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Pharmacologic class: Xanthine derivative
Therapeutic class: Bronchodilator, spasmolytic
Pregnancy risk category C
Relaxes bronchial smooth muscles, suppressing airway response to stimuli. Also inhibits phosphodiesterase and release of slow-reacting substance of anaphylaxis and histamine.
Capsules (immediate-release): 100 mg, 200 mg
Capsules (extended-release, 8 to 12 hours): 50 mg, 60 mg, 65 mg, 75 mg, 100 mg, 125 mg, 130 mg
Capsules (extended-release, 12 hours): 50 mg, 125 mg, 130 mg, 250 mg, 260 mg
Capsules (extended-release, 24 hours): 100 mg, 200 mg, 300 mg, 400 mg
Elixir: 80 mg/15 ml
Injection (with dextrose): 0.4 mg/ml, 0.8 mg/ml, 1.6 mg/ml, 2 mg/ml, 3.2 mg/ml, 4 mg/ml
Syrup (cherry): 80 mg/15 mg, 150 mg/15 ml
Tablets (immediate-release): 100 mg, 125 mg, 200 mg, 250 mg, 300 mg
Tablets (extended-release, 12 to 24 hours): 100 mg, 200 mg, 300 mg, 400 mg, 450 mg, 600 mg
Tablets (extended-release, 24 hours): 400 mg, 600 mg
Indications and dosages
➣ Acute bronchospasm in patients not receiving theophylline
Adults (otherwise healthy nonsmokers): Initially, 6 mg/kg P.O., followed in next 12 to 16 hours by 3 mg/kg P.O. q 6 hours for two doses, then a maintenance dosage of 3 mg/kg P.O. q 8 hours
Children ages 9 to 16; young adult smokers: Initially, 6 mg/kg P.O., followed in next 12 to 16 hours by 3 mg/kg P.O. q 4 hours for three doses, then a maintenance dosage of 3 mg/kg P.O. q 6 hours
Children ages 1 to 9: Initially, 6 mg/kg P.O., followed in next 12 to 16 hours by 4 mg/kg P.O. q 4 hours for three doses, then a maintenance dosage of 4 mg/kg P.O. q 6 hours
➣ Acute bronchospasm in patients receiving theophylline
Adults and children: Loading dose based partly on time, amount, and administration route of last dose and on expectation that each 0.5 mg/kg will produce 1 mcg/ml rise in theophylline blood level. In significant respiratory distress, loading dose may be 2.5 mg/kg P.O. or I.V. to increase theophylline level by approximately 5 mcg/ml.
➣ Chronic bronchospasm
Adults and children: Immediate-release forms-16 mg/kg or 400 mg P.O. daily (whichever is lower) in three to four divided doses q 6 to 8 hours. Timed-release forms-12 mg/kg or 400 mg P.O. daily (whichever is lower) in three to four divided doses q 8 to 12 hours. May increase dosage of either immediate- or timed-release form at 2- to 3-day intervals, to a maximum of 13 mg/kg or 900 mg daily (whichever is lower) in patients older than age 16, 18 mg/kg daily in children ages 12 to 16, 20 mg/kg daily in children ages 9 to 12, or 24 mg/kg daily in children up to age 9.
• Cor pulmonale or heart failure
• Elderly patients
• Young adults
• Essential tremor
• Apnea and bradycardia in premature infants
• Hypersensitivity to drug or other xanthines (such as coffee, theobromine)
• Active peptic ulcer
• Seizure disorder
Use cautiously in:
• alcoholism; heart failure or other cardiac or circulatory impairment; hypertension; renal or hepatic disease; COPD; hypoxemia; hyperthyroidism; diabetes mellitus; glaucoma; peptic ulcer disease
• elderly patients
• children younger than age 1.
• For I.V. delivery, use infusion solution designed for drug, or mix with dextrose 5% in water. Administer by controlled infusion pump.
• Know that for acute bronchospasm, theophylline preferably is given I.V. as 20 mg/ml of theophylline (or 25 mg/ml of aminophylline).
• Don't give timed-release form to patient with acute bronchospasm.
