Oxaprozin - Indication, Dosage, Precautions, Side Effects, and Pharmacological Aspects

Drug Overview:

Oxaprozin is a nonsteroidal anti-inflammatory medicine (NSAID) used both for the treatment of moderate to severe pain and the symptoms of arthritis, including inflammation, edema, stiffness, and joint discomfort (including rheumatoid arthritis, juvenile rheumatoid arthritis, and osteoarthritis).

For Patients:

What Is Rheumatoid Arthritis?

Rheumatoid arthritis, often known as RA, is an inflammatory and autoimmune disorder where the immune system unintentionally harms healthy cells of the body, leading to inflammation (painful swelling) in the areas of the body affected. RA primarily targets joints, typically several joints at once. Hand, wrist, and knee joints are frequently affected by RA.

Rheumatoid arthritis damages the lining of the joints, causing a painful swelling that can ultimately result in bone deterioration and deformity of the joint, unlike osteoarthritis, which causes damage from wear and strain.

Long-lasting or chronic discomfort, unsteadiness (loss of balance), and deformities (misshapenness) can all result from tissue injury. In addition to these tissues, RA can harm other organs, including the heart, lungs, eyes, and other tissues all over the body.

What Are the Clinical Indications For Rheumatoid Arthritis?

There are periods when RA symptoms worsen, known as flares, and periods when they improve, known as remissions.

Clinical indications for rheumatoid arthritis include:

• Pain in the joints.

• Stiffness of the joints.

• Tenderness and inflammation were observed in multiple joints.

• Fatigue and weakness.

• Fever.

• Loss in weight and appetite.

• Identical signs and symptoms are on either side of the body (for instance, in both knees or hands).

What Are the Side Effects of Oxaprozin?

The common side effects of the drug are listed below:

• Vomiting.

• Bloating of the stomach.

• Dizziness and drowsiness.

• Diarrhea.

• Constipation.

• Pain in the head.

• Difficulty sleeping.

• Ringing sound in the ears.

• Depression and confusion.

The serious side effects of the drug are:

• Swelling is seen on the face, lips, eyes, throat, hands, or tongue.

• Difficulty breathing and swallowing.

• Blisters and fever.

• Itching and rashes.

• Stomach upset and appetite loss.

• Increased heartbeat and pale skin.

• Painful urination.

• Lack of energy.

• Discolored, dark, and brown urine.

How Is the Medicine Stored and Disposed Of?

The medicine must be kept in the original, tightly secured container. It is important to store it in a location inaccessible to children. The drug should be kept in a location without excessive heat and moisture, especially in the bathroom. Safety caps must be secured immediately after using the medication. Prescriptions that have not been used must be properly disposed of to keep dogs, children, and others from consuming them. The medication should, however, always be retained in the bathroom. Instead, using a drug take-back program is the best way to dispose of the medicines. More information regarding the take-back program can be provided by the chemist or the city's recycling department. One can also visit the FDA (Food and Drug Administration) website for the safe disposal of medicines to learn more about the take-back program.

What Specific Safety Measures Should Be Taken?

• Inform the physician and pharmacist about any drug allergies, including those to Oxaprozin, Aspirin, other NSAIDs like Ibuprofen and Naproxen, other drugs, or any inactive components in Oxaprozin tablets.

• Inform the doctor if the patient has had asthma, heart failure, swollen hands, feet, ankles, lower legs, renal disease, or liver illness.

• The patient should inform the doctor if they are expecting, want to get pregnant, or are nursing a baby. Oxaprozin may damage the fetus and complicate delivery if it is used beyond 20 weeks of pregnancy. Except as directed by the physician, avoid using Oxaprozin during or after the first 20 weeks of pregnancy. Call the doctor if the patient becomes pregnant while taking Oxaprozin.

How Is Oxaprozin Taken by the Patient?

Oxaprozin is available in the form of a tablet to be swallowed. Typically, it is taken two or three times a day. Every day, take Oxaprozin around the indicated time. Patients should ask the physician or chemist to clarify instructions on the prescription label they are unsure about following. The dosage should be taken as prescribed by the doctor.

For Doctors:

What Are the Pharmacological Aspects of Oxaprozin?

Physical Properties of the Drug

• Color - White to off-white with a slight odor.

• Drug Group - NSAIDs (nonsteroidal anti-inflammatory drugs).

