Pylera
BISMUTH SUBCITRATE POTASSIUM, METRONIDAZOLE, and TETRACYCLINE HYDROCHLORIDE · Capsule · Oral
Uses
1 INDICATIONS AND USAGE PYLERA is a combination of metronidazole, a nitroimidazole antimicrobial, tetracycline,- a tetracycline class antimicrobial and bismuth subcitrate potassium, indicated for use, in combination with omeprazole, for the treatment of patients with Helicobacter pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori. ( 1.1 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of PYLERA and other antibacterial drugs, PYLERA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. ( 1.2 ) 1.1 Eradication of Helicobacter pylori in Patients with Active Duodenal Ulcer or History of Duodenal Ulcer Disease PYLERA in combination with omeprazole are indicated for the treatment of patients with Helicobacter pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori . The eradication of Helicobacter pylori has been shown to reduce the risk of duodenal ulcer recurrence. 1.2 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of PYLERA and other antibacterial drugs, PYLERA should be used to treat only indicated infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Dosage and administration
Administer three PYLERA capsules 4 times a day (after meals and at bedtime) for 10 days. One omeprazole 20 mg capsule should be taken twice a day with PYLERA after the morning and evening meal for 10 days ( Table 1 ). Table 1: Daily Dosing Schedule for PYLERA Time of dose Number of capsules of PYLERA Number of capsules of omeprazole 20 mg After morning meal 3 1 After lunch 3 0 After evening meal 3 1 At bedtime 3 0 Instruct patients to swallow the PYLERA capsules whole with a full glass of water (8 ounces). Ingestion of adequate amounts of fluid, particularly with the bedtime dose, is recommended to reduce the risk of esophageal irritation and ulceration by tetracycline hydrochloride. If a dose is missed, patients should continue the normal dosing schedule until medication is gone. Patients should not take double doses. If more than 4 doses are missed, the prescriber should be contacted. Administer three PYLERA capsules 4 times a day (after meals and at bedtime) for 10 days. ( 2 ) Administer PYLERA with omeprazole 20 mg twice daily (after the morning and evening meals). ( 2 )
Dosage forms and strengths
Each PYLERA capsule contains 140 mg of bismuth subcitrate potassium, 125 mg of metronidazole, and a smaller capsule inside containing 125 mg of tetracycline hydrochloride. The capsules are white and opaque, with the APTALIS ™ logo printed on the body and "BMT" printed on the cap. Each capsule of PYLERA contains: ( 3 ) 140 mg of bismuth subcitrate potassium 125 mg metronidazole 125 mg of tetracycline hydrochloride
Contraindications
Disulfiram usage within the last two weeks. ( 4.1 , 7.1 ) Alcoholic beverage consumption for at least three days during or after therapy. ( 4.2 , 7.2 ) Patients with Cockayne syndrome. ( 4.3 , 6.3 ) Severe renal impairment. ( 4.4 ) Women who are pregnant. ( 4.5 , 8.1 ) Known hypersensitivity to product components. ( 4.6 ) 4.1 Disulfiram PYLERA is contraindicated in patients who have taken disulfiram within the last two weeks. Psychotic reactions have been reported in alcoholic patients who are using metronidazole, a component of PYLERA, and disulfiram concurrently [see Drug Interactions (7.1) ] . 4.2 Alcohol Alcoholic beverages or other products containing propylene glycol should not be consumed during and for at least 3 days after therapy with PYLERA. A disulfiram-like reaction (abdominal cramps, nausea, vomiting, headaches, and flushing) may occur due to the interaction between alcohol or propylene glycol and metronidazole, a component of PYLERA [see Drug Interactions (7.2) ] . 4.3 Cockayne Syndrome PYLERA is contraindicated in patients with Cockayne syndrome. Severe irreversible hepatotoxicity/acute liver failure with fatal outcomes have been reported after initiation of metronidazole in patients with Cockayne syndrome [see Adverse Reactions (6.3) ]. 4.4 Severe Renal Impairment PYLERA is contraindicated in patients with severe renal impairment. The antianabolic action of the tetracyclines may cause an increase in blood urea nitrogen (BUN) [see Adverse Reactions (6.3) ] . In patients with significantly impaired renal function, higher serum concentrations of tetracyclines may lead to azotemia, hyperphosphatemia, and acidosis. 4.5 Pregnancy PYLERA is contraindicated during pregnancy [see Use in Specific Populations (8.1) ] . 4.6 Hypersensitivity Reactions PYLERA is contraindicated in patients with known hypersensitivity (e.g. urticaria, erythematous rash, flushing, and fever) to bismuth subcitrate potassium, metronidazole or other nitroimidazole derivatives, or tetracycline [see Adverse Reactions (6.3) ].
