- Triple Therapy (Oral)
- Commonly used brand name(s)
- Uses for Triple Therapy
- Before using Triple Therapy
- Proper use of lansoprazole, amoxicillin, and clarithromycin
- Precautions while using Triple Therapy
- Triple Therapy side effects
- Further information
- More about amoxicillin / clarithromycin / lansoprazole
- What are the best natural H. pylori treatments?
- Treating Helicobacter pylori effectively while minimizing misuse of antibiotics
- How does this medication work? What will it do for me?
- What form(s) does this medication come in?
- How should I use this medication?
- Who should NOT take this medication?
- What side effects are possible with this medication?
- Are there any other precautions or warnings for this medication?
- What other drugs could interact with this medication?
Amoxicillin is a penicillin antibiotic. Clarithromycin is a macrolide antibiotic. These antibiotics fight bacteria in the body.
Lansoprazole decreases the amount of acid produced in the stomach.
Amoxicillin, clarithromycin, and lansoprazole is a combination medicine used in people with Helicobacter pylori (H. pylori) infection and stomach ulcers. Treating H. pylori infection can help prevent future stomach ulcers.
Amoxicillin, clarithromycin, and lansoprazole may also be used for purposes not listed in this medication guide.
You should not take this medicine if you’ve ever had a severe allergic reaction to certain antibiotics, if you’ve had certain heart rhythm disorders, or if you’ve had liver problems caused by taking clarithromycin.
Tell your doctor about all your current medicines and any you start or stop using. Many drugs can interact, and some drugs should not be used together.
You should not take this medicine if you are allergic to amoxicillin (Amoxil), clarithromycin (Biaxin), or lansoprazole (Prevacid), or if:
- you have a history of long QT syndrome or certain heart rhythm disorders;
- you have ever had liver problems or jaundice caused by taking clarithromycin;
- you are allergic to azithromycin (Zithromax, Z-Pak), erythromycin, or telithromycin;
- you have had a severe allergic reaction to a penicillin antibiotic, including ampicillin, Augmentin, Principen, Timentin, Trimox, and others; or
- you have had a severe allergic reaction to a cephalosporin antibiotic such as cefdinir, cefprozil, cefuroxime, cephalexin, Duricef, Omnicef, Cefzil, Keflex, Spectracef, and others.
Some medicines can cause unwanted or dangerous effects when used with amoxicillin, clarithromycin, and lansoprazole. Your doctor may change your treatment plan if you also use:
- colchicine (if you also have liver or kidney disease);
- dihydroergotamine or ergotamine;
- lovastatin (Advicor, Altoprev, Mevacor) or simvastatin (Zocor, Simcor, Vytorin, Juvisync); or
Tell your doctor if you have ever had:
- liver disease;
- kidney disease;
- myasthenia gravis;
- osteoporosis or low bone mineral density (osteopenia); or
- an electrolyte imbalance or metabolic disorder.
You may be more likely to have a broken bone while taking this medicine long term or more than once per day. Talk with your doctor about ways to keep your bones healthy.
This medicine may harm an unborn baby. Use effective birth control to prevent pregnancy, and tell your doctor if you become pregnant.
Amoxicillin can make birth control pills less effective. Ask your doctor about using a non-hormonal birth control (condom, diaphragm with spermicide) to prevent pregnancy.
You should not breast-feed while using this medicine.
This medicine is not approved for use by anyone younger than 18 years old.
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 8.
Table 8: Adverse Reactions Most Frequently Reported in Clinical Trials (≥3%)
|Adverse Reaction||Triple Therapy
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.
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 9: Incidence of Possibly or Probably Treatment-Related Adverse Reactions in Short-Term, Placebo-Controlled PREVACID Studies
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:
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
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
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.
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 (see WARNINGS).
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 OVERDOSAGE).
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 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 (see WARNINGS, Hepatotoxicity)
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 (see CONTRAINDICATIONS and WARNINGS).
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 (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 entire FDA prescribing information for Prevpac (Lansoprazole, Amoxicillin and Clarithromycin)
Triple Therapy (Oral)
Generic Name: lansoprazole, amoxicillin, and clarithromycin (Oral route)
lan-SOE-pra-zole, a-mox-i-SIL-in, kla-rith-roe-MYE-sin
Medically reviewed by Drugs.com. Last updated on Jan 12, 2019.
- Side Effects
Commonly used brand name(s)
In the U.S.
- Triple Therapy
Available Dosage Forms:
- Capsule, Delayed Release
Uses for Triple Therapy
Prevpac® is a product containing three components: lansoprazole, amoxicillin, and clarithromycin. This medicine is used to treat patients with H. pylori infection and duodenal ulcers caused by H. pylori bacteria.
Lansoprazole is a proton pump inhibitor (PPI). It works by decreasing the amount of acid produced by the stomach. Amoxicillin and clarithromycin both belong to the class of medicines known as antibiotics. They work by killing bacteria or preventing their growth. However, this medicine will not work for colds, flu, or other virus infections.
This medicine is available only with your doctor’s prescription.
Before using Triple Therapy
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Appropriate studies have not been performed on the relationship of age to the effects of Prevpac® in the pediatric population. Safety and efficacy have not been established.
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of Prevpac® in the elderly. However, elderly patients are more likely to have kidney or liver problems, which may require caution and an adjustment in the dose for patients receiving this medicine.
|All Trimesters||C||Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.|
There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.
Interactions with medicines
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
- Ergoloid Mesylates
- Isavuconazonium Sulfate
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Ado-Trastuzumab Emtansine
- Aripiprazole Lauroxil
- Arsenic Trioxide
- Cholera Vaccine, Live
- Dabigatran Etexilate
- Doxorubicin Hydrochloride Liposome
- Eslicarbazepine Acetate
- Inotuzumab Ozogamicin
- Irinotecan Liposome
- Morphine Sulfate Liposome
- Mycophenolate Mofetil
- Secretin Human
- Sodium Phosphate
- Sodium Phosphate, Dibasic
- Sodium Phosphate, Monobasic
- St John’s Wort
- Vincristine Sulfate Liposome
Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Interactions with food/tobacco/alcohol
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.
Other medical problems
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:
- Allergy to amoxicillin or penicillins or cephalosporins, history of or
- Allergy to clarithromycin, erythromycin, or macrolide antibiotics or
- Allergy to lansoprazole—Should not be used in patients with these conditions.
