Theophyllines

Symptomatic management or prevention of asthma and reversible bronchospasm associated with COPD, including chronic bronchitis and emphysema.211 212 221 222 223 226 229 230 231 a d e f g h i j m n

Aminophylline and dyphylline generally share the same indications as theophylline.a d h i

Bronchospasm in Asthma

Symptomatic management or prevention of bronchospasm in patients with reversible, obstructive airway disease (e.g., asthma).211 212 221 222 223 226 227 228 229 230 231 a d e f g h i k l m n

In the stepped-care approach recommended in current asthma management guidelines,m n a selective, short-acting, inhaled β2-adrenergic agonist is used as needed to control acute asthma symptoms in all patients; use of such a β2-adrenergic agonist alone generally sufficient for patients with intermittent asthma.211 212 213 214 215 m n

Consider short-acting theophylline (if extended-release theophylline not already used) as less-effective alternative to short-acting inhaled β2-agonist for relief of acute asthma symptoms (i.e., as temporary measure if inhaled or parenteral β2-agonist not available); theophylline has slower onset of action and greater risk of adverse effects.212 226 229 f i n

Consider extended-release theophylline as less-effective alternative to low-dose inhaled corticosteroid for long-term control and prevention of symptoms in adults and children ≥5 years of age with mild persistent asthma.211 212 m n Also consider extended-release theophylline as less-effective alternative to long-acting inhaled β2-adrenergic agonist for use as adjunct to inhaled corticosteroid therapy in adults and children ≥5 years of age with moderate persistent asthma.211 212 f i m n Some clinicians do not recommend use of extended-release theophylline as alternative or add-on long-term control therapy in children <5 years of age with mild persistent asthma.211 m (See Pediatric Use under Cautions.)

Consider extended-release theophylline as add-on therapy in adults and children ≥5 years of age with severe persistent asthma inadequately controlled by high dosages of an orally inhaled corticosteroid and a long-acting inhaled β2-adrenergic agonist.212 m n

IV theophylline and aminophylline are FDA-labeled for use as an adjunct to inhaled β2-adrenergic agonists and systemic corticosteroids in the treatment of acute asthma exacerbations.227 228 k l However, some experts do not recommend theophylline derivatives for treatment of severe, acute asthma exacerbations because such therapy does not appear to provide additional benefit to optimal therapy with inhaled short-acting β2-adrenergic agonists and is associated with an increased risk of adverse effects.m Other experts suggest consideration of IV theophylline or aminophylline as add-on therapy for treatment of severe, acute exacerbations of asthma in hospitalized patients not responding adequately to oxygen, inhaled short-acting β2-adrenergic agonists, and systemic corticosteroids.212

Dyphylline not indicated for the management of status asthmaticus.230 231 d e h

Bronchospasm in COPD

Management of symptoms and reversible airflow obstruction in patients with COPD.221 222 223 226 227 228 230 231 d e f g h i

Consider extended-release theophylline in patients with stable COPD as less-preferred alternative to inhaled bronchodilators (e.g., long-acting β2-adrenergic agonist, long-acting anticholinergic agent [e.g., tiotropium]) depending on individual response/tolerance and availability.j

Some experts consider extended-release theophylline as add-on therapy in patients with severe symptoms of COPD inadequately controlled with other therapy (long-acting β2-adrenergic agonist, long-acting anticholinergic bronchodilator [e.g., tiotropium], and inhaled corticosteroid).q

IV theophylline and aminophylline are FDA-labeled for use as an adjunct to inhaled β2-adrenergic agonists and systemic corticosteroids for acute exacerbations of COPD.227 228 k l However, such use considered controversial by some experts because of modest/inconsistent response and frequent adverse effects;219 j q use suggested in patients with severe exacerbations who have inadequate response to short-acting bronchodilators (e.g., inhaled β2-adrenergic agonist).k l j

Other Uses

Has been used to relieve periodic apnea and increase arterial blood pH in patients with Cheyne-Stokes respiration†.a o r

Has been used to stimulate respiration and myocardial contractility associated with apnea in infants†.a p

Not for treatment of coronary thrombosis.a

General

• Extended-release preparations indicated in patients with relatively continuous or frequently recurring asthma symptoms; may be particularly useful in patients in whom theophylline elimination is rapid (e.g., children, adult smokers).221 222 223 a g

• Do not use extended-release dosage forms for treatment of acute bronchospasm.221 222 223 a g

Monitoring Serum Theophylline Concentrations

• Base dosage adjustments on peak serum theophylline concentrations along with patient response and tolerance to drug.212 221 222 223 226 227 228 229 a f g i k l

• Therapeutic serum concentrations of 10–15 mcg/mL generally produce bronchodilation without serious risk of toxicity, although lower concentrations may provide beneficial effects in some patients with mild asthma and may be effective for neonatal apnea.221 222 223 226 227 228 229 a f g i k l Some experts recommend maintaining serum theophylline concentrations in the range of 5–15 mcg/mL during long-term therapy.211 m Toxicity may occur with serum concentrations >20 mcg/mL.221 222 223 226 227 228 229 a f g i k l

• Measure serum concentrations (1) when initiating therapy to guide final dosage adjustments after titration; (2) before increasing dosage in patients with persistent symptoms; (3) if manifestations of toxicity are present; and (4) in case of new or worsening illness or a change in treatment regimen that alters theophylline clearance (e.g., fever >39°C for ≥24 hours, hepatitis, addition or discontinuance of interacting drugs).221 222 223 226 227 228 229 f g i k l Prior to increasing dosage based on low serum concentration, consider whether blood sample was obtained at an appropriate time and whether patient adhered to dosing regimen.223 226 g

• To guide dosing after oral administration, obtain a blood sample at the time of the expected steady-state peak serum concentration, generally achieved 3 days after initiating therapy or a change in dosage provided no doses have been missed or added and none have been taken at unequal intervals.221 222 223 229 f g i

• After steady state achieved, measure serum theophylline concentration 1–2 hours after administration of an oral solution or uncoated immediate-release tablet226 229 f i or 4–12 hours (depending on the particular preparation; consult manufacturer's labeling) after administration of an extended-release preparation to obtain estimate of peak serum concentration.222 223 g

• To guide dosing decisions after IV administration, measure serum concentration 30 minutes after completion of IV loading dose to determine whether concentration is <10 mcg/mL (indicating need for additional loading dose) or >20 mcg/mL (indicating need for delay in initiating maintenance IV infusion).227 228 k l

• Do not increase IV dosage for acute exacerbation of symptoms unless serum theophylline concentrations are <10 mcg/mL.228 k

Administration

Usually, administer theophyllines (e.g., theophylline, aminophylline) and dyphylline orally as a tablet, capsule, or solution;221 222 223 226 229 230 231 d e f g h i may also administer theophylline or aminophylline by slow IV injection or slow IV infusion.227 228 a k l (See IV Administration under Dosage and Administration.)

