Rofecoxib

Rofecoxib is a Cyclooxygenase-2 (COX-2) inhibitor / non-steroidal anti-inflammatory drugs (NSAIDs) belonging to Analgesic / anti-inflammatory.

Rofecoxib is a COX-2 inhibitor NSAID used to treat osteoarthritis, rheumatoid arthritis, acute pain, primary dysmenorrhea, and migraine attacks.

Rofecoxib is well absorbed from the GI tract (oral) approximately 90%. Time taken to reach peak plasma concentrations after 2 hours. The Rofecoxib Protein binding is approximately 85%. Extensively hepatic by reduction to cis- and trans-dihydrorofecoxib. It is excreted in Urine and faeces with 17 hours of elimination T_1/2 at steady state.

Rofecoxib shows common side effects like Headache, Nausea or Vomiting, Swelling of face, lips, eyelids, tongue, hands and feet, Severe stomachache, Blurred vision, Hives and wheezing, Heart attack, Kidney failure, Liver disease, Urinary tract infection.

Rofecoxib is available in the form of oral tablet and oral suspension.

Rofecoxib is available in India, China, Italy, Japan, US, UK, Canada, Philippines, France, Malaysia, Spain, and Russia.

Rofecoxib is an Analgesic / anti-inflammatory belonging to the class Cyclooxygenase-2 (COX-2) inhibitor / non-steroidal anti-inflammatory drug (NSAIDs).

The anti-inflammatory, analgesic, and antipyretic effects of NSAIDs appear to result from the inhibition of prostaglandin synthesis. Although the exact mechanism of action has not been determined, these effects appear to be mediated through the inhibition of the COX-2 isoenzyme at the sites of inflammation with subsequent reduction in the synthesis of certain prostaglandins from their arachidonic acid precursors. Rofecoxib selectively inhibits the cyclooxygenase-2 (COX-2) enzyme, which is important for the mediation of inflammation and pain. Unlike non-selective NSAIDs, Rofecoxib does not inhibit platelet aggregation. It also has little to no affinity for COX-1.

The effect of Rofecoxib can be observed within 1-3 hours of administration and its effect lasts for 16-20 hours.

Rofecoxib is available in the form of oral tablet and oral suspension.

Rofecoxib tablet and suspension is taken orally, usually once a day.

Rofecoxib is a medicine belonging to the group non-steroidal anti-inflammatory drugs. It is used for relieving mild to moderate pain and swelling of joints and muscles.

Rofecoxib is a Cyclooxygenase-2 (COX-2) inhibitor / non-steroidal anti-inflammatory drugs (NSAIDs) belonging to Analgesic / anti-inflammatory.

Rofecoxib selectively inhibits cyclooxygenase-2 (COX-2) enzyme that is involved in the synthesis of prostaglandins. It has no significant inhibitory action on cyclooxygenase-1 (COX-1) enzymes.

Rofecoxib is approved for use in the following clinical indications

• For relief of the signs and symptoms of osteoarthritis.
• For the management of acute pain in adults.
• For the treatment of primary dysmenorrhea.

• Osteoarthritis

Adult: Initially, 12.5 mg once daily. Max: 25 mg/day.

• Pain relief

Adult: Initially, 50 mg once daily followed by daily doses of 25-50 mg. Max: 50 mg/day. Treatment duration >5days is not recommended.

• Rheumatoid arthritis

Adult: 25 mg daily. Max: 25 mg/day.

Rofecoxib is available in various strengths as 12.5 mg; 25 mg; 50 mg; 12.5 mg/5 mL; 25 mg/5 mL.

Rofecoxib is available in the form of oral tablet and oral suspension.

• Dosage Adjustment in Hepatic impairment Patient

Maximum dose: 12.5 mg/day.

Rofecoxib is contraindicated in patients with

• Rofecoxib is contraindicated in patients with known hypersensitivity to rofecoxib or any other components of Rofecoxib.
• Rofecoxib should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients.

• Heart disease and fatality

Rofecoxib has been associated with severe to fatal adverse effects on the heart and hence should be used with extreme caution. It should not be used if you have moderate to severe heart block, angina, heart attack etc.

• Stomach ulcer and bleeding

Use of Rofecoxib can cause moderate to severe ulcers in the stomach.

• Other medicine

Rofecoxib is known to interact with many other medicines that you might possibly be taking.

