Ibuprofen and famotidine tablets, 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 tablets, 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 tablets are 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 tablets 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 tablets 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 tablets 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 tablets are contraindicated in patients with aspirin-sensitive asthma. Monitor patients with preexisting asthma (without aspirin-sensitivity). ( 5.10 ) Serious Skin Reactions: Discontinue ibuprofen and famotidine tablets 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 tablets, between about 20 weeks 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 days to 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 tablets in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If ibuprofen and famotidine tablets are 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 months to 6 months and in about 2% to 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 tablets 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 tablets, 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
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Interactions
See Table 3 for clinically significant drug interactions with ibuprofen. Table 3 Clinically Significant Drug Interactions with Ibuprofen and Famotidine 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 ibuprofen and famotidine tablets 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 ( 5.16 )].
Aspirin Clinical Impact: Pharmacodynamic (PD) studies have demonstrated interference with the antiplatelet activity of aspirin when ibuprofen 400 mg, given three times daily, is administered with enteric-coated low-dose aspirin. The interaction exists even following a once-daily regimen of ibuprofen 400 mg, particularly when ibuprofen is dosed prior to aspirin. The interaction is alleviated if immediate-release low-dose aspirin is dosed at least 2 hours prior to a once-daily regimen of ibuprofen; however, this finding cannot be extended to enteric-coated low-dose aspirin [see Clinical Pharmacology ( 12.2 )].
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 ( 5.2 )]. Intervention: Because there may be an increased risk of cardiovascular events due to the interference of ibuprofen with the antiplatelet effect of aspirin, for patients taking low-dose aspirin for cardioprotection who require analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin or non-NSAID analgesics, where appropriate.
Concomitant use of ibuprofen and famotidine tablets and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [see Warnings and Precautions ( 5.3 )]. Ibuprofen and famotidine tablets are 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 ibuprofen and famotidine tablets and ACE-inhibitors, ARBs or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained.
During concomitant use of ibuprofen and famotidine tablets 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 ( 5.7 )] . Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic 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 ibuprofen and famotidine tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions ( 5.7 )]. 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 ibuprofen and famotidine tablets 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 ibuprofen and famotidine tablets 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 ibuprofen and famotidine tablets and methotrexate, monitor patients for methotrexate toxicity.
Cyclosporine Clinical Impact: Concomitant use of ibuprofen and cyclosporine may increase cyclosporine's nephrotoxicity. Intervention: During concomitant use of ibuprofen and famotidine tablets 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 [see Warnings and Precautions ( 5.2 )].
Intervention: The concomitant use of ibuprofen and famotidine tablets with other NSAIDs or salicylates is not recommended. Pemetrexed Clinical Impact: Concomitant use of ibuprofen and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal and GI toxicity (see the pemetrexed prescribing information). Intervention: During concomitant use of ibuprofen and famotidine tablets and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 mL/min 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 pemetrexed 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.
Drugs Dependent on Gastric pH for Absorption Clinical Impact Because famotidine lowers intra-gastric acidity, this may result in reduced absorption and loss of efficacy of concomitant drugs. Intervention Concomitant administration of ibuprofen and famotidine tablets is not recommended with dasatinib, delavirdine mesylate, cefditoren and fosamprenavir. For administration instructions of other drugs whose absorption is dependent on gastric pH, refer to their prescribing information (e.g., atazanavir, erlotinib, ketoconazole, itraconazole, nilotinib, ledipasvir/sofosbuvir and rilpivirine).
Tizanidine (CYP1A2 Substrate) Clinical Impact Famotidine is considered a weak CYP1A2 inhibitor and may lead to substantial increases in blood concentrations of tizanidine, a CYP1A2 substrate. Intervention Avoid concomitant use with ibuprofen and famotidine tablets. If concomitant use is necessary, monitor for hypotension, bradycardia or excessive drowsiness. Refer to the full prescribing information for tizanidine. See full prescribing information for a list of clinically important drug interactions.
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Pregnancy and breastfeeding
8.1 Pregnancy Risk Summary Use of NSAIDs, including ibuprofen and famotidine tablets, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of ibuprofen and famotidine tablets use between about 20 weeks and 30 weeks of gestation and avoid ibuprofen and famotidine tablets use at about 30 weeks of gestation and later in pregnancy (see Clinical Considerations, Data).
Premature Closure of Fetal Ductus Arteriosus Use of NSAIDs, including ibuprofen and famotidine tablets, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios and in some cases, neonatal renal impairment.
There are no available data with ibuprofen and famotidine tablets use in pregnant women to inform a drug-associated risk for major birth defects and miscarriage; however, there are published studies with each individual component of ibuprofen and famotidine tablets. Ibuprofen Data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive.
In animal reproduction studies, there were no clear developmental effects at doses up to 0.4-times the maximum recommended human dose (MRHD) in the rabbit and 0.5-times in the MRHD rat when dosed throughout gestation. In contrast, an increase in membranous ventricular septal defects was reported in rats treated on Gestation Days 9 & 10 with 0.8-times the MRHD. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation and decidualization.
