Eradication of H. Pylori will be confirmed through UBT, and resistance will be evaluated in case of treatment failure. These subjects will undergo an endoscopy. Omeprazole 20 mg is administered twice daily. Drug: Pylera Bismuth subcitrate potassium, metronidazole, tetracycline given in combination with omeprazole Pylera is a three in one capsule containing bismuth subcitrate potassium mg, metronidazole mg and tetracycline mg given as 3 capsules QID, with omeprazole 20 mg BID.
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Because of tetracycline's toxicity, use in children younger than 8 years of age is not recommended. Tetracycline may cause permanent discoloration of the teeth. Safety and efficacy have not been established in this age group. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution and an adjustment in the dose for patients receiving this medicine. 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. 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.
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. 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. 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. Using this medicine with any of the following is not recommended.
Your doctor may decide not to treat you with this medication, change some of the other medicines you take, or give you special instructions about the use of food, alcohol, or tobacco. 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. 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:.
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. Your doctor will also prescribe another medicine called omeprazole that must be taken with this medicine. Aseptic meningitis: Cases of aseptic meningitis have been reported with metronidazole. Symptoms can occur within hours of dose adiminstration and generally resolve after metronidazole therapy is discontinued. Tetracycline: Cases of pseudotumor cerebri in adults have been associated with the use of tetracycline.
The usual clinical manifestations are headache and blurred vision. While this condition and related symptoms usually resolve soon after discontinuation of the tetracycline, the possibility for permanent sequelae exists. Bismuth-containing products: Cases of neurotoxicity associated with excessive doses of various bismuth-containing products have been reported.
Effects have been reversible with discontinuation of bismuth therapy. Known or previously unrecognized candidiasis may present more prominent symptoms during therapy with metronidazole and requires treatment with an antifungal agent. As with other antibiotics, use of tetracycline hydrochloride may result in overgrowth of nonsusceptible organisms, including fungi.
Photosensitivity, manifested by an exaggerated sunburn reaction, has been observed in patients taking tetracycline [See Adverse Reactions 6. Patients apt to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline drugs. Discontinue treatment at the first evidence of skin erythema. Stool darkening should not be confused with melena.
Metronidazole is a nitroimidazole, and should be used with care in patients with evidence or history of blood dyscrasia. A mild leukopenia has been observed during its administration; however, no persistent hematologic abnormalities attributable to metronidazole have been observed in clinical studies.
Total and differential leukocyte counts are recommended before and after therapy [See Adverse Reactions 6. Bismuth absorbs x-rays and may interfere with x-ray diagnostic procedures of the gastrointestinal tract. Bismuth subcitrate potassium may cause a temporary and harmless darkening of the stool. However, this change does not interfere with standard tests for occult blood.
Values of zero may be observed. Interference is due to the similarity in absorbance peaks of NADH nm and metronidazole nm at pH 7. Prescribing PYLERA in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
There were no adverse reactions leading to discontinuation of the study during the clinical trial. Additionally, the following adverse reactions, presented by system organ class in alphabetical order, have been identified during post approval use of PYLERA.
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: reversible neutropenia, leucopenia in cases of prolonged treatment; rarely reversible thrombocytopenia however no persistent haematological abnormalities attributable to metronidazole have been observed [See Warnings and Precautions 5.
Cardiac disorders: Flattening of the T-wave may be seen in electrocardiographic tracings. Gastrointestinal disorders: Furry tongue, glositis, stomatitis; these may be associated with a sudden overgrowth of candida which may occur during therapy[See Warnings and Precautions 5. Immune system disorders: Urticaria, erythematous rash, Stevens - Johnson syndrome, toxic epidermal necrolysis, flushing, nasal congestion, and fever [See Contraindications 4.
Metabolism and nutrition disorders: Cases of pancreatitis have been reported, which abated on withdrawal of the drug, have been reported. Nervous system disorders: The most serious adverse reactions reported in patients treated with metronidazole have been convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity. In addition, patients have reported syncope, vertigo, incoordination, ataxia, confusion, dysarthria, irritability, depression, weakness and insomnia [See Warnings and Precautions 5.
Blood and lymphatic system disorders: Hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, neutropenia, and eosinophilia. Gastrointestinal disorders: Rare instances of esophagitis and esophageal ulceration have been reported in patients taking the tetracycline-class antibiotics in capsule and tablet form.
Most of the patients who experienced esophageal irritation took the medication immediately before going to bed. Permanent discoloration of teeth may be caused when tetracycline is used during tooth development.
Enamel hypoplasia has also been reported [See Warnings and Precautions 5. Nervous system disorders: Pseudotumor cerebri benign intracranial hypertension in adults and bulging fontanels in infants. Tinnitus and myasthenic syndrome have been reported rarely. Skin and subcutaneous tissue disorders: Exfoliative dermatitis and photosensitivity have been rarely reported [See Warnings and Precautions 5.