- Cholestatic jaundice, history of or
- Heart rhythm problems (eg, QT prolongation, torsades de pointes, ventricular arrhythmia), history of or
- Liver disease, history of—Should not be used in patients with a history of these conditions caused by clarithromycin.
- Diarrhea or
- Kidney disease or
- Liver disease or
- Myasthenia gravis (severe muscle weakness) or
- Systemic lupus erythematosus (SLE)—Use with caution. May make these conditions worse.
- Hypokalemia (low potassium in the blood), uncorrected or
- Hypomagnesemia (low magnesium in the blood), uncorrected—Should be corrected first before using this medicine.
- Kidney disease, severe—Use is not recommended in patients with this condition.
Proper use of lansoprazole, amoxicillin, and clarithromycin
This section provides information on the proper use of a number of products that contain lansoprazole, amoxicillin, and clarithromycin. It may not be specific to Triple Therapy. Please read with care.
Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.
Prevpac® comes with an individual daily administration card that contains: 2 pink and black capsules of lansoprazole, 4 opaque, yellow capsules of amoxicillin, and 2 yellow tablets of clarithromycin.
Swallow the capsules and tablet whole. Do not crush, break, chew, or open any of them. Take each dose on an empty stomach, before a meal.
Keep using this medicine for the full treatment time, even if you feel better after the first few doses. Your infection may not clear up if you stop using the medicine too soon.
The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
- For oral dosage form (kit):
- For treatment of duodenal ulcers and H. pylori infections:
- Adults—30 milligrams (mg) or 1 capsule of lansoprazole, 1000 mg or 2 capsules of amoxicillin, and 500 mg or 1 tablet of clarithromycin taken together two times per day (morning and evening) for 10 or 14 days.
- Children—Use and dose must be determined by your doctor.
- For treatment of duodenal ulcers and H. pylori infections:
If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
Precautions while using Triple Therapy
It is important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood, urine, and other laboratory tests may be needed to check for unwanted effects. If your condition does not improve, or if it becomes worse, talk with your doctor.
Do not use this medicine if you are also using astemizole (Hismanal®), atazanavir (Reyataz®), cisapride (Propulsid®), lovastatin (Mevacor®), pimozide (Orap®), simvastatin (Zocor®), terfenadine (Seldane®), certain ergot medicines (such as dihydroergotamine, ergotamine, D.H.E. 45®, Ergomar®, Ergostat®, or Migranal®), or medicines containing rilpivirine. If you have kidney or liver disease, do not take this medicine together with colchicine (Colcrys®). Using these medicines together may increase risk for more serious side effects.
This medicine may cause serious allergic reactions, including anaphylaxis. This can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, fever or chills, hoarseness, sores or ulcers on the skin, trouble breathing, trouble swallowing, or any swelling of your hands, face, mouth, or throat while you are using this medicine.
Make sure your doctor knows if you are pregnant or planning to become pregnant. If you become pregnant while using this medicine, tell your doctor right away.
Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, unusual tiredness or weakness, or yellow eyes or skin. These could be symptoms of a serious liver problem.
Contact your doctor right away if you have any changes to your heart rhythm. You might feel dizzy or faint, or you might have a fast, pounding, or uneven heartbeat. Make sure your doctor knows if you or anyone in your family has ever had a heart rhythm problem such as QT prolongation.
Check with your doctor right away if you have a fever, joint pain, skin rash, swelling of the body, feet, or ankles, or unusual weight gain after receiving this medicine. These could be symptoms of serious kidney problem called acute interstitial nephritis.
This medicine may cause diarrhea, and in some cases it can be severe. It may occur 2 months or more after you stop taking this medicine. Do not take any medicine to treat diarrhea without first checking with your doctor. If you have any questions or if mild diarrhea continues or gets worse, check with your doctor.
Cutaneous or systemic lupus erythematosus may occur or get worse in patients receiving a PPI. Call your doctor right away if you have joint pain or a skin rash on your cheeks or arms that gets worse when exposed to the sun.
Make sure any doctor or dentist who treats you knows that you are using this medicine. This medicine may affect the results of certain medical tests.
Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter ) medicines and herbal (eg, St. John’s wort) or vitamin supplements.
Triple Therapy side effects
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
Incidence not known
- Blistering, peeling, or loosening of the skin
- clay colored stools
- dark urine
- difficulty with swallowing
- dizziness or fainting
- fast, slow, or irregular heartbeat
- hives, itching, or skin rash
- joint or muscle pain
- loss of appetite
- puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
- red skin lesions, often with a purple center
- red, irritated eyes
- sores, ulcers, or white spots in the mouth or on the lips
- stomach pain or tenderness
- swelling of the body, feet, and ankles
- tightness in the chest
- unusual tiredness or weakness
- unusual weight gain
- watery and severe diarrhea, which may also be bloody
- yellow eyes or skin
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
- Bad, unusual or unpleasant (after) taste
- change in taste
- discoloration of the tongue
- itching of the vagina or genital area
- pain during sexual intercourse
- redness, swelling, or soreness of the tongue
- sore mouth or tongue
- thick, white vaginal discharge with no odor or with a mild odor
- white patches in the mouth, tongue, or throat
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Copyright 2019 Truven Health Analytics, Inc. All Rights Reserved.
More about amoxicillin / clarithromycin / lansoprazole
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- En Español
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- Drug class: H. pylori eradication agents
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Related treatment guides
- Helicobacter Pylori Infection
What are the best natural H. pylori treatments?
Researchers have conducted a range of studies on natural approaches to treating H. pylori infections. Eight potential natural treatments include:
Share on PinterestPeople with H. pylori infections may find some natural treatments beneficial.
Honey is known for its antibacterial properties, and people have used it as a medicine since ancient times.
One study showed that Manuka honey suppressed the growth of H. pylori in gastric epithelial cells.
Other studies have demonstrated that honey has other anti-H. pylori properties, but more animal studies and clinical trials are needed to assess honey’s efficiency as a complementary or alternative treatment.
2. Aloe vera
Aloe vera is an herbal remedy used to treat a variety of illnesses, including:
- digestive health
In one study, the gel from inside the leaves of an aloe vera plant was effective in both inhibiting growth of and killing H. pylori strains, even those that were drug-resistant in a laboratory environment.
