Interactions with herbs
Cayenne
St. John's Wort
  Interactions with supplements
Vitamin B6 (Pyridoxine)
Look Up > Drugs > Theophylline
Theophylline
Pronunciation
U.S. Brand Names
Generic Available
Canadian Brand Names
Synonyms
Pharmacological Index
Use
Pregnancy Risk Factor
Contraindications
Warnings/Precautions
Adverse Reactions
Overdosage/Toxicology
Drug Interactions
Mechanism of Action
Pharmacodynamics/Kinetics
Usual Dosage
Dietary Considerations
Dental Health: Local Anesthetic/Vasoconstrictor Precautions
Dental Health: Effects on Dental Treatment
Patient Information
Nursing Implications
Dosage Forms

Pronunciation
(thee OF i lin)

U.S. Brand Names
Aerolate III®; Aerolate JR®; Aerolate SR®; Aquaphyllin®; Asmalix®; Elixomin®; Elixophyllin®; Quibron®-T; Quibron®-T/SR; Respbid®; Slo-bid™; Slo-Phyllin®; Sustaire®; Theo-24®; Theobid®; Theochron®; Theoclear-80®; Theoclear® L.A.; Theo-Dur®; Theolair™; Theo-Sav®; Theospan®-SR; Theostat-80®; Theovent®; Theo-X®; T-Phyl®; Uni-Dur®; Uniphyl®

Generic Available

Yes


Canadian Brand Names
Apo®-Theo LA; Phyllocontin®; Pulmophylline

Synonyms
Theophylline Anhydrous

Pharmacological Index

Bronchodilator; Theophylline Derivative


Use

Treatment of symptoms and reversible airway obstruction due to chronic asthma, chronic bronchitis, or COPD


Pregnancy Risk Factor

C


Contraindications

Hypersensitivity to theophylline or any component


Warnings/Precautions

If a patient develops signs and symptoms of theophylline toxicity (eg, persistent, repetitive vomiting), a serum theophylline level should be measured and subsequent doses held. Due to potential saturation of theophylline clearance at serum levels in or (in some patients) less than the therapeutic range, dosage adjustment should be made in small increments (maximum: 25%). Due to wider interpatient variability, theophylline serum level measurements must be used to optimize therapy and prevent serious toxicity. Use with caution in patients with peptic ulcer, hyperthyroidism, seizure disorders, hypertension, and patients with cardiac arrhythmias (excluding bradyarrhythmias).


Adverse Reactions

Adverse reactions/theophylline serum level: (Adverse effects do not necessarily occur according to serum levels. Arrhythmia and seizure can occur without seeing the other adverse effects).

15-25 mcg/mL: GI upset, diarrhea, nausea/vomiting, abdominal pain, nervousness, headache, insomnia, agitation, dizziness, muscle cramp, tremor

25-35 mcg/mL: Tachycardia, occasional PVC

>35 mcg/mL: Ventricular tachycardia, frequent PVC, seizure

Uncommon at serum theophylline concentrations less than or equal to 20 mcg/mL

1% to 10%:

Cardiovascular: Tachycardia

Central nervous system: Nervousness, restlessness

Gastrointestinal: Nausea, vomiting

<1% (Limited to important or life-threatening symptoms): Insomnia, irritability, seizures, tremor


Overdosage/Toxicology

Symptoms of overdose include nausea, vomiting, insomnia, irritability, tachycardia, seizures, tonic-clonic seizures, insomnia, and circulatory failure. If seizures have not occurred, induce vomiting; ipecac syrup is preferred. Do not induce emesis in the presence of impaired consciousness. Repeated doses of charcoal have been shown to be effective in enhancing the total body clearance of theophylline. Do not repeat charcoal doses if an ileus is present. Charcoal hemoperfusion may be considered if serum theophylline levels exceed 40 mcg/mL, the patient is unable to tolerate repeat oral charcoal administrations, or if severe toxic symptoms are present. Clearance with hemoperfusion is better than clearance from hemodialysis. Administer a cathartic, especially if sustained release agents were used. Phenobarbital administered prophylactically may prevent seizures.


Drug Interactions

Decreased effect/increased toxicity: Changes in diet may affect the elimination of theophylline; charcoal-broiled foods may increase elimination, reducing half-life by 50%.

