TDM Theophylline
Theophylline
Theophylline is a methylxanthine, a class of molecule
similar to the xanthines caffeine and theobromine found
in a normal diet
Theophylline is used to prevent and treat wheezing,
shortness of breath, and chest tightness caused by
asthma, chronic bronchitis, emphysema, and other lung
diseases. It relaxes and opens air passages in the lungs,
making it easier to breathe
Theophylline
Theophylline (1,3-dimethylxanthins) can indirectly
stimulate both β1 and β2 receptors through release of
endogenous catecholamines.
It is used for the treatment of pulmonary conditions,
including asthma and chronic obstructive pulmonary
disease (COPD).
In neonates, theophylline can be used for the treatment
of apnea.
WHY TDM for Theophylline?
Dosing is very frequent, It usually is taken every 6, 8, 12, or 24 hours
Drinking or eating foods high in caffeine, like coffee, tea, cocoa,
and chocolate, may increase the side effects caused by
theophylline. Avoid large amounts of these substances while you
are taking theophylline.
Consumption of ethanol [ETOH], cimetidine, oral contraceptives,
allopurinol, macrolide, quinolone antibiotics)
Liver disease/ Viral disease /CHF
Basic Kinetics
It has a half-life of 8 hours in a healthy person but decreases to 4-5 hours in
people who smoke.
In the blood, 40%-50% of theophylline is bound to proteins
Reference ranges of theophylline in the treatment asthma vary by age, as
follows:
Adults: 5-15 µg/mL
Children: 5-10 µg/mL
Toxic levels are considered to be higher than 20 mcg/mL; however, adverse effects
may be evident within the normal therapeutic range
Complications
Severe complications including cardiac dysrhythmias,
seizures, and death can be observed with the levels of
80-100 mcg/mL.
In chronic exposure, those levels could be lower (40-60
mcg/mL)
Symptoms of overdose
Nausea, Vomiting
Abdominal pain
Mild metabolic acidosis
Hypokalemia, Hypophosphatemia, Hypophosphatemia, Hypomagnesemia
Hypocalcemia/hypercalcemia, Hyperglycemia
Tachycardia
Seizures (can occur at 40-60mcg/ml), hypotension, and significant
dysrhythmias usually are observed when serum levels approach 80 mcg/mL
Toxicity of Theophylline
Chronic theophylline toxicity
Acute theophylline toxicity (consumption in large
amount, intentional and non-intentional)
Chronic theophylline toxicity
Drug interactions (eg, ethanol [ETOH], cimetidine, oral
contraceptives, allopurinol, macrolide, quinolone antibiotics)
Liver disease
Congestive heart failure
Febrile viral upper respiratory illness
Loading & Maintenance dose
Loading Dose in bronchospasm = 5-7 mg/kg IV/PO; not to exceed
25 mg/min IV for adults
Loading Dose= 5-7 mg/kg IV/PO; no dose in last 24 hours. Infused
over 20-30 minutes for paediatrics
Loading & Maintenance dose
MD in bronchospasm = 0.4-0.6 mg/kg/hr IV or 4.8-7.2 mg/kg PO (extended
release) q12hr to maintain levels 10-15 mg/L for adults
MD for Peds= 1.5-6 months: 0.5 mg/kg/hr IV or 10 mg/kg/day PO in divided
doses
6-12 months: 0.6-0.7 mg/kg/hr IV or 12-18 mg/kg/day PO in divided doses
Among GERIATRICs After loading dose, 0.47 mg/kg/hr IV for next 12 hours,
then 0.24 mg/kg/hr
STEADY STATE AT 2-3 days or 3rd dose
Loading & Maintenance dose
Neonatal Apnea
Loading: 4-5 mg/kg PO/IV once
Maintenance: 3-6 mg/kg/day PO/IV divided q8hr
Important aspects to consider while
dosing
Aminophylline is approximately 79-86% theophylline.
For PO loading, use immediate-release theophylline
If patient is already taking theophylline, give smaller loading dose
Use ideal body weight to calculate dose
1 mg/kg results in 2 mg/L (34.4 mmol/L) increase in serum
theophylline
Hepatic impairment/Congestive heart failure: After loading dose,
0.39 mg/kg/hr IV for next 12 hours, then 0.08-0.16 mg/kg/hr
Impact of medications, social habits
on dose of Theophylline
Smokers: 0.79 mg/kg/hr IV for next 12 hours after loading dose, then 0.63
mg/kg/hr or 5 mg/kg PO (extended release) q8hr
Co-administration: with drugs that decrease theophylline clearance (eg,
cimetidine, ciprofloxacin, and erythromycin and other macrolides): 0.2-0.3
mg/kg/hr IV or PO (extended release) q12-24hr
Certain diets (such as high protein/low carbohydrate or high
carbohydrate/low protein) may change the effect of theophylline. Patient
counselling is important on this matter
Management of Toxicity
Gut decontamination
Antiemetic's to manage the loss of fluids
Metoclopramide; H2 antagonist that may be a useful adjunct in reducing emesis volume.
Benzodiazipines
Diazepam Muscle Spasm
2-10 mg PO q6-8hr PRN, OR 5-10 mg IV/IM initially; THEN q3-4hr if necessary
Seizure Disorder
2-10 mg PO q6-12hr as adjunct, OR
0.2 mg/kg PR, repeat after 4-12 hours PRN
Cardioselective BBs Esmolol
Load 0.25-0.5 mg/kg IV over 1 min, THEN
0.05-0.1 mg/kg/min IV for 4 min
May repeat loading dose or increase infusion up to 0.3 mg/kg/min if necessary
