Takepron OD Adverse Reactions

The following serious adverse reactions are described as follows and in Precautions: Acute Interstitial Nephritis (see Acute Interstitial Nephritis under Precautions); Clostridium difficile Associated Diarrhea (Clostridium difficile& Associated Diarrhea under Precautions); Bone Fracture (see Bone Fractures under Precautions); Cutaneous and Systemic Lupus Erythematosus (see Cutaneous and Systemic Lupus Erythematosus under Precautions); Cyanocobalamin (Vitamin B-12) Deficiency (see Cyanocobalamin (Vitamin B-12) Deficiency under Precautions); Hypomagnesemia (see Hypomagnesemia under Precautions).
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 clinical practice.
Worldwide, over 10,000 patients have been treated with TAKEPRON in Phase 2 or Phase 3 clinical trials involving various dosages and durations of treatment. In general, TAKEPRON treatment has been well-tolerated in both short-term and long-term trials.
The following adverse reactions were reported by the treating physician to have a possible or probable relationship to drug in 1% or more of TAKEPRON-treated patients and occurred at a greater rate in TAKEPRON-treated patients than placebo-treated patients in Table 20. (See Table 20.)

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Headache was also seen at greater than 1% incidence but was more common on placebo. The incidence of diarrhea was similar between patients who received placebo and patients who received 15 mg and 30 mg of TAKEPRON, but higher in the patients who received 60 mg of TAKEPRON (2.9%, 1.4%, 4.2%, and 7.4%, respectively).
The most commonly reported possibly or probably treatment-related adverse event during maintenance therapy was diarrhea.
In the risk reduction study of TAKEPRON for NSAID-associated gastric ulcers, the incidence of diarrhea for patients treated with TAKEPRON, misoprostol, and placebo was 5%, 22%, and 3%, respectively.
Another study for the same indication, where patients took either a COX-2 inhibitor or lansoprazole and naproxen, demonstrated that the safety profile was similar to the prior study. Additional reactions from this study not previously observed in other clinical trials with TAKEPRON included contusion, duodenitis, epigastric discomfort, esophageal disorder, fatigue, hunger, hiatal hernia, hoarseness, impaired gastric emptying, metaplasia, and renal impairment.
Additional adverse experiences occurring in less than 1% of patients or subjects who received TAKEPRON in domestic trials are shown as follows: Body as a Whole: abdomen enlarged, allergic reaction, asthenia, back pain, candidiasis, carcinoma, chest pain (not otherwise specified), chills,edema, fever, flu syndrome, halitosis, infection (not otherwise specified), malaise, neck pain, neck rigidity, pain, pelvic pain.
Cardiovascular System: angina, arrhythmia, bradycardia, cerebrovascular accident/cerebral infarction, hypertension/hypotension, migraine,myocardial infarction, palpitations, shock (circulatory failure), syncope, tachycardia, vasodilation.
Digestive System: abnormal stools, anorexia, bezoar, cardiospasm, cholelithiasis, colitis, dry mouth, dyspepsia, dysphagia, enteritis, eructation, esophageal stenosis, esophageal ulcer, esophagitis, fecal discoloration, flatulence, gastric nodules/fundic gland polyps, gastritis, gastroenteritis, gastrointestinal anomaly, gastrointestinal disorder, gastrointestinal hemorrhage, glossitis, gum hemorrhage, hematemesis, increased appetite, increased salivation, melena, mouth ulceration, nausea and vomiting, nausea and vomiting and diarrhea, gastrointestinal moniliasis, rectal disorder, rectal hemorrhage, stomatitis, tenesmus, thirst, tongue disorder, ulcerative colitis, ulcerative stomatitis.
Endocrine System: diabetes mellitus, goiter, hypothyroidism.
Hemic and Lymphatic System: anemia, hemolysis, lymphadenopathy.
Metabolism and Nutritional Disorders: avitaminosis, gout, dehydration, hyperglycemia/hypoglycemia, peripheral edema, weight gain/loss.
Musculoskeletal System: arthralgia, arthritis, bone disorder, joint disorder, leg cramps, musculoskeletal pain, myalgia, myasthenia, ptosis, synovitis.
Nervous System: abnormal dreams, agitation, amnesia, anxiety, apathy, confusion, convulsion, dementia, depersonalization, depression, diplopia, dizziness, emotional lability, hallucinations, hemiplegia, hostility aggravated, hyperkinesia, hypertonia, hypesthesia, insomnia, libido decreased/increased, nervousness, neurosis, paresthesia, sleep disorder, somnolence, thinking abnormality, tremor, vertigo.
Respiratory System: asthma, bronchitis, cough increased, dyspnea, epistaxis, hemoptysis, hiccup, laryngeal neoplasia, lung fibrosis, pharyngitis, pleural disorder, pneumonia, respiratory disorder, upper respiratory inflammation/infection, rhinitis, sinusitis, stridor.
