Drug information of Aminophiline

Mechanism of effect

Aminophylline is the ethylenediamine salt of theophylline. Theophylline stimulates the CNS, skeletal muscles, and cardiac muscle. It relaxes certain smooth muscles in the bronchi, produces diuresis, and causes an increase in gastric secretion.

Pharmacodynamic

Aminophylline is the ethylenediamine salt of theophylline. After ingestion, theophylline is released from aminophylline, and theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin.

Pharmacokinetics

Absorption

Not available

Distribution:

Vd: 0.3 to 0.7 L/kg

Protein Binding:  60%

Elimination

Half-life: 7 – 9 hours

Drug indications

Asthma , Chronic obstructive pulmonary disease , Drug action reversal, Adenosine receptor agonist

Dosage

Intravenous Solution: 25 MG/ML

Oral Tablet: 100 MG, 200 MG

Adults:

Asthma:

• Asthma: therapy with methylxanthines (theophylline/aminophylline) for the treatment of acute asthma exacerbations in the emergency department or in hospital is not recommended due to lack of additional benefit to optimal short-acting beta-agonist therapy and increased adverse effects
• Asthma: aminophylline dose equals theophylline dose divided by 0.8
• Asthma: IV, loading dose for acute bronchodilation, theophylline-naive patient, theophylline 4.6 mg/kg (aminophylline 5.7 mg/kg) of ideal body weight IV over 30 min
• Asthma: IV, 16 to 60 yr, nonsmokers, initial (after loading dose), theophylline 0.4 mg/kg/hr IV (aminophylline 0.5 mg/kg/hr); Max dose theophylline 900 mg/day (aminophylline 1125 mg/day) (unless serum levels indicate need for larger dose)
• Asthma: IV, older then 60 yr, initial (after loading dose), theophylline 0.3 mg/kg/hr IV (aminophylline 0.38 mg/kg/hr); Max dose theophylline 400 mg/day (aminophylline 500 mg/day) (unless serum levels indicate need for larger dose)
• Asthma: oral, initial loading dose for acute bronchodilation, theophylline 5 mg/kg (aminophylline 6.25 mg/kg) of lean (ideal) body weight ORALLY to peak theophylline serum concentration of 5 to 15 mcg/mL
• Asthma: oral, initial, theophylline 300 mg/day (aminophylline 380 mg/day) ORALLY in divided doses over 6 to 8 hours; after 3 days (if tolerated), increase to theophylline 400 mg/day (aminophylline 500 mg/day) ORALLY in divided doses over 6 to 8 hours; after 3 more days (if tolerated and needed), increase to theophylline 600 mg/day (aminophylline 760 mg/day) ORALLY in divided doses over 6 to 8 hours
• Asthma: all formulations, maintenance, individualized on serum theophylline concentration and patient tolerance 

Chronic obstructive pulmonary disease:

• Chronic obstructive pulmonary disease: aminophylline dose equals theophylline dose divided by 0.8
• Chronic obstructive pulmonary disease: IV, loading dose for acute bronchodilation, theophylline-naive patient, theophylline 4.6 mg/kg (aminophylline 5.7 mg/kg) of lean (ideal) body weight IV over 30 min
• Chronic obstructive pulmonary disease: IV, 16 to 60 yr, nonsmokers, initial (after loading dose), theophylline 0.4 mg/kg/h IV (aminophylline 0.5 mg/kg/h); Max dose theophylline 900 mg/day (aminophylline 1125 mg/day) (unless serum levels indicate need for larger dose)
• Chronic obstructive pulmonary disease: IV, older then 60 yr, initial (after loading dose), theophylline 0.3 mg/kg/h IV (aminophylline 0.38 mg/kg/hr); Max dose theophylline 400 mg/day (aminophylline 500 mg/day) (unless serum levels indicate need for larger dose)
• Chronic obstructive pulmonary disease: oral, initial loading dose for acute bronchodilation, theophylline 5 mg/kg (aminophylline 6.25 mg/kg) of lean (ideal) body weight ORALLY to peak theophylline serum concentration of 5 to 15 mcg/mL
• Chronic obstructive pulmonary disease: oral, initial, theophylline 300 mg/day (aminophylline 380 mg/day) ORALLY in divided doses over 6 to 8 hours; after 3 days (if tolerated), increase to theophylline 400 mg/day (aminophylline 500 mg/day) ORALLY in divided doses over 6 to 8 hours; after 3 more days (if tolerated and needed), increase to theophylline 600 mg/day (aminophylline 760 mg/day) ORALLY in divided doses over 6 to 8 hours
• Chronic obstructive pulmonary disease: all formulations, maintenance, individualized on serum theophylline concentration and patient tolerance 

Drug action reversal, Adenosine receptor agonist:

• Drug action reversal, Adenosine receptor agonist: 100 mg slow IV over 60 seconds, injected 1 minute following regadenoson 0.4 mg 

Pediatrics:

Asthma:

