THEOPHYLLINE

(thee-off'i-lin)

Elixophyllin, Lanophyllin, PMS Theophylline

, Pulmopylline

, Theo-24, Theolair, Theophylline Ethylenediamine, Theospan-SR, Uniphyl
Classifications: bronchodilator (respiratory smooth muscle relaxant); xanthine;
Therapeutic: bronchodilator
Pregnancy Category: C

Availability

100 mg, 125 mg, 200 mg, 250 mg, 300 mg tablets; 100 mg, 200 mg capsules; 80 mg/15 mL, 150 mg/15 mL liquid; 100 mg, 200 mg, 250 mg, 300 mg, 450 mg, 500 mg, 600 mg sustained release tablets; 50 mg, 75 mg, 100 mg, 125 mg, 200 mg, 250 mg, 260 mg, 300 mg sustained release capsules; 200 mg, 400 mg, 800 mg injection

Action

Xanthine derivative that relaxes smooth muscle by direct action, particularly of bronchi and pulmonary vessels, and stimulates medullary respiratory center with resulting increase in vital capacity.

Therapeutic Effect

Effective for relief of bronchospasm in asthmatics, chronic bronchitis, and emphysema.

Uses

Prophylaxis and symptomatic relief of bronchial asthma, as well as bronchospasm associated with chronic bronchitis and emphysema. Also used for emergency treatment of paroxysmal cardiac dyspnea and edema of CHF.

Unlabeled Uses

Treatment of apnea and bradycardia of premature infants and to reduce severe bronchospasm associated with cystic fibrosis and acute descending respiratory infection.

Contraindications

Hypersensitivity to xanthines; coronary artery disease or angina pectoris when myocardial stimulation might be harmful; severe renal or liver impairment; pregnancy (category C).

Cautious Use

Compromised cardiac or circulatory function, hypertension; acute pulmonary edema; multiple organ failure; CHF; hyperthyroidism; peptic ulcer; prostatic hypertrophy; glaucoma; diabetes mellitus; older adults, children, and neonates.

Route & Dosage

Bronchospasm
Adult/Child: PO/IV Loading Dose 5 mg/kg
Adult: PO/IV Maintenance Dose* Nonsmoker, 0.4 mg/kg/h; Smoker, 0.6 mg/kg/h; with CHF or cirrhosis, 0.2 mg/kg/h
Child: PO/IV Maintenance Dose* 1–9 y, 0.8 mg/kg/h; 10–12 y, 0.6 mg/kg/h
Infant: PO/IV Maintenance Dose* 0.5–0.7 mg/kg/h
Neonate: PO/IV Maintenance Dose* 0.13 mg/kg/h

*IV by continuous infusion, PO divided q6h (immediate release) or q8–12h (sustained release)

Obesity
Dose based on IBW.

Administration

Note: All doses based on ideal body weight.

Oral

Wait 4–6 h after the last IV dose, when switching from IV to oral dosing.
Give with a full glass of water and after meals to minimize gastric irritation.
Give sustained release forms and enteric-coated tablets whole. Chewable tablets must be chewed thoroughly before swallowing. Sustained release granules from capsules can be taken on an empty stomach or mixed with applesauce or water.
Note: Timing of dose is critical. Be certain patient understands necessity to adhere to the correct intervals between doses.

Intravenous

Give prediluted solutions at a rate not to exceed 20 mg/min.

PREPARE: Direct/Intermittent: Dilute, as needed, to a maximum concentration of 20 mg/mL. IV Infusion: Typically diluted to 0.8 mg/mL with D5W.

ADMINISTER: Direct/Intermittent: Typically infused over 20–30 min. DO NOT EXCEED 20 mg/min. IV Infusion: Infuse at a rate based on patient's weight.

INCOMPATIBILITIES Solution/additive: Ascorbic acid, ceftriaxone, cimetidine, hetastarch. Y-site: Hetastarch, phenytoin.