The concurrent use of tetracycline hydrochloride, a component of PYLERA, with methoxyflurane has been reported to result in fatal renal toxicity [See Contraindications 4. Psychotic reactions have been reported in alcoholic patients who are using metronidazole, a component of PYLERA and disulfiram concurrently. Consumption of alcoholic beverages or administration of other products containing propylene glycol during treatment with PYLERA and for at least 3 days afterwards may cause a disulfiram-like reaction abdominal cramps, nausea, vomiting, headaches, and flushing due to the interaction between alcohol or propylene glycol and metronidazole, a component of PYLERA.
Discontinue alcoholic beverage or other products containing propylene glycol during and for at least 3 days after therapy with PYLERA [See Contraindications 4. Breakthrough bleeding has been reported. Metronidazole has been reported to potentiate the anticoagulant effect of warfarin, and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time.
Tetracycline has been shown to depress plasma prothrombin activity. Patients should also be monitored for evidence of bleeding. In patients stabilized on relatively high doses of lithium, short-term use of PYLERA may cause elevation of serum lithium concentrations and signs of lithium toxicity due to the interaction between metronidazole and lithium. Serum lithium and serum creatinine concentrations should be monitored several days after beginning treatment with PYLERA to detect any increase that may precede clinical symptoms of lithium toxicity.
The absorption of PYLERA may be reduced if administered with antacids containing aluminium, calcium, or magnesium; preparations containing iron, zinc, or sodium bicarbonate; or milk or dairy products due to the interaction between these products and tetracycline.
However, the clinical significance of reduced tetracycline systemic exposure is unknown as the relative contribution of systemic versus local antimicrobial activity against Helicobacter pylori has not been established. Bacteriostatic drugs, such as the tetracycline class of antibiotics, may interfere with the bactericidal action of penicillin; therefore, penicillin should not be used concomitantly with PYLERA.
The simultaneous administration of PYLERA and drugs that inhibit microsomal liver enzymes, such as cimetidine, may result in a prolonged half-life and decreased plasma clearance of metronidazole.
The simultaneous administration of PYLERA and drugs that induce microsomal liver enzymes, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole, resulting in reduced plasma concentrations of metronidazole. Impaired clearance of phenytoin has also been reported in this situation. There are no adequate and well-controlled studies of Pylera in pregnant women. However, tetracycline can cause fetal harm when administered to a pregnant woman.
The use of tetracycline during the second and third trimester pregnancy can cause permanent discoloration of the teeth yellow-gray brown and possibly inhibit bone development. Administration of oral tetracycline to pregnant animals at various doses resulted in yellow fluorescence in teeth and bones. Published case reports have described the yellowing of bones and teeth in human infants exposed to tetracycline during the second and third trimester of pregnancy.
The yellowing is caused by the direct deposition of tetracycline during the mineralization process. Most studies did not show an increased risk for congenital anomalies or other adverse fetal outcomes following metronidazole exposure during pregnancy.
Three studies conducted to assess the risk of infant cancer following metronidazole exposure during pregnancy did not show an increased risk; however, the ability of these studies to detect such a signal was limited. Bismuth subcitrate potassium. Results of animal studies indicate that tetracycline crosses the placenta, is found in fetal tissues, and can have toxic effects on the developing fetus often related to reversible retardation of skeletal development.
Evidence of embryotoxicity has also been noted in animals treated early in pregnancy. Multiple studies of limited design were conducted with pregnant and lactating female rats that resulted in fetuses and neonates with yellow discoloration of bones and teeth.
Metronidazole crosses the placental barrier. The relationship of these findings to the drug is unknown. Two of the individual components of PYLERA, tetracycline and metronidazole, are present in human milk at concentrations similar to maternal serum levels.
It is not known what effect metronidazole, tetracycline or bismuth has on the breastfed infant or on milk production. Tetracycline binds with calcium in human milk [ see Clinical Pharmacology Data indicate that oral absorption of tetracycline in infants is low due to the calcium binding in human milk. Metronidazole transfers to human milk, and infant serum levels can be close to or comparable to infant therapeutic levels.
Because of the potential risk of tumorigenicity shown in animal studies with metronidazole, a woman should pump and discard human milk for the duration of PYLERA therapy, and for 2 days after therapy ends, and feed her infant stored human milk collected prior to therapy or formula. Tetracycline use in children may cause permanent discoloration of the teeth. Clinical studies of PYLERA did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.
Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, elderly patients may have a greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapies.
Bismuth subcitrate potassium, a component of PYLERA, is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, additional monitoring may be required [ see Contraindications 4.
The antianabolic action of the tetracyclines may cause an increase in blood urea nitrogen BUN. In patients with severe renal impairment, higher serum concentrations of tetracycline may lead to azotemia, hyperphosphatemia, and acidosis [ see Contraindications 4. Patients with severe hepatic disease metabolize metronidazole slowly, with resultant accumulation of metronidazole and its metabolites in plasma.
In case of an overdose, patients should contact a physician, poison control center, or emergency room. The available overdosage information for each of the individual components in PYLERA Metronidazole, Tetracycline and Bismuth subcitrate potassium are summarized below:. Single oral doses of metronidazole, up to 15 g, have been reported in suicide attempts and accidental overdoses.
