Ibuprofen

Ibuprofen is known to interact with many different drugs.

It's always important to share with your doctor and pharmacist all prescription, non-prescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking..

In general, it is not a good idea to take ibuprofen if you are taking aspirin as a blood thinner to protect your heart.

This is because ibuprofen can block the blood-thinning effects of aspirin. Your options are either to avoid taking ibuprofen or to take ibuprofen one hour before taking aspirin or eight hours after having taken aspirin.

If you are taking any of the following drugs, talk to your doctor about prescribing an alternative to ibuprofen:

• Eliquis (apixaban)
• Aspirin (both pill and suppository forms)
• Alka-Seltzer (aspirin/citric acid/sodium bicarbonate)
• Stirbild (elvitegravir/cobicistat/emtricitabine/tenofovir)
• The cancer medications called disease modifying anti-rheumatic drugs (DMARDs) Trexall (methotrexate) or Alimta (Pemetrexed)

Serious Drug Interactions

Ibuprofen interacts with hundreds of drugs, including:

• Blood thinners like Arixtra (fondaparinux), Pradaxa (dabigatran), and Jantoven, Coumadin (warfarin)
• Heparin
• Antidepressants including Celexa (citalopram), Paxil (paroxetine), and Lexapro (escitalopram)
• Water pills (diuretics) like Esidrix, Microzide (hydrochlorothiazide), Thalitone (chorthalidone), and Diuril (chlorothiazide)
• Beta blockers like Sectral (acebutolol), Zebeta (bisoprolol), Tenormin (atenolol), and Coreg (carvedilol)
• Other NSAIDS like Celebrex (celecoxib), Aleve, Naprosyn, (naproxen), Mobic (meloxicam), Relafen (nabumetone), Lodine (etodolac), Toradol (ketorolac)

If you have been taking ibuprofen for a long time while taking certain blood pressure medicines called ACE inhibitors and ARBs, you may notice that your blood pressure has become harder to control.

Examples of these medications include:

• Altace (ramipril)
• Vasotec (enalapril)
• Mavik (trandopril)
• Accupril (quinapril)
• Monopril (fosinopril)
• Univasc (moexipril)
• Avapro (irbesartan)
• Atacand (candesartan)
• Cozaar (losartan)
• Benicar (omesartan)

It's important to note that some herbal and other supplements can thin the blood and/or may increase blood pressure.

Using such supplements while taking ibuprofen may increase risk of bleeding and/or increase blood pressure.

Examples of these herbal products include:

• Pau d'arco
• Ginseng
• Ginger
• Garlic
• Gingko biloba
• Nettle
• Dong quai
• Cordyceps
• Feverfew
• Green tea

Ibuprofen and Alcohol

You should not drink alcohol while taking ibuprofen.

Drinking alcohol while taking ibuprofen can increase the risk of stomach bleeds and may even cause damage to your kidneys.

Ibuprofen and Grapefruit Juice

Because your liver processes grapefruit juice differently than it does ibuprofen, there are no known problems associated with taking ibuprofen and grapefruit juice together.

Ibuprofen is both an over-the-counter and a prescription medication. The over-the-counter form is used to treat mild to moderate pain associated with headaches, muscle aches, menstrual periods, the common cold, toothaches, and backaches. It can also be used to reduce fever. The prescription form is used to treat pain, tenderness, swelling, and stiffness caused by osteoarthritis and rheumatoid arthritis. This medication page refers to the prescription form of ibuprofen.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with ibuprofen including the following:

