Generic: VONOPRAZAN FUMARATE AND AMOXICILLIN
1 INDICATIONS AND USAGE VOQUEZNA TRIPLE PAK, is a co-packaged product containing vonoprazan, a potassium-competitive acid blocker (PCAB), amoxicillin, a penicillin class antibacterial, and clarithromycin, a macrolide antimicrobial, indicated for the treatment of Helicobacter pylori (H. pylori) infection in adults. ( 1.1 ) VOQUEZNA DUAL PAK, is a co-packaged product containing vonoprazan, a PCAB, and amoxicillin, a penicillin class antibacterial, indicated for the treatment of H. pylori infection in adults. ( 1.1 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of VOQUEZNA TRIPLE PAK, VOQUEZNA DUAL PAK and other antibacterial drugs, VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. ( 1.2 ) 1.1 Helicobacter pylori Infection VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK are indicated for the treatment of Helicobacter pylori ( H. pylori ) infection in adults [see Clinical Studies (14) ]. 1.2 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of VOQUEZNA TRIPLE PAK, VOQUEZNA DUAL PAK and other antibacterial drugs, VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
5 WARNINGS AND PRECAUTIONS VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK : Hypersensitivity Reactions : Serious and occasionally fatal reactions (e.g., anaphylaxis) have been reported with components of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK. If hypersensitivity reactions occur, discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK and institute immediate therapy (e.g., anaphylaxis management). ( 5.1 ) Acute Tubulointerstitial Nephritis : Discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK and evaluate patients. ( 5.1 ) Severe Cutaneous Adverse Reactions (SCAR) : Discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK at the first signs or symptoms of SCAR or other signs of hypersensitivity and consider further evaluation. ( 5.1 ) Drug-induced enterocolitis syndrome (DIES) has been reported with use of amoxicillin, a component of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK. If this occurs, discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK and institute appropriate therapy. ( 5.1 ) Clostridioides difficile -associated diarrhea (CDAD) : Evaluate if diarrhea occurs with VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK. ( 5.1 ) VOQUEZNA TRIPLE PAK Due to the Clarithromycin Component : QT Prolongation : Avoid VOQUEZNA TRIPLE PAK in patients with known QT prolongation or receiving drugs known to prolong the QT interval, ventricular arrhythmia ( torsades de pointes ), hypokalemia/hypomagnesemia, significant bradycardia, or taking Class IA or III antiarrhythmics. ( 5.2 ) Hepatotoxicity : Discontinue if signs and symptoms of hepatitis occur with VOQUEZNA TRIPLE PAK. ( 5.2 ) Serious Adverse Reactions Due to Concomitant Use with Other Drugs : Serious adverse reactions can occur with VOQUEZNA TRIPLE PAK due to drug interactions of clarithromycin with colchicine, some lipid lowering agents, some calcium channel blockers, and other drugs. ( 5.2 ) Embryo-Fetal Toxicity : Based on the findings from animal studies and human observational studies in pregnant women treated with clarithromycin, VOQUEZNA TRIPLE PAK is not recommended for use in pregnant women except in clinical circumstances where no alternative therapy is appropriate. ( 5.2 ) Myasthenia Gravis : Exacerbation of myasthenia gravis can occur with VOQUEZNA TRIPLE PAK since it has been reported in patients receiving clarithromycin tablets. ( 5.2 ) 5.1 Warnings and Precautions for VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK Hypersensitivity Reactions Serious and occasionally fatal hypersensitivity reactions (e.g., anaphylaxis, anaphylactic shock, rash, erythema multiforme, and Henoch-Schonlein purpura) have been reported with components of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK [see Contraindications (4.1) ]. Before initiating therapy with VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, macrolide antibacterial drugs or other allergens. Discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK immediately and institute appropriate treatment if hypersensitivity occurs. Acute Tubulointerstitial Nephritis Acute tubulointerstitial nephritis (TIN) has been reported with vonoprazan, a component of VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK [see Adverse Reactions (6.1) ] . If suspected, discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK and evaluate patients with suspected acute TIN. Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with the components of VOQUEZNA TRIPLE PAK: vonoprazan, amoxicillin, and clarithromycin and VOQUEZNA DUAL PAK: vonoprazan and amoxicillin [see Adverse Reactions (6.2) ] . In addition, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported with amoxicillin and clarithromycin. Discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK at the first signs or symptoms of SCAR or other signs of hypersensitivity and consider further evaluation. Drug-Induced Enterocolitis Syndrome Drug-induced enterocolitis syndrome (DIES) has been reported with use of amoxicillin, a component of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK [see Adverse Reactions (6.2) ] , with most cases occurring in pediatric patients ≤18 years of age. DIES is a non-IgE mediated hypersensitivity reaction characterized by protracted vomiting occurring 1 to 4 hours after drug ingestion in the absence of skin or respiratory symptoms. DIES may be associated with pallor, lethargy, hypotension, shock, diarrhea within 24 hours after ingesting amoxicillin, and leukocytosis with neutrophilia. If DIES occurs, discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK and institute appropriate therapy. Clostridioides difficile -Associated Diarrhea Clostridioides difficile- associated diarrhea (CDAD) has been reported with use of acid suppressing therapies and nearly all antibacterial agents, including amoxicillin (component of VOQUEZNA DUAL PAK and TRIPLE PAK) and clarithromycin (component of VOQUEZNA TRIPLE PAK), and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of Clostridioides difficile (C. difficile) . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is confirmed, VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK should be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated. Rash in Patients with Mononucleosis A high percentage of patients with mononucleosis who receive amoxicillin (a component of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK) develop an erythematous skin rash. Avoid use of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK in patients with mononucleosis. Interactions with Diagnostic Investigations for Neuroendocrine Tumors Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Assess CgA levels at least 4 weeks after VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK treatment and consider repeating the test if initial CgA levels are high [see Drug Interactions (7) and Clinical Pharmacology (12.2) ]. Development of Drug-Resistant Bacteria Prescribing VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK in the absence of a proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to the patient, and increases the risk of the development of drug-resistant bacteria. 5.2 Additional Warnings and Precautions for VOQUEZNA TRIPLE PAK Due to the Clarithromycin Component QT Prolongation Clarithromycin (a component of VOQUEZNA TRIPLE PAK) has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving clarithromycin. Fatalities have been reported. Avoid VOQUEZNA TRIPLE PAK in the following patients: Patients with known prolongation of QT interval, ventricular cardiac arrhythmia, including torsades de pointes. Patients receiving drugs known to prolong the QT interval (e.g., pimozide). Patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia and in patients receiving Class IA (e.g., quinidine, procainamide, disopyramide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval [see Use in Specific Populations (8.5) ]. Hepatotoxicity Hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been reported with clarithromycin (a component of VOQUEZNA TRIPLE PAK). This hepatic dysfunction may be severe and is usually reversible. In some instances, hepatic failure with fatal outcome has been reported and generally has been associated with serious underlying diseases and/or concomitant medications. Symptoms of hepatitis can include anorexia, jaundice, dark urine, pruritus, or tender abdomen. Discontinue VOQUEZNA TRIPLE PAK immediately if signs and symptoms of hepatitis occur. Serious Adverse Reactions Due to Concomitant Use of Clarithromycin with Other Drugs Drugs metabolized by CYP3A4 Serious adverse reactions have been reported in patients taking clarithromycin (a component of VOQUEZNA TRIPLE PAK) concomitantly with CYP3A4 substrates. These include colchicine toxicity with colchicine; markedly increased transaminases with lomitapide; rhabdomyolysis with simvastatin, lovastatin, and atorvastatin; hypoglycemia and cardiac arrhythmias (e.g., torsades de pointes ) with disopyramide; and hypotension and acute kidney injury with calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, amlodipine, diltiazem, nifedipine). Most reports of acute kidney injury with calcium