Warnings and precautions
Fetal Toxicity: Advise pregnant women of the risk throughout pregnancy for retardation of skeletal development seen in animal studies and permanent discoloration of teeth with tetracycline if used during the second or third trimester. ( 5.2 , 8.1 ) Maternal Toxicity: Risk of hepatotoxicity in pregnant women with high doses of intravenous tetracycline also resulting in stillborn or premature birth. ( 5.3 , 8.1 ) Tooth Enamel discoloration and hypoplasia: permanent discoloration may develop with use during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years). ( 5.4 ) Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions (SCARs) including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported with metronidazole. If symptoms or signs of SCARs develop, discontinue PYLERA immediately and institute appropriate therapy. ( 5.5 ) Central and Peripheral Nervous System Effects: encephalopathy, convulsive seizures, aseptic meningitis and peripheral neuropathy with metronidazole, intracranial hypertension with tetracycline and neurotoxicity with bismuth-containing products. Monitor patients with CNS conditions closely and discontinue promptly if abnormal neurologic signs develop. ( 5.6 ) Photosensitivity: avoid exposure to sun and sun lamps. ( 5.8 ) Blood Dyscrasias: Use with caution in patients with a history of blood dyscrasias. ( 5.10 ) Hepatic Impairment: Not recommended in patients with severe hepatic impairment. ( 5.11 ) 5.1 Potential for Carcinogenicity Metronidazole, a component of PYLERA, has been shown to be carcinogenic in mice and rats. Tumors affecting the liver, lungs, mammary and lymphatic tissues have been detected in several studies of metronidazole in rats and mice, but not hamsters [see Nonclinical Toxicology (13) ] . It is unknown whether metronidazole is associated with carcinogenicity in humans. 5.2 Fetal Toxicity Tetracycline can cause fetal harm when administered to a pregnant woman. Based on animal data, use of drugs of the tetracycline class during the second and third trimester of pregnancy can cause permanent discoloration of the teeth (yellow-gray brown) and possibly inhibit bone development [see Warnings and Precautions (5.4) ] . Administration of oral tetracycline to pregnant rats at various doses resulted in yellow fluorescence in teeth and bones in the newborn animals. If PYLERA is used during pregnancy, or if the patient becomes pregnant while taking PYLERA, advise the patient of the potential risk to the fetus [see Contraindications (4.5) and Use in Specific Populations (8.1) ] . 5.3 Maternal Toxicity Tetracycline, a component of PYLERA, administered during pregnancy at high doses (> 2 g IV) was associated with rare but serious cases of maternal hepatotoxicity. This syndrome may result in stillborn or premature birth due to maternal pathology [see Contraindications (4.5) and Use in Specific Populations (8.1) ] . 5.4 Tooth Enamel Discoloration and Hypoplasia The use of drugs of the tetracycline class during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the drug, but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. PYLERA, therefore, should not be used in this age group unless other drugs are not likely to be effective or are contraindicated [see Use in Specific Populations (8.4) ] . 