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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 6.
Table 6. Adverse Reactions Most Frequently Reported in Clinical Trials (≥3%)
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
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.
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 7. Incidence of Possibly or Probably Treatment-Related Adverse Reactions in Short-Term, Placebo-Controlled PREVACID Studies
|Body as a Whole|
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
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
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
Infections and infestations – Clostridium difficile-associated diarrhea
Metabolism and Nutritional Disorders – hypomagnesemia
Musculoskeletal System – bone fracture, myositis
Special Senses – speech disorder
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
Hypersensitivity Reactions – Anaphylaxis (see WARNINGS), 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 (see OVERDOSE).
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.
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 abnorma
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
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
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 (see WARNINGS, Hepatotoxicity)
Immune System Disorders-Anaphylactic reaction
Infections and Infestations -Pseudomembranous colitis
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 (see CONTRAINDICATIONS and WARNINGS).
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 (see WARNINGS and PRECAUTIONS).
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.
Read the Prevpac (lansoprazole, amoxicillin and clarithromycin) Side Effects Center for a complete guide to possible side effects
No drug interaction studies have been conducted specifically with PREVPAC. The following drug interactions are for the individual drug components: PREVACID(lansoprazole), amoxicillin, and clarithromycin. Therefore, the decision to adjust dosage should depend on the clinician’s assessment of among other things, the cumulative or net effect of the drug components of PREVPAC.
Drugs with pH-Dependent Absorption
Due to its effects on gastric acid secretion, PREVACID can reduce the absorption of drugs where gastric pH is an important determinant of their bioavailability. As with other drugs that decrease the intragastric acidity, the absorption of drugs such as ampicillin esters, ketoconazole, atazanavir, nelfinavir, iron salts, erlotinib, and mycophenolate mofetil can decrease, while the absorption of drugs such as digoxin can increase during treatment with PREVACID.
Atazanavir And Nelfinavir
PREVACID substantially decreases the systemic concentrations of HIV protease inhibitors, such as atazanavir and nelfinavir, which are dependent upon the presence of gastric acid for absorption, and may result in a loss of therapeutic effect of atazanavir or nelfinavir and the development of HIV resistance. Therefore, PREVACID should not be co-administered with atazanavir or nelfinavir.
Co-administration of PPIs in healthy volunteers and in transplant patients receiving mycophenolate mofetil has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in mycophenolate mofetil solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving PPIs and mycophenolate mofetil. Use PPIs with caution in transplant patients receiving mycophenolate mofetil.
Drugs Metabolized By P450 Enzymes
PREVACID is metabolized through the cytochrome P450 system (CYP450), specifically through the CYP3A and CYP2C19 isozymes. Studies in healthy subjects have shown that PREVACID does not have clinically significant interactions with other drugs metabolized by CYP450, such as warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propranolol, prednisone, diazepam, or clarithromycin in healthy subjects. These compounds are metabolized through various CYP450 enzymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A. However, other studies or post-marketing reports have shown that the interaction of PREVACID with other drugs metabolized by these CYP450 enzymes may be clinically significant.
When PREVACID was administered concomitantly with theophylline (CYP1A2, CYP3A), a minor increase (10%) in the clearance of theophylline was seen. Because of the small magnitude and the direction of the effect on theophylline clearance, this interaction is unlikely to be of clinical concern. Nonetheless, individual patients may require additional titration of their theophylline dosage when PREVACID is started or stopped to ensure clinically effective blood levels.
Concomitant administration of lansoprazole and tacrolimus may increase whole blood levels of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19.
In a study of healthy subjects, neither the pharmacokinetics of warfarin enantiomers nor prothrombin time were affected following single or multiple 60 mg doses of lansoprazole. However, there have been reports of increased International Normalized Ratio (INR) and prothrombin time in patients receiving proton pump inhibitors, including PREVACID, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.
In a single-dose crossover study examining PREVACID 30 mg and omeprazole 20 mg each administered alone and concomitantly with sucralfate 1 gram, absorption of the proton pump inhibitors was delayed and their bioavailability was reduced by 17% and 16%, respectively, when administered concomitantly with sucralfate. Therefore, proton pump inhibitors should be taken at least 30 minutes prior to sucralfate. In clinical trials, antacids were administered concomitantly with PREVACID and there was no evidence of a change in the efficacy of PREVACID.
Concomitant administration of lansoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition. No dose adjustment of clopidogrel is necessary when administered with an approved dose of PREVACID.
Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of high dose methotrexate with PPIs have been conducted.
In a study of rheumatoid arthritis patients receiving low-dose methotrexate, PREVACID and naproxen, no effect on pharmacokinetics of methotrexate was observed.
Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use of amoxicillin and probenecid may result in increased and prolonged blood levels of amoxicillin.
