MOTRIN LIQUID

8 Dosing Considerations • Do not take for fever for more than 3 days or for pain for more than 5 days unless directed by a physician. The safety issues to consider when developing a dosage regimen of MOTRIN® Liquid Gels 200 mg/ MOTRIN® Liquid Gels 400 mg for individual patients are applicable to: • Elderly patients older than 65 years who are frail or debilitated and consideration should be given to a starting dose lower than the one usually recommended (See 7 WARNINGS AND PRECAUTIONS, Geriatrics).

2 Recommended Dose and Dosage Adjustment MOTRIN® Liquid Gels 200 mg: • Adults and Children over 12: Take 1 (every 4 hours) or 2 (every 6-8 hours) capsules as needed. Do not exceed six 200 mg capsules in 24 hours, unless directed by a physician.

MOTRIN® Liquid Gels 400 mg MOTRIN® LIQUID GELS 200 mg and MOTRIN® LIQUID GELS 400 mg (Ibuprofen Capsules) Page 7 of 50 • Adults and Children over 12: Take 1 400 mg capsule every 6-8 hours as needed. Do not exceed 3 400 mg capsules in 24 hours, unless directed by a physician.

The administration of ibuprofen with food or milk is recommended since occasional and mild heartburn, upset stomach or stomach pain may occur with its use. 5 Missed 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 your missed dose.

Do not take two doses at the same time.

8 Adverse Reaction Overview Experience reported with prescription use of ibuprofen has included the adverse reactions listed in this section.

Note:

Reactions listed under Causal Relationship Unknown are those MOTRIN® LIQUID GELS 200 mg and MOTRIN® LIQUID GELS 400 mg (Ibuprofen Capsules) Page 18 of 50 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.

The adverse reactions most frequently seen with ibuprofen therapy involve the gastrointestinal system. 2 Clinical Trial Adverse Reactions Not available. 4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data Gastrointestinal: 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.

Renal:

Renal blood flow glomerular filtration rate decreased in patients with mild impairment of renal functions who took 1200 mg/day of ibuprofen for one week. Renal papillary necrosis has been reported. A number of factors appear to increase the risk of renal toxicity.

5 Post-Market Adverse Reactions (Prescription Experience) The following adverse reactions have been noted in patients treated with prescription doses (≥1200 mg/day).

Note:

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

Gastrointestinal The adverse reactions most frequently seen with prescribed ibuprofen therapy involve the gastrointestinal system. Incidence 3 to 9%: nausea, epigastric pain, heartburn Incidence 1 to 3%: diarrhea, abdominal distress, nausea and vomiting, indigestion, constipation, abdominal cramps or pain, fullness of the gastrointestinal tract (bloating or flatulence).

Incidence less than 1%: gastric or duodenal ulcer with bleeding and/or perforation, gastrointestinal haemorrhage, melena, hepatitis, jaundice, abnormal liver function (SGOT, serum bilirubin and alkaline phosphatase), pancreatitis, oral discomfort (local burning, sensation, irritation).

MOTRIN® LIQUID GELS 200 mg and MOTRIN® LIQUID GELS 400 mg (Ibuprofen Capsules) Page 19 of 50 Allergic Incidence less than 1%: anaphylaxis (see CONTRAINDICATIONS). Causal relationship unknown: fever, serum sickness, lupus erythematosus.

Central Nervous System Incidence 3 to 9%: dizziness Incidence 1 to 3%: headache, nervousness Incidence less than 1%: depression, insomnia Causal relationship unknown: paresthesias, hallucinations, dream abnormalities Aseptic meningitis and meningoencephalitis, in one case accompanied by eosinophilia in the cerebrospinal fluid, have been reported in patients who took ibuprofen intermittently and did not have any connective tissue disease, psychomotor hyperactivity.

Dermatologic Incidence 3 to 9%: rash (including maculopapular type). Incidence 1 to 3%: pruritus Incidence less than 1%: vesiculobullous eruptions, urticaria, erythema multiforme, fixed eruption Causal relationship unknown: alopecia, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP).

Cardiovascular Incidence less than 1%: congestive heart failure in patients with marginal cardiac function, elevated blood pressure (hypertension), angioedema, myocardial infarction, stroke (cerebrovascular accident). Causal relationship unknown: arrhythmias (sinus tachycardia, sinus bradycardia, palpitations), hemorrhage (non-GI), Kounis syndrome.

Special Senses Incidence 1 to 3%: tinnitus Incidence less than 1%: amblyopia (blurred and/or diminished vision, scotomata and/or changes in colour vision). Any patient with eye complaints during ibuprofen therapy should have an ophthalmological examination.

MOTRIN® LIQUID GELS 200 mg and MOTRIN® LIQUID GELS 400 mg (Ibuprofen Capsules) Page 20 of 50 Causal relationship unknown: conjunctivitis, diplopia, optic neuritis. Hematologic Incidence less than 1%: leukopenia, and decreases in haemoglobin and hematocrit.

