Prescription Drugs

CLINICAL PHARMACOLOGY Orphenadrine citrate is a cen-trallyacting(brain stem) compound which in animals selectively blocks facilitatory functions of the reticularformation. Orphenadrine does not produce myoneural block, nor does it affect crossed extensor reflexes. Orphenadrine prevents nicotine-induced convulsions but not those pro-ducedby strychnine. Chronic administration of Or-phenadrine Citrate, Aspirin and Caffeine to dogsandratshas revealed no drug-related toxi-city. Nobloodorurine changes were observed, nor were there any macroscopic or microscopic pathological changes detected. Extensive experience with combinations containing aspirin and caffeine hasestablished them as safe agents. The addition oforphen-adrine citrate does not alter the toxicity of aspirin and caffeine. The mode of therapeutic action of orphenadrine has not been clearly identified, but may be related to its analgesic prop-erties. Orphenadrine citrate also possesses anti-cholinergic actions.

Orphengesic (orphenadrine citrate, aspirin and caffeine) Tablets 25 mg/385 mg/30 mg) and Orphengesic Forte Tablets (orphenadrine citrate, aspirin and caffeine) Tablets 50 mg/770 mg/60 mg DESCRIPTION Each Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Tablet, for oral administration contains Orphenadrine Citrate 25mg, Aspirin 385mg and Caffeine 30 mg. Each Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Forte Tablet, fororaladministration contains OrphenadrineCitrate 50 mg, Aspirin 770 mg and Caffeine 60 mg. In addition, each tablet contains the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, D&C yellow #10, FD&C blue #1, povi-done, pregelatinized starch, stearic acid, and zinc stearate. Orphenadrine Citrate is (2-dimethylaminoethyl 2-methyl-benzhydryl ether citrate). It is a white, practically odorless, crystalline powder, having a bitter taste. It is sparingly soluble in water, slightly soluble in alcohol. It has the following structural formula: C18H23NO•C6H8O7 MW 461.51 Aspirin, salicylic acid acetate, is a non-opiate analgesic, anti-inflammatory and anti-pyretic agent. It occurs as a white, crystalline tabular or needle-like powder and is odorless or has a faint odor. It is sparingly soluble in water, freely soluble in alcohol and chloroform. It has the following structural formula: C9H8O4MW 180.16 Caffeine is a central nervous system stimulant which occurs as a white powder or white glistening needles, usually matted together. It is sparingly soluble in alcohol, and freely soluble in chloroform. The chemical name forcaffeineis, 1,3,7-Trimethylxanthine. It has thefollowing structural formula: C8H10N4O2MW 194.19

INDICATIONS Orphengesic (orphenadrine citrate, asprin and caffeine tablets) (Orphenadrine Citrate, Aspirin and Caffeine 25mg/385mg/30 mg) and Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Forte (Orphen-adrine Citrate, Aspirin and Caffeine 50 mg/770 mg/60 mg) Tablets are indicated in: Symptomatic relief of mild to moderate pain of acute musculoskeletal disorders. The orphenadrine compon-nent is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painfulmusculoskel-etal conditions. The mode or action of or-phenadrine has not been clearly identified, but may be related to its analgesic properties. Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Tablets and Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Forte Tablets do not directly relax tense skeletal muscles in man. DOSAGE AND ADMINISTRATION Orphengesic (orphenadrine citrate, asprin and caffeine tablets) : Adults 1 to 2 tablets 3 to 4 times daily. Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Forte: Adults 1/2 to 1 tablet 3 to 4 times daily. HOW SUPPLIED Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Tablets (Orphen-adrine Citrate 25mg, Aspirin 385mg and Caffeine 30 mg): Two-layered white/green, round, unscored, flatfaced, beveled-edge tablets debossed “Par” over “472” on the white side and plain on the green side are available in bottles of 100 tablets (NDC 49884-472-01) and 500 tablets (NDC 49884-472-05). Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Forte Tablets (Orphenadrine Citrate 50 mg, Aspirin 770 mg and Caffeine 60 mg): Two-layered, white/ green capsule shaped tablets debossed “Par” and “473” with bisect on the white side and plain on the green side are available in bottles of 100 tablets (NDC 49884-473-01) and 500 tablets (NDC 49884-473-05). Store below 30°C(86°F). Manufactured by: PAR PHARMACEUTICAL,INC., Spring Valley, NY 10977. Revised:06/00. FDA revision date: 5/29/1998

PATIENT INFORMATION No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

OVERDOSE No information provided. CONTRAINDICATIONS Becauseofthemildanti-cho-linergic effect of orphenadrine, Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Tablets, or Or-phengesicForteTabletsshould not be used in patients with glaucoma, pyloric or duodenal obstruction, achalasia, prostat-ic hypertrophy orobstructions at the bladder neck. Orphen-gesic Tablets or Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Forte Tablets are also contraindicated in patients withmy-astheniagravis and in patients known to be sensitive to aspirin or caffeine. The drug is contraindicated in patients who have demonstrated a previous hypersensi-tivitytothe drug.

SIDE EFFECTS Side effects of Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Tablets or Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Forte Tablets are those seen with aspirin and caffeine or those usually associated with mild anticholinergic agents. These may include tachycardia, palpitation, urinary hesitancy or retention, dry mouth, blurred vision, dilatation of the pupil, increased intraocular tension, weakness, nausea, vomiting, headache, dizziness, constipa-tion, drowsiness, and rarely, urticaria and other derma-toses. Infrequently, an elderly patientmayexperiencesome degree of confusion. Mild central excitation and occasional hallucinations may be ob-served. These mild side effects can usually be eliminated by reduction in dosage. One case of aplastic anemia associated with the use of orphenadrine citrate, aspirin and caffeine has been reported. Nocasual relationship has been established. Rare G.I. hemorrhage due to aspirin content may be associated with the administration of Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Tablets or Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Forte Tablets. Somepatients may experience transient episodes of lightheadedness, dizziness or syncope. DRUG INTERACTIONS No information provided.

WARNINGS Reye's Syndrome may develop inindividualswhohave chicken pox, influenza, orflusymp-toms. Some studies suggest a possible association between the developmentof Reye's Syndrome and the use of medicines containing salicylate or aspirin. Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Tablets (Orphenadrine Citrate, Aspirin and Caffeine Tablets 25mg/ 385mg/30 mg) and Orphen-gesic Forte Tablets (Orphen-adrine Citrate, Aspirin andCaf-feine Tablets 50 mg/770 mg/ 60 mg) contain aspirin and therefore are not recommended for use in patients with chicken pox, influenza, orflu symptoms. Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Tablets and Or-phengesic Forte Tablets 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. Aspirin should be used with extreme caution in the presence of peptic ulcers andcoag-ulationabnormalities. Usage in Pregnancy: Since safety of the use of this preparation in pregnancy, during lactation, or in the childbearing age has not been established, use of the drug in such patients requires that the potentialben-efits of the drug be weighed against its possible hazard to the mother and child. Usage in Children: The safe and effective use of this drug in children has not been established. Usage of this drug in children under 12 years of age is not recommended. PRECAUTIONS Confusion, anxiety and tremors have been reportedin a few patients receiving propoxyphene and orphena-drineconcomitantly. Asthese 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. Safety of continuous long term therapy with Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Tablets and Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Forte Tablets has not been established; therefore, if Orphen-gesic Tablets or Orphengesic (orphenadrine citrate, asprin and caffeine tablets) Forte Tablets are prescribed for prolonged use, periodic monitoringof blood, urine and liver function values is recommended.