Chloramphenicol, macrolides, sulfonamides, and tetracyclines may interfere with bactericidal effects of penicillin. This has been demonstrated in vitro; however, the clinical significance of this interaction is not well documented.
Table 5: Clinically Significant Drug Interactions with BIAXIN
|Drugs That Are Affected By BIAXIN|
|Drug(s) with Pharmacokinetics Affected by BIAXIN||Recommendation||Comments|
|Not Recommended||Disopyramide, Quinidine: There have been postmarketing
reports of torsades de pointes occurring with concurrent
use of clarithromycin and quinidine or disopyramide.
Electrocardiograms should be monitored for QTc
prolongation during coadministration of clarithromycin with
these drugs (see WARNINGS).
Serum concentrations of these medications should also be monitored. There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with disopyramide and quinidine.
There have been postmarketing reports of hypoglycemia with the concomitant administration of clarithromycin and disopyramide. Therefore, blood glucose levels should be monitored during concomitant administration of clarithromycin and disopyramide.
|Digoxin||Use With Caution||Digoxin: Digoxin is a substrate for P-glycoprotein (Pgp) and clarithromycin is known to inhibit Pgp. When clarithromycin and digoxin are co-administered, inhibition of Pgp by clarithromycin may lead to increased exposure of digoxin. Elevated digoxin serum concentrations in patients receiving clarithromycin and digoxin concomitantly have been reported in postmarketing surveillance. Some patients have shown clinical signs consistent with digoxin toxicity, including potentially fatal arrhythmias. Monitoring of serum digoxin concentrations should be considered, especially for patients with digoxin concentrations in the upper therapeutic range.|
|Warfarin||Use With Caution||Oral anticoagulants: Spontaneous reports in the postmarketing period suggest that concomitant administration of clarithromycin and oral anticoagulants may potentiate the effects of the oral anticoagulants. Prothrombin times should be carefully monitored while patients are receiving clarithromycin and oral anticoagulants simultaneously (see WARNINGS).|
|Carbamazepine||Use With Caution||Carbamazepine: Concomitant administration of single doses of clarithromycin and carbamazepine has been shown to result in increased plasma concentrations of carbamazepine. Blood level monitoring of carbamazepine may be considered. Increased serum concentrations of carbamazepine were observed in clinical trials with clarithromycin. There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with carbamazepine.|
|Itraconazole||Use With Caution||Itraconazole: Both clarithromycin and itraconazole are substrates and inhibitors of CYP3A, potentially leading to a bi-directional drug interaction when administered concomitantly (see also Itraconazole under “Drugs That Affect BIAXIN” in the table below). Clarithromycin may increase the plasma concentrations of itraconazole. Patients taking itraconazole and clarithromycin concomitantly should be monitored closely for signs or symptoms of increased or prolonged adverse reactions.|
|Fluconazole||No Dose Adjustment||Fluconazole: No dosage adjustment of clarithromycin is necessary when co-administered with fluconazole.|
|Colchicine (in patients with renal or hepatic impairment)||Contraindicated||Colchicine: Colchicine is a substrate for both CYP3A and the efflux transporter, P-glycoprotein (Pgp). Clarithromycin and other macrolides are known to inhibit CYP3A and Pgp. The dose of colchicine should be reduced when coadministered with clarithromycin in patients with normal renal and hepatic function (see CONTRAINDICATIONS, WARNINGS).|
|Colchicine (in patients with normal renal and hepatic function)||Use With Caution|
|Pimozide||Contraindicated||Pimozide: (see CONTRAINDICATIONS).|
|Quetiapine||Quetiapine: Quetiapine is a substrate for CYP3A4, which is inhibited by clarithromycin. Co-administration with clarithromycin could result in increased quetiapine exposure and possible quetiapine related toxicities. There have been postmarketing reports of somnolence, orthostatic hypotension, altered state of consciousness, neuroleptic malignant syndrome, and QT prolongation during concomitant administration. Refer to quetiapine prescribing information for recommendations on dose reduction if co-administered with CYP3A4 inhibitors such as clarithromycin.|
|Tolterodine (patients deficient in CYP2D6 activity)||Use With Caution||Tolterodine: The primary route of metabolism for tolterodine is via CYP2D6. However, in a subset of the population devoid of CYP2D6, the identified pathway of metabolism is via CYP3A. In this population subset, inhibition of CYP3A results in significantly higher serum concentrations of tolterodine. Tolterodine 1 mg twice daily is recommended in patients deficient in CYP2D6 activity (poor metabolizers) when co-administered with clarithromycin.|
|Atazanavir||Use With Caution||Atazanavir: Both clarithromycin and atazanavir are substrates and inhibitors of CYP3A, and there is evidence of a bi-directional drug interaction (see Atazanavir under “Drugs That Affect BIAXIN” in the table below).|
|Saquinavir (in patients with decreased renal function)||Saquinavir: Both clarithromycin and saquinavir are substrates and inhibitors of CYP3A and there is evidence of a bi-directional drug interaction (see Saquinavir under “Drugs That Affect BIAXIN” in the table below).|
|Ritonavir Etravirine||Ritonavir, Etravirine: (see Ritonavir and Etravirine under “Drugs That Affect BIAXIN” in the table below).|
|Maraviroc||Maraviroc: Clarithromycin may result in increases in maraviroc exposures by inhibition of CYP3A metabolism. See Selzentry® prescribing information for dose recommendation when given with strong CYP3A inhibitors such as clarithromycin.|
|Boceprevir (in patients with normal renal function)||No Dose Adjustment||Boceprevir: Both clarithromycin and boceprevir are substrates and inhibitors of CYP3A, potentially leading to a bi-directional drug interaction when co-administered. No dose adjustments are necessary for patients with normal renal function (see Victrelis® prescribing information).|
|Zidovudine||Zidovudine: Simultaneous oral administration of clarithromycin immediate-release tablets and zidovudine to HIV-infected adult patients may result in decreased steady-state zidovudine concentrations. Administration of clarithromycin and zidovudine should be separated by at least two hours.