• Heart attack or stroke. Tell your healthcare provider right away if you have some or all of the following symptoms of cardiovascular complications:
  • shortness of breath
  • chest pain
  • weakness
  • slurring of speech
• Hypertension (high blood pressure). Ibuprofen can cause new hypertension or worsening of pre-existing hypertension.
• Have your blood pressure monitored by your doctor closely if taking ibuprofen, especially if you have a history of hypertension or are taking medications to treat hypertension.
• Congestive heart failure (CHF): Tell your healthcare provider right away if you have some or all of the following symptoms of CHF:
  • swelling in the arms or legs
  • shortness of breath
  • unexplained weight gain
  • fatigue
• Serious skin reaction. Tell your healthcare provider right away if you have some or all of the following symptoms of a potentially serious skin reaction:
  • rash
  • blistering
  • itching
  • fever
• Stomach bleeding and/or ulceration: Tell your healthcare provider right away if you have some or all of the following symptoms of stomach bleeding:
  • abdominal pain
  • blood in stools (black or tarry stools)
  • coughing up of blood
  • indigestion or general stomach discomfort
• Liver toxicity: Tell your healthcare provider right away if you have some or all of the following symptoms of liver dysfunction:
  • flu-like symptoms
  • fatigue
  • nausea
  • yellowing of the skin or eyes
• Kidney damage. Patients with preexisting renal dysfunction, heart failure,liver injury, those taking diuretics or ACE inhibitors, and the elderly are at the greatest risk of kidney injury. Ibuprofen is not recommended in these patients with advanced renal disease.
• Allergic reaction. Tell your healthcare provider right away if you have some or all of the following symptoms of an anaphylactoid allergic reaction:
  • swelling of the face or throat
  • difficulty breathing
• Changes in vision. Tell your healthcare provider right away if you have some or all of the following symptoms of changes in vision:
  • blurred or decreased vision
  • changes in color vision
  • dark or gray spots in field of vision

Ibuprofen can cause blurred vision, drowsiness, and dizziness. Do not drive or operate heavy machinery until you know how ibuprofen affects you.

Do not take ibuprofen if you:

• are allergic to ibuprofen or to any of its ingredients
• have experienced asthma, itching or rash, or allergic-type reaction to aspirin or other NSAIDs
• are undergoing coronary artery bypass graft (CABG) surgery

Before taking ibuprofen, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to ibuprofen or to any of its ingredients
• have liver problems
• have heart disease, including heart attack and stroke, or anyone in your family has had these conditions
• have high cholesterol
• have high blood pressure
• have kidney disease
• have diabetes
• have asthma
• have swelling of the hands, arms, feet, ankles, or legs
• have lupus
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if ibuprofen crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using ibuprofen.

When used for inflammatory diseases, pain, dysmenorrhea, or fever, consider potential benefits and risks of ibuprofen therapy as well as alternative therapies before initiating therapy with the drug.192 Use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.192

Inflammatory Diseases

Symptomatic treatment of osteoarthritis and rheumatoid arthritis.100

Management of juvenile rheumatoid arthritis in children.106

Pericarditis

Reduction of pain, fever, and inflammation of pericarditis†;174 however, in the treatment of post-MI pericarditis, NSAIAs are potentially harmful and aspirin is the treatment of choice.323 (See Cardiovascular Thrombotic Effects under Cautions.)

Pain

Oral ibuprofen used for relief of mild to moderate pain in adults and children; IV ibuprofen used in adults for relief of mild to moderate pain and, in conjunction with opiates, for relief of moderate to severe pain.100 106 210

NSAIAs considered first-line agents for mild to moderate migraine attacks or for severe attacks that have responded in the past to NSAIAs or nonopiate analgesics.186

Self-medication in children and adults for the temporary relief of minor aches and pain associated with the common cold, influenza, or sore throat; headache (including migraine); toothache; muscular aches; backache; minor pain of arthritis.105 164 165 178 179 189

Dysmenorrhea

Symptomatic management of primary dysmenorrhea.100

Self-medication for the temporary relief of minor aches and pain associated with menstrual cramps.165

Fever

Reduction of fever in adults (oral or IV ibuprofen) and children (oral ibuprofen).106 210

Self-medication for reduction of fever in children and adults.164

Patent Ductus Arteriosus (PDA)

Treatment of PDA in premature neonates (designated an orphan drug by FDA for this use).198 206 Used to promote closure of a clinically important PDA in premature neonates weighing 500–1500 g who are ≤32 weeks' gestational age when usual medical management (e.g., fluid restriction, diuretics, respiratory support) is ineffective.198 Limited follow-up data available; reserve for neonates with clinically important PDA.198

No evidence of enzyme induction.100

Specific Drugs

Absorption

Bioavailability

Well absorbed following oral administration; peak plasma concentration usually attained within 1–2 hours.100 106

Onset

Pain relief and/or antipyretic activity achieved within 1 hour.106 107

Food

Food reduces peak plasma concentration by about 30–50% and delays time to reach peak plasma concentration by about 30–60 minutes but does not affect extent of absorption.100 106

Distribution

Plasma Protein Binding

>99%.106

Elimination

Metabolism

Extensively metabolized.100 106

Elimination Route

Excreted mainly in urine as metabolites.100 106

Half-life

1.8–2.4 hours.100 210

Half-life 10-fold longer in neonates than in adults.198

Storage

Oral

20–25°C.100 165

20–25°C.106

Parenteral

20–25°C.210

The most frequent type of adverse reaction occurring with Ibuprofen tablets is gastrointestinal. In controlled clinical trials the percentage of patients reporting one or more gastrointestinal complaints ranged from 4% to 16%.