CNS: irritability, dizziness, nervousness, restlessness, headache, insomnia, reflex hyperexcitability, seizures
CV: palpitations, marked hypotension, sinus tachycardia, extrasystole, circulatory failure, ventricular arrhythmias
GI: nausea, vomiting, diarrhea, hematemesis, gastroesophageal reflux
GU: increased diuresis, proteinuria
Metabolic: hyperglycemia, syndrome of inappropriate antidiuretic hormone secretion
Musculoskeletal: muscle twitching
Respiratory: tachypnea, respiratory arrest
Skin: urticaria, rash, alopecia, flushing
Other: fever, hypersensitivity reaction
Drug-drug. Allopurinol, calcium channel blockers, cimetidine, corticosteroids, disulfiram, ephedrine, hormonal contraceptives, influenza virus vaccine, interferon, macrolides, mexiletine, nonselective beta-adrenergic blockers, quinolones, thiabendazole: increased theophylline blood level, greater risk of toxicity
Aminoglutethimide, barbiturates, ketoconazole, rifampin, sulfinpyrazone, sympathomimetics: decreased theophylline blood level and effects
Carbamazepine, isoniazid, loop diuretics: increased or decreased theophylline blood level
Halothane: increased risk of arrhythmias
Hydantoins: decreased hydantoin blood level
Lithium: decreased therapeutic effect of lithium
Nondepolarizing muscle relaxants: reversal of neuromuscular blockade
Propofol: antagonism of propofol's sedative effects
Tetracyclines: increased risk of adverse reactions to theophylline
Drug-diagnostic tests. Glucose: increased level
Drug-food. Any food: altered bioavailability and absorption of some timed-release theophylline forms, causing rapid release and possible toxicity
Caffeine- or xanthine-containing foods and beverages: increased theophylline blood level and greater risk of adverse CNS and cardiovascular reactions
Diet high in protein and charcoal-broiled beef and low in carbohydrates: increased theophylline elimination, decreased efficacy
High-carbohydrate, low-protein diet: decreased theophylline elimination, increased risk of adverse reactions
Drug-herbs. Caffeine-containing herbs (such as cola nut, guarana, maté): increased theophylline blood level, greater risk of adverse CNS and cardiovascular reactions
Ephedra (ma huang): increased stimulant effect
St. John's wort: decreased theophylline blood level and efficacy
Drug-behaviors. Nicotine (in cigarettes, gum, transdermal patches): increased theophylline metabolism, decreased efficacy
• Monitor for signs and symptoms of hypersensitivity reaction, including rash and fever.
• Assess respiratory status. Monitor pulmonary function tests to gauge drug efficacy and identify adverse effects.
• Monitor cardiovascular and neurologic status carefully.
• Assess glucose level in diabetic patient.
• Advise patient to take oral form with 8 oz of water 1 hour before or 2 hours after meals.
• Tell patient not to crush or chew timed-release form.
• Caution patient not to use different drug brands interchangeably.
Instruct patient to immediately report worsening dyspnea and other respiratory problems.
• Teach patient to recognize and report adverse neurologic reactions.
• Tell patient that all nicotine forms (including cigarettes, patches, and gum) decrease drug efficacy. Discourage nicotine use.
• Advise patient that a diet high in protein and charcoal-broiled beef and low in carbohydrates makes drug less effective.
• Tell patient that a high-carbohydrate, low-protein diet increases risk of adverse reactions, as do products containing caffeine.
• Caution patient to avoid herbs, especially ephedra and St. John's wort.
• Advise patient not to take over-the-counter drugs without prescriber's approval. Tell him to inform all prescribers he's taking drug, because it interacts with many other drugs.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviors mentioned above.
- CNS stimulation,
- Positive inotropic and chronotropic effects,
- Gastric acid secretion.
