MOTRIN

1 Dosing Considerations • Do not take for pain for more than 5 consecutive days or fever for more than 3 days unless directed by a physician. • If your condition deteriorates or new symptoms occur (such as the painful area becomes unusually red, swollen or tender), consult a physician.

• Individuals older than 65 years who are frail or debilitated should be given a starting dose lower than the one usually recommended, with individual adjustments when necessary. • Use the lowest effective dose for the shortest duration.

2 Recommended Dose and Dosage Adjustment Mild to moderate pain or fever.

Adults:

Single oral dose may be taken every 4–6 hours, as required, not to exceed the maximum daily dose (1200 mg) in 24 hours unless directed by a physician. Product Strength (ibuprofen mg/tablet) Single Oral Dose Maximum Daily Dose (1200 mg) (Regular Strength) MOTRIN® 200 mg 200 mg 1 or 2 tablets 6 tablets (Extra Strength) MOTRIN® 300 mg 300 mg 1 tablet 4 tablets (Super Strength) MOTRIN® 400 mg 400 mg 1 tablet 3 tablets Children: Children’s MOTRIN® formulations are available to treat children under 12 years of age.

Children’s MOTRIN® may be also used for adults requiring liquid dosage forms (see Children’s MOTRIN® Administration) The administration of ibuprofen with food or milk is recommended since occasional and mild MOTRIN® 200 mg / MOTRIN® 300 mg / MOTRIN® 400 mg (Ibuprofen Tablets USP) Page 7 of 41 heartburn, upset stomach or stomach pain may occur with its use.

5 Missed Dose If you miss a dose, take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take your medicine and skip the missed dose. Do not take two doses at the

1 Adverse Reaction Overview Clinical Trial & Post-Market Adverse Drug Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. The most common adverse reactions encountered with nonsteroidal anti-inflammatory drugs are gastrointestinal, of which gastric or duodenal ulcer, with or without bleeding, is the most severe.

Fatalities have occurred, particularly in the elderly. Experience reported with prescription use of ibuprofen has included the following adverse reactions.

Note:

Reactions listed below under Causal Relationship Unknown are those where a causal relationship could not be established; however, in these rarely reported events, the possibility of a relationship to ibuprofen also cannot be excluded.

MOTRIN® 200 mg / MOTRIN® 300 mg / MOTRIN® 400 mg (Ibuprofen Tablets USP) Page 16 of 41 Adverse Effect Common (>1% but <10%) Less Common (<1%)Incidence 3-9% Incidence 1-3% Allergic • anaphylaxis (See Contraindications) Also reported but with unknown causal relationship, rarely: • fever • serum sickness • lupus erythematosus syndrome Cardiovascular • congestive heart failure in patients with marginal cardiac function • elevated blood pressure • Conditions such as congestive heart failure and hypertension may be aggravated by sodium retention and edema caused by ibuprofen in such patients • myocardial infarction • stroke (cerebrovascular accident) Also reported but with unknown causal relationship, rare cases of: • arrhythmias (sinus tachycardia, sinus bradycardia, palpitations) • hemorrhage (non-GI) • Kounis syndrome Central Nervous System • dizziness • headache • nervousness • drowsiness/s omnolence • depression • insomnia MOTRIN® 200 mg / MOTRIN® 300 mg / MOTRIN® 400 mg (Ibuprofen Tablets USP) Page 17 of 41 Adverse Effect Common (>1% but <10%) Less Common (<1%)Incidence 3-9% Incidence 1-3% Also reported but with unknown causal relationship: • paresthesias • hallucinations • dream abnormalities • aseptic meningitis has been reported in patients with systemic lupus erythematosus or other connective tissue disease • aseptic meningitis and meningioencephalitis, in one case accompanied by eosinophilia in the cerebrospinal fluids, has been reported in patients who took ibuprofen intermittently and did not have any connective tissue disease • cognitive dysfunction has been observed in elderly patients who took ibuprofen • psychomotor hyperactivity Immune System Disorders Rare: • hypersensitivity Dermatologic • rash (including maculopapular type) • pruritis • vesiculobullous eruptions • urticaria • erythema • erythema multiforme • angioedema • fixed eruption Also reported but with unknown causal relationship: • alopecia • Stevens-Johnson Syndrome • toxic epidermal necrolysis • Drug reaction with eosinophilia and systemic symptoms (DRESS) • Acute generalised exanthematous pustulosis (AGEP) Endocrine Also reported but with unknown causal relationship, rare cases of: • gynecomastia • hypoglycemic reaction • menstrual delays of up to two weeks and dysfunctional uterine bleeding occurred in nine patients taking ibuprofen 400 mg three times a day for three days before menses MOTRIN® 200 mg / MOTRIN® 300 mg / MOTRIN® 400 mg (Ibuprofen Tablets USP) Page 18 of 41 Adverse Effect Common (>1% but <10%) Less Common (<1%)Incidence 3-9% Incidence 1-3% Gastrointestinal • nausea • epigastric pain • heartburn • diarrhea • abdominal distress • nausea and vomiting • indigestion (dyspepsia) • constipation • abdominal cramps and pain • gastrointestinal tract fullness (bloating or flatulence) • gastric or duodenal ulcer with bleeding and/or perforation • gastrointestinal hemorrhage • melena • hepatitis • jaundice • abnormal liver function (SGOT, serum bilirubin and alkaline phosphatase) • pancreatitis • oral discomfort (local burning, sensation, irritation) The generally modest elevations of serum transaminase activity that has been observed are usually without clinical sequelae but severe, potentially fatal toxic hepatitis can occur.