The impact of co-administration of clarithromycin extended-release tablets or granules and zidovudine has not been evaluated.
|Calcium Channel Blockers:|
|Verapamil||Use With Caution||Verapamil: Hypotension, bradyarrhythmias, and lactic acidosis have been observed in patients receiving concurrent verapamil (see WARNINGS).|
|Amlodipine Diltiazem||Amlodipine, Diltiazem: (see WARNINGS).|
|Nifedipine||Nifedipine: Nifedipine is a substrate for CYP3A. Clarithromycin and other macrolides are known to inhibit CYP3A. There is potential of CYP3A-mediated interaction between nifedipine and clarithromycin. Hypotension and peripheral edema were observed when clarithromycin was taken concomitantly with nifedipine (see WARNINGS).|
|Ergotamine Dihydroergotamine||Contraindicated||Ergotamine, Dihydroergotamine: Postmarketing reports indicate that coadministration of clarithromycin with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system (see CONTRAINDICATIONS).|
|Cisapride||Contraindicated||Cisapride: (see CONTRAINDICATIONS).|
|HMG-CoA Reductase Inhibitors:|
|Lovastatin Simvastatin||Contraindicated||Lovastatin, Simvastatin, Atorvastatin, Pravastatin, Fluvastatin: (see CONTRAINDICATIONS, WARNINGS).|
|Atorvastatin Pravastatin||Use With Caution|
|Fluvastatin||No Dose Adjustment|
|Nateglinide Pioglitazone Repaglinide Rosiglitazone||Use With Caution||Nateglinide, Pioglitazone, Repaglinide, Rosiglitazone: (see WARNINGS, ADVERSE REACTIONS).|
|Insulin||Insulin: (see WARNINGS, ADVERSE REACTIONS).|
|Cyclosporine||Use With Caution||Cyclosporine: There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with cyclosporine.|
|Tacrolimus||Tacrolimus: There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with tacrolimus.|
|Sildenafil Tadalafil Vardenafil||Use With Caution||Sildenafil, Tadalafil, Vardenafil: Each of these phosphodiesterase inhibitors is primarily metabolized by CYP3A, and CYP3A will be inhibited by concomitant administration of clarithromycin. Co-administration of clarithromycin with sildenafil, tadalafil, or vardenafil will result in increased exposure of these phosphodiesterase inhibitors. Co-administration of these phosphodiesterase inhibitors with clarithromycin is not recommended. Increased systemic exposure of these drugs may occur with clarithromycin; reduction of dosage for phosphodiesterase inhibitors should be considered (see their respective prescribing information).|
|Proton Pump Inhibitors:|
|Omeprazole||No Dose Adjustment||Omeprazole: The mean 24-hour gastric pH value was 5.2 when omeprazole was administered alone and 5.7 when coadministered with clarithromycin as a result of increased omeprazole exposures (see also Omeprazole under “Drugs That Affect BIAXIN” in the table below).|
|Theophylline||Use With Caution||Theophylline: Clarithromycin use in patients who are receiving theophylline may be associated with an increase of serum theophylline concentrations. Monitoring of serum theophylline concentrations should be considered for patients receiving high doses of theophylline or with baseline concentrations in the upper therapeutic range.|
|Triazolobenzodiazepines and Other Related Benzodiazepines:|
|Midazolam||Use With Caution||Midazolam: When oral midazolam is co-administered with clarithromycin, dose adjustments may be necessary and possible prolongation and intensity of effect should be anticipated (see WARNINGS).|
|Alprazolam Triazolam||Triazolam, Alprazolam: Caution and appropriate dose
adjustments should be considered when triazolam or alprazolam is co-administered with clarithromycin. There have been postmarketing reports of drug interactions and central nervous system (CNS) effects (e.g., somnolence and confusion) with the concomitant use of clarithromycin and triazolam. Monitoring the patient for increased CNS pharmacological effects is suggested.
