NEODOSE

INDICATIONS

• Crying and irritability: In otherwise healthy term infants, histamine2 receptor antagonists or proton pump inhibitors should not be used for the treatment of crying and distress. No improvement in crying and irritability was provided by proton pump inhibitors in infants in a systematic review of 5 randomized clinical trials (n=430).
• Gastroesophageal Reflux (GER): The risks associated with acid reducing agents outweighs the benefits in preterm infants for GER. Acid blocking agents should not be used and if used in preterm infants, use sparingly. In otherwise healthy term infants, histamine2 receptor antagonists or proton pump inhibitors should not be used for the treatment of visible regurgitation.
• Gastroesophageal reflux disease (GERD): Proton pump inhibitors (PPIs) are the firstline agents for erosive esophagitis in infants and children with GERD. Histamine2 receptor antagonists are the second-line agent if PPIs are not available or are contraindicated. A duration of treatment for 4 to 8 weeks for GERD symptoms is recommended. Regularly reassess the need for long-term acid suppression. If no response after 4 to 8 weeks, then reevaluate for other causes of symptoms. H2RAs and PPIs are not recommended for extraesophageal symptoms (e.g. cough, wheezing, asthma), unless GERD symptoms are present and/or GERD has been diagnosed. A trial use of PPIs as a diagnostic test for GERD is not recommended in infants or in patients presenting with extraesophageal symptoms. However, in children with typical GERD symptoms, a trial of 4 to 8 weeks with a PPI may be used as a diagnostic test. A systematic review of 5 placebo-controlled studies demonstrated a lack of effectiveness of proton pump inhibitors (lansoprazole, omeprazole, and pantoprazole) in reducing GERD symptoms in infants (34 weeks’ postmenstrual age to 12 months). Pantoprazole did not improve symptoms in 129 pediatric patients 1 through 11 months of age with symptomatic GERD in a multicenter, randomized, double-blind, placebo-controlled study.
• Stress ulcer prophylaxis: Despite the lack of data, prophylaxis with a proton pump inhibitor or H2RA is frequently used in pediatric and neonatal intensive care units. Prophylaxis in critically ill children admitted to the intensive care unit may be beneficial based on a systematic review of 2 studies; however the evidence was of low quality. The treatments were almagate, ranitidine, sucralfate, and omeprazole. In prepubertal children with severe sepsis, experts provide no recommendation on the use of stress ulcer prophylaxis . Based on low to very low quality evidence in patients older than 16 years some experts suggest acid suppression (PPIs or H2RA) in the intensive care setting for acutely ill patients for the primary prevention of upper gastrointestinal bleeding. In adults, prophylaxis (proton pump inhibitor or H2RA) is recommended in patients with sepsis or septic shock who have risk factors for gastrointestinal bleeding. Prophylaxis should only be used in patients with risk factors .
• Upper Gastrointestinal (UGI) bleeding: Acid suppression is recommended in pediatric UGI bleeds, which is supported by adult data using proton-pump inhibitors.

FDA APPROVED INDICATION

Not FDA approved in neonate patients.

CONTRAINDICATIONS :

• Known hypersensitivity to any component or any substituted benzimidazole.
• Concomitant use of rilpivirine-containing products.

PRECAUTIONS:

