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Duexis




Side Effects
Interactions

SIDE EFFECTS

The following serious adverse reactions are discussed in greater detail in other sections of 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

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: hypotension

Read the Duexis (ibuprofen and famotidine tablets) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

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.

See Table 3 for clinically significant drug interactions with ibuprofen.

Table 3: Clinically Significant Drug Interactions with Ibuprofen

Drugs That Interfere with Hemostasis
Clinical Impact:
  • Ibuprofen and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of ibuprofen and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone.
  • Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone.
Intervention: Monitor patients with concomitant use of DUEXIS with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding [see WARNINGS AND PRECAUTIONS].
Aspirin
Clinical Impact: Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone [see WARNINGS AND PRECAUTIONS].
Intervention: Concomitant use of DUEXIS and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [see WARNINGS AND PRECAUTIONS]. DUEXIS is not a substitute for low dose aspirin for cardiovascular protection.
ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-blockers
Clinical Impact:
  • NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers (including propranolol).
  • In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible.
Intervention:
  • During concomitant use of DUEXIS and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained.
  • During concomitant use of DUEXIS and ACE-inhibitors or ARBs in patients who are elderly, volume-depleted or have impaired renal function, monitor for signs of worsening renal function [see WARNINGS AND PRECAUTIONS].
Diuretics
Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriurectic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis.
Intervention: During concomitant use of DUEXIS with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see WARNINGS AND PRECAUTIONS].
Digoxin
Clinical Impact: The concomitant use of ibuprofen with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin.
Intervention: During concomitant use of DUEXIS and digoxin, monitor serum digoxin levels.
Lithium
Clinical Impact: NSAIDs have produced elevations of plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis.
Intervention: During concomitant use of DUEXIS and lithium, monitor patients for signs of lithium toxicity.
Methotrexate
Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction).
Intervention: During concomitant use of DUEXIS and methotrexate, monitor patients for methotrexate toxicity.
Cyclosporine
Clinical Impact: Concomitant use of DUEXIS and cyclosporine may increase cyclosporine’s nephrotoxicity.
Intervention: During concomitant use of DUEXIS and cyclosporine, monitor patients for signs of worsening renal function.
NSAIDs and Salicylates
Clinical Impact: Concomitant use of ibuprofen with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy [seeWARNINGS AND PRECAUTIONS].
Intervention: The concomitant use of ibuprofen with other NSAIDs or salicylates is not recommended.
Pemetrexed
Clinical Impact: Concomitant use of DUEXIS and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information).
Intervention: During concomitant use of DUEXIS and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and GI toxicity. NSAIDs with short elimination half-lives (e.g., diclofenac, indomethacin) should be avoided for a period of two days before, the day of, and two days following administration of pemetrexed. In the absence of data regarding potential interaction between permetrexed and NSAIDs with longer half-lives (e.g., meloxicam, nabumetone), patients taking these NSAIDs should interrupt dosing for at least five days before, the day of, and two days following pemetrexed administration.
This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 5/23/2016

Side Effects
Interactions

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