This suggests that aloe vera could be effective against H. pylori infection when used in combination with antibiotics.
3. Broccoli sprout
Sulforaphane, a compound found abundantly in broccoli sprout, has been shown to kill H. pylori.
Studies performed both in test tubes and on animal and human subjects have demonstrated the favorable effects of sulforaphane against H. pylori bacteria. Broccoli sprout also decreased gastric inflammation in H. pylori-infected mice.
Lactoferrin, a glycoprotein found in both human and cow’s milk, has shown inhibitory activity against H. pylori. One study used a combination of antibiotics and lactoferrin from cow’s milk, which resulted in a 100 percent eradication rate of H. pylori in 150 affected people.
Also, a compound called melanoidin appears to inhibit the growth of H. pylori bacteria. Melanoidin is a compound formed by a chemical reaction between the sugar lactose and a protein called casein in milk and dairy products. Research has shown that melanoidin suppresses H. pylori colonization in both mice and humans.
5. Lemongrass oil
People must not ingest essential oils. Instead, they can inhale them and use them as part of an aromatherapy approach. According to studies carried out on humans and animals, lemongrass essential oil inhibits the growth of H. pylori.
In a study on mice, the density of H. pylori colonization in the stomach was significantly reduced compared to mice not treated with lemongrass oil.
6. Green tea
Green tea is one of the healthiest and most widely consumed beverages in the world. It contains many antioxidants and nutrients.
In an animal study, green tea decreased both the number of bacteria and the inflammation score of H. pylori-infected mice. However, researchers found that mice that received green tea before infection achieved better results.
According to the Food and Agriculture Organization, probiotics are live microorganisms that offer health benefits to people. Interest in probiotics as a treatment for H. pylori is increasing.
There are numerous types of probiotics. Many people use Bifidobacterium, which is found in dairy and fermented products, to prevent gastrointestinal infection.
Research has shown that Bifidobacterium exerts its effect against H. pylori by competing with the bacteria to stick to the mucous lining of the stomach.
Research suggests that H. pylori bacteria are sensitive to ultraviolet light. During phototherapy, an ultraviolet light source illuminates the whole stomach.
Phototherapy has been shown to reduce the number of bacteria in the stomach significantly. However, the bacteria will repopulate a few days after illumination.
While phototherapy is not a complete fix, it may have the potential to become an effective treatment against H. pylori, particularly for people who cannot take antibiotics.
Treating Helicobacter pylori effectively while minimizing misuse of antibiotics
Bismuth quadruple therapy is an alternative
Bismuth quadruple therapy (Table 1) consists of:
- A proton pump inhibitor.
This was the first truly effective regimen for H pylori. Its advantage is that it can partially or completely overcome metronidazole resistance.21,22 As such, it is potentially ideal, as it should be effective despite resistance to clarithromycin, metronidazole, or levofloxacin, and it can be used in patients allergic to penicillin.
The major downside is a high frequency of side effects, particularly abdominal pain, nausea, and vomiting, often resulting in poor adherence. Most regimens that contain antibiotics have side effects, but adherence seems to be more of a problem with bismuth quadruple therapy, probably because of the combination of the high doses of metronidazole and tetracycline.22 In our experience, this regimen can be effective if the physician takes the time to explain to the patient that side effects are common but treatment success depends on completing the full course of 14 days.
Another problem is that tetracycline has become difficult to obtain in many areas, and doxycycline cannot be substituted in those with metronidazole resistance. To date, it has been difficult or impossible to obtain the same excellent results with doxycycline as can be obtained with tetracycline. It is not clear why.21
To use bismuth quadruple therapy one must often use a name-brand product, Pylera. Pylera is packaged as a 10-day course, which is effective against metronidazole-susceptible infections. However, 14 days are generally required to achieve a high cure rate with metronidazole-resistant infections, which are the main indication for use of this product. Moreover, Pylera does not include a proton pump inhibitor, which must be prescribed separately.
In the United States, Pylera is expensive, costing $740 to $790 with a coupon for a 10-day supply and proportionally more for the required 14-day supply (www.goodrx.com/pylera?drug-name=pylera), whereas in Europe it costs less than 70 Euros ($73).21 If generic tetracycline is available, the US cost for 14 days of generic bismuth quadruple therapy is less than $50.
An alternate and simpler approach is to substitute amoxicillin for tetracycline.23 This regimen has been used successfully in China and was shown to be noninferior to the tetracycline-containing regimen in a head-to-head comparison.24
Recent studies have confirmed earlier Italian studies suggesting that twice-a-day bismuth and tetracycline is effective, which would further simplify therapy and possibly reduce side effects.21,23,24 These variations on bismuth quadruple therapy have not yet been optimized to where one can reliably achieve 95% or greater cure rates, and further studies are needed.
Why include more than 1 antibiotic?
The H pylori load in the stomach is typically large, which increases the odds that a subpopulation of resistant organisms is present. Resistance may be due to a relatively high rate of mutation in certain bacterial genes.25 This is particularly a problem with clarithromycin, metronidazole, and fluoroquinolones and is reflected in a high rate of resistance among patients for whom single-drug regimens have failed. These drugs are always given with a second antimicrobial to which H pylori rarely becomes resistant, such as amoxicillin or tetracycline.
Why include a proton pump inhibitor?
An antisecretory drug is needed to increase the gastric pH, which makes antimicrobial therapy more effective. It also decreases antibiotic washout from the stomach and likely protects and increases the gastric concentration of some antibiotics.
The activities of amoxicillin, fluoroquinolones, and to a lesser degree clarithromycin are pH-dependent. For example, keeping the gastric pH above 6.0 promotes H pylori replication,26,27 making it is more susceptible to amoxicillin (reviewed in detail by Dore et al21). A gastric pH of 6.0 or more is very difficult to achieve with proton pump inhibitors, and has been accomplished regularly only in people who metabolize these drugs slowly (“slow metabolizers”) who received both the proton pump inhibitor and amoxicillin every 6 hours for 14 days.21
With standard clarithromycin, metronidazole, or fluoroquinolone triple therapy, proton pump inhibitors appear to provide satisfactory cure rates when given for 14 days in standard doses. However, double doses (eg, 40 mg of omeprazole or an equivalent) may be slightly better, especially in the presence of resistance.