In postmarketing experience, erythromycin has been reported to decrease the clearance of triazolam and midazolam, and thus, may increase the pharmacologic effect of these benzodiazepines.
|Temazepam Nitrazepam Lorazepam||No Dose Adjustment||Temazepam, Nitrazepam, Lorazepam: For benzodiazepines which are not metabolized by CYP3A (e.g., temazepam, nitrazepam, lorazepam), a clinically important interaction with clarithromycin is unlikely.|
|Cytochrome P450 Inducers:|
|Rifabutin||Use With Caution||Rifabutin: Concomitant administration of rifabutin and clarithromycin resulted in an increase in rifabutin, and decrease in clarithromycin serum levels together with an increased risk of uveitis (see Rifabutin under “Drugs That Affect BIAXIN” in the table below).|
|Other Drugs Metabolized by CYP3A:|
St. John’s Wort
|Use With Caution||There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with alfentanil, methylprednisolone, cilostazol, bromocriptine, vinblastine, phenobarbital, and St. John’s Wort.|
|Other Drugs Metabolized by CYP450 IsoformsOther than CYP3A:|
|Hexobarbital Phenytoin Valproate||Use With Caution||There have been postmarketing reports of interactions of clarithromycin with drugs not thought to be metabolized by CYP3A, including hexobarbital, phenytoin, and valproate.|
|Drugs that Affect BIAXIN|
|Drug(s) that Affect thePharmacokinetics of BIAXIN||Recommendation||Comments|
|Itraconazole||Use With Caution||Itraconazole: Itraconazole may increase the plasma concentrations of clarithromycin. Patients taking itraconazole and clarithromycin concomitantly should be monitored closely for signs or symptoms of increased or prolonged adverse reactions (see also Itraconazole under “Drugs That Are Affected By BIAXIN” in the table above).|
|Atazanavir||Use With Caution||Atazanavir: When clarithromycin is co-administered with atazanavir, the dose of clarithromycin should be decreased by 50%.
Since concentrations of 14-OH clarithromycin are significantly reduced when clarithromycin is coadministered with atazanavir, alternative antibacterial therapy should be considered for indications other than infections due to Mycobacterium avium complex. Doses of clarithromycin greater than 1000 mg per day should not be co-administered with protease inhibitors.
|Ritonavir (in patients with decreased renal function)||Ritonavir: Since concentrations of 14-OH clarithromycin are significantly reduced when clarithromycin is coadministered
with ritonavir, alternative antibacterial therapy should be considered for indications other than infections due to Mycobacterium avium.
Doses of clarithromycin greater than 1000 mg per day should not be co-administered with protease inhibitors.
|Saquinavir (in patients with decreased renal function)||Saquinavir: When saquinavir is co-administered with ritonavir, consideration should be given to the potential effects of ritonavir on clarithromycin (refer to ritonavir above).|
|Etravirine||Etravirine: Clarithromycin exposure was decreased by etravirine; however, concentrations of the active metabolite, 14-OH-clarithromycin, were increased. Because 14-OHclarithromycin has reduced activity against Mycobacterium avium complex (MAC), overall activity against this pathogen may be altered; therefore alternatives to clarithromycin should be considered for the treatment of MAC.|
|Saquinavir (in patients with normal renal function)
Ritonavir (in patients with normal renal function)
|No Dose Adjustment|
|Proton Pump Inhibitors:|
|Omeprazole||Use With Caution||Omeprazole: Clarithromycin concentrations in the gastric tissue and mucus were also increased by concomitant administration of omeprazole.|
|Miscellaneous Cytochrome P450 Inducers:|
|Use With Caution||Inducers of CYP3A enzymes, such as efavirenz, nevirapine, rifampicin, rifabutin, and rifapentine will increase the metabolism of clarithromycin, thus decreasing plasma concentrations of clarithromycin, while increasing those of 14-OH-clarithromycin. Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers. Alternative antibacterial treatment should be considered when treating patients receiving inducers of CYP3A. There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with rifabutin (see Rifabutin under “Drugs That Are Affected By BIAXIN” in the table above).|
Drug/Laboratory Test Interactions
High urine concentrations of ampicillin may result in false-positive reactions when testing for the presence of glucose in urine using CLINITEST, Benedict’s Solution or Fehling’s Solution. Since this effect may also occur with amoxicillin, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as CLINISTIX) be used.
Following administration of ampicillin or amoxicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been noted.
Read the Prevpac Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 3/27/2017
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