Naproxen Prescribing Information
WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS
- Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. ()
5.1 Cardiovascular Thrombotic EventsClinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.
To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as naproxen, increases the risk of serious gastrointestinal (GI) events [
see Warnings and Precautions]Status Post Coronary Artery Bypass Graft (CABG) Surgery
Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10–14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG [see Contraindications]Post-MI Patients
Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up.Avoid the use of Naproxen Suspension in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If Naproxen Suspension is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.
- Naproxen Suspension is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. (,
4 CONTRAINDICATIONSNaproxen Suspension is contraindicated in the following patients:
- Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen or any components of the drug product [see Warnings and Precautions]
- History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see Warnings and Precautions]
- In the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions]
- Known hypersensitivity to naproxen or any components of the drug product
- History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs
- In the setting of CABG surgery
)5.1 Cardiovascular Thrombotic EventsClinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.
To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as naproxen, increases the risk of serious gastrointestinal (GI) events [
see Warnings and Precautions]Status Post Coronary Artery Bypass Graft (CABG) Surgery
Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10–14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG [see Contraindications]Post-MI Patients
Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up.Avoid the use of Naproxen Suspension in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If Naproxen Suspension is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.
- Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen or any components of the drug product [
- NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events. ()
5.2 Gastrointestinal Bleeding, Ulceration, and PerforationNSAIDs, including naproxen, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDS.
Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occurred in approximately 1% of patients treated for 3-6 months, and in about 2%-4% of patients treated for one year. However, even short-term NSAID therapy is not without risk.
Risk Factors for GI Bleeding, Ulceration, and Perforation
Patients with a prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients. Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding.Strategies to Minimize the GI Risks in NSAID-treated patients:- Use the lowest effective dosage for the shortest possible duration.
- Avoid administration of more than one NSAID at a time.
- Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. For such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs.
- Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy.
- If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue Naproxen Suspension until a serious GI adverse event is ruled out.
- In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding [see Drug Interactions]
Naproxen Suspension is indicated for:
the relief of the signs and symptoms of:
- rheumatoid arthritis
- osteoarthritis
- ankylosing spondylitis
- polyarticular juvenile idiopathic arthritis
- tendonitis
- bursitis
- acute gout
the management of:
- pain
- primary dysmenorrhea
Use the lowest effective dose for shortest duration consistent with individual patient treatment goals. (
Use the lowest effective dose for shortest duration consistent with individual patient treatment goals.
| Naproxen Suspension | 250 mg (10 mL) or 375 mg (15 mL) or 500 mg (20 mL) | twice daily twice daily twice daily |
The dose may be adjusted up or down depending on the clinical response of the patient. In patients who tolerate lower doses well, the dose may be increased to naproxen 1500 mg/day for up to 6 months.
Recommended total daily dose of naproxen is approximately 10 mg/kg given in 2 divided doses.
The following table may be used as a guide for dosing of naproxen suspension:
Patient’s Weight | Dose | Administered as |
| 13 kg (29 lb) | 62.5 mg twice daily | 2.5 mL (1/2 tsp) twice daily |
| 25 kg (55 lb) | 125 mg twice daily | 5.0 mL (1 tsp) twice daily |
| 38 kg (84 lb) | 187.5 mg twice daily | 7.5 mL (1 1/2 tsp) twice daily |
The recommended starting dose of Naproxen Suspension is 500 mg (20 mL), followed by 250 mg (10 mL) every 6 to 8 hours as required.
The recommended starting dose is 750 mg (30 mL) of Naproxen Suspension followed by 250 mg (10 mL) every 8 hours until the attack has subsided.
Carefully consider the potential benefits and risks of Naproxen Suspension and other treatment options before deciding to use Naproxen Suspension. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals [
After observing the response to initial therapy with Naproxen Suspension, the dose and frequency should be adjusted to suit an individual patient’s needs.
