laboratory abnormalities may
progress, may remain essentially unchanged, or may be transient with continued
therapy. The SGPT (ALT) test is probably the most sensitive indicator of liver
dysfunction. Notable elevations of ALT or AST (3 times the upper limit of normal)
occurred in controlled clinical trials in less than 1% of patients. In addition, rare cases
of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver
necrosis and hepatic failure, some of them with fatal outcomes have been reported. A
patient with symptoms and/or signs suggesting liver dysfunction, or in whom an
abnormal liver test has occurred, should be evaluated for evidence of the development
of more severe hepatic reaction while on therapy with this drug. Severe hepatic
reactions, including jaundice and cases of fatal hepatitis, have been reported with this
drug as with other nonsteroidal anti-inflammatory agents. Although such reactions are
rare, if abnormal liver tests persist or worsen, if clinical signs and symptoms consistent
with liver disease develop, or if systemic manifestations occur (e.g. eosinophilia, rash,
etc.) this drug should be discontinued.

Renal Effects
Long-term administration of NSAIAs has resulted in renal papillary necrosis and other
renal injury. 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 NSAIAs may cause a dose-dependent reduction in prostaglandin
formation and, secondarily in renal blood flow, which may precipitate overt renal
decompensation. . Patients at greatest risk of this reaction are those with impaired
renal function, cardiac impairment, liver dysfunction, those taking diuretics and the
elderly. Renal function should be monitored in these patients.

Haematological Effects
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.

Anaphylactic Reactions
Anaphylactic reactions occur usually in patients with a history of hypersensitivity to
aspirin, other nonsteroidal anti-inflammatory agents , or naproxen. They may however
also occur in patients without a known previous exposure or hypersensitivity to these
agents. Both types of anaphylactic reactions have the potential for being fatal.
Anaphylactic reactions may also occur in individuals with a history of angioedema,
bronchospastic reactivity (e.g. asthma), rhinitis and nasal polyps.

Preexisting Asthma:
Patients with asthma may have aspirin-sensitive asthma. The use of 431 aspirin in
patients with aspirin-sensitive asthma has been associated with severe 432

NAXYN, 28.09.2017 LK
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bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm,

between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in
such aspirin-sensitive patients, NSAIAs including naproxen should not be administered
to patients with this form of aspirin sensitivity and should be used with caution in
patients with preexisting asthma.

Ocular Effects
Studies have not shown changes in the eye attributable to naproxen administration.
In rare cases, adverse ocular disorders including papillitis, retrobulbar optic neuritis and
papilloedema, have been reported in users of NSAIAs including naproxen, although a
cause-and-effect relationship cannot be established; accordingly, patients who develop
visual disturbances during treatment with naproxen-containing products should have an
ophthalmological examination.

Dermatological Effects
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 NSAIAs. Patients appear to be at highest risk for these
reactions early in the course of therapy: the onset of the reactions occurring in the
majority of cases within the first month of treatment. naproxen should be discontinued
at the first appearance of skin rash, mucosal lesions, or any other sign of
hypersensitivity.

Steroids
If steroid dosage is reduced or eliminated during therapy, the steroid dosage should
be reduced slowly and the patients must be observed closely for any evidence of
adverse effects, including adrenal insufficiency and exacerbation of symptoms of
arthritis.

Use in Pregnancy
Reproduction studies performed in animals at doses up to six times the human dose
revealed no evidence of harm to the fetus due to the drug. However, because animal
reproduction studies are not always predictive of human response, the drug should not
be used during pregnancy, especially during the first and third trimesters, unless clearly
needed.
Because of the known effect of drugs of this class on the human cardiovascular
system (closure of ductus arteriosus), use during late pregnancy should be avoided.

Precautions Related to Fertility

The use of naproxen, as with any drug known to inhibit cyclooxygenase/prostaglandin
synthesis, may impair fertility and is not recommended in women attempting to
conceive. In women who have difficulty conceiving or are undergoing investigation of
infertility, withdrawal of naproxen should be considered.

Use in Breastfeeding
Naproxen anion has been found in the milk of lactating women, therefore, use in
nursing mothers should be avoided.

Use in Pediatrics
Rheumatoid arthritis in children over 5 years of age is the only pediatric indication for
which Naxyn is approved.
Safety and effectiveness of the use of naproxen in the pediatric age group for other
indications have not been established.