The cure rate reflects the sum of the 2 populations of organisms: the susceptible and the resistant. In triple therapy, increasing the gastric pH with a proton pump inhibitor makes the amoxicillin component of the regimen more effective against resistant organisms and thus increases the cure rate. For example, in Western countries, esomeprazole 40 mg (approximately equivalent to rabeprazole 40 mg, omeprazole or lansoprazole 60 mg, or pantoprazole 240 mg)28 given twice a day in a 14-day triple therapy regimen cures about 40% to 50% of resistant infections. This benefit will be evident in an improvement in cure rates in populations in which resistance has reduced the average cure rate. This is also why meta-analyses have shown better results with second-generation proton pump inhibitors and with longer duration of therapy.29,30
Generally, we recommend omeprazole 40 mg twice a day or an equivalent (Tables 1–3).
Would a potassium-competitive acid blocker be better than a proton pump inhibitor?
Vonoprazan is a potassium-competitive acid blocker. It does not require intermediate complex formation and is stable at low pH. It has a longer half-life than proton pump inhibitors, and its bioavailability is unaffected by food.31 It was recently approved in Japan for H pylori eradication in combination with clarithromycin or metronidazole plus amoxicillin.18
Vonoprazan is more effective than current proton pump inhibitors for keeping the gastric pH high. There are no published studies of vonoprazan dual therapy in Western countries, but given twice a day for 7 days along with twice-daily amoxicillin it cured only approximately 80% of clarithromycin-resistant strains. Further studies are needed to identify the optimum proton pump inhibitor or potassium-competitive acid blocker, dose, and duration.
How does this medication work? What will it do for me?
This is a product that contains three separate medications: lansoprazole, clarithromycin, and amoxicillin. Lansoprazole belongs to the group of medications called proton pump inhibitors (PPIs). Clarithromycin and amoxicillin belong to the group of medications called antibiotics. Together these medications are used to treat H. pylori (bacteria that cause inflammation in the stomach) for people with a duodenal ulcer (an ulcer at the beginning of the small intestine).
These medications are also used to reduce the risk of another duodenal ulcer occurring for people who have recently had a duodenal ulcer and who have tested positive for H. pylori. Lansoprazole helps to lower the acidity of the stomach, which helps the antibiotics (clarithromycin and amoxicillin) kill the bacteria and to heal the ulcer.
This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.
Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.
Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.
What form(s) does this medication come in?
Each triple therapy HP-PAC (lansoprazole – clarithromycin – amoxicillin) daily administration blister pack contains:
Lansoprazole 30 mg
Each opaque, hard gelatin, pink and black, delayed-release capsule, with the TAP logo and “PREVACID 30” imprinted on the capsule, contains lansoprazole 30 mg. Nonmedicinal ingredients: cellulosic polymers, colloidal silicon dioxide, D&C Red No. 28, FD&C Blue No. 1, FD&C Red No. 40, gelatin, magnesium carbonate, methacrylic acid copolymer, polyethylene glycol, polysorbate 80, starch, sucrose, sugar spheres, talc, and titanium dioxide.
Clarithromycin 500 mg
Each pale yellow, oval, film-coated tablet, with the Abbott logo printed on one side, contains clarithromycin 500 mg. Nonmedicinal ingredients: cellulosic polymers, croscarmellose sodium, D&C Yellow No. 10, magnesium stearate, povidone, propylene glycol, silicon dioxide, sorbic acid, sorbitan monooleate, stearic acid, talc, titanium dioxide, and vanillin. Tartrazine-free.
Amoxicillin 500 mg
Each opaque, scarlet and yellow capsule, with the Abbott logo and “500” imprinted on the capsule, contains amoxicillin trihydrate 500 mg. Nonmedicinal ingredients: colloidal silicon dioxide, D&C Yellow No. 10, dry-flo starch, FD&C Blue No. 1, FD&C Red No. 3, FD&C Red No. 40, FD&C Yellow No. 6, gelatin, magnesium stearate, sodium lauryl sulfate, talc, and titanium dioxide. Gluten- and tartrazine-free.
How should I use this medication?
The usual adult dose of this combination of medications is 30 mg of lansoprazole, 500 mg of clarithromycin and 1 g (two 500 mg capsules) of amoxicillin, twice a day before meals for 7, 10, or 14 days.
Lansoprazole capsules should be swallowed whole with water – do not crush or chew them.
Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.
It is important to take this medication exactly as prescribed by your doctor and to finish all this medication. Not doing so may decrease the effectiveness of this medication and may increase the chances of bacteria developing resistance to amoxicillin and clarithromycin.
If you miss a dose, take it as soon as possible and continue with your regular schedule. If it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.
Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children.
Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.
Who should NOT take this medication?
Do not take this medication if you:
- are allergic to lansoprazole, clarithromycin, amoxicillin, or any ingredients of these medications
- are allergic to other penicillins (e.g., cloxacillin, penicillin), cephalosporins, or other macrolide antibiotics (e.g., erythromycin, azithromycin)
- are taking astemizole, terfenadine, cisapride, pimozide, ergotamine, or dihydroergotamine
- have or may have mononucleosis
What side effects are possible with this medication?
Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.
The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.
The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.
Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.
- difficulty sleeping
- dry mouth
- heartburn or indigestion
- muscle pain
- taste changes
Although most of the side effects listed below don’t happen very often, they could lead to serious problems if you do not check with your doctor or seek medical attention.
Check with your doctor as soon as possible if any of the following side effects occur:
- abdominal pain
- irregular heartbeat
- lightheadedness or dizziness
- severe abdominal pain or cramps
- severe diarrhea with or without blood or mucus
- symptoms of a bladder infection (pain or burning when urinating)
- symptoms of an upper airway infection such as cough, nasal congestion, sinus pain, runny nose, or sore throat
Stop taking the medication and seek immediate medical attention if any of the following occur:
- abnormal heart rhythms (such as fast or slow heart rate, palpitations), fainting or seizures
- signs of an allergic reaction (e.g., hives; difficulty breathing; swelling of the face, mouth, tongue, or throat)
- signs of a severe skin reaction such as blistering, peeling, a rash covering a large area of the body, a rash that spreads quickly, or a rash combined with fever or discomfort
Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.