• Pediatric use

Rofecoxib is not recommended for use by children under 16 years.

• Kidney impairment

Rofecoxib can cause some serious side effects on the kidney.

Restrict or minimize the use of alcohol while taking Rofecoxib.

Rofecoxib is excreted in the milk of lactating rats at concentrations like those in plasma. There was an increase in pup mortality and a decrease in pup body weight following exposure of pups to milk from dams administered Rofecoxib during lactation. The dose tested represents approximately 18- and 6-fold human exposure at 25 and 50 mg based on AUC0-24. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Rofecoxib, a decision should be made whether to discontinue nursing or to discontinue the drug, considering the importance of the drug to the mother.

Pregnancy Category C

Rofecoxib was not teratogenic in rats at doses up to 50 mg/kg/day (approximately 28- and 10-fold human exposure at 25 and 50 mg daily based on AUC0-24). There was a slight, non-statistically significant increase in the overall incidence of vertebral malformations only in the rabbit at doses of 50 mg/kg/day (approximately 1- or <1-fold human exposure at 25 and 50 mg daily based on AUC0-24). There are no studies in pregnant women. Rofecoxib should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Common

Mouth ulcers, chest pain, weight gain, atopic eczema, muscle cramps, diarrhea, headache, nausea; upper respiratory tract infection, hypertension, ischaemia, dyspepsia, epigastric discomfort, heart burn, nausea, sinusitis, back pain, headache, bronchitis, urinary tract infections.

• ACE-inhibitors

Reports suggest that NSAIDs may diminish the antihypertensive effect of Angiotensin Converting Enzyme (ACE) inhibitors. In patients with mild to moderate hypertension, administration of 25 mg daily of Rofecoxib with the ACE inhibitor benazepril, 10 to 40 mg for 4 weeks, was associated with an average increase in mean arterial pressure of about 3 mm Hg compared to ACE inhibitor alone. This interaction should be given consideration in patients taking Rofecoxib concomitantly with ACE-inhibitors.

• Aspirin

Concomitant administration of low-dose aspirin with Rofecoxib may result in an increased rate of GI ulceration or other complications, compared to use of Rofecoxib alone. At steady state, Rofecoxib 50 mg once daily had no effect on the anti-platelet activity of low-dose (81 mg once daily) aspirin, as assessed by ex vivo platelet aggregation and serum TXB2 generation in clotting blood. Rofecoxib is not a substitute for aspirin for cardiovascular prophylaxis.

• Digoxin

Rofecoxib 75 mg once daily for 11 days does not alter the plasma concentration profile or renal elimination of digoxin after a single 0.5 mg oral dose.

Furosemide: Clinical studies, as well as post marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis.

• Ketoconazole

Ketoconazole 400 mg daily did not have any clinically important effect on the pharmacokinetics of rofecoxib.

• Lithium

NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. Thus, when Rofecoxib and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.

• Methotrexate

Rofecoxib 75 mg administered once daily for 10 days increased plasma concentrations by 23% as measured by AUC0-24 hours in patients receiving methotrexate 7.5 to 15 mg/week for rheumatoid arthritis. An equivalent magnitude of reduction in methotrexate renal clearance was observed. At 24 hours postdose, a similar proportion of patients treated with methotrexate alone (94%) and subsequently treated with methotrexate co-administered with 75 mg of rofecoxib (88%) had methotrexate plasma concentrations below the measurable limit (5 ng/mL). The effects of the recommended doses for osteoarthritis (12.5 and 25 mg) of Rofecoxib on plasma methotrexate levels are unknown. Standard monitoring of methotrexate-related toxicity should be continued if Rofecoxib and methotrexate are administered concomitantly.

• Oral Contraceptives

Rofecoxib did not have any clinically important effect on the pharmacokinetics of ethinyl estradiol and norethindrone. Prednisone/prednisolone: Rofecoxib did not have any clinically important effect on the pharmacokinetics of prednisolone or prednisone.

