Vobifen

Flurbiprofen

Chemical Structure of Vobifen

Uses and Administration Vobifen, a propionic acid derivative, is an NSAID. It is used in musculoskeletal and joint disorders such as ankylosing spondylitis, osteoarthritis, and rheumatoid arthritis, in soft-tissue disorders such as sprains and strains, for postoperative pain, and in mild to moderate pain including dysmenorrhoea and migraine. For pain and inflammation, Vobifen is given in usual oral doses of 150 to 200 mg daily in divided doses, increased to 300 mg daily in acute or severe conditions if necessary. Patients with dysmenorrhoea may be given an initial dose of 100 mg followed by 50 to 100 mg every four to six hours to a maximum total daily dose of 300 mg.

Indications Low back pain Soft tissue pain & Inflammation (ENT, Dysmenorrhea) Posttraumatic pain (postoperative pain dental pain)

Joint pain (Osteo and rheumatoid arthritis) Mechanism of Action Inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclooxygenase, which results in decreased formation of prostaglandin precursors Pharmacodynamics/Kinetics Onset of action: ~1-2 hours Distribution: Vd: 0.12 L/kg Protein binding: 99%, primarily albumin Metabolism: Hepatic via CYP2C9; forms metabolites Half-life elimination: 5.7 hours Time to peak: 1.5 hours Excretion: Urine

Dosage 200-300 mg/day in 2-, 3-, or 4 divided doses; do not administer more than 100 mg for any single dose; maximum: 300 mg/day Dental: Management of postoperative pain: 100 mg every 12 hours

Administration Tablet: Take with a full glass of water. Dietary Considerations Tablet may be taken with food, milk, or antacid to decrease GI effects.

Pregnancy/breast-feeding precautions: NSAIDs should not be used in the 3rd trimester of pregnancy. Breast-feeding is not recommended. Contraindications Hypersensitivity to Vobifen or any component of the formulation; dendritic keratitis; pregnancy (3rd trimester); patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) Warnings/Precautions Fatal asthmatic and anaphylactoid reactions have occurred in patients with "aspirin triad." Use with caution in patients with CHF, hypertension, dehydration, decreased renal or hepatic function, history of GI disease (bleeding, ulcers, or previous GI symptoms with NSAID use), or those receiving anticoagulants and/or corticosteroids. Use of NSAIDs can compromise existing renal function especially when Clcr<30 mL/minute.

Adverse Reactions Cardiovascular: Edema Central nervous system: Amnesia, anxiety, depression, dizziness, headache, insomnia, malaise, nervousness, somnolence Dermatological: Rash Gastrointestinal: Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, nausea, vomiting, weight changes Hepatic: Liver enzymes elevated Neuromuscular & skeletal: Reflexes increased, tremor, vertigo, weakness Ocular: Vision changes

Otic: Tinnitus Respiratory: Rhinitis

Overdosage/Toxicology Symptoms of overdose include apnea, metabolic acidosis, coma, leukocytosis, and renal failure. Management of NSAID intoxication is supportive and symptomatic. Since many NSAIDs undergo enterohepatic cycling, multiple doses of charcoal may be needed to reduce the potential for delayed toxicities. Drug Interactions ACE inhibitors: Antihypertensive effects may be decreased by concurrent therapy with NSAIDs; monitor blood pressure. Angiotensin II antagonists: Antihypertensive effects may be decreased by concurrent therapy with NSAIDs; monitor blood pressure. Anticoagulants (warfarin, heparin, LMWHs) in combination with NSAIDs can cause increased risk of bleeding. Vobifen (Flurbiprofen) shows superior results as compared to competition with the following attributes:

Vobifen has a longer duration of action, thus giving your patient longer duration of RELIEF

6 5 4 3 2 1 0 Flurbiprofen Ketoprofen Fenoprofen Ibuprofen Diclofeanc

Half Life of Various NSAIDs

Vobifen has rapid onset of action. (Starts its action faster then competition)

4 3.5 3 2.5 2 1.5 1 0.5 0

Flurbiprofen Aspirin Ketoprofen Fenoprofen Diclofenac Ibuprofen Diclofenac Naproxen Piroxicam

Time to reach Peak Plasma Concentration (Hrs)

Vobifen has convenient minimal per day dosage to provide RELIEF.

Flurbiprofen 4000 3500 3000 2500 2000 1500 1000 500 0 Celecoxib Naproxen Oxaprozin Nabum etone Ibuprofen Ketoprofen

Maximum Recommended Dose Per Day

References
Albert KS, Gillespie WR, Raabe A, et al, "Determination of Vobifen in Human Serum by Reverse-Phase High-Performance Liquid Chromatography With Fluorescence Detection," J Pharm Sci , 1984, 73(12):1823-5. Bragger U, Muhle T, Fourmousis I, et al, "Effect of the NSAID Vobifen on Remodeling After Periodontal Surgery," J Periodontal Res , 1997, 32(7):575-82. Brooks CD, Linet OI, Schellenberg D, et al, "Clinical Safety of Vobifen," J Clin Pharmacol , 1990, 30(4):342-51. Brooks PM and Day RO, "Nonsteroidal Anti-inflammatory Drugs - Differences and Similarities," N Engl J Med , 1991, 324(24):1716-25. Clinch D, Banerjee AK, and Ostick G, "Absence of Abdominal Pain in Elderly Patients With Peptic Ulcer," Age Ageing , 1984, 13(2):120-3. Clive DM and Stoff JS, "Renal Syndromes Associated With Nonsteroidal Anti-inflammatory Drugs," N Engl J Med , 1984, 310(9):563-72. Conlin P, Moore T, Swartz S, et al, "Effect of Indomethacin on Blood Pressure Lowering by Captopril and Losartan in Hypertensive Patients," Hypertension , 2000, 36(3):461-5. Cooper SA and Kupperman A, "The Analgesic Efficacy of Vobifen Compared to Acetaminophen With Codeine," J Clin Dent , 1991, 2(3):70-4. Cooper SA, Mardirossian G, and Miles M, "Analgesic Relative Potency Assay Comparing Vobifen 50, 100, and 150 mg, Aspirin 600 mg, and Placebo in Postsurgical Dental Pain," Clin J Pain , 1988, 4:175-81. Court H and Volans GN, "Poisoning After Overdose With Nonsteroidal Anti-inflammatory Drugs," Adverse Drug React Acute Poisoning Rev , 1984, 3(1):1-21. Davis NM, "Clinical Pharmacokinetics of Vobifen and its Enantiomers," Clin Pharmacokinet , 1995, 28(2):100-14. Dionne RA, "Suppression of Dental Pain by the Preoperative Administration of Vobifen," Am J Med , 1986, 80(3A):41-9.