Aminophylline has been administered by IM injection†; however, IM administration may cause intense local pain and is not recommended.a

Oral Administration

Immediate-Release Preparations

Administer conventional oral preparations with a full glass of water on an empty stomach 30–60 minutes before meals or 2 hours after meals for faster absorption and to minimize GI irritation.a

Food or antacids do not cause clinically important changes in the absorption of theophylline from immediate-release dosage forms.222 f

Extended-Release Preparations

Administration of some extended-release preparations with food may affect the rate and/or extent of drug absorption.221 222 223 a g Administer extended-release preparations in a consistent manner, either always with or always without food; follow manufacturer’s recommendations for specific preparations.222 223 a g

Administer extended-release preparations every 8, 12, or 24 hours (depending on particular preparations; consult manufacturer's labeling) to provide therapeutic serum theophylline concentrations in patients who have relatively continuous or recurrent symptoms.222 223 a g

Do notcrush or chew extended-release preparations; patients who have difficulty swallowing solid dosage forms may mix contents of some extended-release capsules with soft food and swallow without chewing.222 223 a g May split scored, extended-release tablets of Uniphyl for once-daily dosing.223 May also split scored, extended-release Theochron tablets for twice-daily dosing but not for once-daily dosing.g

Administer extended-release (Theo-24) capsules at same time in the morning when given once daily; evening administration not recommended.222 In patients who require twice-daily dosing, administer second dose 10–12 hours after morning dose and before evening meal.222 In patients with more rapid metabolism (e.g., young individuals, smokers, some nonsmoking adults), administer smaller doses more frequently (e.g., twice daily) to avoid breakthrough symptoms resulting from low trough concentrations.222 223

Administer extended-release (Uniphyl) tablets at same time each day, either morning or evening.223 Consider that peak and trough serum theophylline concentrations produced by once-daily dosing may vary from those produced by the previous product and/or regimen.223

NG Tubing Administration

May pour contents of extended-release capsules down feeding tube; however, do not crush drug pellets.b

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer aminophylline and theophylline solutions undiluted by slow IV injection or, preferably, diluted in large-volume parenteral fluids by slow IV infusion.227 228 k l

For single-dose administration; solutions do not contain bacteriostatic or antimicrobial agents.k l Discard unused portions.k l

Dilution

Prepare aminophylline solutions for IV infusion by diluting an appropriate volume of a commercially available aminophylline injection or pharmacy bulk package injection in a compatible IV infusion fluid.a l

Rate of Administration

Administer slowly IV over 30 minutes (≤20 mg/minute);227 228 if acute adverse effects occur during infusion, stop infusion for 5–10 minutes or administer at a slower rate.228 a

After therapeutic serum theophylline concentration is attained, administer maintenance dosage by continuous IV infusion; infusion rate depends on patient's age, clinical characteristics, pharmacokinetic parameters, and target serum theophylline concentration (generally 10 mcg/mL).227 228

In patients with cardiac decompensation, cor pulmonale, liver dysfunction, sepsis with multi-organ failure, shock, or those taking drugs that markedly reduce theophylline clearance, do not exceed a maximum rate of 17 mg/hour unless serum concentrations are monitored at 24-hour intervals.227 228

Dosage

Available as aminophylline anhydrous, aminophylline hydrous, and theophylline monohydrate; dosage of theophylline and aminophylline preparations is expressed in terms of anhydrous theophylline.a i

Anhydrous Theophylline Content in Theophylline Derivativesa

Drug	Anhydrous Theophylline Content
Aminophylline anhydrous	85.7% (±1.7%)
Aminophylline hydrous	78.9% (±1.6%)
Theophylline monohydrate	90.7% (±1.1%)

Also available as dyphylline; dosage expressed in terms of dyphylline.a

Low therapeutic index; cautious dosage determination essential.a Do not exceed recommended dosage adjustments; risk of potentially serious adverse effects associated with large increases in serum theophylline concentration.222 223 226 227 228 229 a f g i k l

Dosage required to achieve therapeutic serum concentration varies fourfold among otherwise similar patients in absence of factors known to affect theophylline clearance.221 222 223 226 227 228 229 a f g i k l Adjust dosage carefully according to individual requirements and response, pulmonary function, and serum theophylline concentrations.221 222 223 226 227 228 229 a f g i k l

Calculate dosage based on ideal body weight.221 222 223 226 227 228 229 a f g i k l

Adjust dosage based on peak serum theophylline concentration.221 222 223 226 227 228 229 a f g i k l

Pediatric Patients

Carefully consider use and individualize dosage of the drug in children <1 year of age, particularly premature and term neonates; if used, administer conservative initial and maintenance dosages (particularly the latter).a Do not exceed recommended maintenance dosage and do not continue use of the drug unless well tolerated and clinically beneficial.a

Asthma Acute Bronchospasm Oral

Oral solutions, immediate-release tablets, extended-release tablets, and capsules: For acute exacerbations of reversible airway obstruction (when an inhaled, short-acting β2-adrenergic agonist or systemic corticosteroids not available),226 229 f i n may administer a loading dose of 5 mg/kg (in patients who have not received any theophylline in the previous 24 hours) using an immediate-release preparation to produce an average peak serum concentration of 10 mcg/mL (range 5–15 mcg/mL).226 229 f

Some experts suggest initiating therapy with a theophylline dosage of 10 mg/kg (up to 300 mg in adolescents ≥12 years of age) daily in divided doses, with titration up to a usual maximum dosage of 16 mg/kg daily in divided doses in children 1–11 years of age or 800 mg daily in divided doses in adolescents ≥12 years of age.m

Following loading dose, titrate theophylline dosage for subsequent therapy in pediatric patients using an immediate-release preparation as follows:

Patients with more rapid metabolism, identified clinically by higher than average dosage requirements, may require smaller doses given more frequently to prevent breakthrough symptoms resulting from low trough theophylline concentrations; such patients may benefit from therapy with an extended-release preparation.

See Warnings/Precautions under Cautions and also see Interactions for information on risk factors for decreased theophylline clearance.