Use in the Elderly

Studies indicate that although total plasma concentration of naproxen is unchanged,
the unbound plasma fraction of naproxen is increased in the elderly. The implication of

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this finding for naproxen dosing is unknown. As with other drugs used in the elderly, it
is prudent to use the lowest effective dose.
Experience indicates that geriatric patients may be particularly sensitive to certain
adverse effects of nonsteroidal anti-inflammatory agents. Elderly or debilitated patients
seem to tolerate peptic ulceration or bleeding less well when these events do occur.
Most spontaneous reports of fatal GI events are in the geriatric population.
Naproxen is known to be substantially excreted by the kidney, and the risk of toxic
reactions to this drug may be greater in patients with impaired renal function. Because
elderly patients are more likely to have decreased renal function, care should be taken
in dose selection, and it may be useful to monitor renal function. Geriatric patients may
be at a greater risk for the development of a form of renal toxicity precipitated by
reduced prostaglandin formation during administration of nonsteroidal anti-
inflammatory agents.

Use in Patients with Impaired Renal Function

Since naproxen and its metabolites are eliminated to a large extent (95%) by urinary
excretion via glomerular filtration, the drug should be used with great caution in patients
with significantly impaired renal function, and the monitoring of their serum-creatinine
and/or creatinine clearance is advised. In such cases, a reduction in daily dosage
should be considered to avoid the possibility of excessive drug accumulation.
Naproxen should not be used chronically in patients having baseline creatinine
clearance less than 30 ml/min.
Certain patients, specifically those where renal blood flow is compromised, such as in
extracellular volume depletion, cirrhosis of the liver, sodium restriction, congestive
heart failure, and pre-existing renal disease, should have renal function assessed
before and during Naxyn therapy.
Some elderly, in whom impaired renal function may be expected, could also fall within
this category. The lowest effective dose should be considered to avoid the possibility of
excessive accumulation of naproxen metabolites in these patients.
Haemodialysis does not decrease the plasma concentration of naproxen because of
the high degree of protein binding.

Use in Patients with Impaired Hepatic Function

Chronic alcoholic liver disease and probably also other forms of cirrhosis, reduce the
total plasma concentration of naproxen, but the plasma concentration of unbound
naproxen is increased. The implication of this finding for naproxen dosing is unknown,
but it is prudent to use the lowest effective dose.
As with nonsteroidal anti-inflammatory agents, borderline elevations of one or more
liver tests may occur. Symptoms and/or signs suggesting liver dysfunction or the
appearance of abnormal liver tests, command periodic liver evaluation during therapy
with this drug.

Laboratory Tests:
Because serious GI tract ulcerations and bleeding can occur without warning
symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients
on long-term treatment with NASIAs should have their CBC and a chemistry profile
checked periodically. If clinical signs and symptoms consistent with liver or renal
disease develop, systemic manifestations occur (eg, eosinophilia, rash, etc.) or if
abnormal liver tests persist or worsen, naproxen should be discontinued.

Adverse Reactions
Naproxen is generally well tolerated, however, the following adverse reactions have
been reported:

Gastrointestinal

NAXYN, 28.09.2017 LK
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Heartburn, nausea, vomiting, epigastric distress, abdominal pain/discomfort,

dyspepsia, flatulence, constipation, diarrhea and stomatitis.
More serious reactions which may occur are gastrointestinal bleeding, which is
sometimes fatal, particularly in the elderly, peptic ulceration, perforation, non-peptic
gastro-intestinal ulceration, melena, haematemesis, stomatitis, ulcerative stomatitis,
exacerbation of ulcerative colitis and Crohn's disease, oesophagitis, gastritis and
pancreatitis.

Central Nervous System

Headache, dizziness, drowsiness, lightheadedness, and vertigo.

Dermatologic
Itching, skin eruptions, ecchymoses and sweating.

Cardiovascular
Edema, palpitations and dyspnea.

Special Senses
Tinnitus, hearing and visual disturbances.

Adverse reactions of lower incidence (less than 1%) include convulsions, peptic
ulceration with bleeding and/or perforation, gastrointestinal bleeding and/or perforation;
colitis, vomiting; jaundice, hepatitis; nephropathy; hematuria; thrombocytopenia,
granulocytopenia; inability to concentrate, cognitive dysfunction, depression,
hallucinations, dream abnormalities, confusion, insomnia; alopecia, erythema
multiforme, Stevens-Johnson syndrome, epidermal necrolysis; photosensitivity
reactions including rare cases in which skin is resembling porphyria cutanea tarda or
epidermolysis bullosa, vasculitis and eosinophilic pneumonitis. Anaphylactic reactions,
whether of the true allergic type or the pharmacological idiosyncratic (e.g. aspirin
syndrome) type, usually but not always, occur in patients with a known history of such
reactions.
The following have also been reported rarely: hepatitis, hyperkalemia, renal disease
(including but not limited to glomerular nephritis, interstitial nephritis, renal papillary
necrosis, nephrotic syndrome, and renal failure), ulcerative stomatitis.

