Dose:     5 to 6 mg/kg/dose IV as loading dose
               2 mg/kg/dose as maintenance dose

Frequency:     Q 8 hours (Q 6 to 12 hours)

Comments: Aminophylline is a methylxanthine derivative that acts directly to relax the smooth muscle of the bronchi and the pulmonary vascular bed, acts as a central nervous system stimulant, and acts to increase gastric acid secretion, reduces the lower lower esophageal sphincter tone, and induces diuresis. There were three indications for its use in newborns: treatment of apnea, treatment of bronchopulmonary dysplasia, and use as an aid in extubation, but these better treated using caffeine . A meta-analysis of published studies of caffeine versus theophylline for the treatment of apnea by Henderson-Smart and Steer confirmed the advantages of caffeine over theophylline. Though the number of episodes of apnea were greater during the first 1 to 3 days in caffeine-treated infants, there was no difference in the number of episodes of apnea by 5 to 7 days. The doses used in the studies were lower than we routinely use. However, because of the advantages caffeine has over theophylline (a higher therapeutic ratio, more reliable enteral absorption, and a longer half-life), caffeine appears to be the preferred treatment for apnea in preterm infants. However, aminophylline might still be useful for those infants with an older gestational age that might only be on the medication for a few days given its much shorter half-life. Do not use aminophylline with an oral beta agonist such as albuterol.   Further comments on aminophylline.

Toxicity:  Symptoms such as failure to gain weight, sleeplessness, irritability, and tachycardia should be considered to be warning signs of the more ominous toxicities seen in older patients.  Tachycardia has occurred with serum concentrations ranging from 13 to 32 mcg/ml.  Maintenance of serum levels below 15 mcg/ml should be associated with negligible CNS excitation and other major complications. However there is no follow up data to judge aminophylline's safety beyond a few days (Schmidt. J Pediatr 1999; 135:526-8). Animal data suggests that aminophylline at therapeutic levels interfers with the neuroprotective effects of adenosine during hypoxemia or ischemia. Further adverse effects of aminophylline.

Preparation:
IV: Aminophylline (single dose for immediate use) will be prepared in the pharmacy in a 5 mg/ml concentration. Aminophylline is an ethylenediamine complex of theophylline. As noted above, aminophylline contains 80% theophylline which is the active component of the drug. Therefore a 4 mg dose of theophylline is equivalent to 5 mg dose of aminophylline. The drug can be given by IVP over 3 to 5 minutes. It can also be given as a continuous infusion alone or "piggy-backed" into an IV. Refrigerate.

Aminophylline drip

Compatibility: Compatible with TPN & filter. Aminophylline may precipitate in the presence of MVI in the TPN. Flush IV lines containing TPN with NS before and after administering the drug.   Aminophylline is also compatible with dextrose and saline solutions including D5W, D5 with sodium chloride, D5LR, D10W, D20W, and LR. It is also compatible with allopurinol, amrinone, calcium gluconate, ceftazidime (Y-site only) chloramphenicol, dexamethasone, dopamine, enalaprilat, erythromycin lactobionate, esmolol, famotidine, fluconazole, flumazenil, furosemide, heparin, hydrocortisone, labetalol, lidocaine, meropenem, metaclopromide,  morphine, pancuronium, piperacillin-tazobactam, phenobarbital, ranitidine, and sodium bicarbonate.  Incompatible with atracurium, ceftriaxone, cephalothin, cefotaxime, clindamycin, dobutamine, doxapram, epinephrine, erythromycin gluceptate, hydralazine, insulin, isoproterenol, methadone, methicillin, morphine, and penicillin .  It is equivocally compatible with amikacin, lipids, morphine, nafcillin, and vancomycin.