Theophylline 450 mg Tablet, Extended Release, 100-count
Other active recalls for Theophylline (different manufacturers) — 2 · tap to view
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Methylxanthine class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Theophylline is used to prevent and treat wheezing, shortness of breath, and chest tightness caused by asthma, chronic bronchitis, emphysema, and other lung diseases. It relaxes and opens air passages in the lungs, making it easier to breathe.
Read the full MedlinePlus article ↗- Theophylline is a long-term controller medicine for chronic asthma, emphysema, and chronic bronchitis. It works by relaxing the muscles around your airways so they stay more open,...
- What exactly is theophylline supposed to do for me?
- Yes, timing matters. If you're on Theo-24 extended-release capsules once a day, take it every morning at roughly the same time — taking it at night is not recommended because your...
- How should I take my theophylline, and does it matter when I take it?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Theophylline — tap one for details:
Theophylline may be associated with lower levels of 2 nutrients — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
Where does this data come from?
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
-
UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
-
UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
-
UNII FZ989GH94E
Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
-
UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
5 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $0.8789 | $87.89 / 100 tablets |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Theophylline 450 mg 00480-3309-01 | Teva | 100 tablets | $1.050 | AB | Availability likely | — |
| Theophylline 450 mg 23155-0742-01 | Heritage | 100 tablets | $1.050 | AB | Availability likely | — |
| Theophylline 450 mg 31722-0078-01 | Camber | 100 tablets | $1.050 | AB | Availability likely | — |
| theophylline 450 mg 60219-2046-01 | Amneal | 100 tablets | $1.050 | AB | Availability likely | — |
| Theophylline 450 mg 64380-0244-01 | Strides | 100 tablets | $1.050 | AB | Availability likely | — |
| Theophylline 450 mg 68462-0722-01 | Glenmark | 100 tablets | $1.050 | AB | Availability likely | — |
| Theophylline 450 mg 69315-0227-01 | Leading | 100 tablets | $1.050 | AB | Availability likely | — |
| Theophylline 450 mg 72578-0174-01 | Viona | 100 tablets | $1.050 | AB | Availability likely | — |
| Theophylline 450 mg 27241-0273-01 | Ajanta | 100 tablets | — | — | FDA listed | — |
| Theophylline 450 mg 46708-0026-30 | Alembic | 30 tablets | — | AB | FDA listed | — |
| Theophylline 450 mg 62332-0026-30 | Alembic | 30 tablets | — | AB | FDA listed | — |
| Theophylline 450 mg 70771-1783-01 | Zydus | 100 tablets | — | AB | FDA listed | — |
| Theophylline 450 mg 72789-0442-01 | PD-Rx | 100 tablets | — | AB | FDA listed | — |
| Theophylline 450 mgthis 82638-0106-02 | Harman | 100 tablets | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 82638-0106-02 You're viewing this | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE (82638-106-02) | 2024-07-30 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
Why is there no price listed?
Is the NDC printed on the package the same as the 11-digit billing NDC?
What do the three segments of this NDC mean?
Is this package still being marketed?
Who lists this product with the FDA?
Do I need a prescription for this product?
Where does this data come from?
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
INDICATIONS AND USAGE: Theophylline extended-release tablets are indicated for the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, e.g., emphysema and chronic bronchitis.
⏱️ Dosage and Administration ▾
DOSAGE AND ADMINISTRATION: Taking theophylline extended-release tablets immediately after a high-fat content meal may result in a somewhat higher C max and delayed T max and somewhat greater extent of absorption. However, the differences are usually not great and this product may normally be administered without regard to meals (see CLINICAL PHARMACOLOGY, Drug interactions, Drug-Food Interactions ). Theophylline extended-release tablets are recommended for chronic or long-term management and prevention of symptoms, and not for use in treating acute symptoms of asthma and reversible bronchospasm.
General considerations: The steady-state peak serum theophylline concentration is a function of the dose, the dosing interval, and the rate of theophylline absorption and clearance in the individual patient. Because of marked individual differences in the rate of theophylline clearance, the dose required to achieve a peak serum theophylline concentration in the 10-20 mcg/mL range varies fourfold among otherwise similar patients in the absence of factors known to alter theophylline clearance (e.g., 400- 1600 mg/day in adults <60 years old and 10-36 mg/kg/day in children 1-9 years old).