Skin and Appendages: acne, alopecia, contact dermatitis, dry skin, fixed eruption, hair disorder, maculopapular rash, nail disorder, pruritus, rash, skin carcinoma, skin disorder, sweating, urticaria.
Special Senses: abnormal vision, amblyopia, blepharitis, blurred vision, cataract, conjunctivitis, deafness, dry eyes, ear/eye disorder, eye pain, glaucoma, otitis media, parosmia, photophobia, retinal degeneration/disorder, taste loss, taste perversion, tinnitus, visual field defect.
Urogenital System: abnormal menses, breast enlargement, breast pain, breast tenderness, dysmenorrhea, dysuria, gynecomastia, impotence, kidney calculus, kidney pain, leukorrhea, menorrhagia, menstrual disorder, penis disorder, polyuria, testis disorder, urethral pain, urinary frequency, urinary retention, urinary tract infection, urinary urgency, urination impaired, vaginitis.
Postmarketing Experience: Additional adverse experiences have been reported since TAKEPRON has been marketed. The majority of these cases are foreign-sourced and a relationship to TAKEPRON has not been established. Because these reactions were reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events are listed as follows by COSTART body system.
Body as a Whole: anaphylactic/anaphylactoid reactions, systemic lupus erythematosus.
Digestive System: hepatotoxicity, pancreatitis, vomiting.
Hemic and Lymphatic System: agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic purpura.
Infections and Infestations: Clostridium difficile associated diarrhea.
Metabolism and Nutritional Disorders: hypomagnesemia.
Musculoskeletal System: bone fracture, myositis.
Skin and Appendages: severe dermatologic reactions including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal), cutaneous lupus erythematosus.
Special Senses: speech disorder.
Urogenital System: interstitial nephritis, urinary retention.
Combination Therapy with Amoxicillin and Clarithromycin: In clinical trials using combination therapy with TAKEPRON plus amoxicillin and clarithromycin, and TAKEPRON plus amoxicillin, no adverse reactions peculiar to these drug combinations were observed. Adverse reactions that have occurred have been limited to those that had been previously reported with TAKEPRON, amoxicillin, or clarithromycin.
Triple Therapy: TAKEPRON/amoxicillin/clarithromycin: The most frequently reported adverse reactions for patients who received triple therapy for 14 days were diarrhea (7%), headache (6%), and taste perversion (5%). There were no statistically significant differences in the frequency of reported adverse reactions between the 10- and 14-day triple therapy regimens. No treatment-emergent adverse reactions were observed at significantly higher rates with triple therapy than withany dual therapy regimen.
Dual Therapy: TAKEPRON/amoxicillin: The most frequently reported adverse reactions for patients who received TAKEPRON three times daily plus amoxicillin three times daily dual therapy were diarrhea (8%) and headache (7%). No treatment-emergent adverse reactions were observed at significantly higher rates with TAKEPRON three times daily plus amoxicillin three times daily dual therapy than with TAKEPRON alone.
For information about adverse reactions with antibacterial agents (amoxicillin and clarithromycin) indicated in combination with TAKEPRON, refer to the Adverse Reactions section of their prescribing information.
Laboratory Values: The following changes in laboratory parameters in patients who received TAKEPRON were reported as adverse reactions: Abnormal liver function tests, increased SGOT (AST), increased SGPT (ALT), increased creatinine, increased alkaline phosphatase, increased globulins, increased GGTP, increased/decreased/abnormal WBC, abnormal AG ratio, abnormal RBC, bilirubinemia, blood potassium increased, blood urea increased, crystal urine present, eosinophilia, hemoglobin decreased, hyperlipemia, increased/decreased electrolytes, increased/decreased cholesterol, increased glucocorticoids, increased LDH, increased/decreased/abnormal platelets, increased gastrin levels and positive fecal occult blood. Urine abnormalities such as albuminuria, glycosuria, and hematuria were also reported. Additional isolated laboratory abnormalities were reported.
In the placebo controlled studies, when SGOT (AST) and SGPT (ALT) were evaluated, 0.4% (4/978) and 0.4% (11/2677) patients, who received placebo and TAKEPRON, respectively, had enzyme elevations greater than three times the upper limit of normal range at the final treatment visit. None of these patients who received TAKEPRON reported jaundice at any time during the study.
In clinical trials using combination therapy with TAKEPRON plus amoxicillin and clarithromycin, and TAKEPRON plus amoxicillin, no increased laboratory abnormalities particular to these drug combinations were observed.
For information about laboratory value changes with antibacterial agents (amoxicillin and clarithromycin) indicated in combination with TAKEPRON, refer to the Adverse Reactions section of their prescribing information.