Drug: Duexis

DUEXIS (ibuprofen and famotidine) is supplied as a tablet for oral administration which combines the nonsteroidal anti-inflammatory agent, ibuprofen, and the histamine H2-receptor antagonist, famotidine. Ibuprofen is (±)-2-(p-isobutylphenyl)propionic acid. Its chemical formula is C13H18O2 and molecular weight is 206.28. Ibuprofen is a white powder that is very slightly soluble in water ( < 1 mg/mL) and readily soluble in organic solvents such as ethanol and acetone. Its structural formula is: Famotidine is N'-(aminosulfonyl)-3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propanimidamide. Its chemical formula is C8H15N7O2S3 and molecular weight is 337.45. Famotidine is a white to pale yellow crystalline compound that is freely soluble in glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol. Its structural formula is: Each DUEXIS tablet contains ibuprofen, USP (800 mg) and famotidine, USP (26.6 mg) and the following inactive ingredients: microcrystalline cellulose, anhydrous lactose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, purified water, povidone, titanium dioxide, polyethylene glycol, polysorbate 80, polyvinyl alcohol, hypromellose, talc, FD&C Blue #2/Indigo Carmine Aluminum Lake, and FD&C Blue #1/Brilliant Blue FCF Aluminum Lake.

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The following serious adverse reactions are discussed elsewhere in the labeling:
  • Cardiovascular events [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
  • Gastrointestinal effects [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
  • Renal injury [see WARNINGS AND PRECAUTIONS]
  • Seizures [see WARNINGS AND PRECAUTIONS]
  • Anaphylaxis [see WARNINGS AND PRECAUTIONS]
  • Skin reactions [see WARNINGS AND PRECAUTIONS]
  • Corticosteroid treatment [see WARNINGS AND PRECAUTIONS]
  • Masking of inflammation and fever [see WARNINGS AND PRECAUTIONS]
  • Hepatic injury [see WARNINGS AND PRECAUTIONS]
  • Hematological effects [see WARNINGS AND PRECAUTIONS]
  • Pre-existing asthma [see WARNINGS AND PRECAUTIONS]
  • Aseptic meningitis [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of DUEXIS was evaluated in 1022 patients in controlled clinical studies, including 508 patients treated for at least 6 months and 107 patients treated for approximately 1 year. Patients treated with DUEXIS ranged in age from 39 to 80 years (median age 55 years), with 67% female, 79% Caucasian, 18% African-American, and 3% other races. Two randomized, active-controlled clinical studies (Study 301 and Study 303) were conducted for the reduction of the risk of development of ibuprofen-associated, upper gastrointestinal ulcers in patients who required use of ibuprofen, which included 1022 patients on DUEXIS and 511 patients on ibuprofen alone. Approximately 15% of patients were on low-dose aspirin. Patients were assigned randomly, in a 2:1 ratio, to treatment with either DUEXIS or ibuprofen 800 mg three times a day for 24 consecutive weeks Three serious cases of acute renal failure were observed in patients treated with DUEXIS in the two controlled clinical trials. All three patients recovered to baseline levels after discontinuation of DUEXIS. Additionally, increases in serum creatinine were observed in both treatment arms in the two clinical studies. Many of these patients were taking concomitant diuretics and/or angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers. There were patients with a normal baseline serum creatinine level who developed abnormal values in the controlled trials as presented in Table 1. Table 1: Shift table of serum creatinine, normal** to abnormal*** in controlled studies
Baseline Post-Baseline* Study 301 Study 303 DUEXIS
N=414
% (n) Ibuprofen
N=207
% (n) DUEXIS
N=598
% (n) Ibuprofen
N=296
% (n) Normal** Abnormal*** 4% (17) 2% (4) 2%(15) 4% (12) * At any point after baseline level
