NEODOSE

INDICATIONS

• Facilitate extubation: Low-dose dexamethasone has been used successfully to facilitate extubation and improve lung function acutely in preterm infants at high risk for developing chronic lung disease. Low doses have not been associated with substantial effects with regard to mortality or development of bronchopulmonary dysplasia (BPD) at 36 weeks. High-dose dexamethasone (eg, 0.5 mg/kg/day) has been associated with a reduction in the incidence of BPD, but also an increased risk for short-term adverse effects (hyperglycemia, hypertension, gastrointestinal perforation, infection risk) and adverse long-term neurodevelopmental outcomes (cerebral palsy (CP)). A review of meta-analyses looking at the timing and dosage of postnatal steroids found the development of CP was associated with early steroid use (first week of life) in patients at lower risk for BPD. A prospective cohort study found that higher steroid exposure was associated with an increased risk for CP. High-dose dexamethasone in the first week of life is generally not recommended for the prevention of BPD or for the treatment of BPD after the first week of life; however, the judicious use of late dexamethasone may be considered for infants who cannot be weaned from the ventilator. A shorter course, 7 days, compared with a longer course, 10 days, of dexamethasone for bronchopulmonary dysplasia was as effective in facilitating extubation (56% vs 67%, p=0.42) within 14 days of starting dexamethasone in mechanically-ventilated preterm infants (less than 29 weeks’ gestational age) in a retrospective study (n=59). Mean postnatal age was 36 days and 33 days for the infants treated for 7 days and 10 days, respectively. The total dose for the 7-day regimen was 0.72 mg/kg (0.075 mg/kg/dose every 12 hours for 3 days, 0.05 mg/kg/dose every 12 hours for 2 days, 0.025 mg/kg/dose every 12 hours for 1 day, and 0.01 mg/kg/dose every 12 hours for 1 day). The total dose for the 10-day regimen was 0.89 mg/kg.
• Anthrax, adjunct: Although data are lacking, consider adjunctive corticosteroids for the treatment of severe cerebral edema or meningoencephalitis

FDA APPROVED INDICATION

• ophthalmic: Indicated in pediatric patients of all ages for steroid responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe such as allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, selected infective conjunctivitides when inherent hazard of steroid use is accepted to obtain an advisable diminution in edema and inflammation; corneal injury from chemical, radiation, or thermal burns, or penetration of foreign bodies.
• Systemic: Use as an immunosuppressant and in a variety of antiinflammatory disorders to reduce edema (eg, due to tumors, infection) and to lessen the effects of neurologic disorders based on adult studies. For the treatment of nephrotic syndrome, dexamethasone is approved in patients older than 2 years of age, and for the palliative management of aggressive lymphomas and leukemias, it is approved in patients 29 days and older. Due to its lack of mineralocorticoid effects, dexamethasone is not indicated as replacement therapy for patients with adrenal insufficiency.

CONTRAINDICATIONS

• Systemic Use:
  • Contraindicated in patients with systemic fungal infection
• Ophthalmic Use:
  • Contraindicated in acute, untreated bacterial infections; mycobacterial ocular infections; epithelial herpes simplex (dendritic keratitis); vaccinia, varicella, and most other viral diseases of the cornea and conjunctiva; fungal disease of ocular structures; and in those persons who have shown hypersensitivity to any component of this preparation

PRECAUTIONS

• Systemic Use:
  • Administration
    • Injecting corticosteroids into the epidural space the spine may result in rare but serious neurologic problems (ie, spinal cord infarction, loss of vision, stroke, seizure, paralysis, or death).
  • Immunologic:
    • Contains bisulfate, a sulfite that can cause anaphylactic allergic-type reactions seen more frequently in asthmatic patients.
  • Ophthalmic:
    • Use of corticosteroid-containing product for more than 6 weeks or development of ocular symptoms; consider ophthalmologist referral.

• Ophthamic Use:
  • Ophthalmic:
    • Prolonged use may result in ocular hypertension and/or glaucoma, with damage to the optic nerve, defects in visual acuity and fields of vision, and posterior subcapsular formation; monitoring recommended during long-term (10 day or longer) therapy.
    • Prolonged use may increase the risk of secondary ocular infections due to reduced host response.
    • Prolonged use may result in persistent fungal infection of the cornea.
    • Perforations may occur in patients receiving topical corticosteroids in diseases known to cause thinning of the cornea or sclera.
    • Corticosteroids may mask infection or enhance existing infection in the presence of acute purulent conditions or parasitic infections of the eye.

ADVERSE EFFECTS

The February 2002 AAP and CPS statement strongly discourages routine use ofdexamethasone. If dexamethasone is used for CLD risk reduction, 1) Treat only those infantsm at highest risk; 2) Use lower than traditional pharmacologic doses; 3) Begin treatment after Day 7 but before Day 14 of life; 4) Do not give concurrently with indomethacin; 5) Use preservative-free drug wherever possible. The DART trial found no association with long-term morbidity, but other studies have reported an increased risk of cerebral palsy. Most evidence suggests no increase in the incidence of ROP or the need for cryotherapy. Gastrointestinal perforation and GI hemorrhage occur more frequently in patients treated beginning on Day 1 and in those also being treated concurrently with indomethacin. Hyperglycemia and glycosuria occur frequently after the first few doses, and one case of diabetic ketoacidosis has been reported. Blood pressure increases are common, and hypertension occurs occasionally. Cardiac effects noted by Day 14 of therapy include increased left ventricular wall thickness with outflow tractmobstruction and transient impairment of left ventricular filling, systolic anterior motion of themmitral valve, and ST-segment depression. Other potential short-term adverse effects includemsodium and water retention, hypokalemia, hypocalcemia, hypertriglyceridemia, increased riskmof sepsis, renal stones (in patients receiving furosemide), osteopenia, and inhibition ofmgrowth. Adrenal insufficiency may occur secondary to pituitary suppression.

ADMINISTRATION

• Intravenous: Can be administered undiluted or can be diluted to a concentration of 0.1 to 1 mg/mL in NS for intravenous infusion.
• Ophthalmic: Shake well before use.
• Oral: Take large doses with meals and take antacids between meals to prevent peptic ulcer. Mix the concentrate solution with liquid or semi-solid food such as water, juices, soda, applesauce or puddings and consume immediately; do not store for future use. The IV formulation of dexamethasone has been used orally in pediatric patients, including a one-time dose for asthma exacerbation in a retrospective study. Injectable dexamethasone was mixed with a small amount of juice . Stability data are available; however, there are no bioequivalence data in pediatric patients

MONITORING

• Systemic Use: Assess for hyperglycemia and hyperlipidemia. Monitor blood pressure. Guaiac gastric aspirates. Echocardiogram if treating longer than 7 days.
• Ophthalmic Use: Monitor intraocular pressure during long-term (10 day or longer) therapy Periodic slit-lamp microscopy is required in the treatment of herpes simplex.