Decreased theophylline level

Aminoglutethimide, barbiturates, carbamazepine, charcoal, high protein/low carbohydrate diet, hydantoins, isoniazid, I.V. isoproterenol, ketoconazole, loop diuretics, phenobarbital, phenytoin, rifampin, smoking (cigarettes, marijuana), sulfinpyrazone, sympathomimetics

Increased theophylline level

Allopurinol (>600 mg/day), beta-blockers, calcium channel blockers, carbamazepine, CHF, cimetidine, ciprofloxacin, cor pulmonale, corticosteroids, disulfiram, ephedrine, erythromycin, fever/viral illness, hepatic cirrhosis, influenza virus vaccine, interferon, isoniazid, loop diuretics, macrolides, mexiletine, oral contraceptives, propranolol, quinolones, thiabendazole, thyroid hormones, troleandomycin


Mechanism of Action

Causes bronchodilatation, diuresis, CNS and cardiac stimulation, and gastric acid secretion by blocking phosphodiesterase which increases tissue concentrations of cyclic adenine monophosphate (cAMP) which in turn promotes catecholamine stimulation of lipolysis, glycogenolysis, and gluconeogenesis and induces release of epinephrine from adrenal medulla cells


Pharmacodynamics/Kinetics

Absorption: Oral: Up to 100% absorbed depending upon formulation used

Half-life: Highly variable and dependent upon age, liver function, cardiac function, lung disease, and smoking history


Usual Dosage

Use ideal body weight for obese patients

Children:

6 weeks to 6 months: 0.5 mg/kg/hour

6 months to 1 year: 0.6-0.7 mg/kg/hour

Children >1 year and Adults:

Treatment of acute bronchospasm: I.V.: Loading dose (in patients not currently receiving aminophylline or theophylline): 6 mg/kg (based on aminophylline) given I.V. over 20-30 minutes; administration rate should not exceed 25 mg/minute (aminophylline).

After the loading dose, refer to the following for approximate I.V. theophylline dosages (equivalent hydrous aminophylline dosage indicated in parentheses):

Infants 6 weeks to 6 months:

0.5 mg/kg/hour for next 12 hours

Children 6 months to 1 year:

0.6-0.7 mg/kg/hour for next 12 hours

Children 1-9 years:

0.95 mg/kg/hour (1.2 mg/kg/hour) for next 12 hours; 0.79 mg/kg/hour (1 mg/kg/hour) dosage after 12 hours

Children 9-16 years and young adult smokers:

0.79 mg/kg/hour (1 mg/kg/hour) for next 12 hours; 0.63 mg/kg/hour (0.8 mg/kg/hour) dosage after 12 hours

Healthy, nonsmoking adults:

0.55 mg/kg/hour (0.7 mg/kg/hour) for next 12 hours; 0.39 mg/kg/hour (0.5 mg/kg/hour) dosage after 12 hours

Older patients and patients with cor pulmonale:

0.47 mg/kg/hour (0.6 mg/kg/hour) for next 12 hours; 0.24 mg/kg/hour (0.3 mg/kg/hour) dosage after 12 hours

Patients with congestive heart failure or liver failure:

0.39 mg/kg/hour (0.5 mg/kg/hour) for next 12 hours; 0.08-0.16 mg/kg/hour (0.1-0.2 mg/kg/hour) dosage after 12 hours

Approximate I.V. maintenance dosages are based upon continuous infusions; bolus dosing (often used in children <6 months of age) may be determined by multiplying the hourly infusion rate by 24 hours and dividing by the desired number of doses/day. See the following:

Maintenance dose for acute symptoms:

Premature infant or newborn to 6 weeks (for apnea/bradycardia):

Oral theophylline dose: 4 mg/kg/day

I.V. aminophylline dose: 5 mg/kg/day

6 weeks to 6 months:

Oral theophylline dose: 10 mg/kg/day

I.V. aminophylline dose: 12 mg/kg/day or continuous I.V. infusion*

Infants 6 months to 1 year:

Oral theophylline dose: 12-18 mg/kg/day

I.V. aminophylline dose: 15 mg/kg/day or continuous I.V. infusion*

Children 1-9 years:

Oral theophylline dose: 20-24 mg/kg/day

I.V. aminophylline dose: 1 mg/kg/hour

Children 9-12 years, and adolescent daily smokers of cigarettes or marijuana, and otherwise healthy adult smokers <50 years:

Oral theophylline dose: 16 mg/kg/day

I.V. aminophylline dose: 0.9 mg/kg/hour

Adolescents 12-16 years (nonsmokers):

Oral theophylline dose: 13 mg/kg/day

I.V. aminophylline dose: 0.7 mg/kg/hour

Otherwise healthy nonsmoking adults (including elderly patients):

Oral theophylline dose: 10 mg/kg/day (not to exceed 900 mg/day)

I.V. aminophylline dose: 0.5 mg/kg/hour

Cardiac decompensation, cor pulmonale and/or liver dysfunction

Oral theophylline dose: 5 mg/kg/day (not to exceed 400 mg/day)

I.V. aminophylline dose: 0.25 mg/kg/hour I.V.