** serum creatinine normal range is 0.5 – 1.4 mg/dL or 44-124 micromol/L
*** serum creatinine > 1.4 mg/dL Most Commonly Reported Adverse Reactions The most common adverse reactions ( ≥ 2%), from pooled data from the two controlled studies are presented in Table 2. Table 2: Incidence of Adverse Reactions in Controlled Studies
  DUEXIS
N=1022
% Ibuprofen
N=511
% Blood and lymphatic system disorders   Anemia 2 1 Gastrointestinal disorders   Nausea 6 5   Dyspepsia 5 8   Diarrhea 5 4   Constipation 4 4   Abdominal pain upper 3 3   Gastroesophageal reflux disease 2 3   Vomiting 2 2   Stomach discomfort 2 2   Abdominal pain 2 2 General disorders and administration site conditions   Edema peripheral 2 2 Infections and infestations   Upper respiratory tract infection 4 4   Nasopharyngitis 2 3   Sinusitis 2 3   Bronchitis 2 1   Urinary tract infection 2 2   Influenza 2 2 Musculoskeletal and connective tissue disorders   Arthralgia 1 2   Back pain 2 1 Nervous system disorders   Headache 3 3 Respiratory, thoracic and mediastinal disorders     Cough 2 2   Pharyngolaryngeal pain 2 1 Vascular disorders   Hypertension 3 2 DUEXIS (ibuprofen and famotidine) tablets 800 mg/26.6 mg administered orally three times per day. Ibuprofen 800 mg administered orally three times per day. In controlled clinical studies, the discontinuation rate due to adverse events for patients receiving DUEXIS and ibuprofen alone were similar. The most common adverse reactions leading to discontinuation from DUEXIS therapy were nausea (0.9%) and upper abdominal pain (0.9%). There were no differences in types of related adverse reactions seen during maintenance treatment up to 12 months compared to short-term treatment. Postmarketing Experience Ibuprofen The following adverse reactions have been identified during post-approval use of ibuprofen. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reports are listed below by body system: Cardiac disorders: myocardial infarction Gastrointestinal disorders: nausea, vomiting, diarrhea, abdominal pain General disorders and administration site conditions: pyrexia, pain, fatigue, asthenia, chest pain, drug ineffective, edema peripheral Musculoskeletal and connective tissue disorders: arthralgia Nervous system disorders: headache, dizziness Psychiatric disorders: depression, anxiety Renal and urinary disorders: renal failure acute Respiratory, thoracic, and mediastinal disorders: dyspnea Vascular disorders: hypertension Famotidine The following adverse reactions have been identified during post-approval use of famotidine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reports are listed below by body system: Blood and lymphatic system disorders: anemia, thrombocytopenia Gastrointestinal disorders: nausea, diarrhea, vomiting, abdominal pain General disorders and administration site conditions: pyrexia, condition aggravated, asthenia, drug ineffective, chest pain, fatigue, pain, edema peripheral Hepatobiliary disorders: hepatic function abnormal Infections and infestations: pneumonia, sepsis Investigations: platelet count decreased, aspartate aminotransferase increased, alanine aminotransferase increased, hemoglobin decreased Metabolism and nutrition disorders: decreased appetite Nervous system disorders: dizziness, headache Respiratory, thoracic, and mediastinal disorders: dyspnea Vascular disorders: hyoptension Read the Duexis (ibuprofen and famotidine tablets) Side Effects Center for a complete guide to possible side effectsLearn More »

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The recommended daily dose of DUEXIS (ibuprofen and famotidine) 800 mg/26.6 mg is a single tablet administered orally three times per day. DUEXIS tablets should be swallowed whole, and should not be cut to supply a lower dose. Do not chew, divide, or crush tablets. Patients should be instructed that if a dose is missed, it should be taken as soon possible. However, if the next scheduled dose is due, the patient should not take the missed dose, and should be instructed to take the next dose on time. Patients should be instructed not to take 2 doses at one time to make up for a missed dose.

