Dosage ; see below
Combinations ; - see below
| Brand Name | Manufacturer Name | Distributor | Drug Strength | Packaging | Formulation | Formulation Strength | Price |
|---|---|---|---|---|---|---|---|
| Theo SR | GlaxoSmithkline | GlaxoSmithKline | 200mg | 10 | Tablet | per tablet | KES 239.70 |
| Unicontin | Modi-Mundipharma Ltd | Europa Healthcare Ltd. | 400mg | 100 | Tablet | per tablet | KES 2,945.00 |
| Unicontin | Modi-Mundipharma Ltd | Europa Healthcare Ltd. | 600mg | 100 | Tablet | per tablet | KES 3,850.00 |
| Uniphyllin | Mundipharma/Napp | Lords Healthcare Ltd. | 200mg | 56 | Tablet | per tablet | KES 810.00 |
| Uniphyllin | Mundipharma/Napp | Lords Healthcare Ltd. | 400mg | 56 | Tablet | per tablet | KES 1,510.00 |
| Neulin | iNOVA Pharmaceuticals Ltd (formerly 3M) | Harley's Limited | 250mg | 56 | Tablet | per tablet | KES 290.00 |
| Theophyline More info | |
|---|---|
| Mode Of Action | Phosphodiasterase inhibitors such as theophylline and aminophylline relax smooth muscles of bronchi, and pulmonary blood vessels resulting in increase in intracellular cAMP and subsequent smooth muscle relaxation. |
| Drug Indication | Treatment and prophylaxis of bronchospasm associated with asthma, chronic bronchitis and emphysema. |
| Precautions | Cardiac/hepatic/peptic diseases, hypoxia, hypertension, alcoholism hyperthyroidism, epilepsy, pregnancy and lactation, elderly dehydration. |
| Contra-Indications | Hypersensitivity reactions to any xanthine, peptic ulcers, and epilepsy |
| Side Effects | GI disturbances, tachycardia-palpitation, CNS effects, metallic taste, sweat, tremor, diuresis, seizures, brain damage, alopecia, proteinuria. |
| Pregnancy Category | Category A1: |
| Pregnancy Category Description | Drugs which have been taken by a sizeable number of pregnant women and women of child-bearing age with no any established rise in the frequency of malformations or other direct or indirect detrimental effects on the foetus having been noted. |
| Drug Category | DRUGS ACTING ON RESPIRATORY SYSTEM |
| Drug Sub-Category | Bronchial spasm relaxants |
| Brand Name | Manufacturer Name | Distributor | Drug Strength | Packaging | Formulation | Formulation Strength | Price |
|---|---|---|---|---|---|---|---|
| Asmadeal | Biodeal Laboratories Ltd. | Biodeal Laboratories Ltd. | 15mg/12mg | 60ml | Syrup | per 5ML | KES 50.00 |
| Asmadeal | Biodeal Laboratories Ltd. | Biodeal Laboratories Ltd. | 15mg/12mg | 100ml | Syrup | per 5ML | KES 60.00 |
| Asmadeal | Biodeal Laboratories Ltd. | Biodeal Laboratories Ltd. | 15mg/12mg | 5litres | Suspension | per 5ML | KES 550.00 |
| Asmadeal | Biodeal Laboratories Ltd. | Biodeal Laboratories Ltd. | 1000 | Tablet | per tablet | KES 5,000 | |
| Asmadeal | Biodeal Laboratories Ltd. | Biodeal Laboratories Ltd. | 100 | Tablet | per tablet | KES 600 | |
| Asthmamed | Medivet Products Ltd | Medivet Products Ltd. | 15mg/12mg | 60ml | Syrup | per 5ML | KES POR |
| Asthmamed | Medivet Products Ltd | Medivet Products Ltd. | 15mg/12mg | 100ml | Syrup | per 5ML | KES POR |
| Asthmamed | Medivet Products Ltd | Medivet Products Ltd. | 15mg/12mg | 5litres | Syrup | per 5ML | KES POR |
| Cadrol forte | Cosmos Limited. | Cosmos Limited | 50 | Tablet | per tablet | KES 105 | |
| Ephimax | Sphinx Pharmaceuticals Ltd | Omaera Pharmaceuticals Ltd | 1000 | Tablet | per tablet | KES 360 | |
| Franol | Sanofi Aventis | Surgipharm Ltd | 100 | Tablet | per tablet | KES 533 | |
| Gifol - F | Laboratory & Allied Ltd. | Laboratory & Allied Ltd | 1000 | Tablet | per tablet | KES 4500 | |