*For continuous I.V. infusion, divide total daily dose by 24 = mg/kg/hour.

Dosage should be adjusted according to serum level measurements during the first 12- to 24-hour period. See the following:

Theophylline level within normal limits:

10-20 mcg/mL: Maintain dosage if tolerated.

Recheck serum theophylline concentration at 6- to 12-month intervals.*

Theophylline level too high:

20-25 mcg/mL: Decrease doses by about 10%.

Recheck serum theophylline concentration after 3 days and then at 6- to 12-month intervals.*

25-30 mcg/mL: Skip next dose and decrease subsequent doses by about 25%.

Recheck serum theophylline.

>30 mcg/mL: Skip next 2 doses and decrease subsequent doses by 50%.

Recheck serum theophylline.

Theophylline level too low:

7.5-10 mcg/mL: Increase dose by about 25%**

Recheck serum theophylline concentration after 3 days and then at 6- to 12-month intervals.*

5-7.5 mcg/mL: Increase dose by about 25% to the nearest dose increment ** and recheck serum theophylline for guidance in further dosage adjustment (another increase will probably be needed, but this provides a safety check).

*Finer adjustments in dosage may be needed for some patients.

**Dividing the daily dose into 3 doses administered at 8-hour intervals may be indicated if symptoms occur repeatedly at the end of a dosing interval.

(From Weinberger M and Hendeles L, "Practical Guide to Using Theophylline," J Resp Dis, 1981, 2:12-27.)

Oral theophylline: Initial dosage recommendation: Loading dose (to achieve a serum level of about 10 mcg/mL; loading doses should be given using a rapidly absorbed oral product not a sustained release product):

If no theophylline has been administered in the previous 24 hours: 4-6 mg/kg theophylline

If theophylline has been administered in the previous 24 hours: administer 1/2 loading dose or 2-3 mg/kg theophylline can be given in emergencies when serum levels are not available

On the average, for every 1 mg/kg theophylline given, blood levels will rise 2 mcg/mL

Ideally, defer the loading dose if a serum theophylline concentration can be obtained rapidly. However, if this is not possible, exercise clinical judgment. If the patient is not experiencing theophylline toxicity, this is unlikely to result in dangerous adverse effects.

Oral theophylline dosage for bronchial asthma (by age):

<1 year:

Initial 3 days and second 3 days: 0.2 x (age in weeks) + 5 = mg/kg/24 hours of theophylline

Steady-state maintenance: 0.3 x (age in weeks) + 8 = mg/kg/24 hours of theophylline

1-9 years:

Initial 3 days: 16 mg/kg/24 hours of theophylline, up to a maximum of 400 mg/24 hours

Second 3 days: 20 mg/kg/24 hours of theophylline

Steady-state maintenance: 22 mg/kg/24 hours of theophylline

9-12 years:

Initial 3 days: 16 mg/kg/24 hours of theophylline, up to a maximum of 400 mg/24 hours

Second 3 days: 16 mg/kg/24 hours of theophylline, up to a maximum of 600 mg/24 hours

Steady-state maintenance: 20 mg/kg/24 hours of theophylline, up to a maximum of 800 mg/24 hours

12-16 years:

Initial 3 days: 16 mg/kg/24 hours of theophylline, up to a maximum of 400 mg/24 hours

Second 3 days: 16 mg/kg/24 hours of theophylline, up to a maximum of 600 mg/24 hours

Steady-state maintenance: 18 mg/kg/24 hours of theophylline, up to a maximum of 900 mg/24 hours

Adults:

Initial 3 days: 400 mg/24 hours

Second 3 days: 600 mg/24 hours

Steady-state maintenance: 900 mg/24 hours

Increasing dose: The dosage may be increased in approximately 25% increments at 2- to 3-day intervals so long as the drug is tolerated or until the maximum dose is reached

Maintenance dose: In children and healthy adults, a slow-release product can be used; the total daily dose can be divided every 8-12 hours


Dietary Considerations

Avoid drinking or eating large quantities of caffeine-containing beverages or food; avoid extremes of dietary protein and carbohydrate intake; limit charcoal-broiled foods; should be administered with water 1 hour before or 2 hours after meals


Dental Health: Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions


Dental Health: Effects on Dental Treatment

Prescribe erythromycin products with caution to patients taking theophylline products. Erythromycin will delay the normal metabolic inactivation of theophyllines leading to increased blood levels; this has resulted in nausea, vomiting, and CNS restlessness. Azithromycin does not cause these effects in combination with theophylline products.