Dionne RA, Snyder J, and Hargreaves KM, "Analgesic Efficacy of Vobifen in Comparison With Acetaminophen, Acetaminophen Plus Codeine, and Placebo After Impacted Third Molar Removal," J Oral Maxillofac Surg , 1994, 52(9):919-24. Forbes JA, Yorio CC, Selinger LR, et al, "An Evaluation of Vobifen, Aspirin, and Placebo in Postoperative Oral Surgery Pain," Pharmacotherapy , 1989, 9(2):66-73. Gallardo F and Rossi E, "Analgesic Efficacy of Vobifen as Compared to Acetaminophen and Placebo After Periodontal Surgery," J Periodontol , 1990, 61(4):224-7. Graham DY, "Prevention of Gastroduodenal Injury Induced by Chronic Nonsteroidal Antiinflammatory Drug Therapy," Gastroenterology , 1989, 96(2 Pt 2 Suppl):675-81. Hawkey CJ, Karrasch JA, Szczepa&ntilde;ski L, et al, "Omeprazole Compared With Misoprostrol for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs," N Engl J Med , 1998, 338(11):727-34. Heerdink ER, Leufkens HG, Herings RM, et al, "NSAIDs Associated With Increased Risk of Congestive Heart Failure in Elderly Patients Taking Diuretics," Arch Intern Med , 1998, 158(10):1108-12. Hoppmann RA, Peden JG, and Ober SK, "Central Nervous System Side Effects of Nonsteroidal Anti-inflammatory Drugs. Aseptic Meningitis, Psychosis, and Cognitive Dysfunction," Arch Intern Med , 1991, 151(7):1309-13. Jacobi J, Fraser GL, Coursin DB, et al, "Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult," Crit Care Med , 2002, 30(1):119-41. Available at: http://www.sccm.org/pdf/sedatives.pdf. Accessed August 2, 2003. Jeffcoat MK, Reddy MS, Haigh S, et al, "A Comparison of Topical Ketorolac, Systemic Vobifen, and Placebo for the Inhibition of Bone Loss in Adult Periodontitis," J Periodontol , 1995, 66(5):329-38. Jeffcoat MK, Reddy MS, Wang IC, et al, "The Effect of Systemic Vobifen on Bone Supporting Dental Implants," J Am Dent Assoc , 1995, 126(3):305-11. Knodel LC, "Preventing NSAID-Induced Ulcers: The Role of Misoprostol," Consult Pharm , 1989, 4:37-41. Lesko SM and Mitchell AA, "An Assessment of the Safety of Pediatric Ibuprofen; A PractitionerBased Randomized Clinical Trial," JAMA , 1995, 273(12):929-33. Malmberg AB and Yaksh TL, "Antinociception Produced by Spinal Delivery of the S and R Enantiomers of Vobifen in the Formalin Test," Eur J Pharmacol , 1994, 256(2):205-9. Morgan TO, Anderson A, and Bertram D, "Effect of Indomethacin on Blood Pressure in Elderly People With Essential Hypertension Well Controlled on Amlodipine or Enalapril," Am J Hypertens , 2000, 13(11):1161-7. Page J and Henry D, "Consumption of NSAIDs and the Development of Congestive Heart Failure in Elderly Patients: An Underrecognized Public Health Problem," Arch Intern Med , 2000, 160(6):777-84. Pope JE, Anderson JJ, and Felson DT, "A Meta-analysis of the Effects of Nonsteroidal Antiinflammatory Drugs on Blood Pressure," Arch Intern Med , 1993, 153(4):477-84.

Pounder R, "Silent Peptic Ulceration: Deadly Silence or Golden Silence?" Gastroenterology , 1989, 96(2 Pt 2 Suppl):626-31. Smolinske SC, Hall AH, Vandenberg SA, et al, "Toxic Effects of Nonsteroid Anti-inflammatory Drugs in Overdose. An Overview of Recent Evidence on Clinical Effects and Dose-Response Relationships," Drug Saf , 1990, 5(4):252-74. Vale JA and Meredith TJ, "Acute Poisoning Due to Nonsteroidal Anti-inflammatory Drugs," Med Toxicol , 1986, 1(1):12-31. Verbeeck RK, "Pharmacokinetic Drug Interactions With Nonsteroidal Anti-inflammatory Drugs," Clin Pharmacokinet , 1990, 19(1):44-66. Yeomans ND, Tulassay Z, Juhasz L, et al, "A Comparison of Omeprazole With Ranitidine for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs," N Engl J Med , 1998, 338(11):719-26.