Always use a calibrated measuring device when administering Naproxen Suspension to ensure the dose is measured and administered accurately. A household teaspoon or tablespoon is not an adequate measuring device, especially when one-half of a teaspoonful is to be measured. Given the variability of the household spoon measure, it is strongly recommended that caregivers obtain and use a calibrated measuring device. Health care providers should recommend an appropriate measuring device that can measure and deliver the prescribed dose accurately, and instruct caregivers to use extreme caution in measuring the dosage.
Naproxen-containing products such as Naproxen Suspension, and other naproxen products should not be used concomitantly since they all circulate in the plasma as the naproxen anion.
The recommended dosage of Naproxen Suspension is shown in Table 1.
| Naproxen Suspension | 250 mg (10 mL) or 375 mg (15 mL) or 500 mg (20 mL) | twice daily twice daily twice daily |
Naproxen Suspension should be shaken gently before use.
During long-term administration, the dose of naproxen may be adjusted up or down depending on the clinical response of the patient. A lower daily dose may suffice for long-term administration. The morning and evening doses do not have to be equal in size and the administration of the drug more frequently than twice daily is not necessary.
The morning and evening doses do not have to be equal in size and administration of the drug more frequently than twice daily does not generally make a difference in response.
In patients who tolerate lower doses well, the dose may be increased to naproxen 1500 mg/day for limited periods of up to 6 months when a higher level of anti-inflammatory/analgesic activity is required. When treating such patients with naproxen 1500 mg/day, the physician should observe sufficient increased clinical benefits to offset the potential increased risk.
The use of Naproxen Suspension is recommended for juvenile arthritis in children 2 years or older because it allows for more flexible dose titration based on the child’s weight. In pediatric patients, doses of 5 mg/kg/day produced plasma levels of naproxen similar to those seen in adults taking 500 mg of naproxen [
The recommended total daily dose of naproxen is approximately 10 mg/kg given in 2 divided doses (i.e., 5 mg/kg given twice a day). A measuring cup marked in 1/2 teaspoon and 2.5 milliliter increments is provided with the Naproxen Suspension. The following table may be used as a guide for dosing of Naproxen Suspension:
Patient’s Weight | Dose | Administered as |
| 13 kg (29 lb) | 62.5 mg twice daily | 2.5 mL (1/2 tsp) twice daily |
| 25 kg (55 lb) | 125 mg twice daily | 5.0 mL (1 tsp) twice daily |
| 38 kg (84 lb) | 187.5 mg twice daily | 7.5 mL (1 1/2 tsp) twice daily |
The recommended starting dose of Naproxen Suspension is 500 mg (20 mL), followed by 250 mg (10 mL) every 6 to 8 hours as required. The total daily dose should not exceed 1250 mg (50 mL).
The recommended starting dose is 750 mg (30 mL) of Naproxen Suspension followed by 250 mg (10 mL) every 8 hours until the attack has subsided.
Different dose strengths and formulations (e.g., tablets, suspension) of naproxen are not interchangeable. This difference should be taken into consideration when changing strengths or formulations.
| Naproxen Suspension | 250 mg (10 mL) or 375 mg (15 mL) or 500 mg (20 mL) | twice daily twice daily twice daily |
The dose may be adjusted up or down depending on the clinical response of the patient. In patients who tolerate lower doses well, the dose may be increased to naproxen 1500 mg/day for up to 6 months.
Recommended total daily dose of naproxen is approximately 10 mg/kg given in 2 divided doses.
The following table may be used as a guide for dosing of naproxen suspension:
Patient’s Weight | Dose | Administered as |
| 13 kg (29 lb) | 62.5 mg twice daily | 2.5 mL (1/2 tsp) twice daily |
| 25 kg (55 lb) | 125 mg twice daily | 5.0 mL (1 tsp) twice daily |
| 38 kg (84 lb) | 187.5 mg twice daily | 7.5 mL (1 1/2 tsp) twice daily |
The recommended starting dose of Naproxen Suspension is 500 mg (20 mL), followed by 250 mg (10 mL) every 6 to 8 hours as required.
The recommended starting dose is 750 mg (30 mL) of Naproxen Suspension followed by 250 mg (10 mL) every 8 hours until the attack has subsided.