| Gifol - F | Laboratory & Allied Ltd. | Laboratory & Allied Ltd | 100 | Tablet | per tablet | KES 550 | |
| Theophed | Dawa Limited | Dawa Limited | 1000 | Tablet | per tablet | KES 4,000 | |
| Theophed | Dawa Limited | Dawa Limited | 100 | Tablet | per tablet | KES 500 | |
| Unidril | Pharmaceuticals Manufacturing Co. k Ltd. | Pharmaceutical Manufacturing Co.(K) Ltd | 60ml | Syrup | per 5ML | KES POR | |
| Unidril | Pharmaceuticals Manufacturing Co. k Ltd. | Pharmaceutical Manufacturing Co.(K) Ltd | 5litres | Syrup | per 5ML | KES POR | |
| Unidril | Pharmaceuticals Manufacturing Co. k Ltd. | Pharmaceutical Manufacturing Co.(K) Ltd | 1000 | Tablet | per tablet | KES POR | |
| Cadrolforte | Cosmos Limited. | Cosmos Limited | 15mg/12mg | 100 | Tablet | per tablet | KES 105.00 |
| Theophyline / Ephedrine More info | |
|---|---|
| Mode Of Action | Phosphodiasterase inhibitors such as theophylline and aminophylline relax smooth muscles of bronchi, and pulmonary blood vessels resulting in increase in intracellular cAMP and subsequent smooth muscle relaxation. |
| Drug Indication | Bronchospasm in asthma, bronchitis, chronic bronchitis, ephysema, bronchiectasis, premature labour. |
| Dosage | 1 tab TID. An additional tablet may be taken at bedtime for nocturnal attacks. |
| Drug Category | DRUGS ACTING ON RESPIRATORY SYSTEM |
| Drug Sub-Category | Bronchial spasm relaxants |
Theophylline More info
Dosing: Adult
Doses should be individualized based on steady-state serum concentrations and ideal body weight.
Acute symptoms: Loading dose: Oral, I.V.:
Asthma exacerbations: While theophylline may be considered for relief of asthma symptoms, the role of treating exacerbations is not supported by current practice.
COPD treatment: Theophylline is currently considered second-line intravenous therapy in the emergency department or hospital setting when there is inadequate or insufficient response to short acting bronchodilators (Global Initiative for COPD Guidelines, 2009).
If no theophylline received within the previous 24 hours: 4.6 mg/kg loading dose (~5.8 mg/kg hydrous aminophylline) I.V. or 5 mg/kg orally. Loading dose intended to achieve a serum level of approximately 10 mcg/mL; loading doses should be given intravenously (preferred) or with a rapidly absorbed oral product (not an extended-release product). Note: On the average, for every 1 mg/kg theophylline given, blood levels will rise 2 mcg/mL.
If theophylline has been administered in the previous 24 hours: A loading dose is not recommended without obtaining a serum theophylline concentration. The loading dose should be calculated as follows:
Dose = (desired serum theophylline concentration - measured serum theophylline concentration) (Vd)
Acute symptoms: Maintenance dose: I.V.: Note: To achieve a target concentration of 10 mcg/mL unless otherwise noted. Lower initial doses may be required in patients with reduced theophylline clearance. Dosage should be adjusted according to serum level measurements during the first 12- to 24-hour period.
Adults 16-60 years (otherwise healthy, nonsmokers): 0.4 mg/kg/hour; maximum 900 mg/day unless serum levels indicate need for larger dose
Adults >60 years: 0.3 mg/kg/hour; maximum 400 mg/day unless serum levels indicate need for larger dose
Treatment of chronic conditions: With newer guidelines suggesting lower therapeutic theophylline ranges, it is unlikely that doses larger than >10 mg/kg/day will be required in children ≥1 year of age.
