MOTRIN® (ibuprofen) Suspension 100 mg/5 mL

• NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk (see WARNINGS).
• MOTRIN Suspension is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

• NSAIDs cause an increased risk of serious gastrointestinal 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 are at greater risk for serious gastrointestinal events (see WARNINGS).

The active ingredient in MOTRIN is ibuprofen, which is a member of the propionic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). Ibuprofen is a racemic mixture of [+]S- and [-]R-enantiomers. It is a white to off-white crystalline powder, with a melting point of 74° to 77°C. It is practically insoluble in water (<0.1 mg/mL), but readily soluble in organic solvents such as ethanol and acetone. Ibuprofen has a pKa of 4.43±0.03 and an n-octanol/water partition coefficient of 11.7 at pH 7.4. The chemical name for ibuprofen is (±)-2-(p-isobutylphenyl) propionic acid. The molecular weight of ibuprofen is 206.28. Its molecular formula is C₁₃H₁₈0₂ and it has the following structural formula:

MOTRIN Suspension is a sucrose-sweetened, orange colored, berry flavored suspension containing 100 mg of ibuprofen in 5 mL (20 mg/mL). Inactive ingredients include: acesulfame-K, citric acid, glycerin, polysorbate 80, pregelatinized starch, purified water, sodium benzoate, sucrose, xanthan gum, and natural and artificial flavors. It also may contain one or several of the following colorants: FD&C Red #40, D&C Yellow #10, D&C Red #33, and FD&C Blue #1.

Carefully consider the potential benefits and risks of MOTRIN Suspension and other treatment options before deciding to use MOTRIN Suspension. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

• For reduction of fever in patients aged 6 months up to 2 years of age.
• For relief of mild to moderate pain in patients aged 6 months up to 2 years of age.
• For relief of signs and symptoms of juvenile arthritis.

• For treatment of primary dysmenorrhea.
• For relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis.

Since there have been no controlled trials to demonstrate whether there is any beneficial effect or harmful interaction with the use of ibuprofen in conjunction with aspirin, the combination cannot be recommended. (See PRECAUTIONS – Drug Interactions).

MOTRIN Suspension is contraindicated in patients with known hypersensitivity to ibuprofen.

MOTRIN Suspension should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDS have been reported in such patients (see WARNINGS – Anaphylactoid Reactions, and PRECAUTIONS – Preexisting Asthma).

MOTRIN Suspension is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

NSAIDs, including MOTRIN Suspension, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the 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 occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.

NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population.

To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.

No information is available from controlled clinical studies regarding the use of MOTRIN Suspension in patients with advanced renal disease. Therefore, treatment with MOTRIN Suspension is not recommended in these patients with advanced renal disease. If MOTRIN Suspension therapy must be initiated, close monitoring of the patient's renal function is advisable.

As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to MOTRIN Suspension. MOTRIN Suspension should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS – Preexisting Asthma). Emergency help should be sought in cases where an anaphylactoid reaction occurs.

NSAIDs, including MOTRIN Suspension, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

In late pregnancy, as with other NSAIDs, MOTRIN should be avoided because it may cause premature closure of the ductus arteriosus.

MOTRIN Suspension cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.

The pharmacological activity of MOTRIN Suspension in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including MOTRIN Suspension. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.

A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with MOTRIN Suspension. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), MOTRIN Suspension should be discontinued.

Anemia is sometimes seen in patients receiving NSAIDs, including MOTRIN Suspension. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including MOTRIN Suspension, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.

In two postmarketing clinical studies the incidence of a decreased hemoglobin level was greater than previously reported. Decrease in hemoglobin of 1 gram or more was observed in 17.1% of 193 patients on 1600 mg ibuprofen daily (osteoarthritis), and in 22.8% of 189 patients taking 2400 mg of ibuprofen daily (rheumatoid arthritis). Positive stool occult blood tests and elevated serum creatinine levels were also observed in these studies.

NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving MOTRIN Suspension who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.

Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, MOTRIN Suspension should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.

Aseptic meningitis, with fever and coma, has been observed on rare occasions in patients on ibuprofen therapy. Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease.

MOTRIN Suspension contains 0.3 g sucrose and 1.6 calories per mL, or 1.5 g sucrose and 8 calories per teaspoon, which should be taken into consideration when treating diabetic patients with this product.

Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

• MOTRIN Suspension, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization, and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up (see WARNINGS, Cardiovascular Effects).
• MOTRIN Suspension, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization or even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS, Gastrointestinal Effects: Risk of Ulceration, Bleeding, and Perforation).
• MOTRIN Suspension, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and bulers, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash or contact their physicians as soon as possible.
• Patients should promptly reports signs and symptoms of unexplained weight gain or edema to their physicians.
• Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritis, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.
• Patients should be informed of the signs of an anaphylactoid reaction (e.g. difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS).
• In late pregnancy, as with other NSAIDs, MOTRIN Suspension should be avoided because it may cause premature closure of the ductus arteriosus.