Naproxen Suspension: 125 mg/5 mL (contains 39 mg sodium): Available in 1 pint (473 mL) light-resistant bottles
Naproxen may cause premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Naproxen Suspension, in pregnant women starting at 30 weeks of gestation (third trimester) [
Use of NSAIDs, including Naproxen Suspension, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Naproxen Suspension, in pregnant women starting at 30 weeks of gestation (third trimester).
There are no adequate and well-controlled studies of Naproxen Suspension in pregnant women.
Data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In the general U.S. population, all clinically recognized pregnancies, regardless of drug exposure, have a background rate of 2-4% for major malformations, and 15-20% for pregnancy loss. In animal reproduction studies in rats, rabbits, and mice no evidence of teratogenicity or fetal harm when naproxen was administered during the period of organogenesis at doses 0.13, 0.26, and 0.6 times the maximum recommended human daily dose of 1500 mg/day, respectively. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as naproxen, resulted in increased pre- and post-implantation loss.
There are no studies on the effects of Naproxen Suspension during labor or delivery. In animal studies, NSAIDS, including naproxen, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth.
There is some evidence to suggest that when inhibitors of prostaglandin synthesis are used to delay preterm labor there is an increased risk of neonatal complications such as necrotizing enterocolitis, patent ductus arteriosus and intracranial hemorrhage. Naproxen treatment given in late pregnancy to delay parturition has been associated with persistent pulmonary hypertension, renal dysfunction and abnormal prostaglandin E levels in preterm infants. Because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly starting at 30 weeks of gestation, or third trimester) should be avoided.
Reproduction studies have been performed in rats at 20 mg/kg/day (0.13 times the maximum recommended human daily dose of 1500 mg/day based on body surface area comparison), rabbits at 20 mg/kg/day (0.26 times the maximum recommended human daily dose, based on body surface area comparison), and mice at 170 mg/kg/day (0.6 times the maximum recommended human daily dose based on body surface area comparison) with no evidence of impaired fertility or harm to the fetus due to the drug. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as naproxen, resulted in increased pre- and post-implantation loss.
Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including Naproxen Suspension, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation.
Consider withdrawal of NSAIDs, including Naproxen Suspension, in women who have difficulties conceiving or who are undergoing investigation of infertility.
Naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance <30 mL/min) [
Naproxen Suspension is contraindicated in the following patients:
- Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen or any components of the drug product [see Warnings and Precautions (],
5.7 Anaphylactic ReactionsNaproxen has been associated with anaphylactic reactions in patients with and without known hypersensitivity to naproxen and in patients with aspirin-sensitive asthma [
see Contraindications and Warnings and Precautions]Seek emergency help if an anaphylactic reaction occurs.
)5.9 Serious Skin ReactionsNSAIDs, including naproxen can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions, and to discontinue the use of Naproxen Suspension at the first appearance of skin rash or any other sign of hypersensitivity. Naproxen Suspension is contraindicated in patients with previous serious skin reactions to NSAIDs [
see Contraindications]. - History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see Warnings and Precautions (],
5.7 Anaphylactic ReactionsNaproxen has been associated with anaphylactic reactions in patients with and without known hypersensitivity to naproxen and in patients with aspirin-sensitive asthma [
see Contraindications and Warnings and Precautions]Seek emergency help if an anaphylactic reaction occurs.
)5.8 Exacerbation of Asthma Related to Aspirin SensitivityA subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, Naproxen Suspension is contraindicated in patients with this form of aspirin sensitivity [
see Contraindications].When Naproxen Suspension is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma. - In the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (])
5.1 Cardiovascular Thrombotic EventsClinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.
To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as naproxen, increases the risk of serious gastrointestinal (GI) events [
see Warnings and Precautions]Status Post Coronary Artery Bypass Graft (CABG) Surgery
Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10–14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG [see Contraindications]Post-MI Patients
Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up.Avoid the use of Naproxen Suspension in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If Naproxen Suspension is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.