5.5 Severe Cutaneous Adverse Reactions Metronidazole : Severe cutaneous adverse reactions (SCARs) including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported with the use of metronidazole. Symptoms can be serious and potentially life threatening. If symptoms or signs of SCARs develop, discontinue PYLERA capsules immediately and institute appropriate therapy. Tetracycline : Fixed drug eruptions have occurred with tetracycline and have been associated with worsening severity upon subsequent administrations, including generalize bullous fixed drug eruption [see Adverse Reactions (6.3) ] . If severe skin reactions occur, discontinue PYLERA immediately, and institute appropriate therapy. 5.6 Central and Peripheral Nervous System Effects Metronidazole : Convulsive seizures, encephalopathy, aseptic meningitis and peripheral neuropathy (including optic neuropathy) have been reported. Encephalopathy has been reported in association with cerebellar toxicity characterized by ataxia, dizziness, and dysarthria. CNS lesions seen on MRI have been described in reports of encephalopathy. CNS symptoms are generally reversible within days to weeks upon discontinuation of metronidazole. CNS lesions seen on MRI have also been described as reversible. Peripheral neuropathy, mainly of sensory type has been reported and is characterized by numbness or paresthesia of an extremity. Aseptic meningitis symptoms may occur within hours of dose administration and generally resolve after metronidazole therapy is discontinued. Tetracycline : Intracranial hypertension (IH), including pseudotumor cerebri, has been associated with the use of tetracyclines. Clinical manifestations of IH include headache, blurred vision, diplopia, and vision loss; papilledema can be found on fundoscopy. Women of childbearing age who are overweight or have a history of IH are at greater risk for developing tetracycline associated IH. Concomitant use of isotretinoin should be avoided because isotretinoin is also known to cause IH. Although IH typically resolves after discontinuation of treatment, the possibility for permanent visual loss exists.
Side effects
Most frequently reported adverse reactions (≥5%): abnormal feces, diarrhea, nausea, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact H2-Pharma, LLC at 1-833-520-8580 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of PYLERA plus omeprazole (OBMT) to eradicate Helicobacter pylori was assessed in an open-label, randomized, active-controlled clinical trial conducted in North America. The duration of treatment was 10 days with 147 patients exposed to PYLERA plus omeprazole (OBMT) and 152 exposed to control, consisting of omeprazole, amoxicillin, and clarithromycin (OAC). The age of the population in the study ranged from 18 to 75 years, with 59% male patients and 59% Caucasian patients. Adverse drug reactions were reported in 58% of patients in the OBMT group and 59% of patients in the OAC group. There were no adverse reactions leading to discontinuation of the study during the clinical trial. Adverse reactions with an incidence of ≥ 5% in OBMT group include abnormal feces, diarrhea, nausea, and headache. Adverse drug reactions with an incidence of ≥ 5% in OAC group include diarrhea, dysgeusia, dyspepsia, nausea and headache. Table 2 lists adverse reactions with an incidence of ≥ 1%, in either group (OBMT vs OAC) and in order of decreasing incidence for the OBMT group. Table 2: Adverse reactions with an incidence of ≥ 1% from North American trial, [n (%)] *OBMT = Omeprazole + PYLERA **OAC = Omeprazole + Amoxicillin + Clarithromycin; *** Dark stools [see Warnings and Precautions (5.9) ] Preferred Term OBMT* (n = 147) OAC** (n = 152) Gastrointestinal disorders Abnormal feces*** 23 (15.6%) 7 (4.6%) Nausea 12 (8.2%) 14 (9.2%) Diarrhea 10 (6.8%) 20 (13.2%) Abdominal Pain 