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Co-administration of ibuprofen (800 mg) and famotidine (40 mg) increased ibuprofen Cmax by 15.6% but did not affect its AUC, and increased famotidine AUC and Cmax by 16% and 22%, respectively. Studies with famotidine in man, in animal models, and in vitro have shown no significant interference with the disposition of compounds metabolized by the hepatic microsomal enzymes, e.g., cytochrome P450 system. Compounds tested in man include warfarin, theophylline, phenytoin, diazepam, aminopyrine and antipyrine. Indocyanine green as an index of hepatic drug extraction has been tested, and no significant effects have been found. Warfarin-Type Anticoagulants Several short-term controlled studies failed to show that ibuprofen significantly affected prothrombin times or a variety of other clotting factors when administered to individuals on coumarin-type anticoagulants. However, because bleeding has been reported when ibuprofen and other NSAIDs have been administered to patients on coumarin-type anticoagulants, prescribers should be cautious when administering ibuprofen to patients on anticoagulants. The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that the users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone [see WARNINGS AND PRECAUTIONS]. Aspirin When ibuprofen, which is a component of DUEXIS tablets, is administered with aspirin, its protein binding is reduced, although the clearance of free ibuprofen is not altered. The clinical significance of this interaction is not known. As with other NSAIDs, the concurrent use of aspirin and DUEXIS may increase the risk of adverse events [see WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS, and Clinical Studies]. ACE-Inhibitors Reports suggest that ibuprofen, a component of DUEXIS, may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking DUEXIS concomitantly with ACE-inhibitors. During concomitant therapy with DUEXIS, the patient should be observed closely for signs of renal failure [see WARNINGS AND PRECAUTIONS]. Diuretics Clinical studies, as well as postmarketing observations, have shown that ibuprofen, which is a component of DUEXIS, can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with DUEXIS, the patient should be observed closely for signs of renal failure [see WARNINGS AND PRECAUTIONS], as well as to assure diuretic efficacy. Lithium Ibuprofen, which is a component of DUEXIS tablets, produced an elevation of plasma lithium levels and a reduction in renal lithium clearance in a study of 11 normal volunteers. The mean minimum lithium concentration increased 15% and the renal clearance of lithium was decreased by 20% during this period of concomitant ibuprofen drug administration. This effect has been attributed to inhibition of renal prostaglandin synthesis by ibuprofen. Thus, when ibuprofen and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. Methotrexate NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. NSAIDs have been reported to reduce the tubular secretion of methotrexate in an animal model. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate. Selective Serotonin Reuptake Inhibitors (SSRIs) There is an increased risk of gastrointestinal bleeding when selective serotonin reuptake inhibitors (SSRIs) are combined with NSAIDs including COX-2 selective inhibitors. Caution should be used when NSAIDs are administered concomitantly with SSRIs [see WARNINGS AND PRECAUTIONS]. Cholestyramine As with other NSAIDs, concomitant administration of cholestyramine can delay the absorption of ibuprofen, a component of DUEXIS. Last reviewed on RxList: 1/31/2013
This monograph has been modified to include the generic and brand name in many instances.

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Carefully consider the potential benefits and risks of DUEXIS and other treatment options before deciding to use DUEXIS. Use the shortest duration consistent with individual patient treatment goals [see WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS and Use In Specific Populations]. DUEXIS, a combination of the NSAID ibuprofen and the histamine H2-receptor antagonist famotidine, is indicated for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis and to decrease the risk of developing upper gastrointestinal ulcers, which in the clinical trials was defined as a gastric and/or duodenal ulcer, in patients who are taking ibuprofen for those indications. The clinical trials primarily enrolled patients less than 65 years of age without a prior history of gastrointestinal ulcer. Controlled trials do not extend beyond 6 months. [see Clinical Studies and Use In Specific Populations]

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  • DUEXIS should not be given to patients who have experienced asthma, urticaria, or allergic reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylaxis with NSAIDs have been reported in such patients [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS].
  • DUEXIS is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery [see WARNINGS AND PRECAUTIONS].
  • DUEXIS is contraindicated in patients in late stages of pregnancy [see WARNINGS AND PRECAUTIONS].
  • DUEXIS should not be administered to patients with a history of hypersensitivity to other H2-receptor antagonists. Cross sensitivity with other H2-receptor antagonists has been observed.
Last reviewed on RxList: 1/31/2013
This monograph has been modified to include the generic and brand name in many instances.