Table 1. Recommended Dosage Titration in Pediatric Patients Using Immediate-Release Preparations226229fim

Age	Dosage Titration
Premature neonates <24 days postnatal age	Initially, 1 mg/kg every 12 hours Adjust dosage to maintain a peak steady-state serum concentration of 5–10 mcg/mL
Premature neonates ≥24 days postnatal age	Initially, 1.5 mg/kg every 12 hours Adjust dosage to maintain a peak steady-state serum concentration of 5–10 mcg/mL
Full-term infants ≤26 weeks of age	[(0.2 x age in weeks) + 5] x body weight (kg) = initial total daily dosage (mg); administer in 3 equally divided doses every 8 hours Adjust dosage to maintain a peak steady-state serum concentration of 5–10 mcg/mL in neonates or 10–15 mcg/mL in older infants
Infants >26–52 weeks of age	[(0.2 x age in weeks) + 5] x body weight (kg) = initial total daily dosage (mg); administer in 4 equally divided doses every 6 hours Adjust dosage to maintain a peak steady-state serum concentration of 10–15 mcg/mL
Children 1–15 years of age weighing <45 kg	Initially, 12–14 mg/kg (maximum 300 mg) daily in divided doses; after 3 days, if tolerated, increase dosage to 16 mg/kg (maximum 400 mg) daily in divided doses; after 3 more days, if tolerated and if needed, increase dosage to 20 mg/kg (maximum 600 mg) daily in divided doses Administer in divided doses every 4–6 hours
Children and adolescents ≥1 year of age weighing >45 kg	Initially, 300 mg daily in divided doses; after 3 days, if tolerated, increase dosage to 400 mg daily in divided doses; after 3 more days, if tolerated and if needed, increase dosage to 600 mg daily in divided doses Administer in divided doses every 6–8 hours
Children and adolescents 1–15 years of age with risk factors for reduced theophylline clearance or in whom serum concentrations cannot be monitored	Theophylline: Initially, 12–14 mg/kg (maximum 300 mg) daily in divided doses; after 3 days, if tolerated, increase dosage to maximum 16 mg/kg (maximum 400 mg) daily in divided doses Administer in divided doses every 4–6 hours

Monitor serum theophylline concentrations at 24-hour intervals to adjust final dosage.226 f

For final dosage titration, see Table 2.

Dosage reduction and/or serum theophylline concentration measurement is indicated whenever adverse effects are present, physiologic abnormalities that can reduce theophylline clearance occur (e.g., sustained fever), or a drug that interacts with theophylline is added or discontinued. (See Warnings/Precautions under Cautions and also see Interactions.)

Table 2. Oral Dosage Adjustment in Pediatric Patients Based on Serum Theophylline Concentrationfi

Serum Theophylline Concentration (mcg/mL)	Dosage Adjustment
<9.9	Increase dose by 25% if symptoms are not controlled and current dosage is tolerated; recheck serum concentration after 3 days for further adjustment
10–14.9	Maintain dosage if symptoms are controlled and current dosage is tolerated; recheck serum concentration at 6- to 12-month intervals. Consider adding additional agents if symptoms are not controlled and current dosage is tolerated
15–19.9	Consider 10% decrease in dose to provide greater margin of safety even if current dosage is tolerated
20–24.9	Decrease dose by 25% even if no adverse effects are present; recheck serum concentration after 3 days
25–30	Skip next dose and decrease subsequent doses at least 25% even if no adverse effects are present Recheck serum concentration after 3 days; if symptomatic, consider whether treatment for overdose is indicated
>30	Stop drug and treat overdose as indicated If therapy is resumed, decrease subsequent dosage by ≥50% and recheck serum concentration after 3 days

Dyphylline (tablet or solution): In children ≥6 years of age, 100–200 mg given 3 or 4 times daily.d h Adjust dosage carefully according to individual requirements and response.a d e h

Dyphylline (solution): At least one manufacturer suggests dosage of approximately 0.9–1.4 mg/kg (2–3 mg/pound) daily in divided doses for children ≥6 years of age.e

IV

For acute bronchodilation, administer IV to achieve a therapeutic serum theophylline concentration (i.e., 10–15 mcg/mL).227 228 k l

Generally, each 1 mg/kg (based on ideal body weight) of theophylline given by IV infusion over 30 minutes results in an average 2-mcg/mL increase in serum theophylline concentration.227 228 k l

In patients who have not received any theophylline in the previous 24 hours, administer a loading dose of 4.6 mg/kg of theophylline (approximately equivalent to 5.7 mg/kg of hydrous aminophylline) based on ideal body weight to achieve an average serum theophylline concentration of 10 mcg/mL.227 228 k l

For acute bronchodilation in patients who are currently receiving theophylline preparations, measure serum theophylline concentration immediately to determine loading dose; estimation of serum theophylline concentration based upon patient history is unreliable.227 228 k l Do not administer loading dose before obtaining serum theophylline concentration if patient has received any theophylline in past 24 hours.227 228 k l

Determine loading dose in patients currently receiving theophylline preparations using following formula:227 228 k l

Loading dose= (desired serum concentration – measured serum concentration) × volume of distribution

Assume volume of distribution of 0.5 L/kg for this calculation.228 k l Ensure that desired drug concentration is conservative (e.g., 10 mcg/mL) to allow for variability in volume of distribution.227 228 k l

Measure serum theophylline concentration 30 minutes after administration of loading dose to determine need for and size of subsequent loading doses.227 228 k l After therapeutic serum theophylline concentration attained, adjust maintenance dosage by continuous IV infusion depending on patient's age, clinical characteristics, pharmacokinetic parameters, and target serum theophylline concentration (generally 10–15 mcg/mL).227 228 k l

Following loading dose, initiate continuous IV infusion as shown in Table 3.

To achieve a target theophylline concentration of 10 mcg/mL.228

Approximate aminophylline dosage = theophylline dosage/0.8.228

Use ideal body weight for obese patients. Lower initial dosage may be required for patients with conditions or receiving drugs that decrease theophylline clearance. (See Warnings/Precautions under Cautions and also see Interactions.)227 228

To achieve a target theophylline concentration of 7.5 mcg/mL.227 228

Unless serum concentration indicates need for larger dosage.227 228

Table 3. Initial Theophylline IV Infusion Rate in Pediatric Patients Following Appropriate Loading Dose227228kl

Patient Population	Theophylline Infusion Rate
Neonates, postnatal age ≤24 days	1 mg/kg every 12 hours
Neonates, postnatal age >24 days	1.5 mg/kg every 12 hours
Infants 6 weeks to 1 year of age	mg/kg per hour = (0.008)(age in weeks) + 0.21
Children 1–9 years of age	0.8 mg/kg per hour
Children 9–12 years of age	0.7 mg/kg per hour
Marijuana- or cigarette-smoking adolescents 12–16 years of age	0.7 mg/kg per hour
Nonsmoking adolescents 12–16 years of age	0.5 mg/kg per hour (maximum 900 mg daily)

Measure serum theophylline concentration at 1 expected half-life after starting continuous IV infusion (i.e., after approximately 4 hours for children 1–9 years of age; see Half-life under Pharmacokinetics) to determine if theophylline concentrations are decreasing or increasing from post-loading dose drug concentration.228 If theophylline concentrations decreasing, administer additional loading dose and/or increase infusion rate.228 If theophylline concentration after initiation of continuous IV infusion is higher than post-loading drug concentration, decrease infusion rate before theophylline concentration >20 mcg/mL.228 Measure additional serum theophylline concentration 12–24 hours later to determine if dosage adjustments are required, then measure again at 24-hour intervals to adjust for changes in theophylline concentrations during the initial period of theophylline administration.228

Base IV dosage adjustments on peak serum theophylline concentrations and the clinical response and tolerance of patient as shown in Table 4:

Dosage reduction and/or serum theophylline concentration measurement is indicated whenever adverse effects are present, physiologic abnormalities that can reduce theophylline clearance occur (e.g., sustained fever), or a drug that interacts with theophylline is added or discontinued. (See Warning/Precautions under Cautions and see Interactions.)