7 (4.8%) 2 (1.3%) Dyspepsia 4 (2.7%) 10 (6.6%) Constipation 2 (1.4%) 5 (3.3%) Dry Mouth 2 (1.4%) 1 (0.7%) Flatulence 0 4 (2.6%) Glossitis 0 2 (1.3%) General disorders and administration site conditions Asthenia 5 (3.4%) 2 (1.3%) Infections and infestations Vaginal infection 4 (2.7%) 3 (2.0%) Nervous system disorders Headache 8 (5.4%) 8 (5.3%) Dysgeusia 6 (4.1%) 18 (11.8%) Dizziness 4 (2.7%) 4 (2.6%) Investigations Laboratory test abnormal 3 (2.0%) 4 (2.6%) Alanine aminotransferase increased 2 (1.4%) 0 Aspartate aminotransferase increased 2 (1.4%) 0 Renal and urinary disorders Urine abnormality 2 (1.4%) 0 Skin and subcutaneous tissue disorders Rash Maculo-Papular 2 (1.4%) 0 Rash 1 (0.7%) 3 (2.0%) Pruritus 0 4 (2.6%) Adverse reactions with an incidence of <1% for OBMT group are: back pain, vomiting, tongue darkening [see Warnings and Precautions (5.9) ] , anxiety, gastritis, gastroenteritis, myalgia, chest pain, increased appetite, blood creatine phosphokinase increased, malaise, somnolence, tachycardia, duodenal ulcer, visual disturbance, weight increased. 6.2 Postmarketing Experience 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. Gastrointestinal disorders: abdominal distention, eructation, flatulence General disorders and administration site conditions: chest discomfort, fatigue Infections and infestations : candidiasis, pseudomembranous colitis ( Clostridium difficile colitis) Nervous Systems: peripheral neuropathy Skin and subcutaneous disorders: Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS syndrome (drug rash with eosinophilia and systemic symptoms) [ see Warnings and Precautions (5.5) ] 6.3 Other Important Adverse Reactions from Labeling for the Individual Components of PYLERA Metronidazole Blood and Lymphatic system disorders: Reversible neutropenia (leucopenia) in cases of prolonged treatment; rarely reversible thrombocytopenia however no persistent hematological abnormalities attributable to metronidazole have been observed [see Warnings and Precautions (5.10) ] . Cardiac disorders: QT prolongation has been reported with metronidazole, particularly when administered with drugs with the potential for prolonging the QT interval. Flattening of the T-wave may be seen in electrocardiographic tracings. Gastrointestinal disorders: Nausea, vomiting, diarrhea, abdominal pain, constipation, anorexia, metallic taste, furry tongue, glossitis, stomatitis and candida overgrowth. Hypersensitivity/Immune system disorders: Acute generalized exanthematous pustulosis (AGEP) [see Warnings and Precautions (5.5) ] , urticaria, erythematous rash, flushing, nasal congestion, dryness of the mouth (or vagina or vulva), and fever [see Contraindications (4.6) ] . Metabolism and nutrition disorders: Pancreatitis. Nervous system disorders: Convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, headache, syncope, dizziness, vertigo, incoordination, ataxia, tinnitus, hearing impairment, hearing loss, confusion, dysarthria, irritability, depression, weakness, and insomnia [see Warnings and Precautions (5.6) ] . Dermatologic disorders: Erythematous rash and pruritus. Renal and urinary disorders: Dysuria, cystitis, polyuria, incontinence, darkened urine, and a sense of pelvic pressure. Hepatic: Cases of severe irreversible hepatotoxicity/acute liver failure, including cases with fatal outcomes with very rapid onset after initiation of systemic use of metronidazole, have been reported in patients with Cockayne Syndrome (latency from drug start to signs of liver failure as short as 2 days) [see Contraindications (4.3) ] .