• Asthma: therapy with methylxanthines (theophylline/aminophylline) for the treatment of acute asthma exacerbations in the emergency department or in hospital is not recommended due to lack of additional benefit to optimal short-acting beta-agonist therapy and increased adverse effects
• Asthma: aminophylline dose equals theophylline dose divided by 0.8
• Asthma: IV, loading dose for acute bronchodilation, theophylline-naive patient, theophylline 4.6 mg/kg (aminophylline 5.7 mg/kg) of lean (ideal) body weight IV over 30 min
• Asthma: IV, neonates up to 24 days, initial (after loading dose), theophylline 1 mg/kg IV (aminophylline 1.25 mg/kg) every 12 hr
• Asthma: IV, neonates over 24 days, initial (after loading dose), theophylline 1.5 mg/kg (aminophylline 1.9 mg/kg) IV every 12 hr
• Asthma: IV, infants 6 to 52 wks, initial (after loading dose) mg/kg/hr = (0.008) X (age in wks) + 0.21 IV
• Asthma: IV, 1 to 9 yr, initial (after loading dose), theophylline 0.8 mg/kg/h IV (aminophylline 1 mg/kg/h IV)
• Asthma: IV, 9 to 12 yr, initial (after loading dose), theophylline 0.7 mg/kg/h IV (aminophylline 0.88 mg/kg/h IV)
• Asthma: IV, 12 to 16 yr, smokers, initial (after loading dose), theophylline 0.7 mg/kg/h IV (aminophylline 0.88 mg/kg/h IV)
• Asthma: IV, 12 to 16 yr, nonsmokers, initial (after loading dose), theophylline 0.5 mg/kg/h IV (aminophylline 0.625 mg/kg/h IV); Max dose theophylline 900 mg/day (aminophylline 1125 mg/day) (unless serum levels indicate need for larger dose)
• Asthma: IV, 16 yr and older, nonsmokers, initial (after loading dose), theophylline 0.4 mg/kg/h IV (aminophylline 0.5 mg/kg/h IV); Max dose theophylline 900 mg/day (aminophylline 1125 mg/day) (unless serum levels indicate need for larger dose)
• Asthma: oral , 1 to 15 yr (less than 45 kg), initial, theophylline 12 to 14 mg/kg/day (aminophylline 15.2 to 17.7 mg/kg/day) ORALLY in divided doses over 4 to 6 h, MAX dose theophylline 300 mg/day (aminophylline 380 mg/day); after 3 days (if tolerated), increase to theophylline 16 mg/kg/day (aminophylline 20.3 mg/kg/day) ORALLY in divided doses over 4 to 6 h, MAX dose theophylline 400 mg/day (aminophylline 507 mg/day) after 3 more days (if tolerated and needed), increase to theophylline 20 mg/kg/day (aminophylline 25.3 mg/kg/day) ORALLY in divided doses over 4 to 6 h, MAX dose theophylline 600 mg/day (aminophylline 760 mg/day)
• Asthma: oral, 1 to 15 yr (over 45 kg), initial, theophylline 300 mg/day (aminophylline 380 mg/day) ORALLY in divided doses over 6 to 8 hr; after 3 days (if tolerated), increase to theophylline 400 mg/day (aminophylline 507 mg/day) ORALLY in divided doses over 6 to 8 hr; after 3 more days (if tolerated and needed), increase to theophylline 600 mg/day (aminophylline 760 mg/day) ORALLY in divided doses over 6 to 8 hours
• Asthma: all formulations, maintenance, individualized on serum theophylline concentration and patient tolerance

Chronic obstructive pulmonary disease:

