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theophylline

(thee off' i lin)

theophylline
Immediate-release capsules, tablets:
Bronkodyl, Elixophyllin, Quibron-T Dividose, Slo-Phyllin, Theolair
Timed-release capsules:
Slo-bid Gyrocaps, Slo-Phyllin Gyrocaps, Theo-24, Theobid, Theoclear L.A.,
Theovent
Timed-release tablets:
Quibron-T/SR Dividose, Respbid, Sustaire, Theochron, Theolair-SR, Theo-
X, T-Phyl, Uni-Dur, Uniphyl
Liquids:
Accurbron, Aquaphyllin, Asmalix, Elixomin, Elixophyllin, Lanophyllin, Slo-
Phyllin, Theoclear-80, Theolair

theophylline sodium glycinate


Elixir:
Acet-Amp (CAN)

Pregnancy Category C

Drug classes
Bronchodilator
Xanthine

Therapeutic actions
Relaxes bronchial smooth muscle, causing bronchodilation and increasing vital capacity
that has been impaired by bronchospasm and air trapping; actions may be mediated by
inhibition of phosphodiesterase, which increases the concentration of cyclic adenosine
monophosphate; in concentrations that may be higher than those reached clinically, it also
inhibits the release of slow-reacting substance of anaphylaxis and histamine.

Indications
• Symptomatic relief or prevention of bronchial asthma and reversible
bronchospasm associated with chronic bronchitis and emphysema
• Unlabeled use of 2 mg/kg/day to maintain serum concentrations between 3 and 5
mcg/mL: Treatment of apnea and bradycardia of prematurity

Contraindications and cautions


• Contraindicated with hypersensitivity to any xanthines, peptic ulcer, active
gastritis, pregnancy (neonatal tachycardia, jitteriness, and withdrawal apnea),
underlying seizure disorders (unless receiving appropriate antiepileptic).
• Use cautiously with cardiac arrhythmias, acute myocardial injury, CHF, cor
pulmonale, severe hypertension, severe hypoxemia, renal or hepatic disease,
hyperthyroidism, alcoholism, labor (may inhibit uterine contractions), lactation,
status asthmaticus.

Available forms
Syrup—80, 150 mg/15 mL; elixir—80 mg/15 mL; oral solution—80 mg/15 mL; timed-
release capsules—50, 75, 100, 125, 130, 200, 250, 260, 300 mg; timed-release tablets—
100, 200, 250, 300, 400, 500 mg; injection in 5% dextrose—200, 400, 800 mg/container;
extended-release tablets—100, 400, 450 mg; sustained-release tablets—100, 300 mg;
controlled-release tablets—100, 200, 300 mg