Oral solution: Initial dose: 300 mg/day administered in divided doses every 6-8 hours; Maintenance: 400-600 mg/day (maximum: 600 mg/day)
Oral extended release formulations: Initial dose: 300-400 mg once daily; Maintenance: 400-600 mg once daily (maximum: 600 mg/day)
Dosage adjustment after serum theophylline measurement: Asthma: Within normal limits: Adults: 5-15 mcg/mL: Maintain dosage if tolerated. Recheck serum theophylline concentration at 24-hour intervals (for acute I.V. dosing) or at 6- to 12-month intervals (for oral dosing). Finer adjustments in dosage may be needed for some patients. If levels ≥15 mcg/mL, consider 10% dose reduction to improve safety margin.
Note: Recheck serum theophylline levels after 3 days when using oral dosing, or after 12 hours (children) or 24 hours (adults) when dosing intravenously. Patients maintained with oral therapy may be reassessed at 6- to 12-month intervals.
Doses should be individualized based on steady-state serum concentrations and ideal body weight.
Acute symptoms: Loading dose: Oral, I.V.: Asthma exacerbations: While theophylline may be considered for relief of asthma symptoms, the role of treating exacerbations is not supported by current practice.
If no theophylline received within the previous 24 hours: 4.6 mg/kg loading dose (~5.8 mg/kg hydrous aminophylline) I.V. or 5 mg/kg orally. Loading dose intended to achieve a serum level of approximately 10 mcg/mL; loading doses should be given intravenously (preferred) or with a rapidly absorbed oral product (not an extended-release product). Note: On the average, for every 1 mg/kg theophylline given, blood levels will rise 2 mcg/mL.
If theophylline has been administered in the previous 24 hours: A loading dose is not recommended without obtaining a serum theophylline concentration. The loading dose should be calculated as follows:
Dose = (desired serum theophylline concentration - measured serum theophylline concentration) (Vd)
Acute symptoms: Maintenance dose: I.V.: Note: To achieve a target concentration of 10 mcg/mL unless otherwise noted. Lower initial doses may be required in patients with reduced theophylline clearance. Dosage should be adjusted according to serum level measurements during the first 12- to 24-hour period.
Neonates ≤24 days: 1 mg/kg every 12 hours to achieve a target concentration of 7.5 mcg/mL for apnea of prematurity
Neonates >24 days: 1.5 mg/kg every 12 hours to achieve a target concentration of 7.5 mcg/mL for apnea of prematurity
Infants 6-52 weeks: mg/kg/hour = (0.008) (age in weeks) + 0.21
Children 1-9 years: 0.8 mg/kg/hour
Children 9-12 years: 0.7 mg/kg/hour
Adolescents 12-16 years (cigarette or marijuana smokers): 0.7 mg/kg/hour
Adolescents 12-16 years (nonsmokers): 0.5 mg/kg/hour; maximum 900 mg/day unless serum levels indicate need for larger dose
Treatment of chronic conditions: With newer guidelines suggesting lower therapeutic theophylline ranges, it is unlikely that doses larger than >10 mg/kg/day will be required in children ≥1 year of age.
Oral solution:
Infants <1 year: Note: Doses should be adjusted to maintain the peak steady state serum concentrations. The time to reach steady state will vary based on age and the presence of risk factors which may affect theophylline clearance.
Premature Neonates <24 days postnatal age: 1 mg/kg/dose every 12 hours
Premature Neonates ≥24 days postnatal age: 1.5 mg/kg/dose every 12 hours
Full-term Infants and Infants <26 weeks: Total daily dose (mg)= [(0.2 x age in weeks) +5] x (weight in kg); divide dose into 3 equal amounts and administer at 8-hour intervals
Full-term Infants and Infants ≥26 weeks and <52 weeks: Total daily dose (mg) = [(0.2 x age in weeks) +5] x (weight in kg); divide dose into 4 equal amounts and administer at 6-hour intervals
Children ≥1 year and <45 kg: Initial dose: 10-14 mg/kg/day (maximum 300 mg/day) administered in divided doses every 4-6 hours; Maintenance: Up to 20 mg/kg/day (maximum: 600 mg/day)
Children >45 kg: Refer to adult dosing.