• Chemical Name - 4,5-diphenyl-2-oxazole-propionic acid

• Empirical Formula - C18H15NO3.

• Molecular Weight - 293.

• pka in Water (Acid Dissociation Constant) - 4.3.

• Melting Point - 162 to 163 degrees Celsius.

• Solubility - Does not dissolve in water but is soluble in alcohol.

• Components of the Drug - Starch, polyethylene glycol, titanium dioxide, magnesium stearate, hypromellose, methylcellulose, and microcrystalline cellulose.

Pharmacodynamics - The drug Oxaprozin is a nonsteroidal anti-inflammatory drug (NSAID) that has been shown in animal models to have anti-inflammatory, analgesic, and antipyretic effects. Like other NSAIDs, the exact mechanism of action of Oxaprozin is unknown. However, it may be connected to prostaglandin synthetase inhibition.

Pharmacokinetics:

• Absorption - After oral dosing, Oxaprozin is 95 percent absorbed. The absorption rate is slowed by food, but the amount of absorption remains unaffected. Antacids have no discernible impact on how quickly or thoroughly Oxaprozin is absorbed.

• Distribution - The estimated volume of distribution (Vd/F) for the entire amount of Oxaprozin in the body is roughly 11 to 17 liters per 70 kilograms of body weight.In plasma, albumin is the plasma protein to which Oxaprozin is 99 percent attached. At therapeutic medication doses, Oxaprozin's plasma protein binding is saturable, resulting in an increasing amount of the free drug as the overall drug concentration increases. The observed distribution volume and the clearance of the total amount increased with higher single doses or with repeated once-daily dosing. In contrast, unbound drug clearance declined as a result of nonlinear protein binding. According to its physical-chemical characteristics, Oxaprozin is predicted to be secreted in human milk, although the quantity of Oxaprozin secreted in breast milk is yet to be assessed. In patients with rheumatoid arthritis, Oxaprozin has been found to enter synovial tissues, with concentrations approximately two-fold higher than in plasma and three-fold higher than in synovial fluid.

• Metabolism - Human urine or feces have been shown to contain several Oxaprozin metabolites. The metabolites of Oxaprozin do not have considerable pharmacologic action. In individuals with appropriate renal function, even after prolonged doses, metabolites do not build up in the plasma. Plasma only has relatively small concentrations of the metabolites. The liver is Oxaprozin's main site of metabolism, carrying out microsomal oxidation (65 percent) and glucuronic acid conjugation (35 percent). The two most important conjugated metabolites of Oxaprozin are ether glucuronide and ester. For in vivo animal models and receptor binding experiments, the ester and ether glucuronide conjugated metabolites have been assessed alongside Oxaprozin and have shown little action. Active phenolic metabolites are created in a negligible quantity (five percent), although they contribute very little to total activity.

• Excretion - Around five percent of Oxaprozin is eliminated unaltered in the urine. 65 percent of the dosage is eliminated as metabolites in the urine and 35 percent in the feces. The enterohepatic recycling of Oxaprozin is negligible, and biliary excretion of unaltered Oxaprozin is a minor route. The accumulating half-life after chronic dosage is around 22 hours. Due to higher binding and reduced clearance at lower concentrations, the elimination half-life is typically two times longer than the accumulation half-life.

Drug Use in Specific Populations:

• Pediatric Population - A population pharmacokinetic study found no clinically significant age-dependent changes in the apparent clearance of unbound Oxaprozin between adult and juvenile rheumatoid arthritis patients.

• Geriatric Population - In managing elderly people (65 years and older), care should be used as with any NSAID. Although many older people may require a lower dose due to low body weight or problems linked with aging, there is no need to change the dosage for pharmacokinetic reasons.

• Hepatic Insufficiency - 95 percent of Oxaprozin is metabolized by the liver. There is no difference in the Oxaprozin dose that must be administered in patients with well-compensated cirrhosis compared to individuals with normal hepatic function. Hence, they do not need lower doses of Oxaprozin. However, individuals with significant hepatic impairment should be treated with care.

• Cardiac Failure - Oxaprozin's pharmacokinetics and plasma protein binding are unaffected by well-compensated heart failure.

• Renal Insufficiency:

  • Only five percent of an Oxaprozin dosage is eliminated without any changes in the urine. Renal clearance of Oxaprozin reduces proportionally to creatinine clearance (CrCl). Patients with renal insufficiency have been studied for pharmacokinetics and were treated with Oxaprozin.