Drug interactions
Disulfiram: Psychotic reactions can occur; do not take concurrently or within the last 2 weeks of disulfiram. ( 4.1 , 7.1 ) Alcohol: Abdominal cramps, nausea, vomiting, headaches, and flushing can occur; do not consume during therapy and for at least 3 days afterwards. ( 4.2 , 7.2 ) Oral Contraceptives: Decreased efficacy possibly resulting in pregnancy; use a different or additional form of contraception. ( 5.14 , 7.3 ) Anticoagulants: Potentiation of the anticoagulant effect; Prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests should be closely monitored. ( 5.14 , 7.4 ) Lithium: Increased lithium serum concentrations; measure serum lithium and serum creatinine concentrations during therapy. ( 5.14 , 7.5 ) Antacids, Multivitamins or Dairy Products: Decreased absorption of PYLERA; do not take concomitantly. ( 7.6 ) Busulfan: Increased busulfan serum concentrations; avoid concomitant use, monitor for busulfan toxicity. ( 7.7 ) CYP inducers and CYP inhibitors: Prolonged or accelerated half-life of metronidazole or concomitant medications; use with caution. ( 7.8 , 7.9 ) 7.1 Disulfiram Psychotic reactions have been reported in alcoholic patients who are using metronidazole, a component of PYLERA and disulfiram concurrently. PYLERA should not be given to patients who have taken disulfiram within the last two weeks [see Contraindications (4.1) ] . 7.2 Alcohol 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 (4.2) ] . 7.3 Oral Contraceptives Concurrent use of PYLERA with oral contraceptive may make oral contraceptives less effective due to an interaction with the tetracycline component of PYLERA. Breakthrough bleeding has been reported. Women of child-bearing potential should use a different or additional form of contraception while taking PYLERA [see Warnings and Precautions (5.14) ]. 7.4 Anticoagulants PYLERA may alter the anticoagulant effects of warfarin and other oral coumarin anticoagulants. 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. Prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests should be closely monitored if PYLERA is administered concomitantly with warfarin. Patients should also be monitored for evidence of bleeding [see Warnings and Precautions (5.14) ]. 7.5 Lithium 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 [see Warnings and Precautions (5.14) ]. 7.6 Antacids, Multivitamins, or Dairy Products 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. These products should not be consumed concomitantly with PYLERA. 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. 7.7 Busulfan Metronidazole has been reported to increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity. Do not administer PYLERA concomitantly with busulfan unless the benefit outweighs the risk. If no therapeutic alternatives to PYLERA are available, and concomitant administration with busulfan is medically needed, monitor for busulfan toxicity and busulfan plasma concentrations and adjust the busulfan dose accordingly [see Warnings and Precautions (5.14) ]. 7.8 Inhibitors of CYP450 liver enzymes 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. 7.9 Inducers of CYP450 liver enzymes 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. Monitor phenytoin concentrations during treatment with PYLERA.
Use in specific populations
Lactation: A woman should pump and discard human milk for the duration of PYLERA therapy, and for 2 days after therapy ends. ( 8.2 ) Pediatric Use: Tetracycline may cause permanent discoloration of the teeth. Enamel hypoplasia has also been reported. Do not use in children less than 8 years of age. ( 5.4 , 8.4 ) 8.1 Pregnancy Risk Summary PYLERA is contraindicated in women who are pregnant because treatment of Helicobacter pylori infection can be delayed in pregnant women, and the use of drugs of the tetracycline class during the second and third trimester pregnancy can also cause permanent discoloration of the teeth (yellow-gray brown) and possibly inhibit bone development [see Warnings and Precautions (5.2) and Data ] . Administration of oral tetracycline to pregnant rats at various doses resulted in yellow fluorescence in teeth and bones in the newborn animals. There are maternal risks with high intravenous doses of tetracycline [see Clinical Considerations ]. Metronidazole usage in pregnancy has been associated with certain congenital anomalies [see Data ]. In animals, no fetotoxicity was observed when metronidazole was orally administered to pregnant mice at approximately 5% of the indicated human dose. There are no human or animal data on the use of bismuth subcitrate potassium during pregnancy. Although there are data on the separate components, there are no available data on the use of PYLERA in pregnant women. Clinical Considerations Maternal Adverse Reactions Tetracycline administered during pregnancy at high doses (> 2 g IV) was associated with rare but serious cases of maternal hepatotoxicity. This syndrome may result in stillborn or premature birth due to maternal pathology [see Warnings and Precautions (5.3) ]. Data Human Data Tetracycline 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. This discoloration is more common during long-term use of the drug but has also been observed following repeated short-term courses. All tetracyclines form a stable calcium complex in any bone forming tissue. A decrease in fibula growth rate was observed in premature infants given oral tetracycline in doses of 25 mg/kg every six hours. The effect resolved when the drug was discontinued. One long-term follow-up study in children exposed to tetracycline in-utero showed no adverse effects on bone growth and development. Metronidazole There are published data from case-control studies, cohort studies, and 2 meta-analyses that include more than 5000 pregnant women who used metronidazole during pregnancy. Many studies included first trimester exposures. One study showed an increased risk of cleft lip, with or without cleft palate, in infants exposed to metronidazole in-utero; however, these findings were not confirmed. In addition, more than ten randomized, placebo-controlled clinical trials enrolled more than 5000 pregnant women to assess the use of antibiotic treatment (including metronidazole) for bacterial vaginosis on the incidence of preterm delivery. 