Table 4. IV Dosage Adjustment in Pediatric Patients Based on Serum Theophylline Concentration227228kl

Serum Theophylline Concentration (mcg/mL)	Dosage Adjustment
<9.9	If symptoms are not controlled and current dosage is tolerated, increase infusion rate by 25%. Recheck serum concentration after 12 hours for further dosage adjustment
10–14.9	If symptoms are controlled and current dosage is tolerated, maintain infusion rate and recheck serum concentration at 24-hour intervals. If symptoms are not controlled and current dosage is tolerated, consider adding additional agents to treatment regimen
15–19.9	Consider 10% decrease in infusion rate to provide greater margin of safety even if current dosage is tolerated
20–24.9	Decrease infusion rate by 25% even if no adverse effects are present. Recheck serum concentration after 12 hours to guide further dosage adjustment
25–30	Stop infusion for 12 hours and decrease infusion rate by ≥25% even if no adverse effects are present. Recheck serum concentration after 12 hours to guide further dosage adjustment. If patient symptomatic, stop infusion and consider whether treatment for overdose is indicated
>30	Stop infusion and treat overdose as indicated. If theophylline therapy is resumed, decrease subsequent infusion rate by ≥50% and recheck serum concentration after 12 hours to guide further dosage adjustment

Switching to Extended-release Preparations Oral

With extended-release preparations, establish daily dosage requirement first by monitoring serum theophylline concentrations while patient is receiving immediate-release dosage form; then, initiate therapy with extended-release preparation by administering half of total daily dose every 12 hours.a

In adolescents ≥12 years of age: May transfer patients stabilized on an immediate-release or 8- to 12-hour extended-release theophylline preparation to once-daily (every 24 hours) administration using 400- or 600-mg tablets of Uniphyl on a mg-for-mg basis.223

Chronic Bronchospasm Oral

For chronic maintenance bronchodilator therapy in patients receiving certain extended-release preparations designed to be given every 8–12 hours, dosage titration is shown in Table 5.

Some generic extended-release preparations (e.g., extended-release capsules from Inwood Laboratories) are FDA-labeled for use in children and adolescents 1–15 years of age.221

Administer in divided doses every 8 or 12 hours; consult manufacturer's labeling for specific recommended dosing intervals for individual preparations.221 Generally recommended that daily dosage requirement first be established by monitoring serum theophylline concentrations while patient is receiving an immediate-release dosage form before switching to therapy with an extended-release preparation. (See text.)

Patients with more rapid metabolism, clinically identified by higher than average dosage requirements, should receive a smaller dosage more frequently to prevent breakthrough symptoms resulting from low trough concentrations before the next dose. A reliably absorbed slow-release formulation will decrease fluctuations and permit longer dosing intervals.

See Warning/Precautions under Cautions and also see Interactions for information on risk factors for decreased theophylline clearance.

Table 5. Dosage Titration in Pediatric Patients Using Certain Extended-Release Preparations 221g

Age	Daily Dosage
Children and adolescents 6–15 years of age weighing <45 kg	Initially, 12–14 mg/kg (maximum 300 mg) daily in divided doses; after 3 days, if tolerated, increase dosage to 16 mg/kg (maximum 400 mg) daily in divided doses; after 3 more days, if tolerated and needed, increase dosage to 20 mg/kg (maximum 600 mg) daily in divided doses
Children and adolescents 6–15 years of age weighing >45 kg	Initially, 300 mg daily in divided doses; after 3 days, if tolerated, increase dosage to 400 mg daily in divided doses; after 3 more days, if tolerated and needed, increase dosage to 600 mg daily in divided doses
Children and adolescents 6–15 years of age with risk factors for reduced theophylline clearance or in whom serum concentrations cannot be monitored	Initially, 12–14 mg/kg (maximum 300 mg) daily in divided doses; after 3 days, if tolerated, increase dosage to maximum 16 mg/kg (maximum 400 mg) daily in divided doses

Adjust dosage based on peak serum theophylline concentrations and clinical response and tolerance of patient as follows:a

The clinical characteristics of each patient must be considered when applying these general dosage recommendations to individual patients. In general, dosage adjustments should not exceed these recommendations in order to decrease the risk of potentially serious adverse effects associated with unexpected large increases in serum theophylline concentration.a

Dosage reduction and/or serum theophylline concentration measurement is indicated whenever adverse effects are present, physiologic abnormalities that can reduce theophylline clearance occur (e.g., sustained fever), or a drug that interacts with theophylline is added or discontinued. (See Warning/Precautions under Cautions and see Interactions.)

Table 6. Oral Dosage Adjustment in Pediatric Patients Based on Serum Theophylline Concentrationgi

Serum Theophylline Concentration (mcg/mL)	Dosage Adjustment
<9.9	If symptoms are not controlled and current dosage is tolerated, increase dosage by 25%. Recheck serum concentration after 3 days for further adjustment
10–14.9	If symptoms are controlled and current dosage is tolerated, maintain dosage and recheck serum theophylline concentration at 6- to 12-month intervals. If symptoms are not controlled and current dosage is tolerated, consider adding additional agents to treatment regimen
15–19.9	Consider 10% decrease in dosage to provide greater margin of safety even if current dosage is tolerated
20–24.9	Decrease dosage by 25% even if no adverse effects are present; recheck serum concentration after 3 days to guide further dosage adjustment
25–30	Skip next dose and decrease subsequent dosage by at least 25% even if no adverse effects are present. Recheck serum concentration after 3 days to guide further dosage adjustment; if patient symptomatic, consider whether treatment for overdose is indicated
>30	Stop drug and treat overdose as indicated. If therapy is resumed, decrease subsequent dosage by ≥50% and recheck serum concentration after 3 days to guide further dosage adjustment

When adjusting dosage in this manner, ensure that dosage in previous 48 hours was reasonably typical of prescribed regimen and that patient did not miss a dose or take an additional dose in this time period.a

Adults

Asthma Acute Bronchospasm Oral

For acute exacerbations of reversible airway obstruction (when an inhaled, short-acting β2-adrenergic agonist or systemic corticosteroids not available),226 229 f i n may administer a loading dose of 5 mg/kg (in patients who have not received any theophylline in the previous 24 hours) using an immediate-release preparation to produce an average peak serum concentration of 10 mcg/mL (range 5–15 mcg/mL).226 229 f

Some experts suggest initiating therapy with a theophylline dosage of 10 mg/kg (up to 300 mg) daily in divided doses, with titration up to a usual maximum dosage of 800 mg daily in divided doses.211 m

Following the loading dose, titrate theophylline dosage for subsequent therapy in adults using an immediate-release preparation as follows:

Patients with more rapid metabolism, identified clinically by higher than average dosage requirements, may require smaller doses given more frequently to prevent breakthrough symptoms resulting from low trough theophylline concentrations; such patients may benefit from therapy with an extended-release preparation.