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, MOTRIN Suspension should be discontinued.

In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of MOTRIN Suspension on labor and delivery in pregnant women are unknown. Therefore, administration of MOTRIN Suspension is not recommended during labor and delivery.

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from MOTRIN suspension, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Safety and effectiveness of MOTRIN Suspension in pediatric patients below the age of 6 months have not been established (see CLINICAL PHARMACOLOGY - Clinical Studies). Dosing of MOTRIN Suspension in children 6 months or older should be guided by their body weight (see DOSAGE AND ADMINISTRATION).

As with any NSAIDs, caution should be exercised in treating the elderly (65 years and older).

In patients taking MOTRIN or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1-10% of patients are: Abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, fluid retention, gastrointestinal experiences (including abdominal pain, bloating, constipation, diarrhea, dyspepsia, epigastric pain, flatulence, heartburn, nausea, vomiting), headaches, increased bleeding time, nervousness, pruritus, rashes (including maculopapular) and tinnitus.

The toxicity of ibuprofen overdose is dependent upon the amount of drug ingested and the time elapsed since ingestion, though individual response may vary, which makes it necessary to evaluate each case individually. Although uncommon, serious toxicity and death have been reported in the medical literature with ibuprofen overdosage. The most frequently reported symptoms of ibuprofen overdose include abdominal pain, nausea, vomiting, lethargy and drowsiness. Other central nervous system symptoms include headache, tinnitus, CNS depression and seizures. Metabolic acidosis, coma, acute renal failure and apnea (primarily in very young children) may rarely occur. Cardiovascular toxicity, including hypotension, bradycardia, tachycardia and atrial fibrillation, also have been reported.

The treatment of acute ibuprofen overdose is primarily supportive. Management of hypotension, acidosis and gastrointestinal bleeding may be necessary. In cases of acute overdose, the stomach should be emptied through ipecac-induced emesis or lavage. Emesis is most effective if initiated within 30 minutes of ingestion. Orally administered activated charcoal may help in reducing the absorption and reabsorption of ibuprofen.

In children, the estimated amount of ibuprofen ingested per body weight may be helpful to predict the potential for development of toxicity although each case must be evaluated. Ingestion of less than 100 mg/kg is unlikely to produce toxicity. Children ingesting 100 to 200 mg/kg may be managed with induced emesis and a minimal observation time of four hours. Children ingesting 200 to 400 mg/kg of ibuprofen should have immediate gastric emptying and at least four hours observation in a health care facility. Children ingesting greater than 400 mg/kg require immediate medical referral, careful observation and appropriate supportive therapy. Ipecac-induced emesis is not recommended in overdoses greater than 400 mg/kg because of the risk for convulsions and the potential for aspiration of gastric spans.

In adult patients the history of the dose reportedly ingested does not appear to be predictive of toxicity. The need for referral and follow-up must be judged by the circumstances at the time of the overdose ingestion. Symptomatic adults should be carefully evaluated, observed and supported.

Carefully consider the potential benefits and risks of MOTRIN Suspension and other treatment options before deciding to use MOTRIN Suspension. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

After observing the response to initial therapy with MOTRIN Suspension, the dose and frequency should be adjusted to suit an individual patient's needs.

MOTRIN® (ibuprofen) Suspension, 100 mg/5 mL

Orange-colored, berry- flavored suspension

- Bottles of 120 mL – NDC 0045-0448-04
- Bottles of 480 mL – NDC 0045-0448-16

Shake well before using. Store at controlled room temperature [15º to 30ºC (59º to 86ºF)]

Caution: Federal Law prohibits dispensing without prescription.

McNEIL PEDIATRICS
DIVISION OF McNEIL-PPC, INC.
FORT WASHINGTON, PA 19034-USA

April 2007

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

What are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

NSAID medicines 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 a Non-Steroidal Anti-Inflammatory Drug (NSAID)?

Do not take an NSAID medicine:

• if you had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAID medicine
• for pain right before or after heart bypass surgery

Tell your healthcare provider:

• about all your medical conditions
• about all of the medicines you take. NSAIDs and some other medicines can interact with each other and cause serious side effects. Keep a ul of your medicines to show to your healthcare provider and pharmacist.
• if you are pregnant. NSAID medicines should not be used by pregnant women late in their pregnancy.
• if you are breastfeeding. Talk to your doctor.

What are the possible side effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

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

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

These are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines.

Other information about Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

• Aspirin is an NSAID medicine 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 of these NSAID medicines 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.

NSAID medicines that need a prescription

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