Dosages
Maintain serum levels in the therapeutic range of 10–20 mcg/mL; base dosage on lean
body mass.
ADULTS
theophylline
• Acute symptoms requiring rapid theophyllinization in patients not receiving
theophylline:
Young adult smokers: Oral loading dose of 6 mg/kg followed by 3 mg/kg q 4 hr
for 3 doses. Maintenance, 3 mg/kg q 6 hr.
Otherwise healthy adult nonsmokers: Oral loading dose of 6 mg/kg, followed by
3 mg/kg q 6 hr for 2 doses. Maintenance, 3 mg/kg q 8 hr.
• Acute symptoms requiring rapid theophyllinization in patients receiving
theophylline: A loading dose is required; each 0.5 mg/kg PO administered as a
loading dose will result in about a 1 mcg/mL increase in serum theophylline.
Ideally, defer loading dose until serum theophylline determination is made.
Otherwise, base loading dose on clinical judgment and the knowledge that
2.5 mg/kg of a rapidly absorbed preparation will increase serum theophylline
levels by about 5 mcg/mL and is unlikely to cause dangerous adverse effects if the
patient is not experiencing theophylline toxicity before this dose; maintenance
doses are as above.
• Long-term therapy: Initial dose of 16 mg/kg/24 hr PO or 400 mg/24 hr, whichever
is less, in divided doses q 6–8 hr for immediate-release preparations or liquids, q
8–12 or 24 hr for timed-release preparations (consult manufacturer's
recommendations for specific dosage interval). Increase dosage based on serum
theophylline levels, or if these are unavailable, increase in 25% increments at 3-
day intervals as long as drug is tolerated or until maximum dose of 13 mg/kg/day
or 900 mg, whichever is less, is reached.
• Dosage adjustment based on serum theophylline levels during long-term therapy:
Serum theophylline levels < 10 mcg/mL are too low, levels of 10–20 mcg/mL are
within normal limits, and levels > 20 mcg/mL are too high.
Serum theophylline level 5–7.5 mcg/mL: Increase dose by about 25%, recheck
serum level; may need to increase dose.
Serum theophylline level 7.5–10 mcg/mL: Increase dose by 25%; may need to
give total daily dose at more frequent intervals; recheck at 6- to 12-mo intervals.
Serum theophylline level 10–20 mcg/mL: Maintain dosage; recheck level at 6- to
12-mo intervals.
Serum theophylline level 20–25 mcg/mL: Decrease doses by about 10%; recheck
level.
Serum theophylline level 25–30 mcg/mL: Skip next dose, and decrease subsequent
doses by about 25%; recheck levels.
Serum theophylline level > 30 mcg/mL: Skip next two doses, and decrease
subsequent doses by 50%; recheck level.
• Measurement of serum theophylline levels during chronic therapy: Measure
serum theophylline in blood sample drawn 1–2 hr after administration of
immediate-release preparations, 5–9 hr after administration of most sustained-
release products.
theophylline sodium glycinate (44.5%–47.3% theophylline)
330–660 mg PO q 6–8 hr after meals.
PEDIATRIC PATIENTS
< 6 mo: Not recommended.
< 6 yr: Timed-release products not recommended.
PEDIATRIC PATIENTS > 6 MO
theophylline
• Acute symptoms requiring rapid theophyllinization in patients not receiving
theophylline:
6 mo–9 yr: 6 mg/kg PO loading dose followed by 4 mg/kg q 4 hr for 3 doses.
Maintenance, 2 mg/kg q 8 hr.
9–16 yr: 6 mg/kg PO loading dose followed by 2 mg/kg q 4 hr for 3 doses.
Maintenance, 3 mg/kg q 6 hr
• Long-term therapy: Initial dose of 16 mg/kg/24 hr PO or 400 mg/24 hr, whichever
is less, in divided doses q 6–8 hr for immediate-release preparations or liquids, q
8–12 or 24 hr for timed-release preparations in children < 6 yr (consult
manufacturer's recommendations for specific dosage interval). Increase dosage
based on serum theophylline levels, or if these are unavailable, increase in 25%
increments at 3-day intervals as long as drug is tolerated or until maximum dose
given below is reached:
< 9 yr: Maximum daily dose, 24 mg/kg/day.
9–12 yr: Maximum daily dose, 20 mg/kg/day.
12–16 yr: Maximum daily dose, 18 mg/kg/day.
> 16 yr: Maximum daily dose, 13 mg/kg/day
theophylline sodium glycinate
1–3 yr: 55–110 mg q 6–8 hr PO after meals.
3–6 yr: 110–165 mg q 6–8 hr PO after meals.
6–12 yr: 220–330 mg q 6–8 hr PO after meals.
INFANTS < 6 MO
theophylline
Reduce initial and maintenance doses because elimination of theophylline appears to be
delayed in these patients. Loading dose is 1 mg/kg for each 2 mcg/mL serum
concentration desired.
Preterm infants: For maintenance, 1 mg/kg q 12 hr.
Term infants < 4 wk: For maintenance, 1–2 mg/kg q 12 hr.
Infants 4–8 wk: For maintenance, 1–2 mg/kg q 8 hr.
Infants > 8 wk: For maintenance, 1–3 mg/kg q 6 hr.
GERIATRIC PATIENTS OR IMPAIRED ADULTS
theophylline
Use caution, especially in elderly men, and in patients with cor pulmonale, CHF, or liver
disease.
• Acute symptoms requiring rapid theophyllinization in patients not receiving
theophylline:
Older patients and patients with cor pulmonale: Oral loading dose of 6 mg/kg,
followed by 2 mg/kg q 6 hr for 2 doses. For maintenance, 2 mg/kg q 8 hr.
Patients with CHF: Oral loading dose of 6 mg/kg, followed by 2 mg/kg q 8 hr for
2 doses. For maintenance, 1–2 mg/kg q 12 hr.

Pharmacokinetics
Route Onset Peak
Oral Varies 2 hr

Metabolism: Hepatic; T1/2: 3–15 hr (nonsmoker) or 4–5 hr (smokers)


Distribution: Crosses placenta; enters breast milk
Excretion: Urine

Adverse effects
• CNS: Irritability (especially children); restlessness, dizziness, muscle twitching,
seizures, severe depression, stammering speech; abnormal behavior characterized
by withdrawal, mutism and unresponsiveness alternating with hyperactive periods
• CV: Palpitations, sinus tachycardia, ventricular tachycardia, life-threatening
ventricular arrhythmias, circulatory failure
• GI: Loss of appetite, hematemesis, epigastric pain, gastroesophageal reflux during
sleep
• GU: Proteinuria, increased excretion of renal tubular cells and RBCs; diuresis
(dehydration), urinary retention in men with prostate enlargement
• Respiratory: Tachypnea, respiratory arrest
• Serum theophylline levels < 20 mcg/mL: Adverse effects uncommon.
• Serum theophylline levels > 20–25 mcg/mL: Nausea, vomiting, diarrhea,
headache, insomnia, irritability (75% of patients)
• Serum theophylline levels > 35 mcg/mL: Hyperglycemia, hypotension, cardiac
arrhythmias, tachycardia (> 10 mcg/mL in premature newborns); seizures, brain
damage, death
• Other: Fever, flushing, hyperglycemia, SIADH, rash, increased AST

