NEODOSE

INDICATIONS

• Crying & Irritability: 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 distres.
• Prevention and treatment of stress ulcers and GI hemorrhage: aggravated by gastric acid secretion.
• Apnea of Prematurity: Reducing gastric acidity or increasing gastric motility for the sole purpose to reduce apnea episodes is not supported by the literature.
• 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.

PRECAUTIONS

• Hepatic: Use with caution in patients with hepatic dysfunction.
• Infection: 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.
• Special Populations:
  • Avoid in patients with a history of acute porphyria as raNITIdine may precipitate acute porphyric attacks.
  • In phenylketonuric patients, Zantac® 25 EFFERdose® tablets contain phenylalanine 2.81 mg.

ADVERSE EFFECTS

• General: RaNITIdine is generally well tolerated by infants, children and adults, and has a low incidence of adverse effects, including rash, headache, fatigue, irritability, dizziness, nausea, constipation, and diarrhea, that are usually mild. Elevations in hepatic enzymes, leukopenia, and bradycardia have been reported in adults.
• Hematological: Severe thrombocytopenia (8 X 109/L) developed in a male infant (gestational age 36 weeks and 5 days; weight 1.8 kg) 48 hours (5 days of age) after starting ranitidine 0.5 mg/kg IV every 6 hours for prophylaxis of stress ulcer and as a potential gastric emptying stimulator. Ranitidine was discontinued on day 6, platelets increased on day 8, then normalized on day 12.
• Immunological: The use of H2-blockers in preterm infants has been associated with facilitating Candida species colonization, and an increased risk for late-onset bacterial and fungal sepsis. In a prospective, multicenter, observational study comparing VLBW neonates receiving raNITIdine (n=91) to those not receiving raNITIdine (n=183), neonates receiving raNITIdine had an increased rate of infection (37.4% versus 9.8%; OR 5.5; 95% CI, 2.9 to 10.4), increased risk for NEC (9.8% versus 1.6%; OR 6.6; 95% CI, 1.7 to 25), and increased mortality (9.9% versus 1.6%). In a retrospective, case-control study, H2-blocker use in VLBW infants was associated with an increased incidence of NEC (OR 1.7; 95% CI, 1.34 to 2.19).

ADMINISTRATION

• IV Bolus: May use 1 mg/mL preservative-free solution for injection or dilute in NS to a maximum concentration of 2.5 mg/mL and give over at least 5 minutes (maximum 4 mL/minute).
• Intermittent IV infusion: Dilute in D5W or other compatible solution to a concentration of no greater than 0.5 mg/mL and give over 15 to 20 minutes (maximum 5 to 7 mL/minute). A standard concentration of 1 mg/mL may be used.
• Continuous IV infusion: Dilute in D5W or other compatible solution to a concentration of 0.5 mg/mL or less. A standard concentration of 1 mg/mL may be used.

MONITORING

Gastric pH may be measured to assess efficacy.