See Warning/Precautions under Cautions and also see Interactions for information on risk factors for decreased theophylline clearance.

Table 7. Recommended Dosage Titration Using Immediate-Release Preparations for Adults226229fi

Age	Dosage Titration
Adults ≥16 years of age (weighing >45 kg) without risk factors for reduced theophylline clearance	Initially, 300 mg daily in divided doses; after 3 days, if tolerated, increase dosage to 400 mg daily in divided doses; after 3 more days, if tolerated and if needed, increase dosage to 600 mg daily in divided doses Administer in divided doses every 6–8 hours
Adults ≥16 years of age with risk factors for reduced theophylline clearance, including patients >60 years of age and those in whom serum concentrations cannot be monitored	Initially, 300 mg daily in divided doses; after 3 days, if tolerated, increase dosage to maximum 400 mg daily in divided doses; do not exceed 400 mg/day in the presence of risk factors for reduced theophylline clearance Administer in divided doses every 6–8 hours

Monitor serum theophylline concentrations at 24-hour intervals to adjust final dosage.226 f For final dosage titration based on serum theophylline concentration, see Table 8:

Dosage reduction and/or serum theophylline concentration measurement is indicated whenever adverse effects are present, physiologic abnormalities that can reduce theophylline clearance occur (e.g., sustained fever), or a drug that interacts with theophylline is added or discontinued. (See Warning/Precautions under Cautions and see Interactions.)

Table 8. Oral Dosage Adjustment Based on Serum Theophylline Concentrationfi

Serum Theophylline Concentration (mcg/mL)	Dosage Adjustment
<9.9	Increase dose by 25% if symptoms are not controlled and current dosage is tolerated; recheck serum concentration after 3 days for further adjustment
10–14.9	Maintain dosage if symptoms are controlled and current dosage is tolerated; recheck serum concentration at 6- to 12-month intervals Consider adding additional agents if symptoms are not controlled and current dosage is tolerated
15–19.9	Consider 10% decrease in dose to provide greater margin of safety even if current dosage is tolerated
20–24.9	Decrease dose by 25% even if no adverse effects are present; recheck serum concentration after 3 days
25–30	Skip next dose and decrease subsequent doses at least 25% even if no adverse effects are present Recheck serum concentration after 3 days; if symptomatic, consider whether treatment for overdose is indicated
>30	Stop drug and treat overdose as indicated If therapy is resumed, decrease subsequent dosage by ≥50% and recheck serum concentration after 3 days

Dyphylline (tablet or solution): Usually, 15 mg/kg or 100–200 mg every 6 hours;231 d e h one manufacturer recommends a dosage of 200–400 mg every 6 hours in adults.230 Adjust dosage carefully according to individual requirements and response.a d e h

IV

For acute bronchodilation, therapeutic serum theophylline concentration (i.e., 10–15 mcg/mL) best achieved with IV loading dose(s).227 228 k l

Generally, each 1 mg/kg (based on ideal body weight) of theophylline given by IV infusion over 30 minutes results in an average 2-mcg/mL increase in serum theophylline concentration.227 228 k l

In patients who have not received any theophylline in the previous 24 hours, administer loading dose of 4.6 mg/kg of theophylline (approximately equivalent to 5.7 mg/kg of hydrous aminophylline) based on ideal body weight to achieve an average serum theophylline concentration of 10 mcg/mL.227 228 k l

For acute bronchodilation in patients who are currently receiving theophylline preparations, measure serum theophylline concentration immediately to determine loading dose; estimation of serum theophylline concentration based upon patient history unreliable.227 228 k l Do not administer loading dose before obtaining serum theophylline concentration if patient has received any theophylline in past 24 hours.227 228 k l

Determine loading dose in patients who are currently receiving theophylline preparations using following formula:227 228 k l

Loading dose = (desired serum concentration - measured serum concentration) × volume of distribution

Assume volume of distribution of approximately 0.5 L/kg for use in this formula.227 228 k l Ensure that desired drug concentration is conservative (e.g., 10 mcg/mL) to allow for variability in volume of distribution.227 228 k l

Measure serum theophylline concentration 30 minutes after administration of a loading dose to determine the need for and size of subsequent loading doses.228 After a therapeutic serum theophylline concentration is attained, adjust maintenance dosage depending on the patient's age, clinical characteristics, pharmacokinetic parameters, and target serum theophylline concentration (generally 10–15 mcg/mL).227 228

Following loading dose, initiate continuous IV infusion as shown in Table 9:

To achieve target theophylline concentration of 10 mcg/mL.228

Approximate aminophylline dosage = theophylline dosage/0.8.228

Use ideal body weight for obese patients. Lower initial dosage may be required for patients with conditions or receiving drugs that decrease theophylline clearance. (See Warning/Precautions under Cautions and also see Interactions.)227 228

Unless serum concentration indicates need for larger dosage.227 228

Table 9. Initial Theophylline IV Infusion Rate Following Appropriate Loading Dose227228kl

Patient Population	Initial Theophylline Infusion Rate
Adults 16–60 years of age	0.4 mg/kg per hour (maximum 900 mg daily)
Patients >60 years of age	0.3 mg/kg per hour up to maximum 17 mg/hour (maximum 400 mg daily)
Patients with cardiac decompensation, cor pulmonale, hepatic dysfunction, sepsis with multi-organ failure, shock	0.2 mg/kg per hour up to a maximum 17 mg/hour (maximum 400 mg daily) unless serum theophylline concentrations are monitored at 24-hour intervals

Measure serum theophylline concentration at 1 expected half-life after starting continuous IV infusion (i.e., after 8 hours for nonsmoking adults; see Half-life under Pharmacokinetics) to determine if theophylline concentrations are decreasing or increasing from post-loading dose drug concentration.228 If theophylline concentrations are decreasing, administer additional loading dose and/or increase infusion rate.228 If theophylline concentration after initiation of continuous IV infusion is higher than post-loading drug concentration, decrease infusion rate before theophylline concentration >20 mcg/mL.228 Measure additional serum theophylline concentration 12–24 hours later to determine if dosage adjustments are required, then measure again at 24-hour intervals to adjust for changes in theophylline concentrations during the initial period of theophylline administration.228

Base IV dosage adjustments on peak serum theophylline concentrations and clinical response and tolerance of patient as shown in Table 10:

Dosage reduction and/or serum theophylline concentration measurement is indicated whenever adverse effects are present, physiologic abnormalities that can reduce theophylline clearance occur (e.g., sustained fever), or a drug that interacts with theophylline is added or discontinued. (See Warning/Precautions under Cautions and see Interactions.)