For a given population there is no single theophylline dose that will provide both safe and effective serum concentrations for all patients. Administration of the median theophylline dose required to achieve a therapeutic serum theophylline concentration in a given population may result in either sub-therapeutic or potentially toxic serum theophylline concentrations in individual patients. For example, at a dose of 900 mg/d in adults <60 years or 22 mg/kg/d in children 1-9 years, the steady-state peak serum theophylline concentration will be <10 mcg/mL in about 30% of patients, 10-20 mcg/mL in about 50% and 20-30 mcg/mL in about 20% of patients.
The dose of theophylline must be individualized on the basis of peak serum theophylline concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk of adverse effects. Transient caffeine-like adverse effects and excessive serum concentrations in slow metabolizers can be avoided in most patients by starting with a sufficiently low dose and slowly increasing the dose, if judged to be clinically indicated , in small increments (see Table V). Dose increases should only be made if the previous dosage is well tolerated and at intervals of no less than 3 days to allow serum theophylline concentrations to reach the new steady state.
Dosage adjustment should be guided by serum theophylline concentration measurement (see PRECAUTIONS, Laboratory Tests and DOSAGE AND ADMINISTRATION, Table VI ). Health care providers should instruct patients and care givers to discontinue any dosage that causes adverse effects, to withhold the medication until these symptoms are gone and to then resume therapy at a lower, previously tolerated dosage (see WARNINGS ). If the patient's symptoms are well controlled, there are no apparent adverse effects, and no intervening factors that might alter dosage requirements (see WARNINGS and PRECAUTIONS ), serum theophylline concentrations should be monitored at 6 month intervals for rapidly growing children and at yearly intervals for all others.
In acutely ill patients, serum theophylline concentrations should be monitored at frequent intervals, e.g., every 24 hours. Theophylline distributes poorly into body fat, therefore, mg/kg dose should be calculated on the basis of ideal body weight. Table V contains theophylline dosing titration schema recommended for patients in various age groups and clinical circumstances.
Table VI contains recommendations for theophylline dosage adjustment based upon serum theophylline concentrations. Application of these general dosing recommendations to individual patients must take into account the unique clinical characteristics of each patient. In general, these recommendations should serve as the upper limit for d…
⛔ Contraindications ▾
CONTRAINDICATIONS: Theophylline extended-release tablets are contraindicated in patients with a history of hypersensitivity to theophylline or other components in the product.
⚠️ Warnings ▾
WARNINGS: Concurrent Illness: Theophylline should be used with extreme caution in patients with the following clinical conditions due to the increased risk of exacerbation of the concurrent condition: Active peptic ulcer disease Seizure disorders Cardiac arrhythmias (not including bradyarrhythmias) Conditions that Reduce Theophylline Clearance: There are several readily identifiable causes of reduced theophylline clearance. If the total daily dose is not appropriately reduced in the presence of these risk factors, severe and potentially fatal theophylline toxicity can occur.
Careful consideration must be given to the benefits and risks of theophylline use and the need for more intensive monitoring of serum theophylline concentrations in patients with the following risk factors: Age: Neonates (term and premature), Children <1 year, Elderly (>60 years) Concurrent Diseases: Acute pulmonary edema, congestive heart failure, cor-pulmonale, fever (≥102° for 24 hours or more; or lesser temperature elevations for longer periods), reduced renal function in infants <3 months of age, sepsis with multi-organ failure and shock.
Cessation of Smoking Drug Interactions: Adding a drug that inhibits theophylline metabolism (e.g., cimetidine, erythromycin, tacrine) or stopping a concurrently administered drug that enhances theophylline metabolism (e.g., carbamazepine, rifampin). (see PRECAUTIONS, Drug Interactions, Table II ). When Signs or Symptoms of Theophylline Toxicity Are Present: Whenever a patient receiving theophylline develops nausea or vomiting, particularly repetitive vomiting, or other signs or symptoms consistent with theophylline toxicity (even if another cause may be suspected), additional doses of theophylline should be withheld and a serum theophylline concentration measured immediately.