Are there any other precautions or warnings for this medication?
Before you begin taking a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should take this medication.
Allergic reactions: Some people who are allergic to penicillin or cephalosporins also experience allergic reactions to amoxicillin. Some people who are allergic to erythromycin or azithromycin also experience allergic reactions to clarithromycin. Before you take lansoprazole – clarithromycin – amoxicillin, inform your doctor about any previous adverse reactions you have had to medications, especially penicillin or erythromycin antibiotics. Contact your doctor at once if you experience signs of an allergic reaction, such as skin rash, itching, difficulty breathing, or swelling of the face and throat.
Diarrhea: Diarrhea is a common side effect of antibiotics such as amoxicillin and clarithromycin. Diarrhea usually stops when the antibiotic is finished. However, a serious condition called pseudomembranous colitis can occur. If you develop severe watery and bloody diarrhea (with or without stomach cramps and fever) any time during treatment or up to 1 or 2 months after stopping this medication, contact your doctor.
Kidney function: A safe and effective dose of lansoprazole – clarithromycin – amoxicillin for people with reduced kidney function has not been determined. If you have kidney disease or decreased kidney function, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.
Liver function: Liver disease or reduced liver function may cause clarithromycin or lansoprazole to build up in the body, causing side effects. If you have liver problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Your doctor may want to test your liver function regularly with blood tests while you are taking this medication.
Methotrexate: When taken together, proton pump inhibitors such as lansoprazole may cause methotrexate to build up in the body, causing severe side effects, including possible death. Methotrexate is used to treat certain types of cancer, arthritis, and gastrointestinal disease. If you are taking methotrexate for any reason, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.
Stomach cancer: Lansoprazole can improve some of the symptoms of stomach cancer and make it harder for a doctor to diagnose it.
Pregnancy: This medication should not be used during pregnancy, especially during the first 3 months, unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.
Breast feeding: Amoxicillin and clarithromycin pass into breast milk. It is not known if lansoprazole passes into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.
Children: The safety and effectiveness of using this combination of medications have not been established for children.
Seniors: Due to the possibility of reduced kidney and liver function, seniors should discuss with their doctor how this medication may affect their medical condition, how their medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.
What other drugs could interact with this medication?
There may be an interaction between lansoprazole – clarithromycin – amoxicillin and any of the following:
If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:
- stop taking one of the medications,
- change one of the medications to another,
- change how you are taking one or both of the medications, or
- leave everything as is.
An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.
Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.
All material copyright MediResource Inc. 1996 – 2020. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/drug/getdrug/HP-Pac
There was no significant difference in gender, age, and BMI among the 3 groups (P < 0.05), suggesting the comparability of the groups (Table 1).
Table 1 Basic information of the subjects.
H. pylori eradication rate
Gastroscopy revealed that the ulcer healing rate of the TT group (90%) was lower than that of the TP group (100%), but there was no statistically significant difference (P = 0.4682).
A total of 16 cases (80%) in the TT group were successfully eradicated, and 17 cases (85%) were successfully eradicated in the TP group. No difference in the success rate of the H. pylori eradication was observed between the 2 groups (P > 0.05).
Gastric pH value
The gastric pH values of DU patients in the pre-TT and the pre-TP groups were significantly different from that in the HC group (P < 0.01), while the TT and the TP groups after treatment (post-TT and post-TP groups) showed no difference with the HC group (P = 0.274). Significant differences were observed between the pre-TT and the post-TT group (P < 0.01), as well as between the pre-TP and post-TP groups (P < 0.01) (Table 2 and Fig. 1).
Table 2 pH value of gastric juice before and at 4w after treatment (Mean ± SD). Figure 1
Gastric pH value before and after treatment.
Fecal microbiome in DU patients
The average Raw PE number obtained for each bacterial sample was 65630 and fungi sample was 54549. The dilution curve was drawn by 3 methods, including the OTU numbers, the Chao1 and the Shannon 3 for mutual validation, and the results suggested a trend of reaching gentleness at 10,000 sequences.
OTU analysis: Statistical analysis showed that the OTU number was lower in the DU group compared with that in the HC group, either at the 97% OTU species-level (HC group 505.33 ± 133.63 vs DU group 355.07 ± 104.11 P = 0.0003) or at the 95% OTU genus level (HC group 412.17 ± 114.75 vs DU group 271.28 ± 89.73, P = 0.0001). Differences between the 2 groups were statistically significant (Fig. 2).
Comparison of OTUs from the 2 groups at the species and genus levels.
Annotation of species and analysis of differential bacteria: The statistical analysis revealed that the bacterial flora community was derived from 38 bacterial phyla, 110 bacterial classes, 157 bacterial orders, 230 bacterial families, and 275 bacterial genera.
At the phylum level, the abundance distribution showed that in the HC group, the dominant phyla were Firmicutes, Bacteroidetes, and Proteobacteria. These 3 bacterial phyla were abundant in every sample with high percentages, accounting for 45.5%, 33.0%, and 13.2%, respectively, and together accounting for 91.7% of the total bacteria. In the DU group, the dominant phyla were also Firmicutes, Bacteroidetes, and Proteobacteria, accounting for 52.5%, 25.7%, and 15.7%, respectively, and together accounting for 93.9% of the total bacteria. Although the percentages of the 3 bacterial phyla have changed, the differences between the DU group and the HC group were not statistically different. Comparing the other 35 bacterial phyla between the DU group and the HC group revealed a total of 7 bacterial phyla with statistically significant differences: Actinobacteria, Gemmatimonadetes, Nitrospirae, Chlorobi, Thermi, WS3, and Caldithrix. The percentages of these 7 bacterial phyla were all lower in the DU group compared with those in the HC group.
Analysis of species composition: The PCoA analysis found that the intra-group distances between each sample within the HC group and the DU group were smaller than the inter-group distances, suggesting the similarity of the species compositions (Fig. 3).
PCoA analysis (blue denotes the HC group and red denotes the DU group).
The UPGMA (Unweighted Pair Group Method with Arithmetic Mean) method was used to input the unweighted UniFrac clustering matrix, which performed cluster analysis on samples. In the cluster diagram (Fig. 4), we found that the bacterial flora structure among all the samples exhibited both clustering and various degrees of overlapping. However, only a few samples could be clustered between the DU group and the HC group, with a general trend of high similarity between samples within groups. Therefore, the DU group or the HC group was considered as a homologous group, and samples from such groups exhibited internal clustering.