• Concomitant use:
  • Elevation or and prolongation of methotrexate concentrations and/or its metabolite may occur; temporary withdrawal of proton pump inhibitor may be necessary
• Cardiovascular:
  • Thrombophlebitis was associated with IV administration.
• Endocrine and metabolic:
  • Zinc supplementation may be needed in patients who are prone to zinc deficiency and receiving IV pantoprazole, which contains a chelator (edetate disodium (EDTA)). Use caution when other EDTA-containing products are co-administered IV.
  • Hypomagnesemia has been reported in patients treated with proton pump inhibitors for at least 3 months; tetany, arrhythmias, and seizures may occur; discontinuation may be required.
  • Vitamin B12 deficiency may occur with prolonged use (e.g., longer than 3 years).
• Gastrointestinal:
  • Symptomatic response does not preclude presence of gastric malignancy.
  • Clostridium difficile-associated diarrhea may occur, especially in hospitalized patients; use lowest dose and shortest treatment duration.
• Hepatic:
  • Mild, transient transaminase elevations have been observed with pantoprazole; clinical significant is unknown.
• Immunologic:
  • Anaphylaxis and other serious reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported with IV pantoprazole.
  • New or worsening systemic or cutaneous lupus erythematosus has been reported within weeks to years of treatment initiation; avoid using for longer than medically indicated and discontinue use if suspected.
• Infections:
  • Increased risk of infections (necrotizing enterocolitis, pneumonia, upper respiratory tract infections, sepsis, urinary tract infections, and Clostridium difficile infections) in infants and children on H2 blockers or PPIs demonstrated in case-control studies.
• Lab Interfarence:
  • Gastric acid suppression may increase serum chromogranin A (CgA) levels; withhold pantoprazole for at least 14 days prior to neuroendocrine tumor assessment based on CgA levels.
• Musculoskeletal:
  • Osteoporosis-related bone fracture of hip, wrist, or spine may occur, especially with higher (multiple daily) doses or longer duration of therapy (1 year or longer); use lowest dose and shortest treatment duration.
• Renal:
  • Acute interstitial nephritis, typically associated with idiopathic hypersensitivity, has been reported; discontinuation required.
• Respiratory:
  • PPIs, when used for oropharyngeal dysphagia (off-label use), may be associated with an increased risk of hospitalization due to aspiration and isolated laryngeal penetration; demonstrated in a retrospective cohort (n=293 children 2 years or younger)

ADVERSE EFFECTS

Reported adverse effects in neonates:

• Anemia
• Constipation
• Contact dermatitis
• Hypoxia
• Vomiting
• Rhinitis

Adverse effects reported in more than 4% of pediatric patients (1 to 16 years of age) were headache, fever, abdominal pain, vomiting, diarrhea, upper respiratory infection, and rash In a retrospective, single-center, observational, case-control study of 136 children (1 year or older) having protracted diarrhea and stool analysis for Clostridium difficile, the use of PPI therapy was significantly higher in the patients with C difficile-associated diarrhea compared to the control group (22% vs 6%; odds ratio of 4.5 (95% CI, 1.4 to 14.4; p=0.006)).

ADMINISTRATION

• Oral (Delayed-Release Suspension): Mix the pantoprazole with 2.5 mL of water and immediately administer with an oral syringe. Administer 30 minutes before the first feeding at approximately the same time each day .
• Nasogastric or Gastric Tube (Delayed-Release Suspension):Remove the plunger from the barrel of a 60-mL cathetertip syringe. Connect the catheter tip of the syringe to a 16 French (or larger) tube. Hold the syringe attached to the tubing as high as possible while giving to prevent any bending of the tubing. Empty the contents of the packet into the barrel of the syringe and add 10 mL of apple juice; gently tap and/or shake the barrel of the syringe to help rinse the syringe and tube. Repeat at least twice more using the same amount of apple juice (10 mL) each time. No granules should remain in the syringe.
• Intravenous: Administer as an IV infusion over 15 to 30 minutes at a concentration of 0.4 to 0.8 mg/mL or IV push over 2 minutes at a concentration of 4 mg/mL. Flush IV line before and after administration with NS, D5W, or LR.

MONITORING

Laboratory Findings:

• pH: Consider intraesophageal pH monitoring to assess for efficacy (pH greater than 4).
• Magnesium Concentration: Hypomagnesemia has been reported with prolonged administration (in most cases, greater than 1 year). Monitor magnesium levels prior to initiation of therapy and periodically during therapy in patients expected to be on long-term therapy or patients receiving concomitant drugs such as digoxin or those that may cause hypomagnesemia.