Class: Respiratory Smooth Muscle Relaxants
ATC Class: R03DA01
VA Class: RE104
CAS Number: 317-34-0
Brands: Dy-G, Dylix , Dyphylline-GG, Elixophyllin, Lufyllin, Lufyllin GG, Theo-24, Theochron, Uniphyl
Introduction
Xanthine derivative; respiratory smooth muscle relaxant, bronchodilator.221 222 223 226 227 228 229 230 231 a d e f g h i k l m n
Uses for 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
Theophyllines Dosage and Administration
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
Exteneded-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
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
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.
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.)
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
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.)
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.
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.)
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-actin
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