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DAYPRO ALTA™
(oxaprozin potassium) 600mg tablets
Cardiovascular Risk
- NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patient's with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk (see WARNINGS).
- Daypro ALTA™ is contraindicated for treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).
Gastrointestinal Risk
- NSAID's cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events (see WARNINGS).
DESCRIPTION
DAYPRO ALTA (oxaprozin potassium tablets) is a member of the propionic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). Each blue, capsule-shaped tablet contains oxaprozin potassium (678mg equivalent to 600mg of oxaprozin) for oral administration. The chemical name for oxaprozin potassium is 4,5-diphenyl-2-oxazolepropionic acid, potassium salt. Its empirical formula is C18H14NO3K, and molecular weight is 331. Oxaprozin potassium is a white to off white powder with a melting point of 215°C. It is slightly soluble in alcohol and very soluble in water. The PK in water is 9.7.
It has the following structural formula:
Inactive ingredients in DAYPRO ALTA tablets include microcrystalline cellulose, hydroxypropyl methylcellulose, pregelatinized corn starch, stearic acid, colloidal silicon dioxide, polyethylene glycol, titanium dioxide, FD&C Blue #1 Aluminum Lake, and pharmaceutical glaze.
CLINICAL PHARMACOLOGY
Pharmacodynamics
DAYPRO ALTA, the potassium salt of oxaprozin, is a nonsteroidal anti-inflammatory drug (NSAID), which dissociates into the active moiety oxaprozin in vivo. Oxaprozin has been shown to have anti-inflammatory, analgesic, and antipyretic properties in animal models. The mechanism of action of DAYPRO ALTA, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition.
Pharmacokinetics
(see Table 1)
Special Populations
Drug Interactions
(Also see PRECAUTIONS, Drug Interactions)
CLINICAL STUDIES
Osteoarthritis
DAYPRO ALTA 1200 mg once daily was evaluated for the relief of the signs and symptoms of osteoarthritis in a 6-month placebo-controlled study versus oxaprozin acid in over 300 patients. In this trial, treatment with DAYPRO ALTA resulted in improvement in WOMAC (Western Ontario and McMaster Universities) osteoarthritis index, a composite of pain, stiffness, and functional measures in OA. DAYPRO ALTA demonstrated significant reduction in joint pain compared to placebo and was found to be comparable to 1200 mg once daily of oxaprozin acid.
With respect to GI events, DAYPRO ALTA appeared to be less well tolerated than oxaprozin acid in this study. The rates for symptomatic ulcers (2.2%) and nausea (13%) for DAYPRO ALTA treated patients were higher than the rates observed with oxaprozin acid (0% and 6%, respectively) (see ADVERSE REACTIONS).
Rheumatoid arthritis
Oxaprozin, the active component of DAYPRO ALTA (oxaprozin potassium tablets), was evaluated for the relief of the signs and symptoms of rheumatoid arthritis in placebo and active controlled clinical trials in a total of 646 patients. Oxaprozin was given in single or divided daily doses of 600 to 1800 mg/day and was found to be comparable to 2600 to 3900 mg/day of aspirin.
INDICATIONS AND USAGE
Carefully consider the potential benefits and risks of DAYPRO ALTA and other treatment options before deciding to use DAYPRO ALTA. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).
DAYPRO ALTA is indicated:
- For relief of the signs and symptoms of osteoarthritis
- For relief of the signs and symptoms of rheumatoid arthritis
CONTRAINDICATIONS
DAYPRO ALTA is contraindicated in patients with known hypersensitivity to oxaprozin potassium.
DAYPRO ALTA 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 (see WARNINGS - Anaphylactoid Reactions, and PRECAUTIONS – Pre-existing Asthma).
DAYPRO ALTA is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).
WARNINGS
CARDIOVASCULAR EFFECTS
PRECAUTIONS
General
DAYPRO ALTA should not be used concomitantly with other oxaprozin-containing products, since all such products circulate in the plasma as the oxaprozin anion.
