Pharmacology

SANCOXIB (Rofecoxib) is a non-steroidal anti-inflammatory drug which is a specific COX-2 inhibitor.

It exhibits anti-inflammatory, analgesic and antipyretic activities in a number of experimental animal models and numerous clinical trials. It acts by blocking COX-2 and hence inhibiting prostaglandin synthesis and thus relieves  pain and inflammation

The mean oral bioavailability of rofecoxib at therapeutically recommended dose is approximately 93 percent. Rofecoxib can be administered without regard to timing of meals. The peak plasma level [Cmax] of 207±111 ng/ml is achieved within 2-3 hrs after a single oral dose of 25mg. With multiple dosing, steady state concentration is reached by day 4. Rofecoxib is approximately 87 percent bound to human plasma proteins and the apparent volume of distribution at steady state is approximately 91 L following 12.5 mg dose and 86 L following a 25 mg dose. Rofecoxib is metabolised through reduction by cytosolic enzymes and the principal metabolic products are the cis-dihydro and trans-dihydro-derivatives of rofecoxib. Rofecoxib is eliminated predominantly by hepatic metabolism. Approximately, 72 percent of the dose is excreted in the urine as metabolites and 14 percent in the faeces as unchanged drug. The effective half life t 1/2 (based on steady state level) is approximately 17 hrs.

Rofecoxib is approved for the treatment of osteoarthritis, menstrual pain, dental pain and for the management of acute pain in adults. It can also be used in a variety of painful conditions including symptoms associated with influenza or other viral infections, common cold, low back and neck pain, headache, toothache, sprains and strains, myositis, neuralgia, synovitis. arthritis, including rheumatoid arthritis, gout and ankylosing spondylitis, bursitis, injuries, following surgical and dental procedures

• Moderate to severe hepatic in sufficiency.
• Active peptic ulcer disease.
• Severe renal impairment.

Rofecoxib should be prescribed with caution in patients with a prior history of ulcer disease or gastrointestinal bleeding. Use of rofecoxib is not recommended in patients with moderate or severe hepatic insufficiency. It is important to monitor hepatic injury parameters when using rofecoxib. Therefore, it is recommended that the serum levels of liver function tests be assayed periodically when starting rofecoxib for chronic use. Discontinue the drug immediately in cases with worsening of liver tests. Rofecoxib should be prescribed with caution in patients with impaired renal functions and preexisting asthma. Rofecoxib should be prescribed with caution and should be introduced at lowest recommended dose in patients with fluid retention, hypertension or heart failure. Caution should be used when initiating treatment with rofecoxib in patients with considerable dehydration. It is advisable to rehydrate patients first before starting therapy with rofecoxib.

Dosage adjustment in the elderly patients is not necessary. However, therapy with rofecoxib should be initiated at the lowest recommended dose.

Rofecoxib has not been investigated in patients below 18 years of age.

In late pregnancy, rofecoxib should be avoided because it may cause premature closure of the ductus arteriosus.

Rofecoxib is generally well tolerated. It has a lower incidence of Gl tract side effects like irritation, ulcers and even bleeding than other antiinflammatory drugs. The most common adverse effects associated with rofecoxib therapy are upper respiratory infections, diarrhoea and nausea. The other side effects are dizziness, swelling of legs and / or feet due to fluid retention (edema), raised blood pressure, indigestion, heartburn, headache or itchy skin. In addition very rare, abdominal bloating, weakness, fatigue, mild allergic reaction, skin rash or skin allergy may occur.

• Rofecoxib may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors if given concomitantly.
• Concomitant administration of low dose of aspirin and rofecoxib may result in an increased rate of Gl ulcerations.
• When rofecoxib and lithium are administered concurrently, subjects should be observed carefully for signs of  lithium toxicity.
• Standard monitoring of methotrexate related toxicity should be continued if rofecoxib and methotrexate are administered concomitantly.
•  When antacid and rofecoxib are administered concurrently,Cmax of rofecoxib is decreased by 20%.

No data is available on event of overdose. It is reasonable to employ the usual supportive measures e.g. remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring and institute supportive therapy if required.

The usual adult dosage of rofecoxib is 12.5 to 25 mg once daily in osteoarthritis.For acute pain 50 mg once daily can be given to a maximum of 5 days.

Osteoarthritis  : 12.5 mg once daily (in some cases, 25mg once daily may be recommended )

Acute Pain      :  1st day  : 50mg once daily
                 2nd day onwards : 25mg once daily