NEODOSE

INDICATIONS

• Prevention of bronchopulmonary dysplasia (BPD) in ELBW neonates: Hydrocortisone for the first 2 weeks of life should be considered for infants with evidence of fetal inflammation; however, there are insufficient data to support its use in all babies at risk for BPD. A composite outcome of death or BPD at 36 weeks’ postmenstrual age was not different between Hydrocortisone started between 7 and 14 days after birth and placebo (70.7% vs 73.7%; adjusted OR 0.87 (95% CI, 0.54 to 1.38; p = 0.54)) in a randomized double-blinded trial (n=372). The median gestational age was 25.4 weeks (24.9 to 26.4 weeks) for the Hydrocortisone group and 25.6 weeks (24.7 to 26.4 weeks) for the placebo group. Hydrocortisone sodium succinate dosage was 5 mg/kg/day in 4 divided doses for 7 days, 3.75 mg/kg/day in 3 divided doses for 5 days, then subsequently lowering the frequency by 1 dose every 5 days (cumulative dose of 72.5 mg/kg over 22 days). Although, a double-blind, randomized, multicenter trial (n=521) demonstrated that more neonates (24 to 27 weeks of gestation) administered low-dose Hydrocortisone during their first 10 postnatal days survived to 36 weeks of postmenstrual age without bronchopulmonary dysplasia compared with placebo (60% vs 51%; OR, 1.48 (95% CI, 1.02 to 2.16)). The Hydrocortisone dose was 0.5 mg/kg/dose IV every 12 hours for 7 days, followed by 0.5 mg/kg/day IV for 3 days. The rate of gastrointestinal perforation was 5% for the Hydrocortisone group and 4% for the placebo group. Degree of neurodevelopmental impairment was not significantly different between the Hydrocortisone and placebo groups (no impairment, 73% vs 70%; mild impairment, 20% vs 18%; moderate to severe impairment, 7% vs 11%) in 379 children who were evaluated at a median 22 months’ corrected age. Other major neurodevelopmental outcomes, including cerebral palsy, were also not significantly different between groups. At a 2 year follow-up, better global neurodevelopmental outcomes were associated with the 24 and 25 weeks’ gestational age group receiving Hydrocortisone compared with placebo. In contrast, there was no difference between Hydrocortisone and placebo in the 26 and 27 weeks’ gestational age group. Longer-term safety remains to be evaluated. In a randomized, placebo-controlled clinical trial of ELBW neonates receiving low-dose Hydrocortisone or placebo (started within the first 48 hours of life), babies exposed to chorioamnioitis receiving Hydrocortisone had significantly improved survival without BPD and decreased mortality before 36 weeks PMA when compared to those receiving placebo (OR 2.84; 95% CI, 1.21 to 6.67). There were no differences in these outcomes for infants without chorioamnioitis exposure receiving Hydrocortisone when compared with placebo (OR 0.72; 95% CI, 0.31 to 1.65). The trial was stopped early due to an increased incidence of spontaneous GI perforation in the group receiving Hydrocortisone (calculated sample size=712 births; actual final enrollment=360 births).
• Treatment of cortisol deficiency.
• Treatment of pressor-resistant hypotension.
• Adjunctive therapy for persistent hypoglycemia.
• Pressor- and volume-resistant septic shock: Sepsis guidelines suggest Hydrocortisone treatment only in newborns with adrenal insufficiency.

CONTRAINDICATIONS

Intrathecal administration and use in patients with systemic fungal infections is contraindicated. IM administration is contraindicated in patients with idiopathic thrombocytopenic purpura. Live and live, attenuated vaccines are contraindicated in patients receiving immunosuppressive doses of corticosteroids. A-Hydrocort® contains benzyl alcohol and is contraindicated in premature infants

PRECAUTIONS

Pheochromocytoma crisis has been reported and may be fatal. Consider risk prior to initiation. Corticosteroid use may increase the risk of infection and may mask signs of current infection. Corticosteroid use may also exacerbate systemic fungal infections. Avoid use in the presence of systemic fungal infections unless use is required to control drug reactions. Avoid local injection into previously infected sites. Avoid exposure to chicken pox or measles in patients without a past history of disease due to the risk of a serious or fatal course of the disease. Consider prophylaxis with immunoglobulins or treatment with antiviral agents if exposure occurs. Inhibition of bone growth and the development of osteoporosis may occur. Psychic derangements (ie, euphoria, mood swings, personality changes, severe depression) may occur and preexisting psychiatric problems may be exacerbated.

ADVERSE EFFECTS

Hyperglycemia, hypertension, salt and water retention. There is an increased risk of GI perforations when treating concurrently with indomethacin. There is also an increased risk of disseminated Candida infections.

• Endocrine Effects Abnormal response to both adrenocorticotropic hormone and cortisol secretion occurred in 12% of extremely low birthweight infants administered Hydrocortisone for respiratory deterioration or circulatory collapse in a retrospective cohort study (n=58). IV Hydrocortisone 1 to 5 mg/kg for one or more treatments was administered and if needed oral treatment with Hydrocortisone 1 to 2.5 mg/kg/day (10 to 25 mg/m2/day was continued until the infant stabilized. The cumulative IV and oral doses were 9 mg/kg and 68.1 mg/kg, respectively, for a duration period of 57.1 days.
• Neurological Effects Prolonged courses of Hydrocortisone compared with no Hydrocortisone treatment were associated with fine motor and language delay at 8 months corrected age (CA) and motor delay at 20 months CA in a retrospective study of extremely-low-birth-weight infants (n=175). The majority (88%) of Hydrocortisone treatment was used as an adjunct to wean off the ventilator and 9% for treatment-resistent hypotension. Treatment solely for hypotension began at less than 72 hours of age whereas the median start of treatment for ventilator weaning only was 15 days. The mean duration of Hydrocortisone therapy was 49 days. Early, low-dose Hydrocortisone treatment was not associated with increased cerebral palsy. Treated infants had indicators of improved developmental outcome.

ADMINISTRATION

Intravenous: Administer over a period of 30 seconds (eg, 100 mg) to 10 minutes (eg, 500 mg or more). The reconstituted solution (50 and 125 mg/mL) may be given without further dilution. For intravenous infusion, may dilute to 1 mg/mL in D5W or NS for infusion. The preferred concentrations are 50 mg/mL for intermittent IV (bolus) and 1, 2, 5 mg/mL intermittent IV (infusion) Oral: Guideline recommendations suggest crushing the tablet formulation and mixing with small amount of liquid just prior to administration.

MONITORING

Measure blood pressure and blood glucose frequently during acute illness.