Patients should be instructed not to continue any dosage that causes adverse effects and to withhold subsequent doses until the symptoms have resolved, at which time the healthcare professional may instruct the patient to resume the drug at a lower dosage (see DOSAGE AND ADMINISTRATION, Dosing Guidelines, Table VI). Dosage Increases: Increases in the dose of theophylline should not be made in response to an acute exacerbation of symptoms of chronic lung disease since theophylline provides little added benefit to inhaled beta2 -selective agonists and systemically administered cortico-steroids in this circumstance and increases the risk of adverse effects.
A peak steady-state serum theophylline concentration should be measured before increasing the dose in response to persistent chronic symptoms to ascertain whether an increase in dose is safe. Before increasing the theophylline dose on the basis of a low serum concentration, the healthcare professional should consider whether the blood sample was obtained at an appropriate time in relationship to the dose and whether the patient has adhered to the prescribed regimen (see PRECAUTIONS, Laboratory Tests ). As the rate of theophylline clearance may be dose-dependent (i.e., steady-state serum concentrations may increase disproportionately to the increase in dose), an increase in dose based upon a sub-therapeutic serum concentration measurement should be conservative.
In general, limiting dose increases to about 25% of the previous total daily dose will reduce the risk of unintended excessive increases in serum theophylline concentration (see DOSAGE AND ADMINISTRATION, Table VI ).
🤒 Adverse Reactions ▾
ADVERSE REACTIONS: Adverse reactions associated with theophylline are generally mild when peak serum theophylline concentrations are <20 mcg/mL and mainly consist of transient caffeine-like adverse effects such as nausea, vomiting, headache, and insomnia. When peak serum theophylline concentrations exceed 20 mcg/mL, however, theophylline produces a wide range of adverse reactions including persistent vomiting, cardiac arrhythmias, and intractable seizures which can be lethal (see OVERDOSAGE ). The transient caffeine-like adverse reactions occur in about 50% of patients when theophylline therapy is initiated at doses higher than recommended initial doses (e.g.,>300 mg/day in adults and >12 mg/kg/day in children beyond 1 year of age).
During the initiation of theophylline therapy, caffeine-like adverse effects may transiently alter patient behavior, especially in school age children, but this response rarely persists. Initiation of theophylline therapy at a low dose with subsequent slow titration to a predetermined age-related maximum dose will significantly reduce the frequency of these transient adverse effects (see DOSAGE AND ADMINISTRATION, Table V ). In a small percentage of patients (<3% of children and <10% of adults) the caffeine-like adverse effects persist during maintenance therapy, even at peak serum theophylline concentrations within the therapeutic range (i.e., 10-20 mcg/mL).
Dosage reduction may alleviate the caffeine-like adverse effects in these patients, however, persistent adverse effects should result in a reevaluation of the need for continued theophylline therapy and the potential therapeutic benefit of alternative treatment.Other adverse reactions that have been reported at serum theophylline concentrations <20 mcg/mL include diarrhea, irritability, restlessness, fine skeletal muscle tremors, and transient diuresis. In patients with hypoxia secondary to COPD, multifocal atrial tachycardia and flutter have been reported at serum theophylline concentrations 15 mcg/mL.
There have been a few isolated reports of seizures at serum theophylline concentrations <20 mcg/mL in patients with an underlying neurological disease or in elderly patients. The occurrence of seizures in elderly patients with serum theophylline concentrations <20 mcg/mL may be secondary to decreased protein binding resulting in a larger proportion of the total serum theophylline concentration in the pharmacologically active unbound form. The clinical characteristics of the seizures reported in patients with serum theophylline concentrations <20 mcg/mL have generally been milder than seizures associated with excessive serum theophylline concentrations resulting from an overdose (i.e. they have generally been transient, often stopped without anticonvulsant therapy, and did not result in neurological residua).