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No data are available with regard to overdose of DUEXIS. Findings related to the individual active substances are listed below. Ibuprofen Approximately 1 ½ hours after the reported ingestion of from 7 to 10 ibuprofen tablets (400 mg), a 19-month-old child weighing 12 kg was seen in the hospital emergency room, apneic and cyanotic, responding only to painful stimuli. This type of stimulus, however, was sufficient to induce respiration. Oxygen and parenteral fluids were given; a greenish-yellow fluid was aspirated from the stomach with no evidence to indicate the presence of ibuprofen. Two hours after ingestion the child's condition seemed stable; she still responded only to painful stimuli and continued to have periods of apnea lasting from 5 to 10 seconds. She was admitted to intensive care and sodium bicarbonate was administered as well as infusions of dextrose and normal saline. By 4 hours post-ingestion she could be aroused easily, sit by herself, and respond to spoken commands. Blood level of ibuprofen was 102.9 μg/mL approximately 8.5 hours after accidental ingestion. At 12 hours she appeared to be completely recovered. In two other reported cases where children (each weighing approximately 10 kg) accidentally, acutely ingested approximately 120 mg/kg, there were no signs of acute intoxication or late sequelae. Blood level in one child 90 minutes after ingestion was 700 μg/mL — about 10 times the peak levels seen in absorption-excretion studies. A 19-year-old male who had taken 8,000 mg of ibuprofen over a period of a few hours complained of dizziness, and nystagmus was noted. After hospitalization, parenteral hydration and 3 days bed rest, he recovered with no reported sequelae. In cases of acute overdosage, the stomach should be emptied by vomiting or lavage, though little drug will likely be recovered if more than 1 hour has elapsed since ingestion. Because the drug is acidic and is excreted in the urine, it is theoretically beneficial to administer alkali and induce diuresis. In addition to supportive measures, the use of oral activated charcoal may help to reduce the absorption and reabsorption of ibuprofen tablets. Famotidine The adverse reactions in overdose cases are similar to the adverse reactions encountered in normal clinical experience. Oral doses of up to 640 mg/day have been given to adult patients with pathological hypersecretory conditions with no serious adverse effects. In the event of overdosage, treatment should be symptomatic and supportive. Unabsorbed material should be removed from the GI tract, the patient should be monitored, and supportive therapy should be employed.

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Dosage Forms And Strengths DUEXIS (ibuprofen and famotidine) tablets, 800 mg/26.6 mg, are light blue, oval, biconvex, film-coated tablets debossed with “HZT” on one side. Storage And Handling DUEXIS (ibuprofen and famotidine) tablets, 800 mg/26.6 mg, are light blue, oval, biconvex, film-coated tablets debossed with “HZT” on one side and supplied as: NDC Number Size 75987-010-03 Bottle of 90 tablets Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). [See USP Controlled Room Temperature] Distributed by: Horizon Pharma USA, Inc. 1033 Skokie Boulevard, Suite 355 Northbrook, IL 60062. Manufactured by: Pharmaceutics International, Inc. 10819 Gilroy Road Hunt Valley, MD 21031. Revised: April 2011 Last reviewed on RxList: 1/31/2013
This monograph has been modified to include the generic and brand name in many instances.

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Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs, including ibuprofen, which is a component of DUEXIS tablets, of up to 3 years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events. Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke [see CONTRAINDICATIONS]. Hypertension NSAIDs, including ibuprofen, which is a component of DUEXIS tablets, can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including DUEXIS, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy [see DRUG INTERACTIONS]. Congestive Heart Failure and Edema Fluid retention and edema have been observed in some patients taking NSAIDs. DUEXIS should be used with caution in patients with fluid retention or heart failure. Risk of Gastrointestinal Ulceration, Bleeding, and Perforation NSAIDs, including ibuprofen, which is a component of DUEXIS tablets, can cause serious gastrointestinal (GI) adverse reactions including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse reactions can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for 1 year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk. NSAIDs, including DUEXIS, should be prescribed with extreme caution in those with a prior history of ulcer disease or GI bleeding. Patients with a prior history of peptic ulcer disease and/or GI bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients treated with neither of these risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs, including DUEXIS, include concomitant use of oral corticosteroids, anticoagulants, antiplatelet drugs (including low-dose aspirin), longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI reactions are in elderly or debilitated patients, and, therefore, special care should be taken in treating this population with DUEXIS. To minimize the potential risk for an adverse GI reaction in patients treated with an NSAID, the shortest possible duration should be used. Patients and physicians should remain alert for signs and symptoms of GI ulcers and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse reaction is suspected. This should include discontinuation of the NSAID until a serious GI adverse reaction is ruled out. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered. Epidemiological studies of the case-control and cohort design have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. In two studies, concurrent use of concurrent use of an NSAID, COX-2 inhibitor, or aspirin potentiated the risk of bleeding [see DRUG INTERACTIONS]. Although these studies focused on upper gastrointestinal bleeding, bleeding at other sites cannot be ruled out. NSAIDs should be given with care to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn's disease) as their condition may be exacerbated. Because serious GI tract ulcers 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 complete blood count (CBC) and chemistry profile checked periodically. Symptomatic response to therapy with DUEXIS does not preclude the presence of gastric malignancy. Active Bleeding When active and clinically significant bleeding from any source occurs in patients receiving DUEXIS, the treatment should be withdrawn. Patients with initial hemoglobin values of 10 g or less who are to receive long-term therapy should have hemoglobin values determined periodically. Renal Injury Long-term administration of NSAIDs, including ibuprofen, which is a component of DUEXIS tablets, has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and angiotensin-converting enzyme (ACE) inhibitors, and the elderly. If clinical signs (e.g., azotemia, hypertension, and/or proteinuria) and symptoms consistent with renal disease develop, DUEXIS should be discontinued. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state [see ADVERSE REACTIONS and Use In Specific Populations]. Seizures Central nervous system (CNS) adverse effects including seizures, delirium, and coma have been reported with famotidine in patients with moderate (creatinine clearance < 50 mL/min) and severe renal insufficiency (creatinine clearance < 10 mL/min), and the dosage of the famotidine component in DUEXIS is fixed. Therefore, DUEXIS is not recommended in patients with creatinine clearance < 50 mL/min. Anaphylaxis Anaphylaxis may occur in patients without known prior exposure to ibuprofen, which is a component of DUEXIS tablets. DUEXIS should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs [see CONTRAINDICATIONS]. Emergency help should be sought in cases where anaphylaxis, which may have a fatal outcome, occurs. Skin Reactions NSAIDs, including ibuprofen, which is a component of DUEXIS tablets, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity [see CONTRAINDICATIONS and ADVERSE REACTIONS]. Pregnancy Starting at 30 weeks gestation, DUEXIS should be avoided by pregnant women because it may cause premature closure of the ductus arteriosus [see CONTRAINDICATIONS and Use in Specific Population]. Hepatic Injury Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs, including ibuprofen, which is a component of DUEXIS tablets. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (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, 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 with abnormal liver test values, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with DUEXIS. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), DUEXIS should be discontinued. Anemia Anemia is sometimes seen in patients receiving NSAIDs, including ibuprofen which is a component of DUEXIS tablets. 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 DUEXIS, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia. Inhibition of Platelet Aggregation 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 DUEXIS who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored. Pre-existing 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 NSAIDs has been reported in such aspirin-sensitive patients, DUEXIS should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with pre-existing asthma. Concomitant NSAID Use DUEXIS contains ibuprofen as one of its active ingredients. It should not be used with other ibuprofen-containing products. The concomitant use of NSAIDs, including aspirin, with DUEXIS may increase the risk of adverse events [see ADVERSE REACTIONS, DRUG INTERACTIONS, and Clinical Studies]. Aseptic Meningitis Aseptic meningitis with fever and coma has been observed on rare occasions in patients on ibuprofen, which is a component of DUEXIS. Although it is probably more likely to occur in patients with systemic lupus erythematosus (SLE) and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease. If signs or symptoms of meningitis develop in a patient on DUEXIS, the possibility of its being related to ibuprofen should be considered. Corticosteroid Treatment DUEXIS 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 and the patient should be observed closely for any evidence of adverse effects, including adrenal insufficiency and exacerbation of symptoms of arthritis. Masking of Inflammation and Fever The pharmacological activity of DUEXIS in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, noninflammatory painful conditions. Visual Disturbances Blurred and/or diminished vision, scotomata, and/or changes in color vision have been reported. If a patient develops such complaints while receiving DUEXIS, the drug should be discontinued, and the patient should have an ophthalmologic examination which includes central visual fields and color vision testing. Patient Counseling Information “See FDA-approved patient labeling (Medication Guide)” 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.
  • DUEXIS, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even death [see WARNINGS AND PRECAUTIONS].
  • DUEXIS, 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 [see WARNINGS AND PRECAUTIONS].
  • DUEXIS, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, Stevens Johnson Syndrome, and Toxic epidermal necrolysis, which may result in hospitalization and even death. 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 be monitored for development of nephrotoxicity (e.g., azotemia, hypertension, and/or proteinuria). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.
  • DUEXIS is not recommended in patients with creatinine clearance < 50 mL/min because of the seizures, delirium, coma and other CNS effect.
  • 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 anaphylaxis (e.g. difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help [see WARNINGS AND PRECAUTIONS].
  • Patients should be informed that in late pregnancy, as with other NSAIDs, DUEXIS should be avoided because it may cause premature closure of the ductus arteriosus.