  • The clinical significance of the reduction in total body clearance of Oxaprozin arises in those with severely reduced CrCl. Due to its strong protein binding, Oxaprozin is not considerably eliminated from the blood in patients receiving hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

  • Patients with significant renal impairment may see a reduction in the plasma protein binding of Oxaprozin. Patients with renal impairment may require dosage modifications.

What Are the Indications and Contraindications of Oxaprozin?

Before choosing to administer Oxaprozin, the doctor should carefully compare this medication's benefits and drawbacks to other available treatment options before prescribing it. In accordance with each patient's treatment objectives, provide the lowest dose that is effective in the shortest amount of time.

• Indications:

  • Indicated to treat juvenile rheumatoid arthritis, rheumatoid arthritis, and osteoarthritis.

• Contraindications:

  • Patients with known Oxaprozin hypersensitivity should not use Oxaprozin.

  • Oxaprozin is not indicated for managing peri-operative pain during coronary artery bypass graft (CABG) surgery.

  • Patients with asthma, urticaria, or allergic-like symptoms after taking aspirin or other NSAIDs should not be given Oxaprozin, as NSAIDs have been linked to severe, rarely deadly anaphylactic responses in such people.

Warnings and Precautions:

• Cardiovascular Thrombotic Event - A higher incidence of major cardiovascular (CV) thrombotic events, stroke, and myocardial infarction, which can be fatal, has been seen in clinical studies of numerous COX-2 selective and nonselective NSAIDs for up to three years. There may be a comparable risk with all COX-2 selective and nonselective NSAIDs. Patients with known cardiovascular disease or risk factors for developing it may be more susceptible. Two significant, controlled clinical studies of a COX-2 selective NSAID discovered an increased risk of stroke and myocardial infarction. It was given for pain management for the first few days (usually 10 to 14 days) after CABG surgery.

• Hypertension - Some people using NSAIDs have had fluid retention and edema. Patients with fluid retention or heart failure should take Oxaprazin cautiously. NSAIDs, such as Oxaprozin, may cause new hypertension or exacerbate pre-existing hypertension, which may raise the risk of CV events. Patients with hypertension should use NSAIDs, especially Oxaprozin, with care. When starting NSAID medication and for the duration of it, blood pressure (BP) should be constantly monitored.

• Congestive Heart Failure and Edema - Some people using NSAIDs have reported fluid retention and edema. People with fluid retention or heart failure should use Oxaprozin with care.

• Gastrointestinal Effects - NSAIDs, especially Oxaprozin, can result in severe gastrointestinal (GI) adverse effects, including in the stomach, small intestine, or large intestine. It results in ulceration, rupture, bleeding, and inflammation. These severe negative effects can happen to people using NSAIDs at any moment, with or without prior warning signs. The lowest effective dose should be administered for the shortest possible time to reduce GI events in individuals receiving an NSAID. During treatment with Oxaprozin, patients and doctors should be vigilant for signs and symptoms of GI bleeding and ulceration and start extra testing and therapy as soon as a significant GI event is detected. This involves discontinuing the NSAID until a significant gastrointestinal adverse event is ruled out. Alternative treatments without the use of NSAIDs have to be taken into consideration for high-risk individuals.

• Renal Effects - NSAID use over an extended period has caused renal papillary necrosis and other renal damage. Patients in whom renal prostaglandins are compensatory in maintaining renal perfusion have also experienced renal toxicity. Nonsteroidal anti-inflammatory medication therapy in these individuals may result in a dose-dependent decrease in prostaglandin production and, secondarily, renal blood flow, which may lead to overt renal decompensation. Patients with poor renal function, heart failure, liver dysfunction, those on diuretics and ACE inhibitors, and the elderly are those who are most at risk of this reaction. Recovery to the pre-treatment state frequently follows the cessation of NSAID medication.

• Anaphylactic Reactions - Similar to other NSAIDs, Oxaprozin can cause anaphylactoid responses in people who have never taken it. Patients experiencing the aspirin triad should not take Oxaprozin. This symptom cluster is most common in asthmatic patients with rhinitis, whether or not they have nasal polyps, or individuals with severe bronchospasm after taking aspirin or other NSAIDs, including Oxaprozin.