Table IV. Manifestations of theophylline toxicity.* Percentage of patients reported with sign or symptoms Acute Overdose (Large Single Ingestion) Chronic Overdosage (Multiple Excessive Doses) Sign / Symptom Study 1 (n = 157) Study 2 (n = 14) Study 1 (n = 92) Study 2 (n = 102) Asymptomatic NR** 0 NR** 6 Gastrointestinal Vomiting 73 93 30 61 Abdominal Pain NR** 21 NR** 12 Diarrhea NR** 0 NR** 14 Hematemesis NR** 0 NR** 2 Metabolic/Other Hypokalemia 85 79 44 43 Hyperglycemia 98 NR** 18 NR** Acid/base disturbance 34 21 9 5 Rhabdomyolysis NR** 7 NR** 0 Cardiovascular Sinus tachycardia 100 86 100 62 Other Supraventricular Tachycardias 2 21 12 14 Ventricular premature beats 3 21 10 19 Atrial fibrillation or flutter 1 NR** 12 NR** Multifocal atrial tachycardia 0 NR** 2 NR** Ventricular arrhythmias hemodynamic instability 7 14 40 0 Hypotension/shock NR** 21 NR** 8 Neurologic Nervousness NR** 64 NR** 21 Tremors 38 29 16 14 Disorientation NR** 7 NR** 11 Seizures 5 14 14 5 Death 3 21 10 4 * These data are derived from two studies in patients with serum theophylline concentrations >30 mcg/mL.
In the first study (Study #1 - Shanon, Ann Intern Med 1993; 1…
🔄 Drug Interactions ▾
Drug Interactions: Drug-Drug Interactions: Theophylline interacts with a wide variety of drugs. The interaction may be pharmacodynamic, i.e., alterations in the therapeutic response to theophylline or another drug or occurrence of adverse effects without a change in serum theophylline concentration. More frequently, however, the interaction is pharmacokinetic, i.e., the rate of theophylline clearance is altered by another drug resulting in increased or decreased serum theophylline concentrations.
Theophylline only rarely alters the pharmacokinetics of other drugs. The drugs listed in Table II have the potential to produce clinically significant pharmacodynamic or pharmacokinetic interactions with theophylline. The information in the "Effect" column of Table II assumes that the interacting drug is being added to a steady-state theophylline regimen.
If theophylline is being initiated in a patient who is already taking a drug that inhibits theophylline clearance (e.g., cimetidine, erythromycin), the dose of theophylline required to achieve a therapeutic serum theophylline concentration will be smaller. Conversely, if theophylline is being initiated in a patient who is already taking a drug that enhances theophylline clearance (e.g., rifampin), the dose of theophylline required to achieve a therapeutic serum theophylline concentration will be larger. Discontinuation of a concomitant drug that increases theophylline clearance will result in accumulation of theophylline to potentially toxic levels, unless the theophylline dose is appropriately reduced.
Discontinuation of a concomitant drug that inhibits theophylline clearance will result in decreased serum theophylline concentrations, unless the theophylline dose is appropriately increased. The drugs listed in Table III have either been documented not to interact with theophylline or do not produce a clinically significant interaction (i.e., <15% change in theophylline clearance). The listing of drugs in Tables II and III are current as of February 9, 1995.
New interactions are continuously being reported for theophylline, especially with new chemical entities. The healthcare professional should not assume that a drug does not interact with theophylline if it is not listed in Table II. Before addition of a newly available drug in a patient receiving theophylline, the package insert of the new drug and/or the medical literature should be consulted to determine if an interaction between the new drug and theophylline has been reported.
Table II. Clinically significant drug interactions with theophylline.* Drug Type of Interaction Effect** Adenosine Theophylline blocks adenosine receptors. Higher doses of adenosine may be required to achieve desired effect.
Alcohol A single large dose of alcohol (3 mL/kg of whiskey) decreases theophylline clearance for up to 24 hours. 30% increase Allopurinol Decreases Theophylline clearance at allopurinol doses 600 mg/day. 25% increase Aminoglutethimide Increases theophylline clearance by induction of microsomal enzyme activity.
25% decrease Carbamazepine Similar to aminoglutethimide. 30% decrease Cimetidine Decreases theophylline clearance by inhibiting cytochrome P450 1A2. 70% increase Ciprofloxacin Similar to cimetidine.
40% increase Clarithromycin Similar to erythromycin. 25% increase Diazepam Benzodiazepines increase CNS concentrations of adenosine, a potent CNS depressant, while theophylline blocks adenosine receptors. Larger diazepam doses may be required to produce desired level of sedation.