Unweighted UniFra distance clustering tree of samples.
OTU analysis: The OTU number was lower in the DU group compared with that in the HC group, either at the 97% OTU species level (HC group 60.70 ± 14.46 vs DU group 48.65 ± 10.26P = 0.0180) or at the 95% OTU genus level (HC group 51.20 ± 15.49 vs DU group 38.77 ± 9.13P = 0.0141). Differences between the 2 groups were statistically significant (Fig. 5).
Comparison of OTUs of the 2 groups of at the species and genus level.
Annotation of species and analysis of differential fungi: According to the annotation results of species, most of the fungal communities came from 2 fungal phyla, 31 fungal classes, 53 fungal orders, 90 fungal families, and 104 fungal genera.
At the phylum level, the abundance distribution showed that the abundance of Ascomycota was 59.6% in the HC group and 58.8% in the DU group; the abundance of Basidiomycota was 37.0% in the HC group and 40.3% in the DU group. There was no difference in the fungal phyla between the 2 groups.
Analysis of species composition: PCoA analysis was performed, and the results are shown in Fig. 6. It can be seen that the majority of the samples from the DU groups were clustered in the lower left quadrant, whereas samples from the HC group tended to locate in the upper part of the quadrant. These results suggest that the fungal flora compositions between the DU group and the HC group are not exactly the same, while the internal fungal flora structures within groups are more similar.
PCoA analysis (blue represents the HC group, and red represents the DU group).
Next, samples were subjected to cluster analysis (Fig. 7). In the clustering diagram, we found that the fungal flora structure among all the samples exhibited both clustering and various degrees of overlapping. However, only a few samples could be clustered between the DU group and the HC group. The general trend was that samples from the DU group or the HC group were first clustered, suggesting that either the DU group or the HC group had a high intra-group similarity.
Changes of intestinal stool microbiome after anti-H. pylori treatment
OTU analysis: Statistical analysis of OTUs at the bacterial species level was carried out for 4 different time points in the TT group and the TP group (Table 3 and Fig. 8); 0 week (w) represents the DU group before treatment (i.e., with ulcers). Intra-group comparisons were first performed within both groups, and we found that, except in the TT group where differences were observed between DU and TF1 (P = 0.03159) and between DU and TF2 (P = 0.04526), there was no statistical difference in the rest of the pairwise comparisons. In other words, at the end of the anti-H. pylori treatment and at 6w after treatment, the intestinal bacterial flora abundance in the TT group decreased compared with that in the untreated group, whereas the TP group showed no significant changes compared with the untreated group.
Table 3 OTUs at different time points in the two groups. Figure 8
OTUs at different time points before and after treatment.
When the 2 groups were compared with the HC group before and after treatment at different time points, respectively, most of the compared groups showed statistical differences, except between the TP group and the HC group (Table 4).
Table 4 P-values from the inter-group comparisons of the OTUs at different time points.
Annotation of species and analysis of differential bacteria:
The intestinal bacterial changes between groups at the same time points. At the end of the 2w treatment, there was no significant change in intestinal bacterial flora at the phylum level between the 2 groups, whereas at the genus level, a total of 23 differential bacterial genera (P < 0.05) were discovered. After 6w of treatment, there were 28 differential bacterial genera, and at 10w, there were 11. Details of the differential bacterial genera are listed in the following table (Table 5).
Table 5 Differential bacterial genera between the 2 groups at different time points.
The intestinal bacterial changes within groups at different time points. In the TT group, among the top ten bacterial phyla at the phylum level, pairwise comparisons within the group showed that differences were only observed in the Bacteroidetes phylum and the Tenericutes phylum: the relative abundance of the Bacteroidetes phylum increased in TF2 compared with that in DU (P = 0.03664), and the relative abundance of the Tenericutes phylum decreased in TF1 compared with that in DU (P = 0.01807). There was no statistical difference in changes of different bacterial phyla at the remaining time points (Fig. 9).
Abundance changes of bacterial phyla in the TT group before and after treatment.
In the TP group, among the top 10 bacterial phyla at phylum level, pairwise comparisons within the group showed that differences were only observed in the Firmicutes phylum, the relative abundance of which increased in PF2 compared with that in PF1 (P = 0.01356). There was no statistical difference in changes of different bacterial phyla at the remaining time points (Fig. 10).
Abundance changes of bacterial phyla in the TP group before and after treatment.
At the genus level, among the 4 different time points in the TT group, pairwise comparisons within the group revealed a total of 8 significantly different (P < 0.05) bacterial genera, the bacterial flora abundance of which was more than 0.1% of the total samples.
At the genus level, among the 4 different time points in the TP group, pairwise comparisons within the group revealed a total of 5 significantly different (P < 0.05) bacterial genera, the bacterial flora abundance of which was more than 0.1% of the total samples. Such differential bacterial genera were fewer in the TP group than that in the TT group, and their abundance percentage was very low. These results suggest that the changes of bacteria at different time points in the TP group were slight, and were from only a small number of bacteria. These bacterial changes were stable, and exhibited a trend of gradual transition. In the TT group, however, the bacterial changes were larger, came from a larger number of bacteria, and presented more intense amplitudes.
OTU analysis: The results revealed that at the 3 time points after TT treatment, the number of OTUs of the intestinal fungal flora decreased compared with that in DU, and was statistically different (P < 0.05); before and after TP treatment, however, there was no obvious change in the number of OTUs. There were differences between the 2 treatment approaches at the same time points (Table 6 and Fig. 11).
Table 6 OTUs at different time points in the two groups. Figure 11
OTUs at different time points before and after treatment.
When the 2 groups were compared with the HC group before and after treatment at different time points, respectively (Table 7), it could be seen that there was no statistical difference among the 3 time points after TP treatment and the HC group, whereas there were statistically significant differences among the 3 time points in the TT group and the HC group.
Table 7 P values from the inter-group comparisons of the OTUs at different time points.
