Naproxen (Naprosyn)

1. Health Canada Product Monograph — Naproxen

• Naprosyn is used to treat the signs and symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis.
• Naprosyn relieves minor aches and pains in muscles, bones, and joints, including mild to moderate pain from sprains, strains, and other musculoskeletal injuries, as well as menstrual cramps (primary dysmenorrhea).
• As an NSAID, Naprosyn only relieves symptoms and reduces inflammation for as long as it is taken; it does not treat or slow the underlying disease.

Contraindicated in pregnancy. Confirm pregnancy status and discuss alternative therapy with the prescriber before dispensing.

• Naprosyn is contraindicated during the third trimester of pregnancy because of the risk of premature closure of a blood vessel in the baby's heart (the ductus arteriosus) and prolonged labour.
• Caution is needed if Naprosyn is used during the first and second trimesters, since NSAID use from around 20 weeks of pregnancy onward may reduce the baby's amniotic fluid and cause kidney problems in the newborn.
• Early pregnancy use of NSAIDs like naproxen has been linked in some studies to a higher risk of miscarriage and heart-related birth defects.
• Naprosyn is not recommended during labour and delivery, since it may affect the baby's circulation and slow uterine contractions, increasing the risk of bleeding.

• Naprosyn is contraindicated in breastfeeding women because of the potential for serious side effects in the nursing infant.

• Older adults are more likely to experience serious side effects from NSAIDs, including stomach bleeding, and are less able to tolerate ulcers and bleeding when they occur.
• A lower starting dose should be considered in frail or elderly patients, with adjustments made carefully and under close supervision.

• Naprosyn is contraindicated in children and adolescents under 18 years of age, since the enteric-coated and sustained-release tablets have not been studied in this age group.

• For osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis: the enteric-coated tablet is usually taken at 500 mg twice daily (250 mg or 375 mg strengths may also be used), the immediate-release tablet at 250 mg twice daily initially (may be increased to 375 mg or 500 mg twice daily based on response), or the sustained-release tablet at 750 mg once daily.
• For analgesia and acute musculoskeletal injuries (immediate-release tablets only): usual dose is 250 mg three times daily, or 375 mg twice daily, increasing to 500 mg twice daily if needed; use the lowest effective dose. Enteric-coated and sustained-release tablets are not recommended for initial treatment of acute pain because their absorption is delayed.
• For menstrual pain (dysmenorrhea, immediate-release tablets only): a starting dose of 500 mg (or two 250 mg tablets), followed by 250 mg every 6 to 8 hours as needed, to a maximum of 1250 mg per day; alternatively, 500 mg twice daily.
• Studies have not shown any added benefit from doses above 1000 mg per day, though some patients who only partially respond may be increased to 1500 mg per day for a limited time under close monitoring; this higher short-term dose has specifically been used with the standard immediate-release tablets.
• Naprosyn should be used at the lowest effective dose for the shortest duration needed to control symptoms.
• A lower dose should be considered for patients with mild-to-moderate kidney or liver impairment; Naprosyn is contraindicated in severe kidney or liver impairment.
• Take immediate-release tablets with food or milk. Sustained-release and enteric-coated tablets should be swallowed whole with food or milk, never crushed or chewed.
• If a dose is missed, it should be taken as soon as remembered unless it is almost time for the next dose, in which case the missed dose should be skipped; two doses should never be taken together.
• For self-selected, non-prescription use (naproxen sodium 220 mg tablets/caplets, e.g. Aleve): adults and adolescents 12-64 years take 1 tablet every 8 to 12 hours; those over 65 years take 1 tablet every 12 hours; do not take more than 2 tablets in any 24-hour period. Limit self-treatment to a maximum of 5 days for pain or 3 days for fever unless directed by a doctor; not established for use in children under 12 years.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• Overdose symptoms may include drowsiness, dizziness, disorientation, heartburn, indigestion, stomach pain, nausea, and vomiting.
• Overdose can also cause abnormal liver function, low blood clotting protein levels, kidney dysfunction, metabolic acidosis, and slowed breathing.
• Some patients have experienced seizures after overdose, though it is unclear if these were directly caused by naproxen.
• Gastrointestinal bleeding can occur after an overdose.
• There is no specific antidote; treatment is symptomatic and supportive.
• Activated charcoal may help reduce absorption if given within 4 hours of a large overdose; dialysis is not expected to be useful because naproxen is highly protein-bound.