In animal studies, administration of prostaglandin synthesis inhibitors such as ibuprofen, resulted in increased pre-and post-implantation loss. Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. Famotidine Limited published data do not report an increased risk of congenital malformations or other adverse pregnancy effects with use of H 2 -receptor antagonists, including ibuprofen and famotidine tablets, during pregnancy; however, these data are insufficient to adequately determine a drug-associated risk.
Reproductive studies with famotidine have been performed in rats and rabbits at oral doses of up to 2,000 mg/kg/day and 500 mg/kg/day (approximately 243 times 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. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the general U.S. population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including ibuprofen and famotidine tablets, can cause premature closure of the fetal ductus arteriosus (see Data).
Oligohydramnios/Neonatal Renal Impairment If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If ibuprofen and famotidine tablets treatment is needed for a pregnant woman, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue ibuprofen and famotidine tablets and follow up according to clinical practice (see Data).
Labor or Delivery There are no studies on the effects of ibuprofen and famotidine tablets during labor or delivery. In animal studies, NSAIDs, including ibuprofen, inhibit prostaglandin synthesis, cause delayed parturition and increase the incidence of stillbirth. Data Human Data When used to delay preterm labor, inhibitors of prostaglandin synthesis, including NSAIDs such ibuprofen, may increase the risk of neonatal complications such as necrotizing enterocolitis, patent ductus arteriosus and intracranial hemorrhage.
Ibuprofen treatment given in late pregnancy to delay parturition has been associated with persistent pulmonary hypertension, renal dysfunction and abnormal prostaglandin E levels in preterm infants. Ibuprofen Premature Closure of Fetal Ductus Arteriosus: Published literature reports that the use of NSAIDs at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus.
Oligohydramnios/Neonatal Renal Impairment: Published studies and postmarketing reports describe maternal NSAID use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation.
In many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. There have been a limited number of case reports of maternal NSAID use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. Some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. Methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration and timing of drug exposure; and concomitant use of other medications.
These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use. Because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to NSAIDs through maternal use is uncertain. When used to delay preterm labor, inhibitors of prostaglandin synthesis, including NSAIDs such as ibuprofen, may increase the risk of other neonatal complications such as necrotizing enterocolitis and intracranial hemorrhage.
Ibuprofen treatment given in late pregnancy to delay parturition has been associated with persistent pulmonary hypertension, renal dysfunction and abnormal prostaglandin E levels in preterm infants. Animal Data Animal reproduction studies have not been conducted with ibuprofen and famotidine tablets. Ibuprofen In a published study, female rabbits given 7.5 mg/kg, 20 mg/kg or 60 mg/kg ibuprofen (0.04, 0.12 or 0.36-times the maximum recommended human daily dose of 3,200 mg of ibuprofen based on body surface area) from Gestation Days 1 to Days 29, no clear treatment-related adverse developmental effects were noted.
Doses of 20 mg/kg and 60 mg/kg were associated with significant maternal toxicity (stomach ulcers, gastric lesions). In the same publication, female rats were administered 7.5 mg/kg, 20 mg/kg, 60 mg/kg, 180 mg/kg ibuprofen (0.02, 0.06, 0.18, 0.54-times the maximum daily dose) did not result in clear adverse developmental effects. Maternal toxicity (gastrointestinal lesions) was noted at 20 mg/kg and above. In a published study, rats were orally dosed with 300 mg/kg ibuprofen (0.912-times the maximum human daily dose of 3,200 mg based on body surface ar
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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 Viona Pharmaceuticals Inc. at 1-888-304-5011 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 tablets was evaluated in 1,022 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 tablets ranged in age from 39 years 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 1,022 patients on ibuprofen and famotidine tablets 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 tablets 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 tablets in the two controlled clinical trials. All three patients recovered to baseline levels after discontinuation of ibuprofen and famotidine tablets.
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 * At any point after baseline level ** serum creatinine normal range is 0.5 mg/dL to 1.4 mg/dL or 44 micromol/L to 124 micromol/L *** serum creatinine > 1.4 mg/dL Study 301 Study 303 Baseline Post-Baseline * Ibuprofen and Famotidine Tablets N=414 % (n) Ibuprofen N=207 % (n) Ibuprofen and Famotidine Tablets N=598 % (n) Ibuprofen N=296 % (n) Normal ** Abnormal *** 4% (17) 2% (4) 2% (15) 4% (12) 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 Ibuprofen and Famotidine Tablets N=1,022 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 ibuprofen and famotidine tablets 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.
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 Gastrointestinal disorders: nausea, vomiting, diarrhea, abdominal pain General disorders and administration site conditions: pyrexia, pain, fatigue, asthenia, chest pain, drug ineffective, edema peripheral Skin and Appendages: exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE) 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