Interactions
Drug-drug
• Increased effects and toxicity with cimetidine, erythromycin, troleandomycin,
ciprofloxacin, norfloxacin, ofloxacin, hormonal contraceptives, ticlopidine,
ranitidine
• Possibly increased effects with rifampin
• Increased serum levels and risk of toxicity in hypothyroid patients, decreased
levels in patients who are hyperthyroid; monitor patients on thioamines, thyroid
hormones for changes in serum levels as patients become euthyroid
• Increased cardiac toxicity with halothane
• Decreased effects in patients who are cigarette smokers (1–2 packs/day);
theophylline dosage may need to be increased 50%–100%
• Decreased effects with barbiturates, charcoal
• Decreased effects of phenytoins, benzodiazepines, and theophylline preparations
• Decreased effects of nondepolarizing neuromuscular blockers
• Mutually antagonistic effects of beta-blockers and theophylline preparations
Drug-food
• Theophylline elimination is increased by a low-carbohydrate, high-protein diet
and by charcoal-broiled beef
• Theophylline elimination is decreased by a high-carbohydrate, low-protein diet
• Food may alter bioavailability, absorption of timed-release theophylline
preparations; these may rapidly release their contents with food and cause
toxicity. Timed-release forms should be taken on an empty stomach
Drug-lab test
• Interference with spectrophotometric determinations of serum theophylline levels
by furosemide, phenylbutazone, probenecid, theobromine; coffee, tea, cola
beverages, chocolate, acetaminophen cause falsely high values
• Alteration in assays of uric acid, urinary catecholamines, plasma free fatty acids
Drug-alternative therapy
• Decreased effectiveness if taken with St. John's wort

Nursing considerations
Assessment
• History: Hypersensitivity to any xanthines; peptic ulcer, active gastritis; status
asthmaticus; cardiac arrhythmias, acute myocardial injury, CHF, cor pulmonale;
severe hypertension; severe hypoxemia; renal or hepatic disease;
hyperthyroidism; pregnancy, lactation
• Physical: Skin color, texture, lesions; reflexes, bilateral grip strength, affect; P,
auscultation, BP, perfusion; R, adventious sounds; bowel sounds, normal output;
frequency, voiding pattern, normal urinary output; ECG; EEG; thyroid, liver,
kidney function tests

Interventions
• Caution patient not to chew or crush enteric-coated timed-release preparations.
• Give immediate release, liquid dosage forms with food if GI effects occur.
• Do not give timed-release preparations with food; these should be given on an
empty stomach, 1 hr before or 2 hr after meals.
• Advise patients that this drug should not be used during pregnancy; using barrier
contraceptives is recommended.
• Monitor results of serum theophylline level determinations carefully, and reduce
dosage if serum levels exceed therapeutic range of 10–20 mcg/mL.
• Monitor carefully for clinical signs of adverse effects, particularly if serum
theophylline levels are not available.
• Keep diazepam readily available to treat seizures.

Teaching points
• Take this drug exactly as prescribed. If a timed-release product is prescribed, take
it on an empty stomach, 1 hr before or 2 hr after meals. Do not chew or crush
timed-release preparations; it may be necessary for you to take this drug around
the clock for adequate control of asthma attacks.
• Avoid excessive intake of coffee, tea, cocoa, cola beverages, chocolate. These
contain theophylline-related substances that may increase your side effects.
• Smoking cigarettes or other tobacco products may markedly influence the effects
of theophylline. It is preferable not to smoke while you are taking this drug.
Notify your health care provider if you change your smoking habits while you are
taking this drug; it may be necessary to change your drug dosage.
• Have frequent blood tests to monitor drug effects and ensure safe and effective
dosage.
• Do not use this drug during pregnancy; using barrier contraceptives is advised.
• These side effects may occur: Nausea, loss of appetite (take drug with food; if
taking immediate-release or liquid dosage forms); difficulty sleeping, depression,
emotional lability.
• Report nausea, vomiting, severe GI pain, restlessness, seizures, irregular
heartbeat.

Adverse effects in Italic are most common; those in Bold are life-threatening.