Time/action profile (bronchodilation)
|PO||rapid||1–2 hr||6 hr|
|PO-ER||delayed||4–8 hr||8–24 hr|
|IV||rapid||end of infusion||6–8 hr|
Adverse Reactions/Side Effects
Central nervous system
- seizures (life-threatening)
- anxiety (most frequent)
- arrhythmias (life-threatening)
- tachycardia (most frequent)
- nausea (most frequent)
- vomiting (most frequent)
Drug-Drug interactionAdditive CV and CNS side effects with adrenergics (sympathomimetic).May ↓ the therapeutic effect of lithium and phenytoin.Smoking, barbiturates, carbamazepine, phenytoin, nevirapine and rifampin may ↑ metabolism and may decrease effectiveness.Erythromycin, beta blockers, clarithromycin, calcium channel blockerscimetidine,hormonal contraceptives, disulfiram, doxycycline, estrogens, fluvoxamine, isoniazid, ketoconazole, mexiletine, nefazodone, protease inhibitors, quinidine, some fluoroquinolones, and large doses of allopurinol ↓ metabolism and may lead to toxicity.Caffeine-containing herbs (cola nut, guarana, mate, tea, coffee) may ↑ serum levels and risk of CNS and CV side effects.↓ serum levels and effectiveness with St. John’s wort.Excessive regular intake of charcoal-broiled foods may ↓ effectiveness.
Route/DosageDose should be determined by theophylline serum level monitoring. Loading dose should be ↓ or eliminated if theophylline preparation has been used in preceding 24 hr. Aminophylline is 80% theophylline (100 mg aminophylline = 80 mg theophylline). Extended-release (controlled-release, sustained-release) products may be given q 8–24 hr, depending upon the formulation.
Availability (generic available)
- Assess BP, pulse, respiratory status (rate, lung sounds, use of accessory muscles) before and throughout therapy. Ensure that oxygen therapy is correctly instituted during acute asthma attacks.
- Monitor intake and output ratios for an increase in diuresis or fluid overload.
- Patients with a history of cardiovascular problems should be monitored for chest pain and ECG changes (PACs, supraventricular tachycardia, PVCs, ventricular tachycardia). Resuscitative equipment should be readily available.
- Monitor pulmonary function tests before and periodically during therapy to determine therapeutic efficacy in patients with chronic bronchitis or emphysema.
- Lab Test Considerations: Monitor ABGs, acid-base, and fluid and electrolyte balance in patients receiving parenteral therapy or whenever required by patient’s condition. Monitor drug levels routinely, especially in patients requiring high doses or during prolonged intensive therapy. Obtain serum sample at time of peak absorption. Evaluate peak levels 30 min after a 30 min IV loading dose, 12–24 hr after initiation of a continuous infusion and 1–2 hr after rapid-acting oral forms, and 4–12 hr after extended-release oral forms. Therapeutic plasma levels range from 10–15 mcg/mL for asthma and 6–14 mcg/mL for apnea of prematurity. Drug levels in excess of 20 mcg/mL are associated with toxicity. Caffeine ingestion may falsely elevate drug concentration levels.
- Observe patient for symptoms of drug toxicity (anorexia, nausea, vomiting, stomach cramps, diarrhea, confusion, headache, restlessness, flushing, increased urination, insomnia, tachycardia, arrhythmias, seizures). Notify health care professional immediately if these occur. Tachycardia, ventricular arrhythmias, or seizures may be the first sign of toxicity. Geriatric: Patients over 60 yr have ↑ risk of toxicity and sensitivity to toxic effects due to age-related pharmacodynamic and pharmacokinetic changes. Theophylline doses should not exceed 400 mg/d..
Potential Nursing DiagnosesIneffective airway clearance (Indications)
Activity intolerance (Indications)
- Administer around the clock to maintain therapeutic plasma levels. Administer once-a-day doses in the morning.
- Do not refrigerate elixirs or solutions; crystals may form. Crystals should dissolve when liquid is warmed to room temperature.
- Wait at least 4–6 hr after stopping IV therapy to begin immediate-release oral dosage; for extended-release oral dosage form, give 1st oral dose at time of IV discontinuation.
- Oral: Administer oral preparations with food or a full glass of water to minimize GI irritation. Food slows but does not reduce the extent of absorption. May be administered 1 hr before or 2 hr after meals for more rapid absorption. Swallow tablets and capsules whole; do not crush, break, open or chew controlled-release or extended-release tablets or capsules (extended-release tablets may be broken if scored). Pediatric: Use calibrated measuring device to ensure accurate dose of liquid preparations.
- Continuous Infusion: IV theophylline in 5% dextrose are packed in a moisture-barrier overwrap. Remove immediately before administration and squeeze bag to check for leaks. Discard if solution is not clear.
- Loading Dose: Administer over 20–30 min. If patient has had another form of theophylline before loading dose, obtain serum theophylline level and reduce loading dose proportionately.