Oral extended release formulations:
Children ≥1 year and <45 kg: Initial: 10-14 mg/kg once daily (maximum 300 mg/day); Maintenance up to 20 mg/kg/day (maximum: 600 mg/day)
Children >45 kg: Refer to adult dosing.
Dosage adjustment after serum theophylline measurement: Asthma: Within normal limits: Children: 5-10 mcg/mL: Maintain dosage if tolerated. Recheck serum theophylline concentration at 24-hour intervals (for acute I.V. dosing) or at 6- to 12-month intervals (for oral dosing). Finer adjustments in dosage may be needed for some patients. If levels ≥15 mcg/mL, consider 10% dose reduction to improve safety margin.
Note: Recheck serum theophylline levels after 3 days when using oral dosing, or after 12 hours (children) or 24 hours (adults) when dosing intravenously. Patients maintained with oral therapy may be reassessed at 6- to 12-month intervals.
Acute symptoms: Adults >60 years:
Loading dose: Oral, I.V.: Refer to adult dosing.
Maintenance dose: I.V.: 0.3 mg/kg/hour; maximum 400 mg/day unless serum levels indicate need for larger dose
Chronic conditions: Oral: Adults >60 years: Do not exceed a dose of 400 mg/day
Cardiac decompensation, cor pulmonale, hepatic dysfunction, sepsis with multiorgan failure, shock: Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, extended release, oral:
Theo-24®: 100 mg, 200 mg, 300 mg, 400 mg [24 hours]
Infusion, premixed in D5W: 200 mg (100 mL [DSC]); 400 mg (250 mL [DSC], 500 mL); 800 mg (250 mL [DSC], 500 mL, 1000 mL)
Solution, oral: 80 mg/15 mL (15 mL)
Elixophyllin® Elixir: 80 mg/15 mL (473 mL) [contains ethanol 20%; mixed fruit flavor]
Tablet, extended release, oral: 100 mg, 200 mg, 300 mg, 400 mg, 450 mg, 600 mg
Theochron™: 100 mg, 200 mg, 300 mg, 450 mg [scored; 12-24 hours]
Yes: Extended release tablet, infusion, solution
I.V.: Administer loading dose over 30 minutes; follow with a continuous infusion as appropriate
Oral: Long-acting preparations should be taken with a full glass of water, swallowed whole, or cut in half if scored. Do not crush. Extended release capsule forms may be opened and the contents sprinkled on soft foods; do not chew beads.
Stable in D5W.
Y-site administration: Compatible: Acyclovir, ampicillin, ampicillin/sulbactam, aztreonam, bivalirudin, cefazolin, cefotetan, ceftriaxone, cimetidine, cisatracurium, clindamycin, clonidine, dexamethasone sodium phosphate, dexmedetomidine, diltiazem, dobutamine, dopamine, doxycycline, erythromycin lactobionate, famotidine, fenoldopam, fluconazole, gentamicin, haloperidol, heparin, hydrocortisone sodium succinate, hetastarch in lactated electrolyte injection, lidocaine, linezolid, methyldopate, methylprednisolone sodium succinate, metronidazole, micafungin, midazolam, milrinone, nafcillin, nitroglycerin, oxaliplatin, penicillin G potassium, piperacillin, potassium chloride, ranitidine, remifentanil, sodium nitroprusside, ticarcillin, ticarcillin/clavulanate potassium, tigecycline, tobramycin, vancomycin. Incompatible: Cefepime, hetastarch in NS, phenytoin.
Compatibility when admixed: Compatible: Cefepime, chlorpromazine, fluconazole, furosemide, hydrocortisone hemisuccinate, lidocaine, methylprednisolone sodium succinate, papaverine, verapamil. Incompatible: Ascorbic acid injection, ceftriaxone.