DAYPRO ALTA cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.
The pharmacological activity of DAYPRO ALTA in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.
Hepatic Effects
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including DAYPRO ALTA. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.
A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with DAYPRO ALTA. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.). DAYPRO ALTA should be discontinued.
Photosensitivity
Oxaprozin has been associated with rash and/or mild photosensitivity in dermatologic testing. An increased incidence of rash on sun-exposed skin was seen in some patients in clinical trials.
Hematological Effects
Anemia is sometimes seen in patients receiving NSAIDs, including DAYPRO ALTA. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including DAYPRO ALTA, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.
NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving DAYPRO ALTA who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.
Preexisting Asthma
Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, DAYPRO ALTA should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.
Information for Patients
Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.
- DAYPRO ALTA, like other NSAIDs, may cause CV side effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow‑up (see WARNINGS, Cardiovascular Effects).
- DAYPRO ALTA, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow‑up (see WARNINGS: Gastrointestinal Effects: Risk of Ulceration, Bleeding and Perforation).
- DAYPRO ALTA, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS and TEN, which may result in hospitalization and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and bulers, fever, or other signs hypersensitivity such as itching, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible.
- Patients should promptly report, signs or symptoms of unexplained weight gain, or edema to their physicians.
- Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness and "flu-like" symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.
- Patients should be informed of the signs of an anaphylactoid reaction (e.g. difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS, Anaphylactoid reactions).
- In late pregnancy, as with other NSAIDs, DAYPRO ALTA should be avoided because it may cause premature closure of the ductus arteriosus.
Laboratory Tests
Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, DAYPRO ALTA should be discontinued.
Drug Interactions
Laboratory Test Interactions
False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking oxaprozin. This is due to lack of specificity of the screening tests. False-positive test results maybe expected for several days following discontinuation of oxaprozin therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish oxaprozin from benzodiazepines.
Carcinogenesis, mutagenesis, impairment of fertility
In oncogenicity studies, oxaprozin administration for 2 years was associated with the exacerbation of liver neoplasms (hepatic adenomas and carcinomas) in male CD mice, but not in female CD mice or rats. The significance of this species-specific finding to man is unknown.
Oxaprozin did not display mutagenic potential. No evidence of genetic toxicity or cell-transforming ability was found in test results from the Ames test, forward mutation in yeast and Chinese hamster ovary (CHO) cells, DNA repair testing in CHO cells, micronucleus testing in mouse bone marrow, chromosomal aberration testing in human lymphocytes, or cell transformation testing in mouse fibroblast.
Oxaprozin administration was not associated with impairment of fertility in male and female rats at oral doses up to 200mg/kg/day (1180 mg/m2/day); the usual human dose is 17 mg/kg/day, or (629 mg/m2/day). However, testicular degeneration was observed in beagle dogs treated with 37.5 to 150 mg/kg/day (750 to 3000 mg/m2/day) of oxaprozin for 6 months, or 37.5 mg/kg/day for 42 days, a finding not confirmed in other species. The clinical relevance of this finding is not known.
Pregnancy
Teratogenic Effects
Labor and Delivery
In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of DAYPRO ALTA on labor and delivery in pregnant women are unknown.
Nursing Mothers
It is not known whether this drug is excreted in human milk; however, oxaprozin was found in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from DAYPRO ALTA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness of DAYPRO ALTA in pediatric patients have not been established.
Geriatric Use
Age was not shown to have an effect on the pharmacokinetics of DAYPRO ALTA following 600, 1200 and 1800 rug doses or on the incidence of adverse reactions reported (see CLINICAL PHARMACOLOGY, Special Populations). In a controlled 6-month clinical trial of 803 patients (322 of whom received DAYPRO ALTA), about 40% of whom were elderly, there was basically no difference detected in terms of the total number of subjects reporting adverse events with respect to age. As with any NSAID, the elderly are likely to tolerate adverse reactions less well than younger patients. Caution should be exercised in treating the elderly (65 years and older), and extra care should be taken when choosing a dose.
