Ibuprofen and Famotidine
Generic: IBUPROFEN AND FAMOTIDINE
Basic Information
Manufacturer
Viona Pharmaceuticals Inc
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
66524c84-35bc-4e7f-897a-f63fa4bca432
Indications & Usage
1 INDICATIONS AND USAGE 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 )
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 )
Adverse Reactions
6 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.
6.1 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 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.
6.2 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 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
( 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.
6.1 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 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.
6.2 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 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