Ibuprofen and famotidine tablet, a combination of the NSAID ibuprofen and the histamine H 2 -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 (14), Use in Specific Populations (8.5)] . Ibuprofen and famotidine tablet, a combination of a nonsteroidal anti-inflammatory drug (NSAID) ibuprofen and the histamine H 2 -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. (1)
Contraindications
Ibuprofen and famotidine tablet is contraindicated in the following patients: Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to ibuprofen or famotidine or any components of the drug product [see Warnings and Precautions (5.8, 5.11)] . History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see Warnings and Precautions (5.8, 5.10)] .
In the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.1)] . Ibuprofen and famotidine tablet should not be administered to patients with a history of hypersensitivity to other H 2 -receptor antagonists. Cross sensitivity with other H 2 -receptor antagonists has been observed. Known hypersensitivity to ibuprofen or famotidine or any components of the drug product. (4) History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.
(4) In the setting of CABG surgery. (4) Known hypersensitivity to other H 2 -receptor antagonists. (4)
Warnings and precautions
Hepatotoxicity : Inform patients of warning signs and symptoms of hepatotoxicity. Discontinue if abnormal liver tests persist or worsen or if clinical signs and symptoms of liver disease develop. (5.4)
Hypertension : Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure. (5.5, 7)
Heart Failure and Edema : Avoid use of ibuprofen and famotidine tablets in patients with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure. (5.6)
Active Bleeding : Active and clinically significant bleeding from any source can occur; discontinue ibuprofen and famotidine tablet if active bleeding occurs. (5.3)
Renal Toxicity : Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia. Avoid use of ibuprofen and famotidine tablet in patients with advanced renal disease unless benefits are expected to outweigh risk of worsening renal function. (5.7)
Anaphylactic Reactions : Seek emergency help if an anaphylactic reaction occurs. (5.8)
Exacerbation of Asthma Related to Aspirin Sensitivity : Ibuprofen and famotidine tablet is contraindicated in patients with aspirin-sensitive asthma. Monitor patients with preexisting asthma (without aspirin-sensitivity). (5.10)
Serious Skin Reactions : Discontinue ibuprofen and famotidine tablet at first appearance of skin rash or other signs of hypersensitivity (5.11).
Drug Reaction with Eosinophilia and Systematic Symptoms (DRESS) :Discontinue and evaluate clinically (5.12).
Fetal Toxicity : Limit use of NSAIDs, including ibuprofen and famotidine tablet, between about 20 to 30 weeks in pregnancy due to the risk of oligohydramnios/fetal renal dysfunction. Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy due to the risks of oligohydramnios/fetal renal dysfunction and premature closure of the fetal ductus arteriosus (5.13, 8.1)
Hematologic Toxicity : Monitor hemoglobin or hematocrit in patient with any signs or symptoms of anemia. (5.14)
5.1Cardiovascular Thrombotic Events
Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI), and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDS. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease.
However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses. To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible.
Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the 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, such as ibuprofen, increases the risk of serious gastrointestinal GI events [see Warnings and Precautions (5.2)] . Status Post Coronary Artery Bypass Graft (CABG) Surgery 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. NSAIDs are contraindicated in the setting of CABG [see Contraindications (4)] .
Post-MI Patients Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients.
Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up. Avoid the use of ibuprofen and famotidine tablet in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If ibuprofen and famotidine tablet is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.
5.2Gastrointestinal Bleeding, Ulceration, and Perforation
NSAIDs, including ibuprofen, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events 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 occurred in approximately 1% of patients treated for 3-6 months, and in about 2%-4% of patients treated for one year. However, even short-term NSAID therapy is not without risk. Risk Factors for GI Bleeding, Ulceration, and Perforation Patients with a prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors.
Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients. Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding.
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. Strategies to Minimize the GI Risks in NSAID-treated patients: Use the lowest effective dosage for the shortest possible duration. Avoid administration of more than one NSAID at a time. Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding.
For such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs. Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy. If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue ibuprofen and famotidine tablet until a serious GI adverse event is ruled out. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding [see Drug Interactions (7)] .
5.3Active Bleeding
When active and clinically significant bleeding from any source occurs in patients receiving ibuprofen and famotidine tablet, 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.
5.4 Hepa
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Interactions
See Table 3 for clinically significant drug interactions with ibuprofen. See full prescribing information for a list of clinically important drug interactions. (7) table 3.1 table 3.2 table 3.3
Adverse reactions
The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Cardiovascular Thrombotic Events [see Warnings and Precautions (5.1)] GI Bleeding, Ulceration, and Perforation [see Warnings and Precautions (5.2)] Hepatotoxicity [see Warnings and Precautions (5.4)] Hypertension [see Warnings and Precautions (5.5)] Heart Failure and Edema [see Warnings and Precautions (5.6)] Renal Toxicity and Hyperkalemia [see Warnings and Precautions (5.7)] Anaphylactic Reactions [see Warnings and Precautions (5. 8)] Seizures [see Warnings and Precautions (5.9)] Serious Skin Reactions [see Warnings and Precautions (5.11)] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions (5.12)] Fetal Toxicity [see Warnings and Precautions (5.13)] Hematologic Toxicity [see Warnings and Precautions (5.14)] Aseptic Meningitis [see Warnings and Precautions (5.18)] Ophthalmological Effects [see Warnings and Precautions (5.19)] Most common adverse reactions (≥1% and greater than ibuprofen alone) are nausea, diarrhea, constipation, upper abdominal pain, and headache.
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Ascent Pharmaceuticals, Inc., at 1-855-221-1622 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Clinical 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 ibuprofen and famotidine tablet 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 ibuprofen and famotidine tablet 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 ibuprofen and famotidine tablet 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 ibuprofen and famotidine tablet 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 ibuprofen and famotidine tablet in the two controlled clinical trials. All three patients recovered to baseline levels after discontinuation of ibuprofen and famotidine tablet.
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. Most Commonly Reported Adverse Reactions The most common adverse reactions (≥2%), from pooled data from the two controlled studies are presented in Table 2.
In controlled clinical studies, the discontinuation rate due to adverse events for patients receiving ibuprofen and famotidine tablet and ibuprofen alone were similar. The most common adverse reactions leading to discontinuation from ibuprofen and famotidine tablet 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. table 1 table 2.1 table 2.2
6.2Postmarketing 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 Gastro intestinal 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
Composition
Active ingredients
FAMOTIDINE 26.6MG; IBUPROFEN 800MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
At a glance
Brand name
Ibuprofen and Famotidine
Active substance
famotidine
Pharmacologic class
Histamine-2 Receptor Antagonist, Nonsteroidal Anti-inflammatory Drug