In controlled studies when Ibuprofen tablets were compared to aspirin and indomethacin in equally effective doses, the overall incidence of gastrointestinal complaints was about half that seen in either the aspirin or indomethacin-treated patients.

Adverse reactions observed during controlled clinical trials at an incidence greater than 1% are listed in the table. Those reactions listed in Column one encompass observations in approximately 3,000 patients. More than 500 of these patients were treated for periods of at least 54 weeks.

Still other reactions occurring less frequently than 1 in 100 were reported in controlled clinical trials and from marketing experience. These reactions have been divided into two categories: Column two of the table lists reactions with therapy with Ibuprofen tablets where the probability of a causal relationship exists: for the reactions in Column three, a causal relationship with Ibuprofen tablets has not been established.

Reported side effects were higher at doses of 3200 mg/day than at doses of 2400 mg or less per day in clinical trials of patients with rheumatoid arthritis. The increases in incidence were slight and still within the ranges reported in the table.

*Reactions occurring in 3% to 9% of patients treated with Ibuprofen. (Those reactions occurring in less than 3% of the patients are unmarked).

**Reactions are classified under “Probable Causal Relationship (PCR)” if there has been one positive rechallenge or if three or more cases occur which might be causally related. Reactions are classified under “CausalRelationship Unknown” if seven or more events have been reported but the criteria for PCR have not been met 

Medication Guide for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

(See the end of this Medication Guide for a list of prescription NSAID medicines.)

What is the most important information I should know about medicines called Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?  

NSAIDs can cause serious side effects, including:  

·         Increased risk of a heart attack or stroke that can lead to death. This risk may happen early in treatment and may increase:

·      with increasing doses of NSAIDs

·      with longer use of NSAIDs

Do not take NSAIDs right before or after a heart surgery called a “coronary artery bypass graft (CABG)."  

Avoid taking NSAIDs after a recent heart attack, unless your healthcare provider tells you to. You may have an increased risk of another heart attack if you take NSAIDs after a recent heart attack.  

·         Increased risk of bleeding, ulcers, and tears (perforation) of the esophagus (tube leading from the mouth to the stomach), stomach and intestines:  

·           anytime during use

·           without warning symptoms

·           that may cause death

The risk of getting an ulcer or bleeding increases with: 

·         past history of stomach ulcers, or stomach or intestinal bleeding with use of NSAIDs

·         taking medicines called “corticosteroids”, “anticoagulants”, “SSRIs”, or “SNRIs”

·         increasing doses of NSAIDs

·         longer use of NSAIDs

·         smoking

·         drinking alcohol

·         older age

·         poor health

·         advanced liver disease

·         bleeding problems

NSAIDs should only be used:  

·         exactly as prescribed

·         at the lowest dose possible for your treatment

·         for the shortest time needed

What are NSAIDs?

NSAIDs are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as different types of arthritis, menstrual cramps, and other types of short-term pain.

Who should not take NSAIDs?  

Do not take NSAIDs:  

·         if you have had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAIDs.

·         right before or after heart bypass surgery.

Before taking NSAIDS, tell your healthcare provider about all of your medical conditions, including if you:  

·         have liver or kidney problems

·         have high blood pressure

·         have asthma

·         are pregnant or plan to become pregnant. Talk to your healthcare provider if you are considering taking NSAIDs during pregnancy. You should not take NSAIDs after 29 weeks of pregnancy.

·         are breastfeeding or plan to breast feed.

Tell your healthcare provider about all of the medicines you take, including prescription or over-the-counter medicines, vitamins or herbal supplements. NSAIDs and some other medicines can interact with each other and cause serious side effects. Do not start taking any new medicine without talking to your healthcare provider first.

What are the possible side effects of NSAIDs?  

NSAIDs can cause serious side effects, including:  

See “What is the most important information I should know about medicines called Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?  