Table 10. IV Dosage Adjustment Based on Serum Theophylline Concentration228kl

Serum Theophylline Concentration (mcg/mL)	Dosage Adjustment
<9.9	Increase infusion rate by 25% if symptoms are not controlled and current dosage is tolerated; recheck serum concentration after 24 hours in adults
10–14.9	Maintain infusion rate if symptoms are controlled and current dosage is tolerated; recheck serum concentration after 24 hours Consider adding additional agents if symptoms are not controlled and current dosage is tolerated
15–19.9	Consider 10% decrease in infusion rate to provide greater margin of safety even if current dosage is tolerated
20–24.9	Decrease infusion rate by 25% even if no adverse effects are present; recheck serum concentration after 24 hours in adults
25–30	Stop infusion for 24 hours in adults; subsequently, decrease infusion rate by ≥25% even if no adverse effects are present Recheck serum concentration after 24 hours in adults; if symptomatic, stop infusion and consider whether treatment for overdose is indicated
>30	Stop infusion and treat overdose as indicated If therapy is resumed, decrease subsequent infusion rate by ≥50% and recheck serum concentration after 24 hours in adults

Switching to Extended-release Preparations Oral

With extended-release preparations, establish daily dosage requirement first by monitoring serum theophylline concentrations while patient is receiving immediate-release dosage form; then, initiate therapy with extended-release preparation by administering half of total daily dose every 12 hours.a

May transfer patients stabilized on an immediate-release or 8- to 12-hour controlled-release theophylline preparation to once-daily (every 24 hours) administration using 400- or 600-mg tablets of Uniphyl on a mg-for-mg basis.223

Chronic Bronchospasm Oral

For chronic maintenance bronchodilator therapy in patients receiving certain extended-release preparations designed to be given every 8–12 hours, dosage titration is shown in Table 11.

Some generic extended-release preparations (e.g., extended-release capsules from Inwood Laboratories) are FDA-labeled for use in children and adolescents 1–15 years of age.221

Administer in divided doses every 8 or 12 hours; consult manufacturer's labeling for specific recommended dosing intervals for individual preparations.221 Generally recommended that daily dosage requirement first be established by monitoring serum theophylline concentrations while patient is receiving an immediate-release dosage form before switching to therapy with an extended-release preparation. (See text.)

See Warning/Precautions under Cautions and also see Interactions for information on risk factors for decreased theophylline clearance.

Table 11. Dosage Titration Using Certain Extended-Release Preparations Every 8–12 Hours221

Age	Daily Dosage
Adults (≥16 years of age) with risk factors for reduced theophylline clearance or in whom serum concentrations cannot be monitored	Initially, 300 mg daily in divided doses; after 3 days, if tolerated, increase dosage to maximum 400 mg daily in divided doses
Patients >60 years of age	Maximum 400 mg daily unless patient continues to be symptomatic, and peak serum concentration <10 mcg/mL Administer dosages >400 mg daily with caution

Adjust dosage based on peak serum theophylline concentrations and clinical response and tolerance of patient as follows:a

The clinical characteristics of each patient must be considered when applying these general dosage recommendations to individual patients. In general, dosage adjustments should not exceed these recommendations in order to decrease the risk of potentially serious adverse effects associated with unexpected large increases in serum theophylline concentration.

Dosage reduction and/or serum theophylline concentration measurement is indicated whenever adverse effects are present, physiologic abnormalities that can reduce theophylline clearance occur (e.g., sustained fever), or a drug that interacts with theophylline is added or discontinued. (See Warning/Precautions under Cautions and see Interactions.)

Table 12. Oral Dosage Adjustment Based on Serum Theophylline Concentrationa

Serum Theophylline Concentration (mcg/mL)	Dosage Adjustment
<9.9	If symptoms are not controlled and current dosage is tolerated, increase dosage by 25%. Recheck serum theophylline concentration after 3 days for further dosage adjustment
10–14.9	If symptoms are controlled and current dosage is tolerated, maintain dosage and recheck serum theophylline concentration at 6- to 12-month intervals. If symptoms are not controlled and current dosage is tolerated, consider adding additional agents to treatment regimen
15–19.9	Consider 10% decrease in dosage to provide greater margin of safety even if current dosage is tolerated
20–24.9	Decrease dosage by 25% even if no adverse effects are present. Recheck serum theophylline concentration after 3 days to guide further dosage adjustment
25–30	Skip next dose and decrease subsequent dosage by at least 25% even if no adverse effects are present. Recheck serum theophylline concentration after 3 days to guide further dosage adjustment. If patient symptomatic, consider whether treatment for overdose is indicated
>30	Stop drug and treat overdose as indicated. If theophylline therapy is resumed, decrease subsequent dosage by ≥50% and recheck serum concentration after 3 days to guide further dosage adjustment

When adjusting dosage in this manner, ensure that dosage in previous 48 hours was reasonably typical of prescribed regimen and that patient did not miss a dose or take an additional dose in this time period.a

Prescribing Limits

Pediatric Patients

Asthma Oral

Children and adolescents 1–15 years of age without risk factors for reduced theophylline clearance: Maximum of 20 mg/kg (up to 600 mg) daily recommended after at least 6 days of dosage titration.226 229 (See Table 1 under Dosage and Administration.)

Children and adolescents 1–15 years of age with risk factors for reduced theophylline clearance or in whom serum concentrations cannot be monitored: Maximum of 16 mg/kg (up to 400 mg) daily recommended after at least 3 days of dosage titration.226 229 (See Table 1 under Dosage and Administration.)

Regardless of oral preparation, dosage should not exceed the 600 mg maximum daily dosage without measurement of serum theophylline concentration.221 222 223 226 229

IV

Nonsmoking adolescents 12–16 years of age: 0.5 mg/kg per hour up to maximum of 900 mg daily (unless serum concentrations indicate need for larger dosage) following administration of appropriate loading dose.227 228 k l

Adults

Asthma and COPD Oral

Patients without risk factors for reduced theophylline clearance: Maximum 600 mg daily.226 229

Regardless of oral preparation, do not exceed 600 mg daily without measurement of serum theophylline concentration.221 222 223 226 229

Patients with risk factors for reduced theophylline clearance or in whom serum concentrations cannot be monitored: Maximum 400 mg daily.226 229

Geriatric patients: Maximum 400 mg daily.226 229 f g i

IV

In patients who have not received theophylline in previous 24 hours: Maximum 900 mg daily (unless serum concentrations indicate need for larger dosage) following administration of loading dose.227 228 k l

In geriatric patients, patients with cardiac decompensation, cor pulmonale, hepatic dysfunction, sepsis with multi-organ failure, shock, or those taking drugs that markedly reduce theophylline clearance: Maximum initial infusion rate: 17 mg/hour (unless serum concentrations monitored at 24-hour intervals).227 228 k l