Other reactions have been reported in circumstances in which a causal relationship

could not be established. However, in these rarely reported events, the possibility
cannot be excluded. Therefore, these observations are being listed to serve as alerting
information to the physicians:

Hematologic
Neutropenia, thrombocytopenia, eosinophilia, leucopenia, aplastic anaemia,
granulocytopenia, including agranulocytosis, aplastic anemia, hemolytic anemia.

Dermatologic
Urticaria.
Gastrointestinal
Non-peptic gastrointestinal ulceration, ulcerative stomatitis.
General
Angioneurotic edema, hyperglycemia, hypoglycemia, aseptic meningitis.
Other Hypersensitivity Reactions
Fever.

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Other adverse reactions rarely reported with the use of nonsteroidal anti-
inflammatory agents include: hemoptysis (spitting of blood), hematemesis, shortness of
breath or troubled breathing, swollen eyes, and unexplained nosebleed.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product.

Any suspected adverse events should be reported to the Ministry of Health according to the
National Regulation by using an online form

https://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@
moh.gov.il

Precautions
(see also Warnings)
Naxyn (naproxen) should not be used concomitantly with other naproxen or naproxen
sodium preparations since they all circulate in plasma as the naproxen anion.
In patients with a history of gastrointestinal tract disease, naproxen usage should be
carefully monitored.
Although naproxen has been found to be better tolerated by patients exhibiting
dyspepsia with similar agents, the possibility of peptic ulceration and/or episodes of
gastrointestinal bleeding with naproxen usage, should be borne in mind.
Patients with initial hemoglobin values of 10 grams or less who are to receive long-
term therapy should have hemoglobin values determined frequently.
Peripheral edema has been observed in some patients receiving naproxen. Although
sodium retention has not been found in metabolic studies with this drug, caution is
required, as with other non-steroidal anti-inflammatories, in patients with compromised
cardiac function.
Caution should be exercised by patients whose activities require alertness, if they
experience drowsiness, vertigo or depression during Naxyn therapy.
Studies to date have not shown changes in the eye attributable to naproxen
administration; however, because of adverse eye findings in animal studies with drugs
of this class, it is recommended that ophthalmologic studies be carried out within a
reasonable period of time after starting Naxyn therapy, and at periodic intervals
thereafter, if the drug is to be used for an extended period of time.
The antipyretic and anti-inflammatory activities of naproxen may reduce fever and
inflammation, thus diminishing their utility as diagnostic signs.
Naproxen decreases platelet aggregation and prolongs bleeding time. This effect
should be kept in mind when bleeding times are determined. Patients who have
coagulation disorders or are receiving drug therapy that interferes with hemostasis
should be carefully observed if naproxen is administered. Patients on full
anticoagulation therapy (e.g., heparin or dicumarol derivatives) may be at increased
risk of bleeding if given naproxen concurrently. Thus, the benefits should be weighed
against these risks (see Drug Interactions).

Patients Who Require Surgery (Including Dental Surgery)

Caution is recommended in patients who require surgery. Most of the Nonsteroidal
anti-inflammatory agents inhibit platelet aggregation and may prolong bleeding time,
which may increase intra-and postoperative bleeding. Consideration should therefore
be given to discontinuing NSAIAs treatment for an appropriate length of time prior to
elective surgery, depending on the potency and duration of effect of the individual
agent on platelet aggregability.
In case of patients requiring dental surgery, nonsteroidal anti-inflammatory agents
may cause soreness, irritation, or ulceration of the oral mucosa. Most of the
nonsteroidal anti-inflammatory agents may rarely cause leukopenia and/or
thrombocytopenia, which may result in an increased incidence of microbial infection,
delayed healing, and gingival bleeding. If leukopenia or thrombocytopenia occurs,
NAXYN, 28.09.2017 LK
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dental work should be deferred until blood counts return to normal, and patients should
be instructed in proper oral hygiene.