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 There are no human data on the use of bismuth subcitrate potassium during pregnancy. Animal Data Tetracycline 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 Metronidazole crosses the placental barrier. No fetotoxicity was observed when metronidazole was administered orally to pregnant mice at 10 mg/kg/day, approximately 5 percent of the indicated human dose (1500 mg/day) based on body surface area; however in a single small study where the drug was administered intraperitoneally, some intrauterine deaths were observed. The relationship of these findings to the drug is unknown. Bismuth subcitrate potassium Animal reproductive studies have not been conducted with bismuth subcitrate potassium. 8.2 Lactation Risk Summary 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 whether bismuth subcitrate, the third component of PYLERA is present in human milk. 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 (12.3) ]. 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. 8.4 Pediatric Use Safety and effectiveness of PYLERA in pediatric patients infected with Helicobacter pylori have not been established. Tetracycline use in children may cause permanent discoloration of the teeth.
Pregnancy
8.1 Pregnancy Risk Summary PYLERA is contraindicated in women who are pregnant because treatment of Helicobacter pylori infection can be delayed in pregnant women, and the use of drugs of the tetracycline class during the second and third trimester pregnancy can also cause permanent discoloration of the teeth (yellow-gray brown) and possibly inhibit bone development [see Warnings and Precautions (5.2) and Data ] . Administration of oral tetracycline to pregnant rats at various doses resulted in yellow fluorescence in teeth and bones in the newborn animals. There are maternal risks with high intravenous doses of tetracycline [see Clinical Considerations ]. Metronidazole usage in pregnancy has been associated with certain congenital anomalies [see Data ]. In animals, no fetotoxicity was observed when metronidazole was orally administered to pregnant mice at approximately 5% of the indicated human dose. There are no human or animal data on the use of bismuth subcitrate potassium during pregnancy. Although there are data on the separate components, there are no available data on the use of PYLERA in pregnant women. Clinical Considerations Maternal Adverse Reactions Tetracycline administered during pregnancy at high doses (> 2 g IV) was associated with rare but serious cases of maternal hepatotoxicity. This syndrome may result in stillborn or premature birth due to maternal pathology [see Warnings and Precautions (5.3) ]. Data Human Data Tetracycline 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. This discoloration is more common during long-term use of the drug but has also been observed following repeated short-term courses. All tetracyclines form a stable calcium complex in any bone forming tissue. A decrease in fibula growth rate was observed in premature infants given oral tetracycline in doses of 25 mg/kg every six hours. The effect resolved when the drug was discontinued. One long-term follow-up study in children exposed to tetracycline in-utero showed no adverse effects on bone growth and development. Metronidazole There are published data from case-control studies, cohort studies, and 2 meta-analyses that include more than 5000 pregnant women who used metronidazole during pregnancy. Many studies included first trimester exposures. One study showed an increased risk of cleft lip, with or without cleft palate, in infants exposed to metronidazole in-utero; however, these findings were not confirmed. In addition, more than ten randomized, placebo-controlled clinical trials enrolled more than 5000 pregnant women to assess the use of antibiotic treatment (including metronidazole) for bacterial vaginosis on the incidence of preterm delivery. 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 There are no human data on the use of bismuth subcitrate potassium during pregnancy. Animal Data Tetracycline 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 Metronidazole crosses the placental barrier. No fetotoxicity was observed when metronidazole was administered orally to pregnant mice at 10 mg/kg/day, approximately 5 percent of the indicated human dose (1500 mg/day) based on body surface area; however in a single small study where the drug was administered intraperitoneally, some intrauterine deaths were observed. The relationship of these findings to the drug is unknown. Bismuth subcitrate potassium Animal reproductive studies have not been conducted with bismuth subcitrate potassium.