Oxaprozin is substantially excreted by the kidney, and the risk of toxic reactions to DAYPRO ALTA may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see WARNINGS, Renal Effects).
ADVERSE REACTIONS
In patients taking DAYPRO ALTA (oxaprozin potassium tablets), oxaprozin, or other NSAIDs , the following are the most frequently reported adverse experiences occurring in approximately 1–10% of patients (see CLINICAL STUDIES, Osteoarthritis):
Gastrointestinal experiences including:
Abdominal pain, anorexia, constipation, diarrhea, dyspepsia, flatulence, gross gastrointestinal bleeding/perforation, GI ulcers (gastric/duodenal), heartburn, nausea, vomiting.
Non-gastrointestinal experiences including:
abnormal renal function, anemia, confusion, depression, disturbance of sleep, dizziness, dysuria or frequency, edema, elevated liver enzymes, headaches, increased bleeding time, pruritus, rashes, sedation, somnolence, tinnitus.
Additional adverse experiences reported in less than 1% of patients:
Body as a whole-- anaphylactic reactions, appetite changes, death, fever, infection, sepsis, serum sickness.
Cardiovascular system-- arrhythmia, blood pressure changes, congestive heart failure, hypertension, hypotension, myocardial infarction, palpitations, syncope, tachycardia, vasculitis.
Digestive system-- alteration in taste, dry mouth, eructation, esophagitis, gastritis, glossitis, hematemesis, hemorrhoidal or rectal bleeding, hepatitis, jaundice, liver failure, pancreatitis, stomatitis.
Hemic and lymphatic system-- agranulocytosis, aplastic anemia, ecchymosis, eosinophilia, hemolytic anemia, leukopenia, lymphadenopathy, melena, pancytopenia, purpura, thrombocytopenia.
Metabolic and nutritional-- hyperglycemia, weight changes.
Nervous system-- anxiety, asthenia, coma, convulsions, dream abnormalities, drowsiness, hallucinations, insomnia, malaise, meningitis, nervousness, paresthesia, tremors, vertigo, weakness.
Respiratory system-- asthma, dyspnea, pneumonia, pulmonary infections, respiratory depression, sinusitis, symptoms of upper respiratory tract infection.
Skin and appendages-- alopecia. angioedema, increased sweating, photosensitivity, pseudoporphyria, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell'ssyndrome), urticaria.
Special senses-- blurred vision, conjunctivitis, hearing impairment.
Urogenital system--acute interstitial nephritis, acute renal failure, cystitis, decreased menstrual flow, hematuria, increase in menstrual flow, nephrotic syndrome, oliguria/polyuria, proteinuria, renal insufficiency.
OVERDOSAGE
Symptoms following acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression and coma may occur, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDS, and may occur following an overdose.
Patients should be managed by symptomatic and supportive care following NSAID overdose, There are no specific antidotes. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic maybe indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.
DOSAGE AND ADMINISTRATION
Carefully consider the potential benefits and risks of DAYPRO ALTA and other treatment options before deciding to use DAYPRO ALTA. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).
After observing the response to initial therapy with DAYPRO ALTA, the dose and frequency should be adjusted to suit an individual patient's needs.
Osteoarthritis and Rheumatoid Arthritis
The recommended dose of DAYPRO ALTA for the relief of the signs and symptoms of osteoarthritis and rheumatoid arthritis is 1200 mg (two 600 mg tablets) once a day. Divided doses may be tried in patients unable to tolerate single doses. For osteoarthritis patients of low body weight of with milder disease, an initial dose of one 600 mg tablet once a day may be appropriate. The maximum total daily dose is 1200 mg.
HOW SUPPLIED
DAYPRO ALTA 600 mg tablets are blue, capsule-shaped, film-coated, with Searle 1391 printed on one side.