  • DUEXIS tablets should be swallowed whole, and should not be cut to supply a lower dose. Do not chew, divide, or crush tablets [see DOSAGE AND ADMINISTRATION].
  • Patients should be instructed that if a dose is missed, it should be taken as soon possible. However, if the next schedule dose is due, the patient should not take the missed dose, and should be instructed to take the next dose on time. Patients should be instructed not to take 2 doses at one time to make up for a missed dose.
Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment of Fertility Studies to evaluate the potential effects of DUEXIS on carcinogenicity, mutagenicity, or impairment of fertility have not been conducted. In a 106-week study in rats and a 92-week study in mice, famotidine was given at oral doses of up to 2000 mg/kg/day (approximately 122 and 243 times the recommended human dose, respectively, based on body surface area). There was no evidence of carcinogenic potential for famotidine. Famotidine was negative in the microbial mutagen test (Ames test) using Salmonella typhimurium and Escherichia coli with or without rat liver enzyme activation at concentrations up to 10,000 μg/plate. In in vivo mouse micronucleus test and a chromosomal aberration test with famotidine, no evidence of a mutagenic effect was observed. In studies of famotidine in rats at oral doses of up to 2000 mg/kg/day (approximately 243 times the recommended human dose, based on body surface area), fertility and reproductive performance were not affected. Use In Specific Populations Pregnancy Teratogenic Effects - Pregnancy Category C Animal reproduction studies have not been conducted with DUEXIS. Reproductive studies conducted with ibuprofen in rats and rabbits have not demonstrated evidence of developmental abnormalities. Reproductive studies with famotidine have been performed in rats and rabbits at oral doses of up to 2000 and 500 mg/kg/day (approximately 243 and 122 times the recommended human dose, respectively, based on body surface area) and in both species at intravenous (I.V.) doses of up to 200 mg/kg/day, and have revealed no significant evidence of impaired fertility or harm to the fetus due to famotidine. While no direct fetotoxic effects have been observed, sporadic abortions occurring only in mothers displaying marked decreased food intake were seen in some rabbits at oral doses of 200 mg/kg/day (approximately 49 times the recommended human dose based on body surface area) or higher. There are no adequate and well-controlled studies in pregnant women. Animal reproduction studies are not always predictive of human response. DUEXIS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nonteratogenic Effects Because of the known effects of NSAIDs on the fetal cardiovascular system (closure of ductus arteriosus), use during late pregnancy should be avoided [see WARNINGS AND PRECAUTIONS]. 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 DUEXIS on labor and delivery in pregnant women are unknown. Nursing Mothers It is not known whether ibuprofen is excreted in human milk. Famotidine is secreted into breast milk of lactating rats. Transient growth depression was observed in young rats suckling from mothers treated with maternotoxic doses of at least 300 times the usual human dose of famotidine. Famotidine is detectable in human milk. Because of the potential for serious adverse reactions in nursing infants from DUEXIS, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use The clinical trials primarily enrolled patients less than 65 years of age. Of the 1022 subjects in clinical studies of DUEXIS, 18% (249 subjects) were 65 years of age or older. Efficacy results in patients who are greater than or equal to 65 years of age are summarized in the CLINICAL STUDIES section [see Clinical Studies]. Famotidine is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug 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 adjusting dose interval, and it may be useful to monitor renal function [see WARNINGS AND PRECAUTIONS]. As with any NSAIDs, caution should be exercised in treating the elderly (65 years old and older). Experience indicates that geriatric patients may be particularly sensitive to certain adverse effects of NSAIDs. Elderly or debilitated patients seem to tolerate peptic ulceration or bleeding less well when these events do occur. Most spontaneous reports of fatal GI events are in the geriatric population [see WARNINGS AND PRECAUTIONS]. Ibuprofen is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug 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. Geriatric patients may be at a greater risk for the development of a form of renal toxicity precipitated by reduced prostaglandin formation during administration of NSAIDs [see WARNINGS AND PRECAUTIONS]. Renal Insufficiency In adult patients with renal insufficiency (creatinine clearance < 50 mL/min), the elimination half-life of famotidine is increased. Since CNS adverse effects have been reported in patients with creatinine clearance < 50 mL/min and the dosage of the famotidine component in DUEXIS is fixed, DUEXIS is not recommended in these patients [see WARNINGS AND PRECAUTIONS]. Last reviewed on RxList: 1/31/2013
This monograph has been modified to include the generic and brand name in many instances.

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