Drug Interactions
Drug Interactions Caused by Drug Displacement: Because of its affinity for protein,
naproxen may displace other drugs (such as sulfonamides, sulfonylureas, hydantoins,
coumarin anticoagulants, methotrexate) from their protein-binding sites. Patients
should be observed for signs of overdosage to these drugs when receiving them
concomitantly with Naxyn. Patients on full anticoagulation therapy (e.g. heparin or
dicumarol derivatives) may be at increased risk of bleeding if given naproxen
concomitantly.
Naproxen/Antacids/Sucralfate/Cholestyramine: Concomitant administration of some
antacids (magnesium oxide or aluminium hydroxide) and sucralfate or cholestyramine
can delay the absorption of naproxen.
Naproxen/ Beta-Blockers: As with other nonsteroidal anti-inflammatory agents, the
antihypertensive effect of propranolol and other beta-blockers may be reduced.
Naproxen/Aspirin/Other Nonsteroidal Anti-inflammatory Agents
(NSAIAs/Cyclooxygenase-2 Selective Inhibitors): Concurrent use of 2 or more
NSAIAs/cyclooxygenase -2 selective inhibitors, or aspirin or is not recommended, due
to the possible increased risk of adverse effects, and gastrointestinal toxicity including
ulceration or hemorrhage, without providing additional symptomatic relief.
Naproxen/ACE Inhibitors: As with other non-steroidal anti- inflammatory drugs,
naproxen may increase the risk of renal impairment associated with the use of ACE
(angiotensin I-converting enzyme) inhibitors.
Naproxen/ Probenecid: Probenecid given concurrently increases naproxen anion
plasma levels and extends its plasma half-life significantly.
Naproxen/ Lithium: Concurrent administration may cause inhibition of lithium renal
clearance, leading to an increase in plasma lithium concentration.
Naproxen/ Methotrexate: Concomitant administration of naproxen and methotrexate
should be done with caution, because naproxen has been reported among other
nonsteroidal anti-inflammatory agents to reduce the tubular secretion of methotrexate
in an animal model, and thus possibly enhance its toxicity.
Naproxen/ Zidovudine: In vitro studies have shown that naproxen may interfere with
the metabolism of zidovudine, resulting in higher zidovudine plasma levels. Therefore,
consideration should be given to reducing zidovudine doses to avoid the potential of
increased side effects associated with increased zidovudine plasma levels.
Nonsteroidal Anti-inflammatory Agents (NSAIAs)/Selective Serotonin Reuptake Inhibitors
(SSRIs): There is an increased risk of gastrointestinal bleeding when anti-platelet
agents and selective serotonin reuptake inhibitors (SSRIs) are combined with NSAIAs.
Nonsteroidal Anti-inflammatory Agents (NSAIAs)/Corticosteroids: As with all NSAIAs,
caution should be taken when co-administering with corticosteroids because of the
increased risk of gastrointestinal ulceration or bleeding.

Nonsteroidal Anti-inflammatory Agents (NSAIAs)/Cardiac Glycosides:

NSAIAs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac
glycoside levels when co-administered with cardiac glycosides.
Nonsteroidal Anti-inflammatory Agents (NSAIAs)/Mifepristone: NSAIAs should not be
used for 8 - 12 days after mifepristone administration as NSAIAs can reduce the effects
of mifepristone.
Nonsteroidal Anti-inflammatory Agents (NSAIAs)/Quinolone Antibiotics: Animal data
indicate that NSAIAs can increase the risk of convulsions associated with quinolone
antibiotics. Patients taking quinolones may have an increased risk of developing
convulsions.
Nonsteroidal Anti-inflammatory Agents (NSAIAs)/Tacrolimus: There is a possible risk of
nephrotoxicity when NSAIAs are given with tacrolimus.
Nonsteroidal Anti-inflammatory Agents (NSAIAs)/Cyclosporin: Inhibition of renal
prostaglandin activity by NSAIAs may increase the plasma concentration of
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cyclosporine and/or the risk of cyclosporin-induced nephrotoxicity. Therefore, patients

should be carefully monitored during use of this combination.
Nonsteroidal Anti-inflammatory Agents (NSAIAs )/ Furosemide/Thiazides: The
natriuretic effect of furosemide or thaizides has been reported to be inhibited by some
drugs of this class.
Nonsteroidal Anti-inflammatory Agents (NSAIAs)/Alcohol: Concomitant use of
nonsteroidal anti-inflammatory agents (NSAIAs) with alcohol may increase the risk of
gastrointestinal adverse effects, including ulceration or hemorrhage.
Nonsteroidal Anti-inflammatory Agents (NSAIAs)/Valproic Acid: Valproic acid may inhibit
platelet aggregation. Therefore concurrent use of NSAIAs with valproic acid may
increase the risk of bleeding, and caution should therefore be exercised when
administering this combination.