Treatment of symptoms and reversible airway obstruction due to chronic asthma, or other chronic lung diseases; apnea of prematurity
Note: The Global Initiative for Asthma Guidelines (2009) and the National Heart, Lung and Blood Institute Guidelines (2007) do not recommend oral theophylline as a long-term control medication for asthma in children ≤5 years of age; use has been shown to be effective as an add-on (but not preferred) agent in older children and adults with severe asthma treated with inhaled or oral glucocorticoids. The guidelines do not recommend theophylline for the treatment of exacerbations of asthma.
The Global Initiative for Chronic Obstructive Lung Disease Guidelines (2009) suggest that while higher doses of slow release formulations of theophylline have been proven to be effective for use in COPD, it is not a preferred agent due to its potential for toxicity.
Frequency not defined. Adverse events observed at therapeutic serum levels:
Cardiovascular: Flutter, tachycardia
Central nervous system: Headache, hyperactivity (children), insomnia, restlessness, seizures
Endocrine & metabolic: Hypercalcemia (with concomitant hyperthyroid disease)
Gastrointestinal: Nausea, reflux or ulcer aggravation, vomiting
Genitourinary: Difficulty urinating (elderly males with prostatism)
Neuromuscular & skeletal: Tremor
Renal: Diuresis (transient)
Hypersensitivity to theophylline or any component of the formulation; premixed injection may contain corn-derived dextrose and its use is contraindicated in patients with allergy to corn-related products
Concerns related to adverse effects:
• Theophylline toxicity: If a patient develops signs and symptoms of theophylline toxicity (eg, persistent, repetitive vomiting), a serum level should be measured and subsequent doses held. Theophylline clearance may be decreased in patients with acute pulmonary edema, congestive heart failure, cor pulmonale, fever, hepatic disease, acute hepatitis, cirrhosis, hypothyroidism, sepsis with multiorgan failure, and shock; clearance may also be decreased in neonates, infants <3 months of age with decreased renal function, children <1 year of age, the elderly >60 years of age, and patients following cessation of smoking. Note: Elderly >75 years of age have a 16-fold greater risk of death from theophylline overdose than do 25-year-olds due to reduced clearance in the elderly patient.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with tachyarrhythmias (eg, sinus tachycardia, atrial fibrillation) since use may exacerbate these arrhythmias.
• Hyperthyroidism: Use with caution in patients with hyperthyroidism; use may exacerbate this condition.
• Peptic ulcer disease: Use with caution in patient with peptic ulcer disease; use may exacerbate this condition.
• Seizure disorder: Use with caution in patients with a history of seizure disorder; use may exacerbate this condition.
Other warnings/precautions:
• Monitoring: Frequent continued monitoring of serum theophylline after therapeutic levels have been achieved may not be required as long as there is no apparent risk of decreased theophylline metabolism due to concurrent drug therapies or disease states. Monitoring serum theophylline concentrations at yearly intervals should be adequate in such cases.
Substrate of CYP1A2 (major), 2C9 (minor), 2D6 (minor), 2E1 (major), 3A4 (major); Inhibits CYP1A2 (weak)
Abiraterone Acetate: May increase the serum concentration of CYP1A2 Substrates.Risk C: Monitor therapy
Adenosine: Theophylline Derivatives may diminish the therapeutic effect of Adenosine. Risk D: Consider therapy modification
Allopurinol: May increase the serum concentration of Theophylline Derivatives.Risk C: Monitor therapy
Aminoglutethimide: May increase the metabolism of Theophylline Derivatives.Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics.Risk C: Monitor therapy
Barbiturates: May decrease the serum concentration of Theophylline Derivatives.Risk C: Monitor therapy
Benzodiazepines: Theophylline Derivatives may diminish the therapeutic effect of Benzodiazepines. Risk D: Consider therapy modification
Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Theophylline Derivatives. Management: Monitor for reduced theophylline efficacy during concomitant use with any beta-blocker. Beta-1 selective agents are less likely to antagonize theophylline than nonselective agents, but selectivity may be lost at higher doses.Risk C: Monitor therapy
Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Theophylline Derivatives.Risk D: Consider therapy modification
Cannabinoids: May enhance the tachycardic effect of Sympathomimetics.Risk C: Monitor therapy
CarBAMazepine: Theophylline Derivatives may decrease the serum concentration of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Cimetidine: May decrease the metabolism of Theophylline Derivatives.Risk D: Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Management: Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates.Risk D: Consider therapy modification
Contraceptives (Estrogens): May increase the serum concentration of Theophylline Derivatives.Risk C: Monitor therapy
CYP1A2 Inducers (Strong): May increase the metabolism of CYP1A2 Substrates.Risk C: Monitor therapy
