Naproxen – Uses and Precautions

Background

Naproxen is classified as a nonsteroidal anti-inflammatory drug (NSAID) and was initially approved for prescription use in 1976 and then for over-the-counter (OTC) use in 1994. It can effectively manage acute pain as well as pain related to rheumatic diseases, and has a well-studied adverse effect profile. Given its overall tolerability and effectiveness, naproxen can be considered a first line treatment for a variety of clinical situations requiring analgesia. Naproxen is available in both immediate and delayed release formulations, in combination with sumatriptan to treat migraines, and in combination with esomeprazole to lower the risk of developing gastric ulcers.

Properties and Characteristics of Naproxen

Drug class	Nonsteroidal anti-inflammatory drugs
Brand Names	Aleve, EC-Naprosyn, Flanax Pain Reliever, Midol Extended Relief, Naprelan, Naprosyn, Anaprox, Anaprox-DS, Naproxen Sodium, Aleve Caplet, Aleve Gelcap, Aleve Easy Open Arthritis
Synonyms	(S)-Naproxen, Naprolag, Naproxen, Naproxène, Naproxeno, Naproxenum
Molecular Formula	C14H14O3
Molecular Weight	230.26 g/mol
IUPAC Name	(2S)-2-(6-methoxynaphthalen-2-yl)propanoic acid
Structural formula of main components
Pure active ingredient	Naproxen
Appearance	White to off-white crystalline powder
Melting point	152°C
Solubility	15.9mg/L (at 25 °C)
Excretion	Naproxen is excreted in the feces
Storage	Tablets should be stored in well-closed containers at 15 – 30 °C
Available Forms	Tablet and Gel
Prescription	Doctor prescription is required

 Uses

People use naproxen for the following conditions:

• Rheumatoid arthritis
• Osteoarthritis
• Ankylosing spondylitis
• Juvenile arthritis
• Tendonitis
• Bursitis
• Gout attacks
• Muscle aches, strains, and sprains
• Headaches
• Dental pain
• Menstrual cramps
• Fever

Naproxen side effects

Get emergency medical help if you have signs of an allergic reaction to naproxen (runny or stuffy nose, wheezing or trouble breathing, hives, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Stop using naproxen and seek medical treatment if you have a serious drug reaction that can affect many parts of your body. Symptoms may include skin rash, fever, swollen glands, muscle aches, severe weakness, unusual bruising, or yellowing of your skin or eyes.

Get emergency medical help if you have signs of a heart attack or stroke: chest pain spreading to your jaw or shoulder, sudden numbness or weakness on one side of the body, slurred speech, feeling short of breath.

Stop using naproxen and call your doctor at once if you have:

• Shortness of breath (even with mild exertion);
• Swelling or rapid weight gain;
• The first sign of any skin rash, no matter how mild;
• Signs of stomach bleeding – bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;
• Liver problems – nausea, upper stomach pain, itching, tired feeling, flu-like symptoms, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
• Kidney problems – little or no urinating, painful or difficult urination, swelling in your feet or ankles, feeling tired or short of breath;
• Low red blood cells (anemia) – pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or
• Severe skin reaction – fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common naproxen side effects may include:

• Indigestion, heartburn, stomach pain, nausea;
• Headache, dizziness, drowsiness;
• Bruising, itching, rash;
• Swelling; or
• Ringing in your ears.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

Mechanism of action

As with other non-selective NSAIDs, naproxen exerts its clinical effects by blocking COX-1 and COX-2 enzymes leading to decreased prostaglandin synthesis. Although both enzymes contribute to prostaglandin production, they have unique functional differences. The COX-1 enzymes are constitutively active and can be found in normal tissues such as the stomach lining, while the COX-2 enzyme is inducible and produces prostaglandins that mediate pain, fever and inflammation. The COX-2 enzyme mediates the desired antipyretic, analgesic and anti-inflammatory properties offered by Naproxen, while undesired adverse effects such as gastrointestinal upset and renal toxicities are linked to the COX-1 enzyme.

