PREVPAC SIDE EFFECTS

Last updated on MDtodate: 10/10/2022

SIDE EFFECTS

PREVPAC

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.

The most common adverse reactions (≥3%) reported in clinical trials when all three components of this therapy were given concomitantly for 14 days are listed in Table 1.

Table 1: Adverse Reactions Most Frequently Reported in Clinical Trials (≥3%)

Adverse Reaction	Triple Therapy n=138 (%)
Diarrhea	7.0
Headache	6.0
Taste Perversion	5.0

 

The additional adverse reactions which were reported as possibly or probably related to treatment (less than 3%) in clinical trials when all three components of this therapy were given concomitantly are listed below and divided by body system:

Body as a Whole –abdominal pain

Digestive System –dark stools, dry mouth/thirst, glossitis, rectal itching, nausea, oral moniliasis, stomatitis, tongue discoloration, tongue disorder, vomiting

Musculoskeletal System –myalgia

Nervous System –confusion, dizziness

Respiratory System –respiratory disorders

Skin and Appendages –skin reactions

Urogenital System –vaginitis, vaginal moniliasis

There were no statistically significant differences in the frequency of reported adverse events between the 10 and 14 day triple therapy regimens.

PREVACID

The following adverse reactions from the labeling for PREVACID are provided for information:

Worldwide, over 10,000 patients have been treated with PREVACID in Phase 2 or Phase 3 clinical trials involving various dosages and durations of treatment. In general, PREVACID treatment has been well-tolerated in both short-term and long-term trials.

Incidence In Clinical Trials

The following adverse events were reported by the treating physician to have a possible or probable relationship to drug in 1% or more of PREVACID-treated patients and occurred at a greater rate in PREVACID-treated patients than placebo-treated patients:

Table 2: Incidence of Possibly or Probably Treatment-Related Adverse Reactions in Short-Term, Placebo-Controlled PREVACID Studies

Body System/Adverse Event	PREVACID (N= 2768) %	Placebo (N= 1023) %
Body as a Whole
Abdominal Pain	2.1	1.2
Digestive System
Constipation	1.0	0.4
Diarrhea	3.8	2.3
Nausea	1.3	1.2

 

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 30 mg of PREVACID, but higher in the patients who received 60 mg of PREVACID (2.9%, 4.2%, and 7.4%, respectively).

The most commonly reported possibly or probably treatment-related adverse event during maintenance therapy was diarrhea.

Additional adverse experiences occurring in less than 1% of patients or subjects who received PREVACID in domestic trials are shown below:

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

Additional adverse experiences have been reported since PREVACID has been marketed. The majority of these cases are foreign-sourced and a relationship to PREVACID has not been established. Because these events were reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events are listed below 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

Amoxicillin

The following adverse reactions from the labeling for amoxicillin are provided for information:

The most common adverse reactions (>1%) observed in clinical trials of amoxicillin capsules were diarrhea, rash, vomiting and nausea.

The most frequently reported adverse events for patients who received triple therapy (amoxicillin/clarithromycin/lansoprazole) were diarrhea (7%), headache (6%), and taste perversion (5%).

Infections and Infestations – Mucocutaneous candidiasis

Gastrointestinal – Black hairy tongue, and hemorrhagic/pseudomembranous colitis.

Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment.

Hypersensitivity Reactions – Anaphylaxis, serum sickness-like reactions, erythematous maculopapular rashes, erythema multiforme, Stevens-Johnson Syndrome, exfoliative dermatitis, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, hypersensitivity vasculitis and urticaria have been reported.

Liver – A moderate rise in AST and/or ALT has been noted, but the significance of this finding is unknown. Hepatic dysfunction including cholestatic jaundice, hepatic cholestasis and acute cytolytic hepatitis have been reported.

Renal – Crystalluria has also been reported.

Hemic and Lymphatic Systems – Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia and agranulocytosis have been reported. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.

Central Nervous System – Reversible hyperactivity, agitation, anxiety, insomnia, confusion, behavioral changes, and/or dizziness have been reported.

Miscellaneous – Tooth discoloration (brown, yellow, or gray staining) has been reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.

Clarithromycin

The following adverse reactions from the labeling for clarithromycin are provided for information:

The most frequent and common adverse reactions related to clarithromycin therapy for both adult and pediatric populations are abdominal pain, diarrhea, nausea, vomiting, and dysgeusia. These adverse reactions are consistent with the known safety profile of macrolide antibiotics.

There was no significant difference in the incidence of these gastrointestinal adverse reactions during clinical trials between the patient population with or without preexisting mycobacterial infections.