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates.Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates.Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates.Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates.Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates.Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates.Risk C: Monitor therapy
Deferasirox: May increase the serum concentration of Theophylline.Risk X: Avoid combination
Disulfiram: May increase the serum concentration of Theophylline Derivatives.Risk C: Monitor therapy
Febuxostat: May increase serum concentrations of the active metabolite(s) of Theophylline Derivatives. Specifically, concentrations of 1-methylxanthine, a metabolite of unknown clinical importance, may become elevated. Management: The U.S. febuxostat labeling recommends using caution in patients receiving concomitant theophylline due to risks of increased theophylline metabolite exposure. The Canadian febuxostat labeling contraindicates its use with theophylline.Risk C: Monitor therapy
FluvoxaMINE: May decrease the metabolism of Theophylline Derivatives.Risk D: Consider therapy modification
Formoterol: Theophylline Derivatives may enhance the adverse/toxic effect of Formoterol. Theophylline Derivatives may enhance the hypokalemic effect of Formoterol. Risk C: Monitor therapy
Fosphenytoin: Theophylline Derivatives may decrease the serum concentration of Fosphenytoin. Fosphenytoin may decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates.Risk C: Monitor therapy
Interferons: May decrease the metabolism of Theophylline Derivatives.Risk C: Monitor therapy
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Isoniazid: May increase the serum concentration of Theophylline Derivatives.Risk C: Monitor therapy
Isoproterenol: May decrease the serum concentration of Theophylline Derivatives.Risk C: Monitor therapy
Lithium: Theophylline Derivatives may decrease the serum concentration of Lithium. Risk C: Monitor therapy
Macrolide Antibiotics: May decrease the metabolism of Theophylline Derivatives.Exceptions: Azithromycin; Azithromycin (Systemic); Spiramycin; Telithromycin.Risk D: Consider therapy modification
Methotrexate: May increase the serum concentration of Theophylline Derivatives.Risk C: Monitor therapy
Mexiletine: May decrease the metabolism of Theophylline Derivatives.Risk D: Consider therapy modification
Pancuronium: Theophylline Derivatives may enhance the adverse/toxic effect of Pancuronium. Theophylline Derivatives may diminish the neuromuscular-blocking effect of Pancuronium. Management: Pancuronium dosage adjustment may be necessary to induce paralysis in patients receiving concomitant theophylline derivatives. Monitor closely for adverse effects (e.g., cardiac effects) with concomitant use of these agents.Risk D: Consider therapy modification
Pentoxifylline: May increase the serum concentration of Theophylline Derivatives.Risk C: Monitor therapy
Phenytoin: Theophylline Derivatives may decrease the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Propafenone: May increase the serum concentration of Theophylline Derivatives.Risk C: Monitor therapy
Protease Inhibitors: May decrease the serum concentration of Theophylline Derivatives.Exceptions: Fosamprenavir.Risk C: Monitor therapy
QuiNINE: May increase the serum concentration of Theophylline Derivatives.Risk C: Monitor therapy
Quinolone Antibiotics: May decrease the metabolism of Theophylline Derivatives. Ciprofloxacin and enoxacin are of greatest concern. Theophylline/quinolone therapy might augment the seizure-producing potential of each of the individual agents.Exceptions: Gemifloxacin; Levofloxacin; Levofloxacin (Systemic); Lomefloxacin; Moxifloxacin; Moxifloxacin (Systemic); Nalidixic Acid; Sparfloxacin.Risk D: Consider therapy modification
Regadenoson: Theophylline may diminish the vasodilatory effect of Regadenoson. Risk D: Consider therapy modification
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics.Risk C: Monitor therapy
Thiabendazole: May decrease the metabolism of Theophylline Derivatives.Risk D: Consider therapy modification
Thyroid Products: May increase the metabolism of Theophylline Derivatives.Risk C: Monitor therapy
Ticlopidine: May decrease the metabolism of Theophylline Derivatives.Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates.Risk C: Monitor therapy
Zafirlukast: Theophylline Derivatives may decrease the serum concentration of Zafirlukast. Zafirlukast may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Zileuton: May increase the serum concentration of Theophylline.Risk D: Consider therapy modification
Food: Food does not appreciably affect the absorption of liquid, fast-release products, and most sustained release products; however, food may induce a sudden release (dose-dumping) of once-daily sustained release products resulting in an increase in serum drug levels and potential toxicity. Avoid excessive amounts of caffeine. Avoid extremes of dietary protein and carbohydrate intake. Changes in diet may affect the elimination of theophylline; charbroiled foods may increase elimination, reducing half-life by 50%.