channel blockers metabolized by CYP3A4 involved elderly patients 65 years of age or older [see Contraindications (4.2) and Drug Interactions (7) ]. Colchicine Life-threatening and fatal drug interactions have been reported in patients treated with clarithromycin (a component of VOQUEZNA TRIPLE PAK) and colchicine. If co-administration of VOQUEZNA TRIPLE PAK and colchicine is necessary in patients with normal renal and hepatic function, reduce the dose of colchicine. Monitor patients for clinical symptoms of colchicine toxicity. Concomitant administration of VOQUEZNA TRIPLE PAK and colchicine is contraindicated in patients with renal or hepatic impairment [see Contraindications (4.2) and Drug Interactions (7) ]. Lomitapide Concomitant use of VOQUEZNA TRIPLE PAK with lomitapide may increase the risk of elevation in transaminases due to the clarithromycin component. Concomitant use of VOQUEZNA TRIPLE PAK with lomitapide is contraindicated [see Contraindications (4.2) and Drug Interactions (7) ]. If treatment with VOQUEZNA TRIPLE PAK cannot be avoided, therapy with lomitapide must be suspended during the course of treatment. HMG-CoA Reductase Inhibitors (statins) Concomitant use of VOQUEZNA TRIPLE PAK with lovastatin or simvastatin may increase these drug's plasma concentrations due to the clarithromycin component, which may increase the risk of myopathy, including rhabdomyolysis. Cases of rhabdomyolysis have been reported in patients treated concomitantly with clarithromycin (a component of VOQUEZNA TRIPLE PAK) and lovastatin or simvastatin. Concomitant use of VOQUEZNA TRIPLE PAK with lovastatin or simvastatin is contraindicated [see Contraindications (4.2) ] . If treatment with VOQUEZNA TRIPLE PAK cannot be avoided, therapy with lovastatin or simvastatin must be suspended during the course of treatment. Exercise caution when prescribing VOQUEZNA TRIPLE PAK with atorvastatin or pravastatin [see Drug Interactions (7) ] . Hypoglycemic Agents/Insulin Concomitant use of VOQUEZNA TRIPLE PAK, and hypoglycemic agents (such as nateglinide, pioglitazone, repaglinide, or rosiglitazone) and/or insulin can result in significant hypoglycemia due to the clarithromycin component. Carefully monitor glucose levels when these drugs are used concomitantly with VOQUEZNA TRIPLE PAK [see Drug Interactions (7) ]. Quetiapine Concomitant use of VOQUEZNA TRIPLE PAK with quetiapine could result in somnolence, orthostatic hypotension, altered state of consciousness, neuroleptic malignant syndrome, and QT prolongation due to the clarithromycin component. Refer to quetiapine prescribing information for recommended dosage reduction if co-administered with VOQUEZNA TRIPLE PAK [see Drug Interactions (7) ]. Warfarin There is a risk of serious hemorrhage and significant elevations in the international normalized ratio (INR) and prothrombin time when clarithromycin (a component of VOQUEZNA TRIPLE PAK) is used concomitantly with warfarin. Monitor INR and prothrombin times frequently when warfarin is used concomitantly with VOQUEZNA TRIPLE PAK . Benzodiazepines Increased sedation and prolongation of sedation have been reported with concomitant administration when clarithromycin (a component of VOQUEZNA TRIPLE PAK), and triazolobenzodiazepines, such as triazolam and midazolam. Closely monitor patients for signs or symptoms of increased or prolonged central nervous system effects when benzodiazepines such astriazolam or midazolam are used concomitantly with VOQUEZNA TRIPLE PAK [see Drug Interactions (7) ]. Embryo-Fetal Toxicity with Use of VOQUEZNA TRIPLE PAK Based on findings from animal studies and human observational studies in pregnant women with use of clarithromycin, VOQUEZNA TRIPLE PAK is not recommended for use in pregnant women except in clinical circumstances where no alternative therapy is appropriate. If VOQUEZNA TRIPLE PAK is used during pregnancy, or if pregnancy occurs while the patient is taking this drug, advise the patient of the potential risk to the fetus. Clarithromycin demonstrated adverse effects on pregnancy outcome and/or embryo-fetal development, in pregnant animals administered oral clarithromycin. Observational studies in pregnant women also demonstrated adverse effects on pregnancy outcomes, including an increased risk of miscarriage and in some studies an increased incidence of fetal malformations [see Use in Specific Populations (8.1) ]. Exacerbation of Myasthenia Gravis Exacerbation of symptoms of myasthenia gravis and new onset of symptoms of myasthenic syndrome has been reported in patients receiving clarithromycin therapy (a component of VOQUEZNA TRIPLE PAK). Monitor patients for symptoms.