• Rifampin

Co-administration of Rofecoxib with rifampin 600mg daily, a potent inducer of hepatic metabolism, produced an approximate 50% decrease in rofecoxib plasma concentrations. Therefore, a starting daily dose of 25 mg of Rofecoxib should be considered for the treatment of osteoarthritis when Rofecoxib is co-administered with potent inducers of hepatic metabolism. Warfarin: Prothrombin time (measured as INR) increased in both single and multiple dose cross-over studies in healthy individuals receiving both warfarin and rofecoxib. In a 21day multiple dose study in healthy individuals stabilized on warfarin (2 to 8.5 mg daily), administration of rofecoxib 25 mg QD was associated with mean increases in INR of approximately 8% (range of INR on warfarin alone, 1.1 to 2.2; range of INR on warfarin plus rofecoxib, 1.2 to 2.4). Somewhat greater mean increases in INR of approximately 11% (range of maximum INR on warfarin alone, 1.5 to 2.7; range of maximum INR on warfarin plus rofecoxib, 1.6 to 4.4) were also seen in a single dose PK screening study using a 30 mg dose of warfarin and 50 mg of rofecoxib. Standard monitoring of INR values should be conducted when therapy with Rofecoxib is initiated or changed, particularly in the first few days, in patients receiving warfarin or similar agents.

The common side effects of Rofecoxib include the following

• Common side effects

Headache, Nausea or Vomiting, Swelling of face, lips, eyelids, tongue, hands and feet, Severe stomachache, Blurred vision, Hives and wheezing, Heart attack, Kidney failure, Liver disease, Urinary tract infection.

• Pregnancy

Pregnancy Category C

Rofecoxib was not teratogenic in rats at doses up to 50 mg/kg/day (approximately 28- and 10-fold human exposure at 25 and 50 mg daily based on AUC0-24). There was a slight, non-statistically significant increase in the overall incidence of vertebral malformations only in the rabbit at doses of 50 mg/kg/day (approximately 1- or <1-fold human exposure at 25 and 50 mg daily based on AUC0-24). There are no studies in pregnant women. Rofecoxib should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Nursing Mothers

Rofecoxib is excreted in the milk of lactating rats at concentrations like those in plasma. There was an increase in pup mortality and a decrease in pup body weight following exposure of pups to milk from dams administered Rofecoxib during lactation. The dose tested represents approximately 18- and 6-fold human exposure at 25 and 50 mg based on AUC0-24. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Rofecoxib, a decision should be made whether to discontinue nursing or to discontinue the drug, considering the importance of the drug to the mother.

• Pediatric Use

Safety and effectiveness in pediatric patients below the age of 18 years have not been evaluated.

• Geriatric Use

Of the patients who received Rofecoxib in osteoarthritis clinical trials, 1455 were 65 years of age or older (this included 460 who were 75 years or older. No substantial differences in safety and effectiveness were observed between these subjects and younger subjects. Greater sensitivity of some older individuals cannot be ruled out. Dosage adjustment in the elderly is not necessary; however, therapy with Rofecoxib should be initiated at the lowest recommended dose. In one of these studies (a six-week, double-blind, randomized clinical trial), Rofecoxib 12.5 or 25 mg once daily was administered to 174 osteoarthritis patients 80 years of age. The safety profile in this elderly population was like that of younger patients treated with Rofecoxib.

• Pharmacodynamic

Rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Unlike celecoxib, rofecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism. Like other NSAIDs, rofecoxib exhibits anti-inflammatory, analgesic, and antipyretic activity. NSAIDs appear to inhibit prostaglandin synthesis via the inhibition of cyclooxygenase (COX), which are responsible for catalyzing the formation of prostaglandins in the arachidonic acid pathyway. There are at least two isoenzymes, COX-1 and COX-2, that have been identified. Although the exact mechanisms have not been clearly established, NSAIDs exert their anti-inflammatory, analgesic, and antipyretic primarily through the inhibition of COX-2. The inhibition of COX-1 is principally responsible for the negative effects on the GI mucosa.

• Pharmacokinetics

Absorption

Rofecoxib is Well absorbed from the GI tract (oral) approximately 90%. Time taken to reach peak plasma concentrations after 2 hr.

Distribution

The Rofecoxib Protein binding is approximately 85%.

Metabolism and Excretion

Extensively hepatic metabolized by reduction to cis- and trans-dihydrorofecoxib.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21042lbl.pdf
• https://go.drugbank.com/drugs/DB00533
• https://www.drugs.com/sfx/rofecoxib-side-effects.html
• https://www.mims.com/philippines/drug/info/rofecoxib?mtype=generic
• https://www.practo.com/medicine-info/rofecoxib-247-api