NDC Number Size
0025-5500-01 bottle of 100
0025-5500-03 bottle of 500
0025-5500-02 carton of 100 unit dose
Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) (see USP Controlled Room Temperature) in tightly-closed container. Protect from moisture.
Rx only
DAYPRO ALTA™
(oxaprozin potassium tablets)
LAB-0279-5.0
January 2007
Medication Guide for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
(See the end of this Medication Guide for a ul of prescription NSAID medicines.)
What is the most important information I should know about medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
NSAID medicines may increase the chance of a heart attack or stroke that can lead to death. This chance increases:
- with longer use of NSAID medicines
- in people who have heart disease
NSAID medicines should never be used right before or after a heart surgery called a "coronary artery bypass graft (CABG)."
NSAID medicines can cause ulcers and bleeding in the stomach and intestines at any time during treatment. Ulcers and bleeding:
- can happen without warning symptoms
- may cause death
The chance of a person getting an ulcer or bleeding increases with:
- taking medicines called "corticosteroids" and "anticoagulants"
- longer use
- smoking
- drinking alcohol
- older age
- having poor health
NSAID medicines should only be used:
- exactly as prescribed
- at the lowest dose possible for your treatment
- for the shortest time needed
What are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
NSAID medicines are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as:
- different types of arthritis
- menstrual cramps and other types of short-term pain
Who should not take a Non-Steroidal Anti-Inflammatory Drug (NSAID)?
Do not take an NSAID medicine:
- if you had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAID medicine
- for pain right before or after heart bypass surgery
Tell your healthcare provider:
- about all of your medical conditions.
- about all of the medicines you take. NSAIDs and some other medicines can interact with each other and cause serious side effects. Keep a ul of your medicines to show to your healthcare provider and pharmacist.
- if you are pregnant. NSAID medicines should not be used by pregnant women late in their pregnancy.
- if you are breastfeeding. Talk to your doctor.
What are the possible side effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
| Serious side effects include: | Other side effects include: |
|
|
Get emergency help right away if you have any of the following symptoms:
- shortness of breath or trouble breathing
- chest pain
- weakness in one part or side of your body
- slurred speech
- swelling of the face or throat
Stop your NSAID medicine and call your healthcare provider right away if you have any of the following symptoms:
- nausea
- more tired or weaker than usual
- itching
- your skin or eyes look yellow
- stomach pain
- flu-like symptoms
- vomit blood
- there is blood in your bowel movement or it is black and sticky like tar
- skin rash or bulers with fever
- unusual weight gain
- swelling of the arms and legs, hands and feet
These are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines.
Other information about Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
- Aspirin is an NSAID medicine but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines.
- Some of these NSAID medicines are sold in lower doses without a prescription (over –the –counter). Talk to your healthcare provider before using over –the –counter NSAIDs for more than 10 days.
NSAID medicines that need a prescription
| Generic Name | Tradename |
|---|---|
| Celecoxib | Celebrex |
| Diclofenac | Cataflam, Voltaren, Arthrotec (combined with misoprostol) |
| Diflunisal | Dolobid |
| Etodolac | Lodine, Lodine XL |
| Fenoprofen | Nalfon, Nalfon 200 |
| Flurbiprofen | Ansaid |
| Ibuprofen | Motrin, Tab-Profen, Vicoprofen |
| Indomethacin | Indocin, Indocin SR, Indo-Lemmon, Indomethagan |
| Ketoprofen | Oruvail |
| Ketorolac | Toradol |
| Mefenamic Acid | Ponstel |
| Meloxicam | Mobic |
| Nabumetone | Relafen |
| Naproxen | Naprosyn, Anaprox, Anaprox DS, EC-Naproxyn, Naprelan, Naprapac (copackaged with lansoprazole) |
| Oxaprozin | Daypro |
| Piroxicam | Feldene |
| Sulindac | Clinoril |
| Tolmetin | Tolectin, Tolectin DS, Tolectin 600 |
This Medication Guide has been approved by the U.S. Food and Drug Administration.