Annotation of species and analysis of differential fungi:
The intestinal fungal changes between groups at the same time points. At the phylum level, the 2 treatment approaches showed no obvious difference in the intestinal fungal flora at any of the 3 time points after treatment. At the genus level, some of the fungi were significantly different (P < 0.05): at the end of 2w treatment, a total of 5 differential fungal genera were observed. Details of the differential fungal genera are listed in the following table (Table 8).
Table 8 Differential fungal genera between the two groups at different time points.
Intestinal fungal changes within groups at different time points At the phylum level, there was no difference among the 4 time points either in the TP group or in the TT group. At the genus level, among the 4 time points in the TT group, pairwise comparisons within the group revealed that only the Pseudozyma genus and the Cladosporium genus showed significant differences (P < 0.05), and the trends of the changes at the 4 time points are shown in the figure below; among the 4 time points in the TP group, pairwise comparisons within the group revealed a total of 6 differential fungal genera (P < 0.05), more than those in the TT group. Moreover, the relative abundance of the differential fungal genera was higher than that in the TT group, suggesting that the fungal changes at different time points in the TT group were slight and came from only a small number of fungi, whereas the fungal changes in the TP group were larger and came from a larger number of fungi.
FACTORS AFFECTING HELICOBACTER PYLORI ERADICATION USING A SEVEN-DAY TRIPLE THERAPY WITH A PROTON PUMP INHIBITOR, TINIDAZOLE AND CLARITHROMYCIN, IN BRAZILIAN PATIENTS WITH PEPTIC ULCER
Fernando Marcuz Silva, Schlioma Zaterka, Jaime Natan Eisig, Ethel Zimberg Chehter, Décio Chinzon and Antonio Atílio Laudanna
SILVA FM et al. ¾ Factors affecting Helicobacter pylori eradication using a seven-day triple therapy with a proton pump inhibitor, tinidazole and clarithromycin, in brazilian patients with peptic ulcer Rev. Hosp. Clín. Fac. Med. S. Paulo 56(1):11-16, 2001.
Triple therapy is accepted as the treatment of choice for H. pylori eradication. In industrialized countries, a proton pump inhibitor plus clarithromycin and amoxicillin or nitroimidazole have shown the best results. Our aims were: 1. To study the eradication rate of the association of a proton pump inhibitor plus tinidazole and clarithromycin on H. pylori infection in our population. 2. To determine if previous treatments, gender, age, tobacco, alcohol use, and non-steroidal anti-inflammatory drugs (NSAIDs) change the response to therapy.
METHODS: Two hundred patients with peptic ulcer (upper endoscopy) and H. pylori infection
(histology and rapid urease test RUT) were included. A proton pump inhibitor (lansoprazole 30 mg or omeprazole 20 mg), tinidazole 500 mg, and clarithromycin 250 mg were dispensed twice a day for a seven-day period. Eradication was assessed after 10 to 12 weeks of treatment through histology and RUT.
RESULTS: The eradication rate of H. pylori per protocol was 65% (128/196 patients). This rate was 53% for previously treated patients, rising to 76% for not previously treated patients, with a statistical difference p<0.01. No significant difference was observed regarding sex, tobacco use, alcohol consumption, and NSAID use, but for elderly patients the difference was p = 0.05. Adherence to treatment was good, and side effects were mild.
CONCLUSIONS: A proton pump inhibitor, tinidazole, and clarithromycin bid for seven days resulted in H. pylori eradication in 65% of the patients. Previous treatments were the main cause of treatment failure.
DESCRIPTORS: Peptic Ulcer Treatment. Helicobacter pylori Eradication. Proton pump inhibitor. Tinidazole. Clarithromycin.
The identification of H. pylori in the gastric epithelium and its relationship with peptic disease1 resulted in a remarkable change in the management of peptic ulcers. It is a worldwide consensus that eradication of the bacterium is the corner stone of peptic ulcer cure2,3. The low rates of eradication observed in mono therapies and double therapies have encouraged the use of three antibiotics or two antibiotics and a proton pump inhibitor4,5,6 Efficacy, the short period of treatment, low doses, few side effects, and low cost, make triple therapy with a proton pump inhibitor, macrolide, and nitroimidazole a very acceptable treatment for H. pylori eradication7,8,9. In Brazil, as well as in all developing countries, the risk of a therapeutic failure because of H. pylori strains that are resistant to metronidazole has to be considered7, because of its worldwide use. The aim of our study was to observe the eradication rate of H. pylori in a Brazilian peptic ulcer population under this treatment. The influence of previous treatments, gender, age, tobacco, alcohol, and NSAID use on therapy was evaluated.
PATIENTS AND METHOD
Two hundred outpatients seen from December 1995 to September 1996 were invited to participate. Inclusion criteria: 1. Patients with gastric or duodenal peptic ulcer (active or healed). 2. H pylori infection diagnosed by both histology and RUT. 3. Patients with no previous treatment and previously treated with bismuth subcitrate, metronidazole, and amoxicillin or tetracycline. Exclusion criteria: 1. Patients under 16 years of age. 2. Previous use of antibiotic therapy at least three months prior to the inclusion. 3. Pregnant or lactating women. 4. Prior gastric surgery. 5. Patients with any decompensated disease.
The Ethical and Scientific Committee of Hospital das Clinicas approved this protocol. Before inclusion, all participants signed a post-informed consent statement.
Patients’ data were obtained from standard questionnaires conducted at patients’ inclusion in the study.
H. pylori infection was confirmed by histological examination (H&E and Giemsa methods) and rapid urease test (RUT) performed on biopsy material taken during upper endoscopy (2 samples of antrum and 2 samples of gastric body). H. pylori was considered eradicated when the RUT and histological examination performed 10 to 12 weeks after the end of the treatment were negative.
Clarithromycin 250 mg plus tinidazole 500 mg and a proton pump inhibitor (lansoprazole 30 mg or omeprazole 20 mg) were dispensed twice a day for a seven-day period. After treatment, compliance was assessed by pill consumption. Patients were asked about adverse effects. Patients were requested to stop all medications except antacids if needed for dyspeptic symptom relief or other medications for chronic use in concomitant diseases.
Statistical analysis was performed with software package SPSS v.3.0 (SPSS Inc., USA). The variables, gender, age, previous treatment, tobacco, alcohol, and NSAIDs were analyzed by the chi-square method. A p value < 0.05 was taken as being significant. A multiple logistic regression analysis was also performed; eradication was the dependent variable, and gender, age, previous treatment, tobacco, alcohol, and NSAIDs were the independent variables.