·         new or worse high blood pressure

·         heart failure

·         liver problems including liver failure

·         kidney problems including kidney failure

·         low red blood cells (anemia)

·         life-threatening skin reactions

·         life threatening allergic reactions

·         Other side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas, heartburn, nausea, vomiting, and dizziness.

Get emergency help right away if you get any of the following symptoms:

·         shortness of breath or trouble breathing

·         chest pain

·         weakness in one part or side of your body

·         slurred speech

·         swelling of the face or throat

Stop taking your NSAID and call your healthcare provider right away if you get any of the following symptoms:

·         nausea

·         more tired or weaker than usual

·         diarrhea

·         itching

·         your skin or eyes look yellow

·         indigestion or stomach pain

·         flu-like symptoms

·         vomit blood

·         there is blood in your bowel movement or it is black and sticky like tar

·         unusual weight gain

·         skin rash or blisters with fever

·         swelling of the arms, legs, hands and feet

If you take too much of your NSAID, call your healthcare provider or get medical help right away.  

These are not all the possible side effects of NSAIDs. For more information, ask your healthcare provider or pharmacist about NSAIDs.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Other information about NSAIDs  

·         Aspirin is an NSAID but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines.

·         Some NSAIDs are sold in lower doses without a prescription (over-the-counter). Talk to your healthcare provider before using over-the-counter NSAIDs for more than 10 days.

General information about the safe and effective use of NSAIDs

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use NSAIDs for a condition for which it was not prescribed. Do not give NSAIDs to other people, even if they have the same symptoms that you have. It may harm them.

If you would like more information about NSAIDs, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about NSAIDs that is written for health professionals.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Granules India Limited

Hyderabad-500 081, India

MADE IN INDIA

Distributed by:

Ascend Laboratories, LLC

Parsippany, NJ 07054

Toll-free: 1-877-272-7901

Issued: October 2016

• Addaprin [OTC]
• Advil Junior Strength [OTC]
• Advil Migraine [OTC]
• Advil [OTC]
• Caldolor
• Childrens Advil [OTC]
• Childrens Motrin Jr Strength [OTC] [DSC]
• Childrens Motrin [OTC]
• Dyspel [OTC]
• EnovaRX-Ibuprofen
• Genpril [OTC]
• GoodSense Ibuprofen Childrens [OTC]
• GoodSense Ibuprofen [OTC]
• I-Prin [OTC]
• IBU-200 [OTC]
• Ibuprofen Comfort Pac
• Infants Advil [OTC]
• KS Ibuprofen [OTC]
• Motrin IB [OTC]
• Motrin Infants Drops [OTC]
• Motrin Junior Strength [OTC] [DSC]
• Motrin [OTC] [DSC]
• NeoProfen
• Provil [OTC]

Oral: Antipyretic: 6 to 8 hours (Sullivan 2011)

Half-Life Elimination

IV:

Ibuprofen (Caldor):

Pediatric patients: 6 months to <2 years: 1.8 hours; 2 to 16 years: ~1.5 hours

Adults: 2.22 to 2.44 hours

Ibuprofen lysine (Neoprofen):

Premature neonates, GA <32 weeks: Reported data highly variable

R-enantiomer: 10 hours; S-enantiomer: 25.5 hours (Gregoire 2004)

Age-based observations:

PNA <1 day: 30.5 ± 4.2 hours (Aranda 1997)

PNA 3 days: 43.1 ± 26.1 hours (Van Overmeire 2001)

PNA 5 days: 26.8 ± 23.6 hours (Van Overmeire 2001)

Oral:

Children 3 months to 10 years: Oral suspension: 1.6 ± 0.7 hours (Kauffman 1992)

Adults: ~2 hours; End-stage renal disease: Unchanged (Aronoff 2007)

Protein Binding

>90%; Premature infants: ~95% (Aranda 1997)

Oral: Administer with food or milk.

IV:

Caldolor: For IV administration only; infuse over at least 30 minutes (adults) or 10 minutes (pediatric).

NeoProfen (ibuprofen lysine): For IV administration only; administration via umbilical arterial line has not been evaluated. Infuse over 15 minutes through port closest to insertion site. Avoid extravasation. Do not administer simultaneously via same line with TPN. If needed, interrupt TPN for 15 minutes prior to and after ibuprofen administration, keeping line open with dextrose or saline.