Special Populations

Hepatic Impairment

Possible increased risk of toxicity in patients with hepatic impairment; monitor serum theophylline concentrations and adjust dosage accordingly because of decreased clearance.223 226 228

In patients with suspected decreased serum protein binding (e.g., cirrhosis, third trimester of pregnancy), maintain concentrations of unbound (free) theophylline in range of 6–12 mcg/mL.222 228 f i k

Initial infusion rate following appropriate loading dose: 0.2 mg/kg per hour.228

Maximum daily dosage 400 mg unless serum concentration indicates need for larger dosage.228

Renal Impairment

Monitor serum theophylline concentrations and adjust dosage accordingly for neonates and infants ≤3 months of age with renal impairment.228 f

Dosage adjustment not required in adults and children >3 months of age.228 f

Dyphylline: Consider dosage reduction in patients with renal impairment.230 231

Geriatric Patients

Select dosage with caution in geriatric patients because of age-related decreases in hepatic, renal, and/or cardiac function, concomitant disease, and drug therapy.221 222 223 226 227 228 229 f g i k l Theophylline clearance decreased in healthy adults >60 years of age.221 222 223 226 227 228 229 f g i k l (See Elimination: Special Populations under Pharmacokinetics.) Reduced dosage and frequent monitoring of serum theophylline concentrations required in geriatric patients.221 222 223 226 227 228 229 f g i k l

Administer oral dosages >400 mg daily with caution.223 226 g

Initial IV infusion rate following appropriate loading dose: 0.3 mg/kg per hour.228

Patients with Cardiac Decompensation, Cor Pulmonale, Sepsis with Multi-organ Failure, or Shock

Initial infusion rate following appropriate loading dose: 0.2 mg/kg per hour.228 Maximum initial infusion rate: 17 mg/hour unless serum theophylline concentrations monitored at 24-hour intervals.228 k

Maximum daily dosage: 400 mg daily unless serum concentration indicates need for larger dosage.228

Smokers

May require larger than usual or more frequent doses in patients that smoke (cigarettes and/or marijuana).a

Careful attention to dose and frequent monitoring of serum theophylline concentrations required in patients who stop smoking.g (See Elimination: Special Populations under Pharmacokinetics.)

Storage

Oral

Capsules and Tablets

Conventional and extended-release tablets (Theo-24): <25°C.222

Controlled-release (Uniphyl) tablets: Tight, light-resistant containers at 25°C; excursions permitted to 15–30°C.223

Dyphylline and guaifenesin tablets: Tight containers at 20–25°C.h Protect from moisture.h

Aminophylline: Tight, light-resistant containers at 20–25°C.i Protect from light and moisture.i

Solution

Dyphylline and guaifenesin: Tight containers at 20–25°C; excursions permitted to 15–30°C.d e h

Theophylline: Tight containers at 15–30°C.229

Parenteral

Solution

Injection in 5% dextrose: 25°C.k Avoid excessive heat.k Do not freeze.k

Aminophylline ampules/vials: 15–30°C; protect from light.227 l Keep vials in carton until time of use.227 l

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Not recommended in combination with enteric products (Ensure, Ensure Plus, and Osmolite) for nasogastric administration.c

Parenteral

Solution Compatibility (for Aminophylline)HID

Compatible
Amino acids 4.25%, dextrose 25%
Dextrose-Ringer’s injection combinations
Dextrose-Ringer’s injection, lactated, combinations
Dextrose 5% in Ringer’s injection, lactated
Dextrose-saline combinations
Dextrose 5% in sodium chloride 0.2 or 0.9%
Dextrose 2.5, 5, 10, or 20% in water
Ionosol products
Ringer’s injection
Ringer’s injection, lactated
Sodium chloride 0.45 or 0.9%
Sodium lactate (1/6) M
Variable
Fat emulsion 10%, IV

Drug Compatibility (for Aminophylline) Admixture Compatibility (for Aminophylline)HID

Compatible
Calcium gluconate
Chloramphenicol sodium succinate
Dexamethasone sodium phosphate
Diphenhydramine HCl
Dopamine HCl
Erythromycin lactobionate
Esmolol HCl
Flumazenil
Furosemide
Heparin sodium
Hydrocortisone sodium succinate
Lidocaine HCl
Meropenem
Methyldopate HCl
Nitroglycerin
Pentobarbital sodium
Phenobarbital sodium
Potassium chloride
Ranitidine HCl
Sodium bicarbonate
Terbutaline sulfate
Incompatible
Atracurium besylate
Bleomycin sulfate
Cefepime HCl
Ceftazidime
Ceftriaxone sodium
Chlorpromazine HCl
Ciprofloxacin
Clindamycin phosphate
Dobutamine HCl
Doxorubicin HCl
Epinephrine HCl
Hydralazine HCl
Hydroxyzine HCl
Isoproterenol HCl
Norepinephrine bitartrate
Penicillin G potassium
Pentazocine lactate
Prochlorperazine edisylate
Promethazine HCl
Verapamil HCl
Variable
Amikacin sulfate
Ascorbic acid injection
Dimenhydrinate
Methylprednisolone sodium succinate
Midazolam HCl
Nafcillin sodium
Vancomycin HCl

Y-Site Compatibility (for Aminophylline)HID

Compatible
Allopurinol sodium
Amifostine
Amphotericin B cholesteryl sulfate complex
Anidulafungin
Aztreonam
Bivalirudin
Ceftaroline fosamil
Ceftazidime
Cladribine
Clonidine HCl
Dexmedetomidine HCl
Docetaxel
Doripenem
Doxorubicin HCl liposome injection
Enalaprilat
Esmolol HCl
Etoposide phosphate
Famotidine
Filgrastim
Fluconazole
Fludarabine phosphate
Foscarnet sodium
Gallium nitrate
Gemcitabine HCl
Granisetron HCl
Heparin sodium with hydrocortisone sodium succinate
Hetastarch in lactated electrolyte injection (Hextend)
Labetalol HCl
Levofloxacin
Linezolid
Melphalan HCl
Meropenem
Micafungin sodium
Morphine sulfate
Nicardipine HCl
Paclitaxel
Pancuronium bromide
Pemetrexed disodium
Piperacillin sodium-tazobactam sodium
Potassium chloride
Propofol
Ranitidine HCl
Remifentanil HCl
Sargramostim
Tacrolimus
Teniposide
Thiotepa
Vecuronium bromide
Incompatible
Amiodarone HCl
Ciprofloxacin
Clarithromycin
Dobutamine HCl
Fenoldopam mesylate
Hydralazine HCl
Ondansetron HCl
Vinorelbine tartrate
Warfarin sodium
Variable
Cisatracurium besylate
Diltiazem HCl

Drug Compatibility for Theophylline Admixture Compatibility (for Theophylline)HID