1 Pregnant Women [04/2023] TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ............................................................................................

2 TABLE OF CONTENTS .............................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION ......................................................................

4 1 INDICATIONS ............................................................................................................... 4 2 CONTRAINDICATIONS .................................................................................................

4 3 SERIOUS WARNINGS AND PRECAUTIONS BOX ............................................................ 5 4 DOSAGE AND ADMINISTRATION ................................................................................. 7 5 OVERDOSAGE..............................................................................................................

7 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................. 8 7 WARNINGS AND PRECAUTIONS .................................................................................. 15 8 ADVERSE REACTIONS ................................................................................................

15 9 DRUG INTERACTIONS ................................................................................................ 22 10 CLINICAL PHARMACOLOGY .......................................................................................

23 11 STORAGE, STABILITY AND DISPOSAL ......................................................................... 24 12 SPECIAL HANDLING INSTRUCTIONS ........................................................................... 24 PART II: SCIENTIFIC INFORMATION .......................................................................................

The following are contraindications to the use of MOTRIN®: • Patients who are hypersensitive to ibuprofen, other non-steroidal anti-inflammatory drugs (NSAIDs), or to any of the ingredients in the formulation, including any non-medicinal ingredient or component of the container, For a complete listing see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

The potential for cross-reactivity between different NSAIDs must be kept in mind. Ibuprofen should not be used in patients with the complete or partial syndrome of acetylsalicylic acid (ASA) intolerance (rhinosinusitis, urticaria/angioedema, nasal polyps, asthma) in whom asthma, anaphylaxis, urticaria/angioedema, rhinitis or other allergic manifestations are precipitated by ASA or MOTRIN® 200 mg / MOTRIN® 300 mg / MOTRIN® 400 mg (Ibuprofen Tablets USP) Page 5 of 41 other nonsteroidal anti-inflammatory agents.

Fatal anaphylactoid reactions have occurred in such individuals. As well, individuals with the above medical problems are at risk of a severe reaction even if they have taken NSAIDs in the past without any adverse effects. • Active gastric or duodenal ulcer, a history of recurrent ulceration, gastrointestinal bleeding, or active inflammatory disease of the gastrointestinal system.

• Significant hepatic impairment or active liver disease. • Severely impaired or deteriorating renal function (creatinine clearance <30 ml/min). • Ibuprofen should not be used in the presence of known hyperkalemia (also see Warnings and Precautions – Renal section).

• Children with kidney disease and/or who have suffered significant fluid loss. • Ibuprofen is contraindicated in patients with systemic lupus erythematosus as an anaphylaxis-like reaction with fever may occur, particularly when ibuprofen has been administered previously.

• The third trimester of pregnancy, because of risk of premature closure of the ductus arteriosus and prolonged parturition. • Do not use right before or after heart surgery (see Peri-Operative Considerations). See 7 WARNINGS AND PRECAUTIONS and 9 DRUG INTERACTIONS.