Adverse Effects (≥1%)

CNS: Stimulation (irritability, restlessness, insomnia, dizziness, headache, tremor, hyperexcitability, muscle twitching, drug-induced seizures). CV: Palpitation, tachycardia, extrasystoles, flushing, marked hypotension, circulatory failure. GI: Nausea, vomiting, anorexia, epigastric or abdominal pain, diarrhea, activation of peptic ulcer. Urogenital: Transient urinary frequency, albuminuria, kidney irritation. Respiratory: Tachypnea, respiratory arrest. Body as a Whole: Fever, dehydration.

Diagnostic Test Interference

False-positive elevations of serum uric acid (Bittner or colorimetric methods). Probenecid may cause false high serum theophylline readings, and spectrophotometric methods of determining serum theophylline are affected by a furosemide, sulfathiazole, phenylbutazone, probenecid, theobromine.

Interactions

Drug: Increases lithium excretion, lowering lithium levels; cimetidine, high-dose allopurinol (600 mg/d), tacrine, quinolones, macrolide antibiotics, and zileuton can significantly increase theophylline levels; tobacco use significantly decreases levels. Herbal: St. John's wort may decrease theophylline efficacy. Daidzein (in soy), black pepper increase serum concentrations and adverse effects.

Pharmacokinetics

Absorption: Most products are 100% absorbed from GI tract. Peak: IV 30 min; uncoated tablet 1 h; sustained release 4–6 h. Duration: 4–8 h; varies with age, smoking, and liver function. Distribution: Crosses placenta. Metabolism: Extensively in liver. Elimination: Parent drug and metabolites excreted by kidneys; excreted in breast milk.

Nursing Implications

Assessment & Drug Effects

Monitor vital signs. Improvement in respiratory status is the expected outcome.
Observe and report early signs of possible toxicity: Anorexia, nausea, vomiting, dizziness, shakiness, restlessness, abdominal discomfort, irritability, palpitation, tachycardia, marked hypotension, cardiac arrhythmias, seizures.
Monitor for tachycardia, which may be worse in patients with severe cardiac disease. Conversely, theophylline toxicity may be masked in patients with tachycardia.
Lab tests: Monitor plasma level of theophylline. Be aware that therapeutic plasma level ranges from 10–20 mcg/mL (a narrow therapeutic range). Levels exceeding 20 mcg/mL are associated with toxicity.
Monitor drug levels closely in heavy smokers. Cigarette smoking induces hepatic microsomal enzyme activity, decreasing serum half-life and increasing body clearance of theophylline. An increase of dosage from 50–100% is usual in heavy smokers.
Monitor plasma drug level closely in patients with heart failure, kidney or liver dysfunction, alcoholism, high fever. Plasma clearance of xanthines may be reduced.
Take necessary safety precautions and forewarn older adult patients of possible dizziness during early therapy.
Monitor patients on sustained release preparations for S&S of overdosage. Continued slow absorption leads to high plasma concentrations for a prolonged period.
Note: Neonates of mothers using this drug have exhibited slight tachycardia, jitteriness, and apnea.
Monitor CLOSELY for adverse effects in infants <6 mo and prematures; theophylline metabolism is prolonged as is the half-life in this age group.

Patient & Family Education

Take medication at the same time every day.
Avoid charcoal-broiled foods (high in polycyclic carbon content); may increase theophylline elimination and reduce the half-life as much as 50%.
Limit caffeine intake because it may increase incidence of adverse effects.
Cigarette smoking may significantly lower theophylline plasma concentration.
Be aware that a low-carbohydrate, high-protein diet increases theophylline elimination, and a high-carbohydrate, low-protein diet decreases it.
Drink fluids liberally (2000–3000 mL/d) if not contraindicated to decrease viscosity of airway secretions.
Avoid self-dosing with OTC medications, especially cough suppressants, which may cause retention of secretions and CNS depression.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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