• Skin - Oxaprozin can cause deadly toxic epidermal necrolysis (TEN), Stevens-Johnson Syndrome, and exfoliative dermatitis, among other significant side effects. These clinical manifestations occur suddenly, and patients should be educated about them.

• Pregnancy - The ductus arteriosus may close too soon due to exposure to Oxaprozin; hence, it should be avoided.

What Are the Drug Interactions of Oxaprozin?

• Aspirin - Aspirin and Oxaprozin should not be used together because Oxaprozin removes salicylates from plasma protein binding sites. The risk of salicylate toxicity is anticipated to rise with coadministration.

• Methotrexate - Studies suggest that co-administration of Oxaprozin and Methotrexate increases the toxicity of Methotrexate. The oral clearance of Methotrexate is reduced by around 36% when Oxaprozin and Methotrexate are administered together. Since Oxaprozin exposure increases Methotrexate, the dosage of Methotrexate may be reduced.

• ACE Inhibitors - The antihypertensive action of ACE inhibitors may be diminished by NSAIDs. Enalapril and its active metabolite, Enalaprilat, have been demonstrated to have altered pharmacokinetics when administered with Oxaprozin. When patients use NSAIDs and Angiotensin-converting enzyme inhibitors together, this interaction should be taken into account.

• Diuretics - The natriuretic effects of Furosemide and Thiazides can be lessened in certain people by Oxaprozin, according to clinical trials and post-marketing findings. This reaction has been linked to renal prostaglandin production suppression. The patient should be cautiously watched for indications of renal failure while receiving concurrent NSAID medication.

• Warfarin - Due to the synergistic effects of warfarin and NSAIDs on gastrointestinal (GI) bleeding, people who take both medications have a larger risk of experiencing significant GI bleeding than those who take either alone.

• Beta-Blockers - NSAIDs tend to increase the blood pressure in the body. Hence, as with any NSAID, patients commencing Oxaprozin medication should take routine blood pressure monitoring into account.

• H2 Receptor Antagonist - In patients receiving therapeutic dosages of Cimetidine or Ranitidine at the same time as Oxaprozin, the total body clearance of Oxaprozin was lowered by 20 percent. No changes were noticed in other pharmacokinetic parameters.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Oxaprozin did not exhibit any mutagenicity or fertility impairment in trial studies. Carcinogenicity was exhibited in a trial study on male and female mice. The male mice showed increased cases of liver cancer. However, the result is known among humans.

Dosage and Administration:

Use the smallest dose that will be active for the shortest time for each patient's unique treatment objectives. The dose and frequency should be changed to meet each patient's needs after evaluating their first response to Oxaprozin.

• Rheumatoid Arthritis - The typical dose for rheumatoid arthritis treatment is 1200 milligrams. Two 600 mg caplets are taken daily orally.

• Juvenile Rheumatoid Arthritis (JRA) - Based on the patient's body weight, a suggested dose should be administered orally once a day to patients aged 6 to 16 to manage the signs and symptoms of JRA.

What Are the Adverse Reactions of Oxaprozin?

• CVS or Cardiovascular System - Edema.

• Hematological System - Increase in bleeding duration and anemia.

• Nervous System - CNS inhibition (depression, sedation, somnolence, disorientation), headache, and dizziness.

• Digestive System - Abdominal discomfort, diarrhea, gastrointestinal ulcers (gastric or duodenal), dyspepsia, flatulence, anorexia, constipation, extensive bleeding or perforation, nausea, vomiting, elevated liver enzymes, and heartburn.

• Urogenital System - Dysuria (painful urination), and impairment of renal function.

• Skin - Rashes and itching.

Clinical Trial Study and Drug Efficacy:

For three months, 40 patients with active rheumatoid arthritis participated in a parallel, double-blind experiment to examine the anti-inflammatory efficacy and adverse effects of therapy with Oxaprozin and Aspirin. The findings demonstrated that in rheumatoid arthritis, 1200 mg of Oxaprozin daily has anti-inflammatory characteristics comparable to those of 3.9 g of Aspirin. Better outcomes were obtained with a daily dose of 1200 mg Oxaproxin than with a dose level of 600 mg, indicating a tight dose-response relationship. Similar side effects were reported for both Oxaprozin and Aspirin. While rash and headache were more frequently reported in individuals on Oxaprozin, gastrointestinal discomfort was more frequent and severe in the Aspirin group.