Patient Information

Take exactly as directed; do not exceed recommended dosage. Avoid smoking (smoking may interfere with drug absorption as well as exacerbate condition for which medication is prescribed). If you are smoking when dosage is prescribed; inform prescriber if you stop smoking (dosage may need to be adjusted to prevent toxicity). Preferable to take on empty stomach (1 hour before or 2 hours after meals), with a full glass of water. Do not chew of crush sustained release forms; capsules may be opened and contents sprinkled on soft food (do not chew beads). Avoid dietary stimulants (eg, caffeine, tea, colas, or chocolate - may increase adverse side effects). Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience nausea, vomiting, or lose of appetite (frequent small meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report acute insomnia or restlessness, chest pain or rapid heartbeat, emotional lability or agitation, muscle tremors or cramping, acute headache, abdominal pain and cramping, blackened stool, or worsening of respiratory condition. Pregnancy precautions: Inform prescriber if you are or intend to be pregnant.


Nursing Implications

Do not crush Theo-Dur® tablets; tablets may only be cut in half

Monitor heart rate, CNS effects (insomnia, irritability); respiratory rate (COPD patients often have resting controlled respiratory rates in low 20s), serum theophylline level, arterial or capillary blood gases (if applicable)

Stability: Store injection at room temperature; protect from heat and from freezing; use only clear solutions; stability of parenteral admixture at room temperature (25°C): 30 days


Dosage Forms

Capsule:

Immediate release (Bronkodyl®, Elixophyllin®): 100 mg, 200 mg

Timed release:

8-12 hours (Aerolate®): 65 mg [III]; 130 mg [JR], 260 mg [SR]

8-12 hours (Slo-bid™): 50 mg, 75 mg, 100 mg, 125 mg, 200 mg, 300 mg

8-12 hours (Slo-Phyllin® Gyrocaps®): 60 mg, 125 mg, 250 mg

12 hours (Theobid® Duracaps®): 260 mg

12 hours (Theoclear® L.A.): 130 mg, 260 mg

12 hours (Theospan®-SR): 130 mg, 260 mg

12 hours (Theovent®): 125 mg, 250 mg

24 hours (Theo-24®): 100 mg, 200 mg, 300 mg

Elixir (Asmalix®, Elixomin®, Elixophyllin®, Lanophyllin®): 80 mg/15 mL (15 mL, 30 mL, 480 mL, 4000 mL)

Infusion, in D5W: 0.4 mg/mL (1000 mL); 0.8 mg/mL (500 mL, 1000 mL); 1.6 mg/mL (250 mL, 500 mL); 2 mg/mL (100 mL); 3.2 mg/mL (250 mL); 4 mg/mL (50 mL, 100 mL);

Solution, oral:

Theolair™: 80 mg/15 mL (15 mL, 18.75 mL, 30 mL, 480 mL)

Syrup:

Aquaphyllin®, Slo-Phyllin®, Theoclear-80®, Theostat-80®: 80 mg/15 mL (15 mL, 30 mL, 500 mL)

Accurbron®: 150 mg/15 mL (480 mL)

Tablet: Immediate release:

Slo-Phyllin®: 100 mg, 200 mg

Theolair™: 125 mg, 250 mg

Quibron®-T: 300 mg

Tablet:

Controlled release (Theo-X®): 100 mg, 200 mg, 300 mg

Timed release:

12-24 hours: 100 mg, 200 mg, 300 mg, 450 mg

8-12 hours (Quibron®-T/SR): 300 mg

8-12 hours (Respbid®): 250 mg, 500 mg

8-12 hours (Sustaire®): 100 mg, 300 mg

8-12 hours (T-Phyl®): 200 mg

12-24 hours (Theochron®): 100 mg, 200 mg, 300 mg

8-24 hours (Theo-Dur®): 100 mg, 200 mg, 300 mg, 450 mg

8-24 hours (Theo-Sav®): 100 mg, 200 mg, 300 mg

24 hours (Theolair™-SR): 200 mg, 250 mg, 300 mg, 500 mg

24 hours (Uni-Dur®): 400 mg, 600 mg

24 hours (Uniphyl®): 400 mg


Copyright © 1978-2000 Lexi-Comp Inc. All Rights Reserved