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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 groups (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 (%)]

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%)
Glositis 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 svstem 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 urinarv 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%)
*OBMT = Omeprazole + PYLERA
**OAC = Omeprazole + Amoxicillin + Clarithromycin;
*** Dark stools [See WARNINGS AND PRECAUTIONS]

Adverse reactions with an incidence of < 1% for OBMT group are: back pain, vomiting, tongue darkening [See WARNINGS AND PRECAUTIONS], anxiety, gastritis, gastroenteritis, myalgia, chest pain, increased appetite, blood creatine phosphokinase increased, malaise, somnolence, tachycardia, duodenal ulcer, visual disturbance, weight increased.

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.

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 haematological abnormalities attributable to metronidazole have been observed [See WARNINGS AND PRECAUTIONS].

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].

Immune system disorders: Urticaria, erythematous rash, Stevens - Johnson syndrome, toxic epidermal necrolysis, flushing, nasal congestion, and fever [See CONTRAINDICATIONS].

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].

Tetracycline Hydrochloride

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].

Nervous system disorders: Pseudotumor cerebri (benign intracranial hypertension) in adults and bulging fontanels in infants. Tinnitus and myasthenic syndrome have been reported rarely.

Renal and urinary disorders: Rise in BUN has been reported and is possibly dose related [See CONTRAINDICATIONS].

Skin and subcutaneous tissue disorders: Maculopapular and erythematous rashes have been reported. Steven-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme have been reported. Exfoliative dermatitis and photosensitivity have been rarely reported [See WARNINGS AND PRECAUTIONS].