Geriatric:

Although total plasma concentration of naproxen is unchanged, the unbound plasma

fraction of naproxen is increased in the elderly, although the unbound fraction is <1%
of the total naproxen concentration. Unbound trough naproxen concentrations in
elderly subjects have been reported to range from 0.12% to 0.19% of total naproxen
concentration, compared with 0.05% to 0.075% in younger subjects.
Children
WARNING: The pharmacokinetic profile of naproxen in children aged 5-16 years is similar to that
RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS in adults although the clearance is generally higher in children than in adults.
Cardiovascular Thrombotic Events Pharmacokinetic studies of naproxen were not performed in children less than 5
(NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, years of age.
including myocardial infarction and stroke, which can be fatal. This risk may occur
early in treatment and may increase with duration of use. Dosage and administration:
Naproxen sodium tablets are contraindicated in the setting of coronary artery bypass General
graft (CABG) surgery. Naproxen-sodium containing product circulates in the plasma as naproxen. Onset
Gastrointestinal Bleeding, Ulceration and Perforation of pain relief can begin within 30 minutes in patients taking naproxen sodium.
NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events The recommended strategy for initiating therapy is to choose a formulation and a
which can be fatal. These events can occur at any time during use and without starting dose likely to be effective for the patient and then adjust the dosage based
warning symptoms. Elderly patients and patients with a prior history of peptic ulcer on observation of benefit and/or adverse events.
disease and/or GI bleeding are at greater risk for serious GI events. A lower dose should be considered in patients with renal or hepatic impairment or
Composition: in elderly patients.
Each film coated tablet contains: Naproxen Sodium (USP)……...550mg Recommended formulations
Because the sodium salt of naproxen is more rapidly absorbed, Apranax is
Indications: recommended for the management of acute painful conditions when prompt onset
Apranax is indicated for the treatment of: of pain relief is desired. Apranax may be given orally either in fasting state or with
• Rheumatoid arthritis, meals and/or antacids.
• Osteoarthritis, Dose in adults
• Ankylosing spondylitis, Acute conditions
• Gout, Analgesia/Dysmenorrhea/Acute musculoskeletal conditions/Acute pain states in which
• Juvenile rheumatoid arthritis, there is an inflammatory component.
Because the sodium salt of naproxen is more rapidly absorbed, Apranax is
• Dysmenorrhea, recommended for the management of acute painful conditions when prompt onset
• Migraine treatment and prophylaxis, of pain relief is desired.
• Analgesic and antipyretic use in adults including postpartum non-nursing mothers, The recommended starting dose is Apranax 550 mg followed by Apranax 275 mg
• Analgesic and antipyretic use in children, every 6-8 hours as required.
• Periarticular and musculoskeletal indications-such as bursitis, tendinitis, synovitis, Acute gout: The recommended starting dose is 825 mg of Apranax followed by 275
tenosynovitis, low back pain, mg every 8 hours as needed.
• For the relief of acute and/or chronic pain states in which there is an inflammatory Menorrhagia: Apranax 825-1375 mg per day taken in 2 doses on the first day of
component, menstrual bleeding. Thereafter, the total daily dose should not exceed 1100 mg.
• Surgical manipulations and trauma - sprains, strains orthopedic manipulations, Migraine: For treatment of acute migraine headache, the dose is Apranax 825 mg
dental extractions, surgery, at the first symptom of an impending attack. An additional dose of Apranax 275 mg
• Menorrhagia. to 550 mg can be taken throughout the day, if necessary, but not before half an hour
Properties and effects: after the initial dose.
Apranax is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic, anti- For prophylaxis of migraine headache, the dose of Apranax is 550 mg twice daily.
inflammatory and antipyretic properties. The onset of pain relief is more rapid with If no improvement is seen within 4-6 weeks, the drug should be discontinued.
Apranax than with Naprosyn, therefore Apranax is recommended for the management Dose in children
of acute painful conditions. Naproxen is a propionic acid derivative related to the Safety and effectiveness in children below the age of 2 years have not been established.
arylacetic acid class of drugs. The chemical name of naproxen is (+)-6-methoxy-
alpha-methyl-2-naphthaleneacetic acid. Naproxen has been shown to have striking Contraindications:
anti-inflammatory properties when tested in human clinical studies and classical Naproxen sodium is contraindicated in the following patients:
animal test systems. In addition, it has marked analgesic and antipyretic actions. lt • Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to
exhibits its anti-inflammatory effects even in adrenalectomised animals, indicating naproxen or any components of the drug product.
that its action is not mediated through the pituitary axis. It inhibits synthesis of • History of asthma, urticaria, or other allergic-type reactions after taking aspirin or
prostaglandins. As with other similar agents, however, the exact mechanism of its other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been
anti-inflammatory action is not known. reported in such patients.