• hronic obstructive pulmonary disease: aminophylline dose equals theophylline dose divided by 0.8
• Chronic obstructive pulmonary disease: IV, loading dose for acute bronchodilation, theophylline-naive patient, theophylline 4.6 mg/kg (aminophylline 5.7 mg/kg) of lean (ideal) body weight IV over 30 min
• Chronic obstructive pulmonary disease: IV, neonates up to 24 days, initial (after loading dose), theophylline 1 mg/kg IV (aminophylline 1.25 mg/kg) every 12 h
• Chronic obstructive pulmonary disease: IV, neonates over 24 days, initial (after loading dose), theophylline 1.5 mg/kg (aminophylline 1.9 mg/kg) IV every 12 h
• Chronic obstructive pulmonary disease: IV, infants 6 to 52 wks, initial (after loading dose) mg/kg/h = (0.008) X (age in wks) + 0.21 IV
• Chronic obstructive pulmonary disease: IV, 1 to 9 yr, initial (after loading dose), theophylline 0.8 mg/kg/h IV (aminophylline 1 mg/kg/h IV)
• Chronic obstructive pulmonary disease: IV, 9 to 12 yr, initial (after loading dose), theophylline 0.7 mg/kg/h IV (aminophylline 0.88 mg/kg/h IV)
• Chronic obstructive pulmonary disease: IV, 12 to 16 yr, smokers, initial (after loading dose), theophylline 0.7 mg/kg/h IV (aminophylline 0.88 mg/kg/h IV)
• Chronic obstructive pulmonary disease: IV, 12 to 16 yr, nonsmokers, initial (after loading dose), theophylline 0.5 mg/kg/h IV (aminophylline 0.625 mg/kg/h IV); Max dose theophylline 900 mg/day (aminophylline 1125 mg/day) (unless serum levels indicate need for larger dose)
• Chronic obstructive pulmonary disease: IV, 16 yr and older, nonsmokers, initial (after loading dose), theophylline 0.4 mg/kg/h IV (aminophylline 0.5 mg/kg/h IV); Max dose theophylline 900 mg/day (aminophylline 1125 mg/day) (unless serum levels indicate need for larger dose)
• Chronic obstructive pulmonary disease: oral, 1 to 15 yr (less than 45 kg), initial, theophylline 12 to 14 mg/kg/day (aminophylline 15.2 to 17.7 mg/kg/day) ORALLY in divided doses over 4 to 6 h, MAX dose theophylline 300 mg/day (aminophylline 380 mg/day); after 3 days (if tolerated), increase to theophylline 16 mg/kg/day (aminophylline 20.3 mg/kg/day) ORALLY in divided doses over 4 to 6 h, MAX dose theophylline 400 mg/day (aminophylline 507 mg/day) after 3 more days (if tolerated and needed), increase to theophylline 20 mg/kg/day (aminophylline 25.3 mg/kg/day) ORALLY in divided doses over 4 to 6 h, MAX dose theophylline 600 mg/day (aminophylline 760 mg/day)
• Chronic obstructive pulmonary disease: oral, 1 to 15 yr (over 45 kg), initial, theophylline 300 mg/day (aminophylline 380 mg/day) ORALLY in divided doses over 6 to 8 h; after 3 days (if tolerated), increase to theophylline 400 mg/day (aminophylline 507 mg/day) ORALLY in divided doses over 6 to 8 h; after 3 more days (if tolerated and needed), increase to theophylline 600 mg/day (aminophylline 760 mg/day) ORALLY in divided doses over 6 to 8 hours
• Chronic obstructive pulmonary disease: all formulations, maintenance, individualized on serum theophylline concentration and patient tolerance

Drug contraindications

hypersensitivity to this drug

hypersensitivity to theophylline, ethylenediamine, or to any product component

Side effects

Diarrhea , Frequent urination , Headache , nausea , vomiting , vertigo , Restlessness

Interactions

Alprazolam , Adenosine , intralipid , Pralidoxime , Propranolol , pentoxifylline , Ciprofloxacin , Fluvoxamine , Folic acid , Lorazepam , Mexiletine , Clobazam , Clonazepam , formoterol , Disulfiram , Bisoprolol , Carteolol

PDE INHIBITORS
XANTHINE DERIVATIVES
THEOPHYLLINE DERIVATIVES

Alerts

• age; neonates (term and premature), children under 1 yr, elderly (over 60 years) have reduced theophylline clearance; increases risk of severe and potentially fatal theophylline toxicity
• active peptic ulcer; risk of exacerbation of current condition
• cardiac arrhythmias (not including bradyarrhythmias); risk of exacerbation of current condition
• concomitant drugs which inhibit or enhance theophylline metabolism; increases risk of severe and potentially fatal adverse effects
• congestive heart failure; reduced theophylline clearance, increases risk of severe and potentially fatal theophylline toxicity
• dose increases; base on peak steady state serum theophylline concentration
• fever; 102 degrees Fahrenheit or greater for 24 hours or more, or lesser temperature elevations for longer periods; reduced theophylline clearance, increases risk of severe and potentially fatal theophylline toxicity
• hypothyroidism; reduced theophylline clearance, increases risk of severe and potentially fatal theophylline toxicity
• liver disease, cirrhosis, acute hepatitis; reduced theophylline clearance, increases risk of severe and potentially fatal theophylline toxicity
• pulmonary edema (acute) or cor pulmonale; reduced theophylline clearance, increases risk of severe and potentially fatal theophylline toxicity
• seizure disorders; risk of exacerbation of current condition
• sepsis with multi-organ failure; reduced theophylline clearance, increases risk of severe and potentially fatal theophylline toxicity
• serious toxicity is not necessarily preceded by mild or moderate side effects
• shock; reduced theophylline clearance, increases risk of severe and potentially fatal theophylline toxicity

smoking cessation; reduced theophylline clearance, increases risk of severe and potentially fatal theophylline toxicity

Points of recommendation

Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience agitation, insomnia, or polyuria. Have patient report immediately to prescriber signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), muscle pain, muscle weakness, tachycardia, abnormal heartbeat, fast breathing, severe dizziness, passing out, severe anxiety, nausea, vomiting, severe diarrhea, abdominal pain, severe headache, confusion, seizures, or tremors (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note:This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Pregnancy level

C