ORPHENADRINE: 584 Adverse Event Reports & Safety Profile

DESCRIPTION Orphenadrine citrate is the citrate salt of orphenadrine. It occurs as a white, crystalline powder having a bitter taste. It is practically odorless; sparingly soluble in water, slightly soluble in alcohol. The chemical name of orphenadrine citrate is (±)-N,N-Dimethyl-2-[(o-methyl-〈-phenylbenzyl)oxy]ethylamine citrate (1:1) having molecular formula C 18 H 23 NO•C 6 H 8 O 7 and molecular weight of 461.51. It has the following structural formula: Each tablet for oral administration contains 100 mg orphenadrine citrate.

Each

Orphenadrine citrate extended release tablet contains the following inactive ingredients: hydroxypropyl methylcellulose, lactose monohydrate and magnesium stearate. S:\RA\2011 ANDA\Orphenadrine Citrate ER Tablets\CBE - Labeling\Backup\062812\figure-01.jpg

INDICATIONS AND USAGE Orphenadrine citrate is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculo-skeletal conditions. The mode of action of this drug has not been clearly identified, but may be related to its analgesic properties. Orphenadrine citrate does not directly relax tense skeletal muscles in man.

DOSAGE AND ADMINISTRATION Adults: 2 mL (60 mg) intravenously or intramuscularly - May be repeated every 12 hours. Relief may be maintained by one (100 mg) orphenadrine citrate tablet twice daily. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever the solution and container permit.

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Contraindications

Orphenadrine citrate extended-release tablets are contraindicated in patients with glaucoma, pyloric or duodenal obstruction, stenosing peptic ulcers, prostatic hypertrophy or obstruction of the bladder neck, cardio-spasm (mega-esophagus) and myasthenia gravis. Orphenadrine citrate tablets are contraindicated in patients who have demonstrated a previous hypersensitivity to the drug.

ADVERSE REACTIONS Adverse reactions of orphenadrine are mainly due to the mild anti-cholinergic action of orphenadrine, and are usually associated with higher dosage. Dryness of the mouth is usually the first adverse effect to appear. When the daily dose is increased, possible adverse effects include: tachycardia, palpitation, urinary hesitancy or retention, blurred vision, dilatation of pupils, increased ocular tension, weakness, nausea, vomiting, headache, dizziness, constipation, drowsiness, hypersensitivity reactions, pruritus, hallucinations, agitation, tremor, gastric irritation, and rarely urticaria and other dermatoses. Infrequently, an elderly patient may experience some degree of mental confusion. These adverse reactions can usually be eliminated by reduction in dosage. Very rare cases of aplastic anemia associated with the use of orphenadrine tablets have been reported. No causal relationship has been established. Rare instances of anaphylactic reaction have been reported associated with the intramuscular injection of orphenadrine citrate. To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals, Inc. at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

WARNINGS Contains Sodium Metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people. Some patients may experience transient episodes of lightheadedness, dizziness or syncope. Orphenadrine citrate may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or driving a motor vehicle; ambulatory patients should therefore be cautioned accordingly. Usage in Pregnancy: Safe use of orphenadrine citrate has not been established with respect to adverse effects upon fetal development. Therefore, orphenadrine citrate should be used in women of childbearing potential and particularly during early pregnancy only when in the judgment of the physician the potential benefits outweigh the possible hazards. Usage in Children: Safety and effectiveness in children have not been established; therefore, this drug is not recommended for use in the pediatric age group.

PRECAUTIONS Confusion, anxiety and tremors have been reported in few patients receiving propoxyphene and orphenadrine concomitantly. As these symptoms may be simply due to an additive effect, reduction of dosage and/or discontinuation of one or both agents is recommended in such cases. Orphenadrine citrate should be used with caution in patients with tachycardia, cardiac decompensation, coronary insufficiency, cardiac arrhythmias. Safety of continuous long-term therapy with orphenadrine has not been established. Therefore, if orphenadrine is prescribed for prolonged use, periodic monitoring of blood, urine and liver function values is recommended.

Pregnancy Teratogenic Effects Pregnancy

Category C Animal reproduction studies have not been conducted with orphenadrine. It is also not known whether orphenadrine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Orphenadrine should be given to a pregnant woman only if clearly needed.

Pediatric Use

Safety and effectiveness in children have not been established; therefore, this drug is not recommended for use in the pediatric age group.