Discontinuation of Theophylline without reduction of diazepam dose may result in respiratory depression. Disulfiram Decreases theophylline clearance by inhibiting hydroxylation and demethylation. 50% increase Enoxacin Similar to cimetidine.
300% increase Ephedrine Synergistic CNS effects. Increased frequency of nausea, nervousness, and insomnia. Erythromycin Erythromycin metabolite decreases theophylline clearance by inhibiting cytochrome P450 3A3.
35% incr…
🤰 Pregnancy ▾
Pregnancy: Teratogenic Effects: In studies in which pregnant mice, rats and rabbits were dosed during the period of organogenesis, theophylline produced teratogenic effects. In studies with mice, a single intraperitoneal dose at and above 100 mg/kg (approximately equal to the maximum recommended oral dose for adults on a mg/m 2 basis) during organogenesis produced cleft palate and digital abnormalities. Micromelia, micrognathia, clubfoot, subcutaneous hematoma, open eyelids, and embryolethality were observed at doses that are approximately 2 times the maximum recommended oral dose for adults on a mg/m 2 basis.
In a study with rats dosed from conception through organogenesis, an oral dose of 150 mg/kg/day (approximately 2 times the maximum recommended oral dose for adults on a mg/m 2 basis) produced digital abnormalities. Embryolethality was observed with a subcutaneous dose of 200 mg/kg/day (approximately 4 times the maximum recommended oral dose for adults on a mg/m 2 basis). In a study in which pregnant rabbits were dosed throughout organogenesis, an intravenous dose of 60 mg/kg/day (approximately 2 times the maximum recommended oral dose for adults on a mg/m 2 basis), which caused the death of one doe and clinical signs in others, produced cleft palate and was embryolethal.
Doses at and above 15 mg/kg/day (less than the maximum recommended oral dose for adults on a mg/m 2 basis) increased the incidence of skeletal variations. There are no adequate and well-controlled studies in pregnant women. Theophylline should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
🧒 Pediatric Use ▾
Pediatric Use: Theophylline is safe and effective for the approved indications in pediatric patients. The maintenance dose of theophylline must be selected with caution in pediatric patients since the rate of theophylline clearance is highly variable across the pediatric age range (see CLINICAL PHARMACOLOGY, Table I, WARNINGS, and DOSAGE AND ADMINISTRATION, Table V ).
🧓 Geriatric Use ▾
Geriatric Use: Elderly patients are at a significantly greater risk of experiencing serious toxicity from theophylline than younger patients due to pharmacokinetic and pharmacodynamic changes associated with aging. The clearance of theophylline is described by an average of 30% in healthy elderly adults (>60 yrs) compared to healthy young adults. Theophylline clearance may be further reduced by concomitant diseases prevalent in the elderly, which further impair clearance of this drug and have the potential to increase serum levels and potential toxicity.
These conditions include impaired renal function, chronic obstructive pulmonary disease, congestive heart failure, hepatic disease and an increased prevalence of use of certain medications (see P RECAUTIONS: Drug Interactions ) with the potential for pharmacokinetic and pharmacodynamic interaction. Protein binding may be decreased in the elderly resulting in an increased proportion of the total serum theophylline concentration in the pharmacologically active unbound form. Elderly patients also appear to be more sensitive to the toxic effects of theophylline after chronic overdosage than younger patients.
Careful attention to dose reduction and frequent monitoring of serum theophylline concentrations are required in elderly patients (see PRECAUTIONS, Monitoring Serum Theophylline Concentrations, and DOSAGE AND ADMINISTRATION ). The maximum daily dose of theophylline in patients greater than 60 years of age ordinarily should not exceed 400 mg/day unless the patient continues to be symptomatic and the peak steady-state serum theophylline concentration is <10 mcg/mL (see DOSAGE AND ADMINISTRATION ). Theophylline doses greater than 400 mg/d should be prescribed with caution in elderly patients.