• Stomach upset, including indigestion and stomach pain, may occur.
• Constipation may occur.
• Nausea may occur.
• Headache may occur.
• Dizziness or drowsiness may occur.
• Ringing in the ears (tinnitus) may occur.
• Skin itching, bruising, or rash may occur.
• Fluid retention or swelling (edema) may occur.
• Shortness of breath or palpitations may occur.
• Sweating may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Naproxen can increase the risk of serious cardiovascular events such as heart attack or stroke, which can be fatal; this risk may increase with longer use.
• Naproxen can cause serious stomach and intestinal problems, including ulcers, bleeding, and perforation, which can happen without warning and can be fatal, particularly in the elderly.
• Serious, sometimes fatal, skin reactions can occur, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS); these tend to appear within the first month of treatment.
• Kidney problems, including acute kidney failure, can occur, especially in dehydrated patients or those with existing kidney disease.
• Serious liver reactions, including jaundice, hepatitis, and liver failure, have been reported rarely.
• Blood disorders such as low white blood cell counts, low platelet counts, or aplastic anemia can occur rarely but may be severe.
• Aseptic meningitis, with symptoms of stiff neck, severe headache, and fever, has been reported rarely, particularly in patients with autoimmune conditions.
• Severe allergic (anaphylactoid) reactions can occur, even in patients with no prior exposure to naproxen.
• Naproxen can worsen or trigger asthma attacks in patients sensitive to ASA or other NSAIDs.
• New or worsening high blood pressure, or worsening heart failure, can occur.
• Seek urgent medical attention for chest pain, sudden weakness on one side of the body, black or bloody stools, vomiting blood, severe stomach pain, or a severe skin rash with blistering or peeling.

• Use with caution in patients with a history of stomach ulcers or gastrointestinal bleeding, who are at much higher risk of another GI bleed.
• Use with caution in patients with heart disease, high blood pressure, high cholesterol, diabetes, or other cardiovascular risk factors.
• Use with caution in patients with reduced kidney function, dehydration, or those taking diuretics, ACE inhibitors, or angiotensin receptor blockers, since NSAIDs can further reduce kidney blood flow.
• Use with caution in patients taking blood thinners such as warfarin or antiplatelet drugs, since the combination increases bleeding risk.
• Use with caution in frail, elderly, or debilitated patients, who tolerate side effects less well.
• Use with caution in patients with liver disease or a history of alcohol-related liver problems.
• Use with caution in patients with asthma, nasal polyps, or a history of allergic-type reactions to ASA or other NSAIDs.
• Use with caution in patients with a bleeding disorder or platelet problem, such as hemophilia.

• Contraindicated in patients hypersensitive to naproxen or any ingredient in the formulation.
• Contraindicated in patients with a history of asthma, hives, or allergic-type reactions after taking ASA or other NSAIDs.
• Contraindicated in the perioperative period of coronary artery bypass graft (CABG) surgery.
• Contraindicated in patients with active stomach or intestinal ulcers, or active gastrointestinal bleeding.
• Contraindicated in patients with bleeding disorders or a history of bleeding in the brain.
• Contraindicated in patients with inflammatory bowel disease.
• Contraindicated in patients with severe liver impairment or active liver disease.
• Contraindicated in patients with severe kidney impairment or worsening kidney disease.
• Contraindicated in patients with known high potassium levels (hyperkalemia).
• Contraindicated in patients with severe, uncontrolled heart failure.
• Contraindicated during the third trimester of pregnancy and in breastfeeding women.
• Contraindicated in children and adolescents under 18 years of age.

• Combining naproxen with other NSAIDs, including ASA, does not improve pain relief but increases the risk of stomach bleeding.
• Naproxen can reduce the antihypertensive effect of ACE inhibitors, angiotensin receptor blockers, and beta-blockers, and combining them can raise the risk of kidney problems, especially in the elderly or dehydrated.
• Naproxen combined with anticoagulants such as warfarin increases the risk of serious bleeding and requires close INR monitoring.
• Naproxen combined with antiplatelet drugs increases the risk of bleeding through added effects on platelet function.
• Antacids containing magnesium oxide or aluminum hydroxide, and sucralfate, can delay naproxen absorption and are not recommended together.
• Naproxen combined with cyclosporine or tacrolimus may increase the risk of kidney toxicity.
• Cholestyramine can delay naproxen absorption if taken together.
• Naproxen combined with digoxin can raise digoxin blood levels and prolong its half-life, requiring monitoring for digoxin toxicity.
• Naproxen can reduce the effectiveness of diuretics.
• Combining naproxen with oral corticosteroids increases the risk of stomach ulcers and bleeding, especially in older patients.
• Naproxen can raise lithium blood levels and reduce its clearance, requiring monitoring of lithium levels.
• Combining naproxen with methotrexate may increase the risk of methotrexate toxicity.
• Naproxen combined with SSRIs increases the risk of bleeding.
• Naproxen combined with quinolone antibiotics has rarely been linked to seizures.
• Naproxen is highly bound to blood proteins and can theoretically interact with other protein-bound drugs, such as warfarin, sulfa drugs, and other NSAIDs.

• Naprosyn enteric-coated and sustained-release tablets should be taken with food or milk, which helps protect the stomach; taking food with the tablets delays but does not reduce the total amount of naproxen absorbed.

• Naprosyn tablets should be taken with food or milk at each dose, and swallowed whole rather than crushed or chewed, to help minimize stomach upset.

• Store Naprosyn tablets at room temperature (15°C to 30°C) and keep out of the reach of children.

• Take Naprosyn with food or milk to help protect your stomach.
• Use the lowest dose that controls your symptoms for the shortest time needed.
• Watch for signs of stomach bleeding, such as black stools or vomiting blood, and seek care right away if these occur.
• Tell your doctor about all medicines you take, especially blood thinners, other pain relievers, and blood pressure medicines.
• Naprosyn should not be used in the third trimester of pregnancy or while breastfeeding.