Teratogenic effects were observed in animal reproduction studies. Theophylline crosses the placenta; adverse effects may be seen in the newborn. Use is generally safe when used at the recommended doses (serum concentrations 5-12 mcg/mL) however maternal adverse events may be increased and efficacy may be decreased in pregnant women. Theophylline metabolism may change during pregnancy; the half-life is similar to that observed in otherwise healthy, nonsmoking adults with asthma during the first and second trimesters (~8.7 hours), but may increase to 13 hours (range: 8-18 hours) during the third trimester. The volume of distribution is also increased during the third trimester. Monitor serum levels. The recommendations for the use of theophylline in pregnant women with asthma are similar to those used in nonpregnant adults (National Heart, Lung, and Blood Institute Guidelines, 2004).
Enters breast milk/compatible (AAP rates “compatible”; AAP 2001 update pending)
The concentration of theophylline in breast milk is similar to the maternal serum concentration. Irritability may be observed in the nursing infant. Serious adverse events in the infant are unlikely unless toxic serum levels are present in the mother.
Should be taken with water 1 hour before or 2 hours after meals. Premixed injection may contain corn-derived dextrose and its use is contraindicated in patients with allergy to corn-related products.
Monitor heart rate, CNS effects (insomnia, irritability); respiratory rate (COPD patients often have resting controlled respiratory rates in low 20s); arterial or capillary blood gases (if applicable)
Theophylline levels: Serum theophylline levels should be monitored prior to making dose increases; in the presence of signs or symptoms of toxicity; or when a new illness, worsening of a present illness, or medication changes occur that may change theophylline clearance
I.V. loading dose: Measure serum concentrations 30 minutes after the end of an I.V. loading dose
I.V. infusion: Measure serum concentrations one half-life after starting a continuous infusion, then every 12-24 hours
Therapeutic levels: Asthma:
Children: 5-10 mcg/mL
Adults: 5-15 mcg/mL
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
Absorption: Oral: Dosage form dependent
Distribution: 0.45 L/kg (range: 0.3-0.7 L/kg) based on ideal body weight; distributes poorly into body fat; Vd may increase in premature neonates, patients with hepatic cirrhosis, acidemia (uncorrected), the elderly
Metabolism: Children >1 year and Adults: Hepatic; involves CYP1A2, 2E1 and 3A4; forms active metabolites (caffeine and 3-methylxanthine)
Protein binding: 40%, primarily to albumin
Half-life elimination: Highly variable and dependent upon age, liver function, cardiac function, lung disease, and smoking history
Premature infants, postnatal age 3-15 days: 30 hours (range: 17-43 hours)
Premature infants, postnatal age 25-57 days: 20 hours (range: 9.4-30.6 hours)
Children 6-17 years: 3.7 hours (range: 1.5-5.9 hours)
Adults 16-60 years with asthma, nonsmoking, otherwise healthy: 8.7 hours (range: 6.1-12.8 hours)
Time to peak, serum:
Oral: Liquid: 1 hour
I.V.: Within 30 minutes
Excretion: Urine
Neonates: 50% as unchanged theophylline
Children >3 months and Adults: ~10% as unchanged theophylline