🆘 Overdosage ▾
OVERDOSAGE: General: The chronicity and pattern of theophylline overdosage significantly influences clinical manifestations of toxicity, management and outcome. There are two common presentations: (1) acute overdose , i.e., ingestion of a single large excessive dose (>10 mg/kg) as occurs in the context of an attempted suicide or isolated medication error, and (2) chronic overdosage , i.e., ingestion of repeated doses that are excessive for the patient's rate of theophylline clearance. The most common causes of chronic theophylline overdosage include patient or care giver error in dosing, healthcare professional prescribing of an excessive dose or a normal dose in the presence of factors known to decrease the rate of theophylline clearance, and increasing the dose in response to an exacerbation of symptoms without first measuring the serum theophylline concentration to determine whether a dose increase is safe.
Severe toxicity from theophylline overdose is a relatively rare event. In one health maintenance organization, the frequency of hospital admissions for chronic overdosage of theophylline was about 1 per 1000 person-years exposure. In another study, among 6000 blood samples obtained for measurement of serum theophylline concentration, for any reason, from patients treated in an emergency department, 7% were in the 20-30 mcg/mL range and 3% were >30 mcg/mL.
Approximately two-thirds of the patients with serum theophylline concentrations in the 20-30 mcg/mL range had one or more manifestations of toxicity while >90% of patients with serum theophylline concentrations >30 mcg/mL were clinically intoxicated. Similarly, in other reports, serious toxicity from theophylline is seen principally at serum concentrations >30 mcg/mL. Several studies have described the clinical manifestations of theophylline overdose and attempted to determine the factors that predict life-threatening toxicity.
In general, patients who experience an acute overdose are less likely to experience seizures than patients who have experienced a chronic overdosage, unless the peak serum theophylline concentration is >100 mcg/mL. After a chronic over dosage, generalized seizures, life-threatening cardiac arrhythmias, and death may occur at serum theophylline concentrations >30 mcg/mL. The severity of toxicity after chronic over dosage is more strongly correlated with the patient's age than the peak serum theophylline concentration; patients >60 years are at the greatest risk for severe toxicity and mortality after a chronic overdosage.
Preexisting or concurrent disease may also significantly increase the susceptibility of a patient to a particular toxic manifestation, e.g., patients with neurologic disorders have an increased risk of seizures and patients with cardiac disease have an increased risk of cardiac arrhythmias for a given serum theophylline concentration compared to patients without the underlying disease. The frequency of various reported manifestations of theophylline overdose according to the mode of overdose are listed in Table IV. Other manifestations of theophylline toxicity include increases in serum calcium, creatine kinase, myoglobin and leukocyte count, decreases in serum phosphate and magnesium, acute myocardial infarction, and urinary retention in men with obstructive uropathy.
Seizures associated with serum theophylline concentrations >30 mcg/mL are often resistant to anticonvulsant therapy and may result in irreversible brain injury if not rapidly controlled. Death from theophylline toxicity is most often secondary to cardiorespiratory arrest and/or hypoxic encephalopathy following prolonged generalized seizures or intractable cardiac arrhythmias causing hemodynamic compromise. Overdose Management General Recommendations for Patients with Symptoms of Theophylline Overdose or Serum Theophylline Concentrations >30 mcg/mL (Note: Serum theophylline concentrations may continue to increase after presentation of the patient for medical care.)…
🧬 Clinical Pharmacology ▾
CLINICAL PHARMACOLOGY: Mechanism of Action: Theophylline has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects). While the mechanisms of action of Theophylline are not known with certainty, studies in animals suggest that bronchodilation is mediated by the inhibition of two isozymes of phosphodiesterase (PDE III and, to a lesser extent, PDE IV) while non-bronchodilator prophylactic actions are probably mediated through one or more different molecular mechanisms, that do not involve inhibition of PDE III or antagonism of adenosine receptors.
Some of the adverse effects associated with theophylline appear to be mediated by inhibition of PDE III (e.g., hypotension, tachycardia, headache, and emesis) and adenosine receptor antagonism (e.g., alterations in cerebral blood flow). Theophylline increases the force of contraction of diaphragmatic muscles. This action appears to be due to enhancement of calcium uptake through an adenosine-mediated channel.