, purpura, epistaxis, hematuria, menorrhagia). Renal Causal relationship unknown: decreased creatinine clearance, polyuria, azotemia, nephritis, nephrotic syndrome, renal failure. Like other non-steroidal anti-inflammatory drugs, ibuprofen inhibits renal prostaglandin synthesis, which may decrease renal function and cause sodium retention.

Renal blood flow and glomerular filtration rate decreased in patients with mild impairment of renal function who took 1200 mg/day of ibuprofen for one week. Renal papillary necrosis has been reported. A number of factors appear to increase the risk of renal toxicity (See 7 WARNINGS AND PRECAUTIONS).

Hepatic Incidence less than 1%: hepatitis, jaundice, abnormal liver function (SGOT, serum bilirubin, and alkaline phosphatase), vanishing bile duct syndrome. Endocrine Causal relationship unknown: gynecomastia, hypoglycaemic reaction.

, for three days before menses. Metabolic Incidence 1 to 3%: decreased appetite, oedema, fluid retention. Fluid retention generally responds promptly to drug discontinuation (See 7 WARNINGS AND PRECAUTIONS). General Incidence less than 1%: hypothermia Respiratory MOTRIN® LIQUID GELS 200 mg and MOTRIN® LIQUID GELS 400 mg (Ibuprofen Capsules) Page 21 of 50 Incidence less than 1%: asthma, bronchospasms Non-Prescription Experience: Literature (1992-1999) (at dosages ≤ 1200 mg/day) One researcher conducted an extensive analysis of published data concerning the relative safety of non-prescription doses of ibuprofen and […]

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 ............................................................ 6 4 DOSAGE AND ADMINISTRATION ................................................................................. 7 5 OVERDOSAGE..............................................................................................................

7 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................. 8 7 WARNINGS AND PRECAUTIONS .................................................................................. 17 8 ADVERSE REACTIONS ................................................................................................

18 9 DRUG INTERACTIONS ................................................................................................ 26 10 CLINICAL PHARMACOLOGY .......................................................................................

27 11 STORAGE, STABILITY AND DISPOSAL ......................................................................... 29 12 SPECIAL HANDLING INSTRUCTIONS ........................................................................... 29 PART II: SCIENTIFIC INFORMATION .......................................................................................

30 13 PHARMACEUTICAL INFORMATION ............................................................................ 30 14 CLINICAL TRIALS ........................................................................................................

33 15 MICROBIOLOGY ........................................................................................................ 34 16 NON-CLINICAL TOXICOLOGY .....................................................................................

34 17 SUPPORTING PRODUCT MONOGRAPHS .................................................................... 36 PATIENT MEDICATION INFORMATION .................................................................................. 37 PATIENT MEDICATION INFORMATION […]

• Active peptic ulcer, a history of recurrent ulceration or active inflammatory disease of the gastrointestinal system. • Known or suspected hypersensitivity to the drug or other non-steroidal anti-inflammatory drugs. Patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container.

For a complete listing, see 6 Dosage Forms, Strengths, Composition and Packaging section of the product monograph. The potential for cross- MOTRIN® LIQUID GELS 200 mg and MOTRIN® LIQUID GELS 400 mg (Ibuprofen Capsules) Page 5 of 50 reactivity between different NSAIDs must be kept in mind.

• MOTRIN® Liquid Gels 200 mg/ MOTRIN® Liquid Gels 400 mg should not be used in patients with the complete or partial syndrome of nasal polyps, or in whom asthma, anaphylaxis, urticarial/angioedema, rhinitis or other allergic manifestations are precipitated by ASA or 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. • Significant hepatic impairment or active liver disease.

• Severely impaired or deteriorating renal function (creatinine clearance <30 mL/min). Individuals with lesser degrees of renal impairment are at risk of deterioration of their renal function when prescribed NSAIDs and must be monitored.

• Ibuprofen is not recommended for use with other NSAIDs because of the absence of any evidence demonstrating synergistic benefits and the potential for additive side effects (See 9 DRUG INTERACTIONS). • Children with kidney disease and children who have suffered significant fluid loss due to vomiting, diarrhea or lack of fluid intake, should not be given ibuprofen.

• The third trimester of pregnancy, because of risk of premature closure of the ductus arteriosus, and prolonged parturition. • 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.

• Known hyperkalemia (see 7 WARNINGS AND PRECAUTIONS, Fluid and Electrolyte Balance) • Right before or after heart surgery • Children and adolescents (see 1 INDICATIONS). MOTRIN® LIQUID GELS 200 mg and MOTRIN® LIQUID GELS 400 mg (Ibuprofen Capsules) Page 6 of 50