Naproxen may interact with other medications

Prescription naproxen oral tablets can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk with your doctor or pharmacist.

Examples of drugs that can cause interactions with naproxen are listed below.

Antidepressant drugs

Combining selective serotonin reuptake inhibitors (SSRIs) with naproxen increases your risk of stomach and intestinal bleeding. Examples of these drugs include:

• Citalopram (Celexa)
• Fluoxetine (Prozac)
• Fluvoxamine (Luvox)
• Paroxetine (Brisdelle, Paxil)

Blood pressure drugs

Naproxen might make your blood pressure medications less effective. If you’re older than 65 years, combining naproxen with certain blood pressure medications may damage your kidneys. Examples of these medications include:

• Angiotensin-converting enzyme (ACE) inhibitors, such as lisinopril (Zestril)
• Angiotensin II receptor blockers, such as valsartan (Diovan) and losartan (Cozaar)
• Beta-blockers, such as propranolol (Inderal LA) and metoprolol tartrate (Lopressor)
• Diuretics, such as hydrochlorothiazide and furosemide (Lasix)

Heartburn drugs and drugs that protect the stomach

Taking any of these medications with naproxen may make naproxen treat your pain more slowly:

• Aluminum hydroxide
• Magnesium oxide
• Sucralfate (Carafate)

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Combining naproxen with other NSAIDs increases your risk of stomach and intestinal bleeding. Examples of these medications include:

• Aspirin (Bayer, Bufferin)
• Ibuprofen (Advil, Motrin)
• Etodolac
• Diclofenac (Cambia)
• Flurbiprofen
• Ketoprofen
• Ketorolac

Cholestyramine: If you take cholestyramine (Prevalite) with naproxen, your body may absorb naproxen more slowly than usual. That means it may take longer to work.

Lithium: If you take naproxen with lithium (Lithobid), it may increase the lithium in your body to harmful levels.

Methotrexate: Taking methotrexate (Trexall) with naproxen can lead to harmful levels of methotrexate in your body.

Warfarin: Taking warfarin (Jantoven) with naproxen increases your risk of stomach and intestinal bleeding.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For naproxen (eg, Naprosyn®) tablet and oral suspension dosage forms

For rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis:

• Adults—At first, 250 milligrams (mg) (10 milliliters (mL)/2 teaspoonfuls), 375 mg (15 mL/3 teaspoonfuls), or 500 mg (20 mL/4 teaspoonfuls) 2 times a day, in the morning and evening. Your doctor may adjust your dose as needed. However, the dose is usually not more than 1500 mg per day.
• Children 2 years of age and older—Dose is based on body weight and must be determined by your doctor. The dose is usually 5 milligrams (mg) per kilogram (kg) of body weight 2 times a day.
• Children younger than 2 years of age—Use and dose must be determined by your doctor.

For acute gout:

• Adults—750 milligrams (mg) for the first dose, then 250 mg every 8 hours until the attack is relieved.
• Children—Use and dose must be determined by your doctor.

For naproxen controlled-release tablet (eg, Naprelan®) dosage form

For rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis:

• Adults—At first, 750 milligrams (mg) (taken as one 750 mg or two 375 mg tablets) or 1000 mg (taken as two 500 mg tablets) once a day. Your doctor may adjust your dose as needed. However the dose is usually not more than 1500 mg (taken as two 750 mg or three 500 mg tablets) per day.
• Children—Use and dose must be determined by your doctor.

For bursitis, tendinitis, menstrual cramps, and other kinds of pain:

• Adults—At first, 1000 milligrams (mg) (taken as two 500 mg tablets) once a day. Some patients may need 1500 mg (taken as two 750 mg or three 500 mg tablets) per day, for a limited period. However, the dose is usually not more than 1000 mg per day.
• Children—Use and dose must be determined by your doctor.