Serum Concentration-Effect Relationship: Bronchodilation occurs over the serum theophylline concentration range of 5-20 mcg/mL. Clinically important improvement in symptom control has been found in most studies to require peak serum theophylline concentrations > 10 mcg/mL, but patients with mild disease may benefit from lower concentrations. At serum theophylline concentrations > 20 mcg/mL, both the frequency and severity of adverse reactions increase.
In general, maintaining peak serum theophylline concentrations between 10 and 15 mcg/mL will achieve most of the drug's potential therapeutic benefit while minimizing the risk of serious adverse events. Pharmacokinetics: Overview: Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form. Theophylline does not undergo any appreciable pre-systemic elimination, distributes freely into fat-free tissues and is extensively metabolized in the liver.
The pharmacokinetics of theophylline vary widely among similar patients and cannot be predicted by age, sex, body weight or other demographic characteristics. In addition, certain concurrent illnesses and alterations in normal physiology (see Table I) and co-administration of other drugs (see Table II) can significantly alter the pharmacokinetic characteristics of theophylline. Within-subject variability in metabolism has also been reported in some studies, especially in acutely ill patients.
It is, therefore, recommended that serum theophylline concentrations be measured frequently in acutely ill patients (e.g., at 24-hr intervals) and periodically in patients receiving long-term therapy, e.g., at 6-12 month intervals. More frequent measurements should be made in the presence of any condition that may significantly alter theophylline clearance (see PRECAUTIONS, Laboratory Tests ). Table I.
Mean and range of total body clearance and half-life of theophylline related to age and altered physiological states. ¶ Population Characteristics Total body clearance* mean (range)†† (mL/kg/min) Half-life mean (range)†† (hr) Age Premature neonates postnatal age 3-15 days 0.29 (0.09-0.49) 30 (17-43) postnatal age 25-57 days 0.64 (0.04-1.2) 20 (9.4-30.6) Term infants postnatal age 1-2 days NR† 25.7 (25-26.5) postnatal age 3-30 weeks NR† 11 (6-29) Children 1-4 years 1.7 (0.5-2.9) 3.4 (1.2-5.6) 4-12 years 1.6 (0.8-2.4) NR† 13-15 years 0.9 (0.48-1.3) NR† 6-17 years 1.4 (0.2-2.6) 3.7 (1.5-5.9) Adults (16-60 years) otherwise healthy non-smoking asthmatics 0.65 (0.27-1.03) 8.7 (6.1-12.8) Elderly (>60 years) non-smokers with normal cardiac, liver, and renal function 0.41 (0.21-0.61) 9.8 (1.6-18) Concurrent illness or altered physiological state Acute pulmonary edema 0.33** (0.07-2.45) 19** (3.1-82) COPD->60 years, stable non-smoker >1 year 0.54 (0.44-0.64) 11 (9.4-12.6) C…
📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED: Theophylline Extended-Release Tablets: 300 mg: White to off-white, capsule shaped, uncoated functionally scored tablet debossed with "3" and "6" separated with a score line on one side and score line on other side. Tablet shall be free from physical defects. NDC 82638-105-02 Bottle of 100 450 mg: White to off-white, capsule shaped, uncoated functionally scored tablet debossed with "3" and "7" separated with a score line on one side and score line on other side.
Tablet shall be free from physical defects. NDC 82638-106-02 Bottle of 100 Dispense in a well-closed container, with child resistant closure [as defined in the USP]. Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature]
📋 Description ▾
DESCRIPTION Theophylline is structurally classified as a methylxanthine. It occurs as a white, odorless, crystalline powder with a bitter taste. Anhydrous theophylline has the chemical name 1 H -Purine -2, 6-dione, 3,7-dihydro-1, 3-dimethyl-, and is represented by the following structural formula: C 7 H 8 N 4 O 2 M.W.
180.17. This product allows a 12-hour dosing interval for a majority of patients and a 24-hour dosing interval for selected patients (see DOSAGE AND ADMINISTRATION section for description of appropriate patient populations). Each extended-release tablet for oral administration contains either 300 mg or 450 mg of anhydrous theophylline.
Tablets also contain as inactive ingredients: hypromellose, lactose monohydrate, magnesium stearate, povidone and colloidal silicone dioxide. image description