6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Drug-Induced Enterocolitis Syndrome (DIES) [see Warnings and Precautions (5.1) ] Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.1) ] Clostridioides difficile -Associated Diarrhea [see Warnings and Precautions (5.1) ] QT Prolongation [see Warnings and Precautions (5.2) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Serious Adverse Reactions Due to Concomitant Use with Other Drugs [see Warnings and Precautions (5.2) ] Exacerbation of Myasthenia Gravis [see Warnings and Precautions (5.2) ] VOQUEZNA TRIPLE PAK : Most common adverse reactions (≥ 2%) were dysgeusia, diarrhea, vulvovaginal candidiasis, headache, abdominal pain, and hypertension. ( 6.1 ) VOQUEZNA DUAL PAK : Most common adverse reactions (≥ 2%) were diarrhea, abdominal pain, vulvovaginal candidiasis, and nasopharyngitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Phathom Pharmaceuticals, Inc. at toll-free phone 1-888-775-7428 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. Adverse Reactions with VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK The safety of VOQUEZNA TRIPLE PAK was evaluated in 675 adult patients (aged 20 to 82 years) in clinical trials in the United States, Europe and Japan and VOQUEZNA DUAL PAK was evaluated in 348 adult patients (aged 20 to 80 years) in a clinical trial in the United States and Europe. All the patients were screened and found to be positive for H. pylori infection. The safety of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK was evaluated in a randomized, controlled, double-blind triple therapy/open-label dual therapy study conducted in the United States and Europe in treatment-naïve H. pylori -positive adult patients. Patients were randomized 1:1:1 to vonoprazan 20 mg twice daily plus amoxicillin 1,000 mg twice daily plus clarithromycin 500 mg twice daily (VOQUEZNA TRIPLE PAK) or vonoprazan 20 mg twice daily plus amoxicillin 1,000 mg three times daily (VOQUEZNA DUAL PAK) or lansoprazole 30 mg twice daily plus amoxicillin 1,000 mg twice daily plus clarithromycin 500 mg twice daily (LAC) administered for 14 consecutive days. A total of 346 patients received VOQUEZNA TRIPLE PAK in the study, 348 received VOQUEZNA DUAL PAK and 345 received LAC. These patients had a mean age of 51 years (range 20 to 87 years); 62.2% were female, 89.3% were White, 7.4% Black or African American, 1.5% were Asian and 1.8% were others with 72.5% non-Hispanic or Latino. Adverse Reactions Leading to Discontinuation Treatment discontinuation due to an adverse reaction occurred in 2.3% (8/346) of the VOQUEZNA TRIPLE PAK-treated patients, 0.9% (3/348) of the VOQUEZNA DUAL PAK-treated patients and 1.2% (4/345) of the LAC-treated patients. The most common adverse reactions leading to discontinuation of VOQUEZNA TRIPLE PAK were diarrhea (0.6%) and hypertension (0.6%) and the most common adverse reaction leading to discontinuation of VOQUEZNA DUAL PAK was rash (0.6%). Most Common Adverse Reactions The adverse reactions occurring in ≥2% of patients are described in Table 3. Table 3: Adverse Reactions Occurring in ≥2% of Adult Patients Receiving VOQUEZNA DUAL PAK or VOQUEZNA TRIPLE PAK Adverse Reactions VOQUEZNA DUAL PAK VOQUEZNA TRIPLE PAK LAC (N=348) n (%) (N=346) n (%) (N=345) n (%) Diarrhea 18 (5.2) 14 (4.0) 33 (9.6) Dysgeusia Dysgeusia also includes taste disorder. 2 (0.6) 16 (4.6) 21 (6.1) Vulvovaginal candidiasis Vulvovaginal candidiasis includes: urogenital infection fungal, vulvovaginal candidiasis, vulvovaginal mycotic infection, vulvovaginal pruritus, pruritus genital, genital infection fungal. 7 (2.0) 11 (3.2) 5 (1.4) Abdominal pain Abdominal pain includes: abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper. 9 (2.6) 8 (2.3) 10 (2.9) Headache 5 (1.4) 9 (2.6) 5 (1.4) Hypertension Hypertension also includes blood pressure increased. 4 (1.1) 7 (2.0) 3 (0.9) Nasopharyngitis 7 (2.0) 1 (0.3) 3 (0.9) This study was not designed to evaluate meaningful comparisons of the incidence of adverse reactions in the VOQUEZNA DUAL PAK, VOQUEZNA TRIPLE PAK, and LAC treatment groups. Other Adverse Reactions Other adverse reactions occurring in <2% of patients with VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK are listed below by body system: Blood and lymphatic system disorders: anemia, leukocytosis, leukopenia, neutropenia . Cardiac disorders: QT prolongation, tachycardia. Eye disorders: orbital edema. Gastrointestinal disorders: abdominal distension, constipation, dry mouth, duodenal polyp, duodenal ulcer, dyspepsia, flatulence, gastric ulcer, gastroesophageal reflux