Pharmacokinetics: • In the setting of coronary artery bypass graft (CABG) surgery.
Absorption Warnings and Precautions:
Naproxen sodium is rapidly and completely absorbed from the gastrointestinal tract Cardiovascular Thrombotic Events
after oral administration. Naproxen sodium is more rapidly absorbed than naproxen. COX-2 selective and nonselective NSAIDs have an increased risk of serious
Concomitant administration of food can delay the absorption of naproxen sodium, cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke,
but does not affect its extent. After oral administration of Apranax Tablets, because which can be fatal. To minimize the potential risk for an adverse CV event in NSAID-
of rapid and complete absorption, clinically significant plasma levels and pain relief treated patients, use the lowest effective dose for the shortest duration possible.
are obtained in patients within 30 minutes of administration. Peak plasma levels are Physicians and patients should remain alert for the development of such events,
attained in 1-2 hours, depending on food intake. The difference in rates between the throughout the entire treatment course, even in the absence of previous CV symptoms.
two products is due to the increased aqueous solubility of the sodium salt of naproxen. Patients should be informed about the symptoms of serious CV events and the steps
Distribution to take if they occur.
Naproxen has a volume of distribution of 0.16 I/kg. At therapeutic levels naproxen The concurrent use of aspirin and an NSAID, such as naproxen, increases the risk
is greater than 99% albumin bound. At doses of naproxen greater than 500 mg/day, of serious gastrointestinal (GI) events
there is less than proportional increase in plasma levels due to an increase in Post-MI Patients
clearance caused by saturation of plasma protein binding at higher doses. However, Avoid the use of naproxen sodium tablets in patients with a recent MI unless the
the concentration of unbound naproxen continues to increase proportionally to dose. benefits are expected to outweigh the risk of recurrent CV thrombotic events including
Steady-state plasma levels of naproxen are reached after 3-4 days. signs of cardiac ischemia.
Naproxen enters synovial fluid, crosses the placenta and has been found in the milk Gastrointestinal ulceration, bleeding and perforation
of lactating mothers at a concentration approximately 1 % of that found in plasma. NSAIDs, including naproxen, cause serious gastrointestinal (GI) adverse events
Metabolism including inflammation, bleeding, ulceration, and perforation of the esophagus,
Naproxen is extensively metabolised in the liver to 6-0-desmethyl naproxen. stomach, small intestine, or large intestine, which can be fatal. These serious adverse
Elimination events can occur at any time, with or without warning symptoms, in patients treated
Approximately 95% of the naproxen from any dose is excreted in the urine, primarily with NSAIDs. serious upper GI adverse event on NSAID therapy is symptomatic.
as naproxen (less than 1%) 6-0-desmethyl naproxen (less than 1%), or their conjugates Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occurred in of
(66-92%). The rate of excretion of metabolites and conjugates has been found to patients treated for one year. However, even short-term NSAID therapy is not without
coincide closely with the rate of naproxen disappearance from the plasma. Small risk.
amounts, 3% or less, are excreted in the feces. Risk Factors for GI Bleeding, Ulceration, and Perforation
The clearance of naproxen is approximately 0.13 ml/min/kg. The elimination half-life Patients with a prior history of peptic ulcer disease and/or GI bleeding who used
of naproxen is approximately 14 hours and is independent of the chemical form or NSAIDs had a greater than 10-fold increased risk for developing a GI bleed compared
the formulation. to patients without these risk factors. Other factors that increase the risk of GI bleeding
Pharmacokinetics in special clinical situations in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant
Hepatic Impairment: use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake
Naproxen pharmacokinetics has not been determined in subjects with hepatic inhibitors (SSRIs); smoking; use of alcohol; older age and poor general health status.
insufficiency. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients.
Chronic alcoholic liver disease and probably other diseases with decreased or Additionally, patients with advanced liver disease and/or coagulopathy are at increased
abnormal plasma proteins (albumin) reduce the total plasma concentration of naproxen, risk for GI bleeding.
but the plasma concentration of unbound naproxen is increased. Strategies to Minimize the GI Risks in NSAID-treated patients:
Renal impairment • Use the lowest effective dosage for the shortest possible duration.
Given that naproxen and its metabolites are primarily excreted by the kidney, the • Avoid administration of more than one NSAID at a time.
potential exists for accumulation in the presence of renal insufficiency. Elimination • Avoid use in patients at higher risk unless benefits are expected to outweigh the
of naproxen is decreased in patients with severe renal impairment. In patients who increased risk of bleeding. For such patients, as well as those with active GI bleeding,
are severely renally impaired (creatinine clearance <10 ml/min), there is higher consider alternate therapies other than NSAIDs.
clearance of naproxen than estimated from the degree of renal impairment alone.
• Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID Dermatologic: alopecia, epidermal necrolysis, erythema multiforme, erythema nodosum,
therapy. fixed drug eruption, lichen planus, pustular reaction, skin rashes, SLE, Stevens-
• If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, Johnson syndrome, urticaria, photosensitivity reactions, including rare cases resembling
and discontinue naproxen sodium until a serious GI adverse event is ruled out. porphyria cutanea tarda ("pseudoporphyria") or epidermolysis bullosa. If skin fragility,
• In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor blistering or other symptoms suggestive of pseudoporphyria occur, treatment should
patients more closely for evidence of GI bleeding. be discontinued and the patient monitored.
Hematological Special senses: hearing impairment, corneal opacity, papillitis, retrobulbar optic neuritis
Naproxen decreases platelet aggregation and prolongs bleeding time. This effect and papilledema.
should be kept in mind when bleeding times are determined. Patients who have Cardiovascular: congestive heart failure, hypertension, pulmonary edema, vasculitis.
coagulation disorders or are receiving drug therapy that interferes with hemostasis Respiratory: asthma, eosinophilic pneumonitis.
should be carefully observed if naproxen-containing products are administered. General: anaphylactoid reactions, angioneurotic edema, pyrexia (chills and fever).
Patients at high risk of bleeding and those on full anticoagulation therapy (e.g. Interactions:
dicoumarol derivatives) may be at increased risk of bleeding if given naproxen- Concomitant administration of antacid or cholestyramine can delay the absorption
containing products concurrently. of naproxen, but does not affect its extent. Concomitant administration of food can
Anaphylactic (anaphylactoid) reactions delay the absorption of naproxen, but does not affect its extent. Naproxen is highly
Hypersensitivity reactions may occur in susceptible individuals. Anaphylactic bound to plasma albumin; it thus has a theoretical potential for interaction with other
(anaphylactoid) reactions may occur, both in patients with and without a history of albumin-bound drugs such as coumarin-type anticoagulants, sulphonylureas,
hypersensitivity or exposure to aspirin, other non-steroidal anti-inflammatory drugs hydantoins, other NSAIDs and aspirin. Patients simultaneously receiving the drug
or naproxen-containing products. They may also occur in individuals with a history and a hydantoin, sulphonamide or sulphonylurea should be observed for adjustment
of angioedema, bronchospastic reactivity (e.g. asthma), rhinitis and nasal polyps. of dose if required.
Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome. Bronchospasm No significant interactions have been observed in clinical studies with naproxen and
may be precipitated in patients suffering from, or with a history of, asthma or allergic coumarin type anticoagulants, however caution is advised since interactions have
disease or aspirin sensitivity. been seen with other nonsteroidal agents of this class, the free fraction of warfarin
Hepatic effects may increase substantially in some subjects and naproxen interferes with platelet
As with other non-steroidal anti-inflammatory drugs, elevations of one or more liver function.
function tests may occur. Hepatic abnormalities may be the result of hypersensitivity Caution is advised when probenecid is administered concurrently, since increases
rather than direct toxicity. Severe hepatic reactions, including jaundice and hepatitis in naproxen plasma concentrations and increased half-life of naproxen have been
(some cases of hepatitis have been fatal) have been reported with this drug as with reported with this combination.
other non-steroidal anti-inflammatory drugs. Cross reactivity has been reported. Caution is advised when methotrexate is administered concurrently, since naproxen
Antipyretic effects and other prostaglandin synthesis-inhibiting drugs have been reported to reduce the
The antipyretic and anti-inflammatory activities of naproxen may reduce fever and c learance of methotrexate, and thus possibly enhance its toxicity.
inflammation, thus diminishing their utility as diagnostic signs. Naproxen can reduce the anti-hypertensive effect of beta blockers.
Steroids As with other non-steroidal anti-inflammatory drugs, naproxen may inhibit the natriuretic
If steroid dosage is reduced or eliminated during therapy, the steroid dosage should effect of furosemide.
be reduced slowly and the patients must be observed closely for any evidence of Inhibition of renal lithium clearance leading to increases in plasma lithium concentrations
adverse effects, including adrenal insufficiency and exacerbation of symptoms of has been reported.
arthritis. It is suggested that Apranax therapy should be temporarily discontinued 72 hours
Ocular effects before adrenal function tests are performed if the Porter-Silber test is to be used
Studies have not shown changes in the eye attributable to naproxen administration. because naproxen may artefactually interfere with some tests for 17-ketogenic
In rare cases, adverse ocular disorders including papillitis, retrobulbar optic neuritis steroids. Similarly, Apranax therapy may interfere with some urinary assays of 5-
and papilledema, have been reported in users of NSAIDs including naproxen, although hydroxy indoleacetic acid (5HIAA).