Adverse Reactions Observed During Clinical Trials Of Clarithromycin

The following adverse reactions were observed in clinical trials with clarithromycin at a rate greater than or equal to 1%:

Gastrointestinal Disorders – Diarrhea, vomiting, dyspepsia, nausea, abdominal pain

Hepatobiliary Disorders – Liver function test abnormal

Immune System Disorders – Anaphylactoid reaction

Infections and Infestations – Candidiasis

Nervous System Disorders – Dysgeusia, headache

Psychiatric Disorders – Insomnia

Skin and Subcutaneous Tissue Disorders – Rash

Other Adverse Reactions Observed During Clinical Trials Of Clarithromycin

The following adverse reactions were observed in clinical trials with clarithromycin at a rate less than 1%:

Blood and Lymphatic System Disorders – Leukopenia, neutropenia, thrombocythemia, eosinophilia

Cardiac Disorders – Electrocardiogram QT prolonged, cardiac arrest, atrial fibrillation, extrasystoles, palpitations

Ear and Labyrinth Disorders – Vertigo, tinnitus, hearing impaired

Gastrointestinal Disorders – Stomatitis, glossitis, esophagitis, gastroesophageal reflux disease, gastritis, proctalgia, abdominal distention, constipation, dry mouth, eructation, flatulence

General Disorders and Administration Site Conditions – Malaise, pyrexia, asthma, chest pain, chills, fatigue

Hepatobiliary Disorders – Cholestasis, hepatitis

Immune System Disorders – Hypersensitivity

Infections and Infestations – Cellulitis, gastroenteritis, infection, vaginal infection

Investigations – Blood bilirubin increased, blood alkaline phosphatase increased, blood lactate dehydrogenase increased, albumin globulin ratio abnormal

Metabolism and Nutrition Disorders – Anorexia, decreased appetite

Musculoskeletal and Connective Tissue Disorders – Myalgia, muscle spasms, nuchal rigidity

Nervous System Disorders – Dizziness, tremor, loss of consciousness, dyskinesia, somnolence

Psychiatric Disorders – Anxiety, nervousness

Renal and Urinary Disorders – Blood creatinine increased, blood urea increased

Respiratory, Thoracic and Mediastinal Disorders – Asthma, epistaxis, pulmonary embolism

Skin and Subcutaneous Tissue Disorders – Urticaria, dermatitis bollus, pruritus, hyperhidrosis, rash maculopapular

The following adverse reactions have been identified during post approval use of clarithromycin. 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.

Blood and Lymphatic System Disorders – Thrombocytopenia, agranulocytosis

Cardiac Disorders – Torsades de pointes, ventricular tachycardia, ventricular arrhythmia

Ear and Labyrinth Disorders – Deafness was reported chiefly in elderly women and was usually reversible.

Gastrointestinal Disorders – Pancreatitis acute, tongue discoloration, tooth discoloration was reported and was usually reversible with professional cleaning upon discontinuation of the drug.

Hepatobiliary Disorders – Hepatic failure, jaundice hepatocellular. Adverse reactions related to hepatic dysfunction have been reported with clarithromycin.

Immune System Disorders – Anaphylactic reaction

Infections and Infestations – Pseudomembranous colitis

Investigations – Prothrombin time prolonged, white blood cell count decreased, international normalized ratio increased. Abnormal urine color has been reported, associated with hepatic failure.

Metabolism and Nutrition Disorders – Hypoglycemia has been reported in patients taking oral hypoglycemic agents or insulin.

Musculoskeletal and Connective Tissue Disorders – Myopathy, rhabdomyolysis was reported and in some of the reports, clarithromycin was administered concomitantly with statins, fibrates, colchicines or allopurinol.

Nervous System Disorders – Convulsion, ageusia, parosmia, anosmia, paresthesia

Psychiatric Disorders – Psychotic disorder, confusional state, depersonalization, depression, disorientation, manic behavior, hallucination, abnormal behavior, abnormal dreams. These disorders usually resolve upon discontinuation of the drug.

There are no data on the effect of clarithromycin on the ability to drive or use machines. The potential for dizziness, vertigo, confusion and disorientation, which may occur with the medication, should be taken into account before patients drive or use machines.

Renal and Urinary Disorders – Nephritis interstitial, renal failure

Skin and Subcutaneous Tissue Disorders – Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS), Henoch-Schonlein purpura, acne

Vascular Disorders – Hemorrhage

There have been reports of colchicine toxicity with concomitant use of clarithromycin and colchicine, especially in the elderly, some of which occurred in patients with renal insufficiency. Deaths have been reported in some such patients.

Laboratory Values

Prevacid

The following changes in laboratory parameters in patients who received PREVACID 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.

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 PREVACID, 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 PREVACID reported jaundice at any time during the study.