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Duexis

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Duexis

SIDE EFFECTS

The following serious adverse reactions are discussed elsewhere in the labeling:

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 effects

DRUG INTERACTIONS

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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Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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