Pediatric use
8.4 Pediatric Use Safety and effectiveness of PYLERA in pediatric patients infected with Helicobacter pylori have not been established. Tetracycline use in children may cause permanent discoloration of the teeth. Enamel hypoplasia has also been reported. PYLERA should not be used in children up to 8 years of age [see Warnings and Precaution (5.4) ].
Geriatric use
8.5 Geriatric Use 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 (4.4) ].
Overdosage
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: Metronidazole: 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 10.4 g every other day. Treatment of Overdosage There is no specific antidote for metronidazole overdose; therefore, management of the patient should consist of symptomatic and supportive therapy. Tetracycline: 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. Bismuth subcitrate potassium: Symptoms of a bismuth subcitrate potassium overdosage are not known.
Description
11 DESCRIPTION PYLERA capsules are a combination antimicrobial product containing bismuth subcitrate potassium, metronidazole, and tetracycline hydrochloride for oral administration. Each size 0 elongated capsule contains: bismuth subcitrate potassium, 140 mg metronidazole, 125 mg smaller capsule (size 3) containing tetracycline hydrochloride, 125 mg Tetracycline hydrochloride is encapsulated within a smaller capsule to create a barrier to avoid contact with bismuth subcitrate potassium. Each PYLERA capsule contains the following inactive ingredients: Magnesium Stearate NF, Lactose Monohydrate NF, Talc USP, Gelatin USP, and Titanium Dioxide NF, Printed in red ink. Bismuth subcitrate potassium is a white or almost white powder. It is a soluble, complex bismuth salt of citric acid. The schematized empirical molecular formula of bismuth subcitrate potassium is Bi (Citrate) 2 K 5 ∙3 H 2 O. The equivalent theoretical molecular formula is BiC 12 H 14 K 5 O 17 . The molecular mass of the theoretical molecular formula of a single unit of bismuth subcitrate potassium is 834.71. Metronidazole is a white to pale yellow crystalline powder. Metronidazole is 2-methyl-5-nitroimidazole-1-ethanol, with a molecular formula of C 6 H 9 N 3 O 3 and the following structural formula: Molecular weight: 171.2 Tetracycline hydrochloride is a yellow, odorless, crystalline powder. Tetracycline hydrochloride is stable in air, but exposure to strong sunlight causes it to darken. Tetracycline hydrochloride is (4S,4aS,5aS,6S,12aS)-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-penta-hydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide hydrochloride, with a molecular formula of C 22 H 24 N 2 O 8 ∙HCl and the following structural formula: Molecular weight: 480.90 Chemical Structure Chemical Structure
Mechanism of action
12.1 Mechanism of Action PYLERA is a combination of antibacterial agents (metronidazole and tetracycline hydrochloride) and bismuth subcitrate potassium [see Microbiology (12.4) ] .
How supplied
16 HOW SUPPLIED/STORAGE AND HANDLING PYLERA is supplied as a white opaque capsule containing 140 mg bismuth subcitrate potassium, 125 mg metronidazole, and 125 mg tetracycline hydrochloride, with the APTALIS ™ logo printed on the body and "BMT" printed on the cap. PYLERA capsules are supplied as the 10 day Therapy pack containing 10 blister cards, with each card containing 12 PYLERA capsules for a total of 120 capsules. NDC Number: 61269-380-12, Blister pack of 120. Storage Store at controlled room temperature [68° to 77°F or 20° to 25°C].
Storage
Storage Store at controlled room temperature [68° to 77°F or 20° to 25°C].