For acute gout:

• Adults—1000 to 1500 milligrams (mg) (taken as two to three 500 mg tablets) once a day for the first dose, then 1000 mg (taken as two 500 mg tablets) once a day until the attack is relieved.
• Children—Use and dose must be determined by your doctor.

For naproxen delayed-release tablet (eg, EC-Naprosyn®) dosage form

For rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis:

• Adults—At first, 375 or 500 milligrams (mg) 2 times a day, in the morning and evening. Your doctor may adjust the dose as needed. However, the dose is usually not more than 1500 mg per day.
• Children—Use and dose must be determined by your doctor.

For naproxen sodium (eg, Anaprox®, Anaprox® DS) tablet dosage form

For rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis:

• Adults—At first, 275 or 550 milligrams (mg) 2 times a day, in the morning and evening. Your doctor may adjust the dose as needed. However, the dose is usually not more than 1500 mg per day.
• Children—Use and dose must be determined by your doctor.

For bursitis, tendinitis, menstrual cramps, and other kinds of pain:

• Adults—550 milligrams (mg) for the first dose, then 550 mg every 12 hours or 275 mg every 6 to 8 hours as needed. Your doctor may adjust the dose as needed. However, the dose is usually not more than 1375 mg per day.
• Children—Use and dose must be determined by your doctor.

For acute gout:

• Adults—825 milligrams (mg) for the first dose, then 275 mg every 8 hours until the attack is relieved.
• Children—Use and dose must be determined by your doctor.

In case of emergency/overdose

In case of overdose, call your nearby poison control helpline. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call emergency services.

Symptoms of overdose may include the following:

• Extreme tiredness
• Drowsiness
• Stomach pain
• Heartburn
• Nausea
• Vomiting
• Slow or difficult breathing

Warnings and what to consider before taking naproxen

If a person has a history of an allergy or intolerance to any NSAID, they should not take naproxen. Cross-allergies and intolerances may occur between NSAIDs.

Aspirin-induced asthma: One type of intolerance to NSAIDs is aspirin-induced asthma. Asthma symptoms and severe allergic reactions may occur when affected individuals take aspirin. These people should avoid naproxen and all other NSAIDs because of the risk of developing severe side effects.

Drug interactions: People should not combine certain antidepressants, high blood pressure, and blood thinners with naproxen.

Medical conditions: Certain diagnoses may increase the likelihood of experiencing side effects, such as heart disease, ulcers, and kidney disease.

Age: Children under 12 years old should avoid using naproxen unless a doctor prescribes the medication.

Pregnancy, breastfeeding and fertility while taking naproxen

Naproxen and pregnancy

Naproxen is not usually recommended in pregnancy. This is because it may affect your baby, in particular causing problems with their circulation and amniotic fluid levels.

Your doctor will only advise you to take naproxen while you’re pregnant if the benefits of taking the medicine clearly outweigh the risks.

There may be other treatments that are safer for you. Paracetamol is generally the best painkiller to take during pregnancy.

Naproxen and breastfeeding

Naproxen is not usually recommended while you are breastfeeding. Other anti-inflammatory medicines, such as ibuprofen, are safer. But if other painkillers are not suitable, your doctor may tell you to take naproxen.

It is better to only take naproxen for a short time if possible.

Naproxen passes into breast milk in small amounts and is unlikely to harm your baby. But there have been 1 or 2 reports of side effects in babies after having naproxen through breast milk. These have included some effects on the babies’ blood, drowsiness and being sick.

If you notice that your baby is not feeding as well as usual, seems drowsy, or has an upset stomach, or if you have any other concerns about your baby, talk to your health visitor, midwife, pharmacist or doctor as soon as possible.

Naproxen and fertility

Taking anti-inflammatory medicines, like naproxen, in large doses or for a long time can affect ovulation, so it may make it more difficult to get pregnant.

Do not take naproxen if you’re trying to get pregnant or you’re having tests for infertility. Paracetamol is a better painkiller.

There’s no clear evidence to suggest that taking naproxen reduces fertility in men.