a cause-and-effect relationship cannot be established; accordingly, patients who Naproxen decreases platelet aggregation and prolongs bleeding time. This effect
develop visual disturbances during treatment with naproxen-containing products should be kept in mind when bleeding times are determined.
should have an ophthalmological examination. Overdosage:
Sodium Significant naproxen overdosage may be characterised by dizziness, drowsiness,
A 275 mg tablet of Apranax contains approximately 25 mg (about 1 mEq) of sodium, epigastric pain, abdominal discomfort, indigestion, nausea, transient alterations in
so the total amount of sodium ingested with the maximum recommended daily dose liver function, hypoprothrom-binemia, renal dysfunction, metabolic acidosis, apnea,
is 125 mg, about 16% of the 800 mg of sodium permitted on a severely sodium- disorientation or vomiting. Because Apranax may be rapidly absorbed, high and early
restricted diet. This should be considered in patients whose overall intake of sodium blood levels should be anticipated. A few patients have experienced convulsions, but
should be markedly restricted. it is not clear whether or not these were naproxen related.
Edema Should a patient ingest a large amount of naproxen-containing products, accidentally
Peripheral edema has been observed in some patients. Although sodium retention or purposefully, the stomach should be emptied and the usual supportive measures
has not been reported in metabolic studies, it is possible that patients with questionable employed. Animal studies indicate that the prompt administration of 50-100 g of
or compromised cardiac function may be at a greater risk when taking naproxen. activated charcoal as an aqueous slurry over 15 minutes within 2 hours of the
Precautions related to elderly patients overdose would tend to reduce markedly the absorption of the drug. Hemodialysis
Elderly patients may be at a greater risk of experiencing undesirable effects than does not decrease the plasma concentration of naproxen because of the high degree
younger patients. In elderly patients the clearance is reduced. Use of the lower end of its protein binding.
of the dosage range is recommended (see Dosage and administration).
Combination with other NSAIDs Stability:
The combination of naproxen-containing products and other NSAIDs is not See expiry on the pack
recommended, because of the cumulative risks of inducing serious NSAID-related
adverse events. Packs:
Pregnancy, nursing mothers: Apranax is supplied in the following dosage forms, strengths and pack sizes:
Pregnancy Tablets (scored) 550mg 20's
As with other drugs of this type, naproxen produces delay in parturition in animals
and also affects the human fetal cardiovascular system (closure of ductus arteriosus). INSTRUCTIONS:
Therefore, Apranax should not be used during pregnancy unless clearly needed. Keep all medicines out of the reach of children.
Labour and deliver Protect from light, heat and moisture. Store below 30oC.
Naproxen-containing products are not recommended in labour and delivery because,
through its prostaglandin synthesis inhibitory effect, naproxen may adversely affect To be sold on prescription of a registered
fetal circulation and inhibit uterine contractions, thus increasing the risk of uterine medical practitioner only.
hemorrhage.
Nursing mothers
The naproxen anion has been found in the milk of lactating women at a concentration
of approximately 1% of that found in plasma. Because of the possible adverse effects
of prostaglandin-inhibiting drugs on neonates, use in nursing mothers is not
recommended.
Undesirable effects:
The following are the adverse events observed most frequently in association with
Apranax: Gastrointestinal: abdominal pain, constipation, diarrhea, dyspepsia, heartburn,
nausea, stomatitis. Central nervous system: dizziness, drowsiness, headache,
lightheadedness, vertigo.
Dermatologic: ecchymoses, itching (pruritus), purpura, skin eruptions, sweating.
Special senses: hearing disturbances, tinnitus, visual disturbances.
Cardiovascular: dyspnea, edema and palpitations.
General: thirst.
The following adverse events have also been reported:
Gastrointestinal: abnormal liver function tests, colitis, esophagitis, gastrointestinal
bleeding and/or perforation, hematemesis, hepatitis (some cases of hepatitis have
been fatal), jaundice, melena, nonpeptic gastrointestinal ulceration, pancreatitis,
peptic ulceration, ulcerative stomatitis, vomiting. Renal: hematuria, hyperkalemia,
interstitial nephritis, nephrotic syndrome, renal disease, renal failure, renal papillary
necrosis, raised serum creatinine.
Hematological: agranulocytosis, aplastic anemia, eosinophilia, hemolytic anemia,
leukopenia thrombocytopenia.
Central nervous system: aseptic meningitis, cognitive dysfunction, convulsions,
depression, dream abnormalities, inability to concentrate, insomnia, malaise, myalgia,
muscle weakness.