Patient information
Lactation Advise the lactating women to pump and discard their milk during treatment with PYLERA and for 2 days after the therapy ends [see Use in Specific Populations (8.2) ]. Hypersensitivity Inform patients that PYLERA may cause allergic reactions and to discontinue PYLERA at the first sign of urticaria, erythematous rash, flushing, and fever or other symptoms of an allergic reaction [see Contraindications (4.6) ]. Severe Cutaneous Adverse Reactions Advise patients that PYLERA capsules may increase the risk of serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN), Stevens- Johnson syndrome (SJS), and drug reaction with eosinophilia and systemic symptoms (DRESS). Instruct the patient to be alert for skin rash, blisters, fever or other signs and symptoms of these hypersensitivity reactions. Advise patients to stop PYLERA capsules immediately if they develop any type of rash and seek medical attention [ see Warnings and Precautions (5.5) ]. Central Nervous System Effects Inform patients of the risk of central and peripheral nervous system effects with PYLERA and to discontinue PYLERA and report immediately to their health-care provider if any neurologic symptoms occur [see Warnings and Precautions (5.6) ]. Photosensitivity Avoid exposure to sun or sun lamps while taking PYLERA [see Warnings and Precautions (5.8) ] . Drug Interactions Advise patients to report to their health-care provider the use of any other medications while taking PYLERA. The administration of any of the following drugs with PYLERA may result in clinically significant adverse reactions or insufficient drug efficacies [see Contraindications (4) and Drug Interactions (7) ] : Disulfiram Alcoholic Beverages, or Products Containing Propylene Glycol Oral Contraceptives Anticoagulants Lithium Antacids, Multivitamins, or Dairy Products Busulfan Cimetidine Phenytoin and Phenobarbital Darkening of the Tongue and/or Stool Inform patients that PYLERA may cause temporary and harmless darkening of the tongue and/or black stool generally reversible within several days after treatment is stopped. Stool darkening should not be confused with melena (blood in the stool) [see Warnings and Precautions (5.9) ]. Dosing Information Inform patients that each dose of PYLERA includes 3 capsules. All 3 capsules should be taken 4 times a day (after meals and at bedtime) for 10 days. One omeprazole 20 mg capsule should be taken twice a day with PYLERA after the morning and evening meal for 10 days. If a dose is missed, advise patient not to make up the dose, but to continue the normal dosing schedule until medication is gone. Patients should not take double doses. If more than 4 doses are missed, advise the patient to contact their health-care provider [see Dosage and Administration (2) ] . Administration with Fluids Instruct patients to swallow the PYLERA capsules whole with a full glass of water (8 ounces). Ingestion of adequate amounts of fluid, particularly with the bedtime dose, is recommended to reduce the risk of esophageal irritation and ulceration by tetracycline hydrochloride [see Dosage and Administration (2) ]. Antibacterial Resistance Patients should be counseled that antibacterial drugs including PYLERA should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When PYLERA is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by PYLERA or other antibacterial drugs in the future.
Label text from the FDA structured product label by H2-Pharma, LLC (revised Jun 29, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Bismuth Subcitrate Potassium in 2 products
- Metronidazole in 2 products
- Tetracycline Hydrochloride in 2 products
Pylera NDC products (2)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 61269-380 | Bismuth Subcitrate Potassium 140 mg/1; Metronidazole 125 mg/1; Tetracycline Hydrochloride 125 mg/1 Capsule | H2-Pharma, LLC | NDA |
| 61269-381 | Bismuth Subcitrate Potassium 140 mg/1; Metronidazole 125 mg/1; Tetracycline Hydrochloride 125 mg/1 Capsule | H2-Pharma, LLC | NDA |
Frequently asked questions
What is Pylera used for?
1 INDICATIONS AND USAGE PYLERA is a combination of metronidazole, a nitroimidazole antimicrobial, tetracycline,- a tetracycline class antimicrobial and bismuth subcitrate potassium, indicated for use, in combination with omeprazole, for the treatment of patients with Helicobacter pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori. (…
What are the side effects of Pylera?
Most frequently reported adverse reactions (≥5%): abnormal feces, diarrhea, nausea, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact H2-Pharma, LLC at 1-833-520-8580 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a… See the full label for the complete list.
Who makes Pylera?
Pylera is listed by 1 labeler in the FDA NDC directory, including H2-Pharma, LLC.