- Rate: Rapid administration may cause chest pain, dizziness, hypotension, tachypnea, flushing, arrhythmias, or a reaction to the solution or administration technique (chills; fever; redness, pain, or swelling at injection site). Infusion rate may be ↑ after 12 hr. Administer via infusion pump to ensure accurate dose. Monitor ECG continuously; tachyarrhythmias may occur.
- Y-Site Compatibility: acyclovir, alemtuzumab, alfentanil, amikacin, aminophylline, amphotericin B lipid complex, amphotericin B liposome, anidulafungin, argatroban, ascorbic acid, atracurium, atropine, aztreonam, benztropine, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium chloride, calcium gluconate, carboplatin, caspofungin, cefazolin, cefoperazone, cefotaxime, cefotetan, cefoxitin, ceftriaxone, cefuroxime, chloramphenicol, chlorpromazine, cisatracurium, cisplatin, clindamycin, cyanocobalamin, cyclophosphamide, cyclosporine, cytarabine, dactinomycin, daptomycin, dexamethasone sodium phosphate, dexmedetomidine, dexrazoxane, digoxin, diltiazem, diphenhydramine, dobutamine, docetaxel, dolasetron, dopamine, doxacurium, doxorubicin hydrochloride, doxycycline, enalaprilat, ephedrine, epinephrine, epirubicin, epoetin alfa, ertapenem, erythromycin lactobionate, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, fluconazole, fludarabine, fluorouracil, folic acid, foscarnet, furosemide, gemcitabine, gentamicin, glycopyrrolate, granisetron, heparin, hydrocortisone sodium succinate, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, indomethacin, insulin, irinotecan, isoproterenol, ketorolac, labetalol, leucovorin, levofloxacin, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, mesna, metaraminol, methotrexate, methyldopate, methylprednisolone sodium succinate, metoclopramide, metoprolol, metronidazole, micafungin, midazolam, milrinone, minocycline, mitomycin, mitoxantrone, mivacurium, morphine, moxifloxacin, multiple vitamins, mycophenolate, nafcillin, nalbuphine, naloxone, nesiritide, nitroglycerin, nitroprusside, norepinephrine, ondansetron, oxacillin, oxaliplatin, oxytocin, paclitaxel, palonosetron, pantoprazole, papaverine, pemetrexed, penicillin G, pentamidine, pentazocine, pentobarbital, phenobarbital, phentolamine, phenylephrine, phytonadione, piperacillin/tazobactam, potassium acetate, potassium chloride, procainamide, prochlorperazine, promethazine, propranolol, protamine, pyridoxime, quinapristin/dalfopristin, ranitidine, remifentanil, rituximab, rocuronium, sodium acetate, sodium bicarbonate, streptokinase, succinylcholine, sufentanil, tacrolimus, teniposide, thiamine, thiotepa, ticarcillin/clavulanate, tigecycline, tirofiban, tobramycin, tolazoline, trastuzumab, vasopressin, vecuronium, verapamil, vinblastine, vincristine, vinorelbine, voriconazole, zolendronic acid
- Y-Site Incompatibility: azathioprine, cefepime, dantrolene, diazepam, diazoxide, doxorubicin liposomal, ganciclovir, hetastarch, inamrinone, phenytoin, trimethoprim/sulfamethoxazole
- Additive Incompatibility: Admixing is not recommended because of dose titration and incompatibilities.
- Emphasize the importance of taking only the prescribed dose at the prescribed time intervals. Take missed doses as soon as possible or omit if close to next dose.
- Encourage the patient to drink adequate liquids (2000 mL/day minimum) to decrease the viscosity of the airway secretions.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially OTC cough, cold, or breathing preparations ; may increase side effects and cause arrhythmias.
- Encourage patients not to smoke. A change in smoking habits may necessitate a change in dose.
- Advise patient to minimize intake of xanthine-containing foods or beverages (colas, coffee, chocolate) and not to eat charcoal-broiled foods daily.
- Instruct patient not to change brands without consulting health care professional.
- Advise patient to contact health care professional promptly if the usual dose of medication fails to produce the desired results, symptoms worsen after treatment, or toxic effects occur.
- Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
- Emphasize the importance of having serum levels routinely tested every 6–12 mo.
- Increased ease in breathing.
- Clearing of lung fields on auscultation.