Two hundred patients were included in the study. There were 196 patients available for analysis “per protocol”, most of them female with mean age = 44 (range = 16 to 80). The demographic data are shown in table 1.
Side effects were observed in 36 patients (18%), usually mild ones. One patient had to stop medication because of severe nausea and vomiting. Taste alterations, nausea, diarrhea, and dizziness were the most frequent side effects observed. One patient reported glossitis and vulvae pruritus.
Patients’ adherence was high. All except 3 patients took more than 90% of the pills.
The objective of H. pylori-dependent peptic ulcer treatment should be healing the ulcer and eradication of the bacteria. Many treatment schedules have been suggested to eradicate H. pylori 6,10,11. Eradication success depends mainly on adherence to treatment and bacterial resistance to medications12-15. There is no doubt that the ideal treatment must be effective at a low cost, besides being simple and free of side effects. It is a consensus in developed countries that an acceptable eradication rate is 90% or more2,9,11,16. Triple therapy with a proton pump inhibitor was considered the treatment of choice to eradicate H. pylori2,3,17-23. Association of a proton pump inhibitor plus amoxicillin or nitroimidazole and clarithromycin results in an eradication rate higher than 90% 6,8,11,17,18,20-22. In populations where resistance to metronidazole is more than 30%, low effectiveness has been reported13,14. In Brazil, H. pylori resistance to metronidazole is over 30%7, so it was not surprising that the 90% success rate in eradication was not reached by our population24-27. In our study, the compliance to treatment was good; all except 3 patients took more than 90% of the pills. Although we do not have data on bacteria sensitivity, the 76% eradication rate observed in the first treated patients was probably due to tinidazole resistance. Similarly, a greater proportion of metronidazole-resistant strains present in patients underwent treatment for the second time, could explain the low 53% eradication rate observed. Moshkowitz28 obtained similar data. These results reinforce that it is preferable that nitroimidazoles not be used in triple therapy schedules in Brazil. Macheda and Zaterka (unpublished results) and Chehter et al.29 obtained 85% eradication in patients undergoing 7-day treatment with lansoprazole 30 mg plus amoxicillin 1.0 g and clarithromycin 0.5 g bid. They show that the use of amoxicillin instead of tinidazole increases the eradication rate, which is similar to the results observed in developed countries. Side effects were reported by 18% of our patients, usually mild ones, therefore not interfering with adherence to treatment. Only one patient with persistent nausea and vomiting resulted in withdrawal from treatment. As observed by other investigators, we expected to find a higher eradication rate in males, since women would theoretically have been exposed to treatment with nitroimidazoles30,31 more often, and consequently would show a higher resistance to tinidazole. However, the eradication rate was similar in males and females. It is possible that males and females are equally exposed to the previous use of nitroimidazole in Brazil7.
In a recent work32, smoking was a predictive factor of treatment failure, but our study failed to confirm this, in agreement with the Kadayifçi report33.
Alcohol and NSAID use did not influence the outcome of eradication therapy.
There was a predominance of women in our study, which is a rule in all outpatient services in Brazil34. We cannot rule out an increase in female prevalence of peptic ulcer as partially responsible for the increased number of women in our study. An increased incidence of women with peptic ulcer disease has been reported in the USA since 198035,36. The better eradication rate of therapy for patients over 44 years old is difficult to explain. Similarly, Cutler and Schubert27and Labens37 also observed this response in elderly patients. Nevertheless, Moayyedi31 did not find any influence of age on eradication rate using a treatment schedule similar to ours.
SILVA FM e col. – Fatores que afetam a erradicação do Helicobacter pylori usando um tratamento triplo de sete dias com um inibidor de bomba de prótons associado ao tinidazol e a claritromicina, em pacientes brasileiros com úlcera péptica. Rev. Hosp. Clín. Fac. Med. S. Paulo 56(1):11-16, 2001.
O esquema tríplice tem sido demonstrado como sendo o melhor tratamento para a erradicação do Helicobacter pylori. Nos países industrializados o uso de um inibidor de bomba de prótons associado a claritromicina e a amoxicilina ou a um nitroimidazólico, tem proporcionado os melhores resultados. Objetivamos estudar na nossa população a taxa de erradicação do H. pylori para a associação de um inibidor de bomba de prótons com o tinidazol e a claritromicina e determinar se a resposta ao tratamento é influenciada pelo tratamento prévio, sexo, tabagismo, alcoolismo, idade e uso de anti-inflamatórios não esteroidais (AINEs).
PACIENTES E PROCEDIMENTOS: Duzentos pacientes com diagnóstico endoscópico de úlcera péptica e com infecção pelo H. pylori, confirmada pelo exame histológico e pelo teste rápido da urease (TRU), foram incluídos no estudo. Um inibidor de bomba de prótons (lansoprazol 30mg ou omeprazol 20 mg), tinidazol 500mg e claritromicina 250mg foram ministrados duas vezes ao dia, por um período de 7 dias. A erradicação era determinada depois de 10 a 12 semanas após o fim do tratamento, por histologia e TRU.
RESULTADOS: O percentual de erradicação do H. pylori (por protocolo) foi de 65% (128/196 pacientes). Para pacientes previamente tratados o valor foi de 53%, aumentando para 76% nos pacientes não previamente tratados com diferença estatística (p<0,01). Não houve diferença significativa para sexo, tabagismo, alcoolismo e uso de AINEs, mas para pacientes de mais idade houve diferença com p = 0,05. A aderência ao tratamento foi boa e os efeitos adversos, leves.
CONCLUSÃO: O esquema inibidor de bomba de prótons, tinidazol e claritromicina, dados duas vezes ao dia por 7 dias proporcionou erradicação do H. pylori em 65% dos pacientes. O tratamento prévio foi o principal fator para seu insucesso.
DESCRITORES: Tratamento da úlcera péptica. Erradicação do Helicobacter pylori. Inibidor de bomba de prótons. Tinidazol. Claritromicina.
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Received for publication on the11/08/00
From the Department of Gastroenterology, Hospital das Clínicas, Faculty of Medicine, University of São Paulo.