Information for Patients

Patients should be informed of the following information before initiating therapy with
an NSAIA and periodically during the course of ongoing therapy.
1. Naproxen, like other NSAIAs, can cause serious cardiovascular side effects
such as MI or stroke, which may result in hospitalization and even death.
Although serious cardiovascular events can occur without warning symptoms,
patients should be alert for the signs and symptoms of chest pain, shortness of
breath, weakness, slurring of speech, and should ask for medical advice when
observing any indicative sign or symptoms. Patients should be apprised of the
importance of this follow-up.
2. Like other NSAIAs, naproxen can cause GI discomfort and, rarely, more serious
side effects, such as ulcers and gastrointestinal bleeding, which may result in
hospitalization and even fatal outcomes. Although serious GI tract ulcerations
and bleeding can occur without warning symptoms, patients should be alert for
the signs and symptoms of ulcerations and bleeding, and should ask for
medical advice when observing any indicative signs or symptoms including
epigastric pain, dyspepsia, melena, and hematemesis. Patients should be
apprised of the importance of this follow-up.
3. Like other NSAIAs, naproxen can cause serious skin side effects such as
exfolative dermatitis, Stevens Johnson Syndrome, and toxic epidermal
necrolysis, which may result in hospitalization and even death. Although serious
skin reactions may may occur without warning, patients should be alert for signs
and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity
such as itching, and should ask for medical advice when observing any
indicative signs of symptoms. Patients should be advised to stop the drug
immediately if they develop any type of rash and contact their physician as soon
as possible.
4. Patients should promptly report signs or symptoms of unexplained weight gain
or edema to their physicians.
5. Patients should be informed of the warning signs and symptoms of
hepatotoxicity (eg, nausea, fatigue, lethargy, pruritus, jaundice, right upper
quadrant tenderness, and “flu-like symptoms"). If these occur, patients should
be instructed to stop therapy and seek immediate medical therapy.
6. Patients should also be instructed to seek immediate emergency help in the
case of an anaphylactoid reaction (e.g., difficulty in breathing swelling of the
face, or throat). If these occur, patients should be instructed to seek immediate
emergency help.
7. In late pregnancy, as with other NSAIAs, naproxen should be avoided because
it may cause premature closure of the ductus arteriosus.
8. Caution should be exercised by patients whose activities require alertness if
they experience drowsiness, dizziness, vertigo or depression during therapy
with naproxen.

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Diagnostic Interference
Since naproxen may interfere with some tests for 17-ketogenic steroids, it is
suggested that naproxen therapy be temporarily discontinued 72 hours before adrenal
function tests are performed.
Naproxen may also interfere with some urinary assays of 5-hyroxyindoleacetic acid.

Dosage and Administration

Rheumatic Diseases
The recommended daily dosage is 500 or 1000 mg taken as a single dose in the
morning or in the evening. Alternatively, 250 or 500 mg may be taken twice daily at 12-
hour intervals, morning and evening.
In patients who tolerate lower doses well and have no history of gastrointestinal
disease, the dose may be increased to 1500 mg/day for flare-ups or acute
exacerbations of disease, for no longer than two weeks. Increased gastrointestinal side
effects have been reported with these higher doses.

Juvenile Rheumatoid Arthritis

In children over 5 years of age: the recommended dosage is 10 mg/kg body weight
day taken in 2 doses at 12-hour intervals.
Periarticular and Musculoskeletal Disorders
500 mg initially, followed thereafter by 250 mg at 8-12 hour intervals.

Acute Gouty Arthritis

750 mg initially followed 8 hours later by 500 mg and thereafter by 250 mg 8-
hourly, until the attack has passed.

Primary Dysmenorrhea
500 mg at the onset of menstrual pain, followed by 250 mg every 6 hours until
symptoms have subsided, up to a total of 1250 mg daily.

Overdosage
Manifestations
Significant overdosage may be characterized by drowsiness, heartburn, indigestion,
nausea or vomiting. A few patients have experienced seizures, but it is not clear
whether these were naproxen- related or not. No evidence of toxicity or late sequelae
have been reported 5-15 months after ingestion, for three to seven days, of doses of
up to 3 g/day. One patient ingested a single dose of 25 g of naproxen and
experienced mild nausea and indigestion. It is not known what dose of the drug would
be life-threatening.

Treatment
Should a patient ingest a large quantity of naproxen accidentally or deliberately, the
stomach may be emptied and usual supportive measures employed. Animal studies
indicate that prompt administration of activated charcoal in adequate amounts, tends to
markedly reduce the absorption of the drug. Hemodialysis does not decrease the
plasma concentration of naproxen because of the high degree of its protein binding.

Pharmaceutical Precautions
Store in a dry place below 25C.

Registration Numbers
055 98 20619 01

Presentation
30 tablets.

NAXYN, 28.09.2017 LK
 11

Manufacturer
Teva Pharmaceutical Industries Ltd
P.O.Box 3190, Petach Tikva.

NAXYN, 28.09.2017 LK