disease, hematochezia, large intestine polyp, nausea, rectal polyp, stomatitis, tongue discomfort, vomiting. General disorders and administration site conditions: fatigue, pyrexia . Immune system disorders: drug hypersensitivity. Infections and infestations: anal fungal infection, gastrointestinal viral infection, oral fungal infection, pneumonia, tongue fungal infection, upper respiratory tract infection, urinary tract infection, viral infection. Investigations: increased liver function test. Metabolism and nutrition disorders: decreased appetite. Musculoskeletal system: bone fracture. Nervous system disorders: ageusia, dizziness, tension headache. Psychiatric disorders: anxiety, depression, insomnia. Renal and urinary disorders: renal hypertrophy, tubulointerstitial nephritis . Reproductive system and breast disorders: vaginal discharge. Respiratory, thoracic and mediastinal disorders: cough, nasal polyps, oropharyngeal pain. Skin and subcutaneous tissue disorders: dermatitis, dry skin, rash. 6.2 Postmarketing Experience with Components of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK The following adverse reactions have been identified during post-approval use of vonoprazan (outside of the United States), amoxicillin, or clarithromycin (all used separately). 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. Vonoprazan Blood and lymphatic system disorders: thrombocytopenia. Immune system disorders: anaphylactic shock, urticaria [see Contraindications (4.1) ]. Infections and Infestations: C. difficile (with concomitant antibacterials) . Investigation: hypomagnesemia, hypokalemia, hypocalcemia, vitamin B12 deficiency. Hepatobiliary disorders: hepatic injury, hepatic failure, jaundice. Skin and subcutaneous tissue disorders: drug eruption, erythema multiforme, SJS, TEN. Amoxicillin Infections and infestations: mucocutaneous candidiasis. Gastrointestinal: Drug-induced enterocolitis syndrome (DIES), black hairy tongue, and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment . Hypersensitivity reactions: anaphylaxis [see Contraindications (4.1) ]. Serum sickness–like reactions, erythematous maculopapular rashes, erythema multiforme, exfoliative dermatitis, hypersensitivity vasculitis, and urticaria have been reported. Renal: crystalluria has been reported [see Overdosage (10) ]. Hemic and lymphatic systems: hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, and agranulocytosis have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. Central nervous system: reversible hyperactivity, agitation, confusion, convulsions, aseptic meningitis, and behavioral changes have been rarely 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. Skin and subcutaneous tissue disorders: TEN, SJS, DRESS, AGEP, and linear IgA bullous dermatosis. Clarithromycin Blood and lymphatic system: thrombocytopenia, agranulocytosis. Cardiac: ventricular arrhythmia, torsades de pointes. Ear and labyrinth: deafness was reported chiefly in elderly women and was usually reversible. Gastrointestinal: pancreatitis acute, tongue discoloration, tooth discoloration was reported and was usually reversible with professional cleaning upon discontinuation of the drug. Hepatobiliary: hepatic failure, jaundice hepatocellular. Adverse reactions related to hepatic dysfunction have been reported with clarithromycin . Infections and infestations: pseudomembranous colitis . Immune system: anaphylactic reactions, angioedema. Investigations: prothrombin time prolonged, white blood cell count decreased, INR increased. Abnormal urine color has been reported, associated with hepatic failure. Metabolism and nutrition: hypoglycemia has been reported in patients taking oral hypoglycemic agents or insulin. Musculoskeletal and connective tissue: myopathy rhabdomyolysis was reported and in some of the reports, clarithromycin was administered concomitantly with statins, fibrates, colchicine or allopurinol [see Contraindications (4.2) ]. Nervous system: parosmia, anosmia, paresthesia and convulsions. Psychiatric: abnormal behavior, confusional state, depersonalization, disorientation, hallucination, manic behavior, abnormal dream, psychotic disorder. These disorders usually resolve upon discontinuation of the drug. Renal and urinary: renal failure. Skin and subcutaneous tissue disorders: TEN, SJS, DRESS, AGEP, Henoch-Schonlein purpura, acne. Vascular: hemorrhage.
Medical Disclaimer: This information is for educational purposes only and does not constitute medical advice. Always consult a licensed healthcare provider before making any decisions about your medications. Data sourced from openFDA.