MOTRIN PLATINUM MUSCLE & BODY

1 Dosing Considerations • Consult a physician if symptoms persist for longer than 5 days. The safety issues to consider when developing a dosage regimen of MOTRIN® Platinum Muscle & Body for individual patients is 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 WARNINGS AND PRECAUTIONS, Elderly).

• Use the lowest effective dose for the shortest duration. 2 Recommended Dose and Dosage Adjustment • Adults and Children over 12: 1 to 2 caplets every 4-6 hours. Do not exceed 6 caplets in 24 hours, unless recommended by a physician.

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.

2 Clinical Trial Adverse 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. 5 Post-Market Adverse Reactions Ibuprofen The following adverse reactions have been noted in patients treated with 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 reported events, the possibility of a causal 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 (dyspepsia), constipation, abdominal cramps or pain, fullness of the gastrointestinal tract (bloating or flatulence).

MOTRIN® Platinum Muscle & Body (Ibuprofen and Methocarbamol Tablets USP, 200 mg, 500 mg) Page 17 of 41 Incidence less than 1%: gastric or duodenal ulcer with bleeding and/or perforation, gastrointestinal hemorrhage, melena, hepatitis, jaundice, abnormal liver function AST, serum bilirubin and alkaline phosphatase, pancreatitis, oral discomfort (local burning sensation, irritation).

Allergic Incidence less than 1%: anaphylaxis. Causal relationship unknown: fever, serum sickness, lupus erythematosus, hypersensitivity reactions. Central Nervous System Incidence 3 to 9%: dizziness. Incidence 1 to 3%: headache, nervousness, drowsiness/somnolence.

Incidence less than 1%: depression, insomnia. Causal relationship unknown: paresthesias, hallucinations, dream abnormalities, psychomotor hyperactivity. 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.

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

Cardiovascular Incidence less than 1%: congestive heart failure in patients with marginal cardiac function, elevated blood pressure (hypertension), angioedema, myocardial infarction, stroke (cerebrovascular accident). MOTRIN® Platinum Muscle & Body (Ibuprofen and Methocarbamol Tablets USP, 200 mg, 500 mg) Page 18 of 41 Causal relationship unknown: arrhythmias (sinus tachycardia, sinus bradycardia, palpitations), hemorrhage (non-GI), Kounis syndrome.

Special Senses Incidence 1 to 3%: tinnitus, asthenia. 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.

Causal relationship unknown: conjunctivitis, diplopia, optic neuritis. Hematologic Incidence less than 1%: leukopenia and decreases in hemoglobin and hematocrit. g. purpura, epistaxis, hematuria, menorrhagia), bone marrow toxicity, eosinophilia.

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 WARNINGS AND PRECAUTIONS).

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

, for three days before menses. Metabolic Incidence 1 to 3%: decreased appetite, edema, fluid retention. MOTRIN® Platinum Muscle & Body (Ibuprofen and Methocarbamol Tablets USP, 200 mg, 500 mg) Page 19 of 41 Fluid retention generally responds to drug discontinuation.

Respiratory Incidence less than 1%: asthma, bronchospasms Methocarbamol May cause drowsiness, dizziness, blurred vision, lightheadedness, somnolence, vertigo, anorexia, headache, fever, nausea, allergic reactions such as urticaria, pruritus, rash, skin eruptions, conjunctivitis with nasal congestion.

Oral administration of methocarbamol may cause the urine in some patients, following elimination from the body, to turn brown, black, blue or green after a period of time.

1 Pregnant Women [08/2023] TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. 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 .................................................................................

6 5 OVERDOSAGE.............................................................................................................. 6 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................. 8 7 WARNINGS AND PRECAUTIONS ..................................................................................

16 8 ADVERSE REACTIONS ................................................................................................ 16 MOTRIN® Platinum Muscle & Body (Ibuprofen and Methocarbamol Tablets USP, 200 mg, 500 mg) Page 3 of 41 9 DRUG INTERACTIONS ................................................................................................

22 10 CLINICAL PHARMACOLOGY ....................................................................................... 23 11 STORAGE, STABILITY AND DISPOSAL ......................................................................... 25 12 SPECIAL HANDLING INSTRUCTIONS ...........................................................................

25 PART II: SCIENTIFIC INFORMATION ....................................................................................... 26 13 PHARMACEUTICAL INFORMATION ............................................................................

26 14 CLINICAL TRIALS ........................................................................................................ 27 15 MICROBIOLOGY ........................................................................................................

32 16 NON-CLINICAL TOXICOLOGY ..................................................................................... 32 17 SUPPORTING PRODUCT MONOGRAPHS .................................................................... 35 PATIENT MEDICATION INFORMATION ..................................................................................

36 MOTRIN® Platinum Muscle & Body (Ibuprofen and Methocarbamol Tablets USP, 200 mg, 500 mg) Page 4 of 41 PART I: HEALTH PROFESSIONAL INFORMATION 1 INDICATIONS Adults and children (>12 years of age): MOTRIN® Platinum Muscle & Body (ibuprofen and methocarbamol caplets) is indicated for the effective relief of pain associated with muscle spasm such as back pain, tense neck muscles, strains and sprains.

1 Pediatrics Pediatrics (< 12 years of age): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use in children under 12 years of age. MOTRIN® Platinum Muscle & Body is not indicated for children <12 years of age.

2 Geriatrics Geriatrics (> 65 years of age): Evidence from clinical studies and experience suggests that use in the geriatric population is associated with differences in safety or effectiveness. Therefore, the use of […]

• Known hypersensitivity to methocarbamol or ibuprofen. 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.

There is a potential for cross-reactivity between different NSAIDs and ibuprofen, and patients sensitive to other carbamate derivatives and methocarbamol. I. system, such as ulcerative colitis and Crohn’s disease. • The combination drug product should not be used in patients who have significant hepatic impairment or active liver disease.

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

• Patients with the complete or partial syndrome of nasal polyps, or in whom asthma, anaphylaxis, urticaria, 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. MOTRIN® Platinum Muscle & Body (Ibuprofen and Methocarbamol Tablets USP, 200 mg, 500 mg) Page 5 of 41 • 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 (equal to or greater than 12 years of age) with kidney disease or who have suffered significant fluid loss due to vomiting, diarrhea or lack of fluid intake, should not be given ibuprofen. • 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). • Ibuprofen should not be used in the presence of known hyperkalemia (also see Warnings and Precautions – Renal section).