Compatible
Cefepime HCl
Chlorpromazine HCl
Fluconazole
Furosemide
Lidocaine HCl
Methylprednisolone sodium succinate
Papaverine HCl
Verapamil HCl
Incompatible
Ascorbic acid injection
Ceftriaxone sodium

Y-Site Compatibility (for Theophylline)HID

Compatible
Acyclovir sodium
Ampicillin sodium
Ampicillin sodium-sulbactam-sodium
Aztreonam
Bivalirudin
Cefazolin sodium
Cefotetan disodium
Ceftriaxone sodium
Cisatracurium besylate
Clindamycin phosphate
Clonidine HCl
Dexamethasone sodium phosphate
Dexmedetomidine HCl
Diltiazem HCl
Dobutamine HCl
Dopamine HCl
Doxycycline hyclate
Erythromycin lactobionate
Famotidine
Fenoldopam mesylate
Fluconazole
Gentamicin sulfate
Haloperidol lactate
Heparin sodium
Hetastarch in lactated electrolyte injection (Hextend)
Hydrocortisone sodium succinate
Lidocaine HCl
Linezolid
Methyldopate HCl
Methylprednisolone sodium succinate
Metronidazole
Micafungin sodium
Midazolam HCl
Milrinone lactate
Nafcillin sodium
Nitroglycerin
Oxaliplatin
Penicillin G potassium
Potassium chloride
Ranitidine HCl
Remifentanil HCl
Sodium nitroprusside
Ticarcillin disodium–clavulanate potassium
Tigecycline
Tobramycin sulfate
Vancomycin HCl
Incompatible
Cefepime HCl
Hetastarch in sodium chloride 0.9%
Phenytoin sodium
Variable
Ceftazidime

• Mechanism(s) of action not known with certainty; appears that bronchodilation is mediated by competitive inhibition of 2 isozymes of phosphodiesterase (PDE III and, to a lesser extent, PDE IV), while non-bronchodilator prophylactic actions are probably mediated through molecular mechanisms that do not involve inhibition of PDE III or antagonism of adenosine receptors.222 a d e f g h i k l m

• Relaxes smooth muscles (i.e., bronchodilation) and suppresses the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects).222 223 f g i k l

• Relieves shortness of breath, wheezing and dyspnea, and improves pulmonary function as measured by increased flow rates and vital capacity.a

• Increases the force of contraction of diaphragmatic muscles.222 f g i k l m

• Theophylline and dyphylline exert identical pharmacologic actions.a

• Positive inotropic effect on the myocardium and a positive chronotropic effect at the sinoatrial (SA) node.a

• Directly dilates coronary, pulmonary, renal, and general systemic arterioles and veins, decreasing peripheral vascular resistance and venous pressure.a Generally only a slight increase in BP following administration of moderate doses of theophylline.a

• Stimulates all levels of CNS but to a lesser degree than caffeine.a Constricts cerebral vasculature; resultant decrease in cerebral blood flow and increase in carbon dioxide tension may result in respiratory center stimulation in some patients.a

• Has a mild diuretic effect.a e

• May increase basal metabolic rate.a

• Stimulates gastric secretion, relaxes smooth muscle of biliary and GI tract.a

• Tolerance of low magnitude may develop to diuretic and sleep-disturbing effects of xanthine derivatives; tolerance to bronchodilator effects rarely occurs.a e

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Aminophylline (Hydrous)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	100 mg (79 mg of anhydrous theophylline)*	Aminophylline Tablets
		200 mg (158 mg of anhydrous theophylline)*	Aminophylline Tablets
Parenteral	Injection	25 mg (19.7 mg of anhydrous theophylline) per mL*	Aminophylline Injection

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Aminophylline (Anhydrous)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Solution	105 mg (90 mg of anhydrous theophylline) per 5 mL*	Aminophylline Oral Solution

Dyphylline

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Solution	33 mg/5 mL	Dylix Elixir	Lunsco
	Tablets	200 mg	Lufyllin (scored)	Meda
		400 mg	Lufyllin (scored)	Meda

Dyphylline and Guaifenesin

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Solution	33.3 mg/5 mL Dyphylline and Guaifenesin 33.3 mg/5 mL	Dyphylline GG	Silarx
			Lufyllin-GG Elixir	Meda
		100 mg/5 mL Dyphylline and Guaifenesin 100 mg/5 mL	Dy-G	Cypress
			Lufyllin-GG Elixir	Meda
	Tablets	200 mg Dyphylline and Guaifenesin 200 mg	Lufyllin-GG (scored)	Meda

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Theophylline (Anhydrous)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Bulk	Powder*
Oral	Capsules, extended-release	100 mg	Theo-24 (24 hours)	UCB
		125 mg	Theophylline Extended-Release Capsules (12 hours)
		200 mg	Theo-24 (24 hours)	UCB
			Theophylline Extended-Release Capsules (12 hours)
		300 mg	Theo-24 (24 hours)	UCB
			Theophylline Extended-Release Capsules (12 hours)
		400 mg	Theo-24 (24 hours)	UCB
	Solution	27 mg/5 mL*	Elixophyllin Elixir	Forest
	Tablets, extended-release	100 mg*	Theochron (12 hours; scored)	Forest
			Theophylline Extended-Release Tablets (12 hours)
		200 mg*	Theochron	Forest
			Theophylline Extended-Release Tablets (12 hours)	Inwood
		300 mg	Theochron (12 hours; scored)	Forest
			Theophylline Extended-Release Tablets (12 hours)	Inwood
		400 mg	Uniphyl Unicontin (24 hours, scored)	Purdue Frederick
		450 mg	Theochron (12 hours, scored)	Forest
		600 mg	Uniphyl Unicontin (24 hours, scored)	Purdue Frederick

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Theophylline (Anhydrous) in Dextrose

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for IV infusion	0.8 mg/mL (400 and 800 mg) Theophylline (anhydrous) in 5% Dextrose*	Theophylline and 5% Dextrose Injection (LifeCare [Hospira], Excel [Braun], Viaflex [Baxter])
		1.6 mg/mL (400 and 800 mg) Theophylline (anhydrous) in 5% Dextrose*	Theophylline and 5% Dextrose Injection (LifeCare [Hospira], Excel [Braun], Viaflex [Baxter])
		2 mg/mL (200 mg) Theophylline (anhydrous) in 5% Dextrose*	Theophylline and 5% Dextrose Injection (LifeCare [Hospira], Viaflex [Baxter])
		3.2 mg/mL (800 mg) Theophylline (anhydrous) in 5% Dextrose*	Theophylline and 5% Dextrose Injection (LifeCare [Hospira], Viaflex [Baxter])
		4 mg/mL (200 and 400 mg) Theophylline (anhydrous) in 5% Dextrose*	Theophylline and 5% Dextrose Injection (LifeCare [Hospira], Viaflex [Baxter])