Symptoms reported include nausea, vomiting, and ataxia. Metronidazole is dialyzable. Neurotoxic effects, including seizures and peripheral neuropathy, have been reported after 5 to 7 days of doses of 6 to There is no specific antidote for metronidazole overdose; therefore, management of the patient should consist of symptomatic and supportive therapy.
In case of overdosage, discontinue medication, treat symptomatically and institute supportive measures. Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdosage. PYLERA capsules are a combination antimicrobial product containing bismuth subcitrate potassium, metronidazole, and tetracycline hydrochloride for oral administration. Each size 0 elongated capsule contains:. Tetracycline hydrochloride is encapsulated within a smaller capsule to create a barrier to avoid contact with bismuth subcitrate potassium.
Bismuth subcitrate potassium is a white or almost white powder. It is a soluble, complex bismuth salt of citric acid. The molecular mass of the theoretical molecular formula of a single unit of bismuth subcitrate potassium is Metronidazole is a white to pale yellow crystalline powder.
Metronidazole is 2-methylnitroimidazoleethanol, with a molecular. Tetracycline hydrochloride is a yellow, odorless, crystalline powder. Tetracycline hydrochloride is stable in air, but exposure to strong sunlight causes it to darken.
PYLERA is a combination of antibacterial agents metronidazole and tetracycline hydrochloride and bismuth subcitrate potassium [ see Microbiology The pharmacokinetics of the individual components of PYLERA, bismuth subcitrate potassium, metronidazole and tetracycline hydrochloride are summarized below. In addition, two studies on PYLERA were conducted to determine the effect of co-administration on the pharmacokinetics of the components.
Orally absorbed bismuth is distributed throughout the entire body. The elimination half-life of bismuth is approximately 5 days in both blood and urine. Elimination of bismuth is primarily through urinary and biliary routes. The rate of renal elimination appears to reach steady state 2 weeks after treatment discontinuation with similar rates of elimination at 6 weeks after discontinuation. The average urinary elimination of bismuth is 2. Following oral administration, metronidazole is well absorbed, with peak plasma concentrations occurring between 1 and 2 hours after administration.
Metronidazole appears in the plasma mainly as unchanged compound with lesser quantities of the 2-hydroxymethyl metabolite also present. Metronidazole also appears in cerebrospinal fluid, saliva, and breast milk in concentration similar to those found in plasma. The average elimination half-life of metronidazole in normal volunteers is 8 hours.
Decreased renal function does not alter the single dose pharmacokinetics of metronidazole. In patients with decreased liver function, plasma clearance of metronidazole is decreased. Absorption, Distribution, Metabolism and Excretion. The presence of food, milk or cations may significantly decrease the extent of absorption. In the plasma, tetracycline is bound to plasma proteins in varying degrees. It is concentrated by the liver in the bile and excreted in the urine and feces at high concentrations in biologically active form.
Tetracycline hydrochloride is distributed into most body tissues and fluids. It is distributed into the bile and undergoes varying degrees of enterohepatic recirculation. Tetracycline hydrochloride tends to localize in tumors, necrotic or ischemic tissue, liver and spleen and form tetracycline-calcium orthophosphate complexes at sites of new bone formation or tooth development.
Tetracycline readily crosses the placenta and is excreted in high amounts in breast milk. A comparative bioavailability study of metronidazole mg , tetracycline hydrochloride mg and bismuth subcitrate potassium mg, equivalent to mg Bi 2 O 3 administered as PYLERA or as 3 separate capsule formulations administered simultaneously was conducted in healthy male volunteers.
The pharmacokinetic parameters for the individual drugs, when administered as separate capsule formulations or as PYLERA, are similar as shown in Table 3. Effect of Bismuth on the Bioavailability of Tetracycline Hydrochloride. There is an anticipated reduction in tetracycline hydrochloride systemic absorption due to an interaction with bismuth. The effect of a reduced tetracycline hydrochloride systemic exposure, due to an interaction with bismuth, on the clinical efficacy of PYLERA is not thought to be clinically meaningful as the contribution of systemic, as compared to local, antimicrobial activity against Helicobacter pylori has not been established.
The pharmacokinetic parameters for metronidazole, tetracycline hydrochloride and bismuth were also determined when PYLERA was administered under fasting and fed conditions, as shown in Table 4.
Reduction in the absorption of all three PYLERA components in the presence of food is not considered to be clinically significant. The effect of omeprazole on bismuth absorption was assessed in 34 healthy volunteers given PYLERA four times daily with or without omeprazole 20 mg twice daily for 6 days.
In the presence of omeprazole, the extent of absorption of bismuth from PYLERA was significantly increased, compared to when no omeprazole was given Table 5. The patient did not exhibit symptoms of neurotoxicity during the study. PYLERA is a combination of antibacterial agents metronidazole and tetracycline hydrochloride and bismuth subcitrate potassium.
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