Uniphyl Information
Uniphyl (Theophylline) Description
Uniphyl (Theophylline) (theophylline, anhydrous) Tablets in a controlled-release system allows a 24-hour dosing interval for appropriate patients.
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 1H-Purine-2,6-dione, 3,7-dihydro-1,3-dimethyl-, and is represented by the following structural formula:
The molecular formula of anhydrous theophylline is CHNO with a molecular weight of 180.17.
Each controlled-release tablet for oral administration, contains 400 or 600 mg of anhydrous theophylline.
Inactive Ingredients: cetostearyl alcohol, hydroxyethyl cellulose, magnesium stearate, povidone and talc.
Uniphyl (Theophylline) Clinical Pharmacology
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 bronchodilatation 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.
Uniphyl (Theophylline) administered in the fed state is completely absorbed after oral administration.
In a single-dose crossover study, two 400 mg Uniphyl (Theophylline) Tablets were administered to 19 normal volunteers in the morning or evening immediately following the same standardized meal (769 calories consisting of 97 grams carbohydrates, 33 grams protein and 27 grams fat). There was no evidence of dose dumping nor were there any significant differences in pharmacokinetic parameters attributable to time of drug administration. On the morning arm, the pharmacokinetic parameters were AUC=241.9±83.0 mcg hr/mL, C=9.3±2.0 mcg/mL, T=12.8±4.2 hours. On the evening arm, the pharmacokinetic parameters were AUC=219.7±83.0 mcg hr/mL, C=9.2±2.0 mcg/mL, T=12.5±4.2 hours.
A study in which Uniphyl (Theophylline) 400 mg Tablets were administered to 17 fed adult asthmatics produced similar theophylline level-time curves when administered in the morning or evening. Serum levels were generally higher in the evening regimen but there were no statistically significant differences between the two regimens.
A single-dose study in 15 normal fasting male volunteers whose theophylline inherent mean elimination half-life was verified by a liquid theophylline product to be 6.9±2.5 (SD) hours were administered two or three 400 mg Uniphyl (Theophylline) Tablets. The relative bioavailability of Uniphyl (Theophylline) given in the fasting state in comparison to an immediate-release product was 59%. Peak serum theophylline levels occurred at 6.9±5.2 (SD) hours, with a normalized (to 800 mg) peak level being 6.2±2.1 (SD). The apparent elimination half-life for the 400 mg Uniphyl (Theophylline) Tablets was 17.2±5.8 (SD) hours.
Steady-state pharmacokinetics were determined in a study in 12 fasted patients with chronic reversible obstructive pulmonary disease. All were dosed with two 400 mg Uniphyl (Theophylline) Tablets given once daily in the morning and a reference controlled-release BID product administered as two 200 mg tablets given 12 hours apart. The pharmacokinetic parameters obtained for Uniphyl (Theophylline) Tablets given at doses of 800 mg once daily in the morning were virtually identical to the corresponding parameters for the reference drug when given as 400 mg BID. In particular, the AUC, C and C values obtained in this study were as follows:
Single-dose studies in which subjects were fasted for twelve (12) hours prior to and an additional four (4) hours following dosing, demonstrated reduced bioavailability as compared to dosing with food. One single-dose study in 20 normal volunteers dosed with two (2) 400 mg tablets in the morning, compared dosing under these fasting conditions with dosing immediately prior to a standardized breakfast (769 calories, consisting of 97 grams carbohydrates, 33 grams protein and 27 grams fat). Under fed conditions, the pharmacokinetic parameters were: AUC=231.7±92.4 mcg hr/mL, C=8.4±2.6 mcg/mL, T=17.3±6.7 hours. Under fasting conditions, these parameters were AUC=141.2±6.53 mcg hr/mL, C=5.5±1.5 mcg/mL, T=6.5±2.1 hours.
Another single-dose study in 21 normal male volunteers, dosed in the evening, compared fasting to a standardized high calorie, high fat meal (870-1,020 calories, consisting of 33 grams protein, 55-75 grams fat, 58 grams carbohydrates). In the fasting arm subjects received one Uniphyl (Theophylline) 400 mg Tablet at 8 p.m. after an eight hour fast followed by a further four hour fast. In the fed arm, subjects were again dosed with one 400 mg Uniphyl (Theophylline) Tablet, but at 8 p.m. immediately after the high fat content standardized meal cited above. The pharmacokinetic parameters (normalized to 800 mg) fed were AUC=221.8±40.9 mcg hr/mL, C=10.9±1.7 mcg/mL, T=11.8±2.2 hours. In the fasting arm, the pharmacokinetic parameters (normalized to 800 mg) were AUC=146.4±40.9 mcg hr/mL, C=6.7±1.7 mcg/mL, T=7.3±2.2 hours.
Thus, administration of single Uniphyl (Theophylline) doses to healthy normal volunteers, under prolonged fasted conditions (at least 10 hour overnight fast before dosing followed by an additional four (4) hour fast after dosing) results in decreased bioavailability. However, there was no failure of this delivery system leading to a sudden and unexpected release of a large quantity of theophylline with Uniphyl (Theophylline) Tablets even when they are administered with a high fat, high calorie meal.
Similar studies were conducted with the 600 mg Uniphyl (Theophylline) Tablet. A single-dose study in 24 subjects with an established theophylline clearance of ≤4 L/hr, compared the pharmacokinetic evaluation of one 600 mg Uniphyl (Theophylline) Tablet and one and one-half 400 mg Uniphyl (Theophylline) Tablets under fed (using a standard high fat diet) and fasted conditions. The results of this 4-way randomized crossover study demonstrate the bioequivalence of the 400 mg and 600 mg Uniphyl (Theophylline) Tablets. Under fed conditions, the pharmacokinetic results for the one and one-half 400 mg tablets were AUC=214.64±55.88 mcg hr/mL, C=10.58±2.21 mcg/mL and T=9.00±2.64 hours, and for the 600 mg tablet were AUC=207.85±48.9 mcg hr/mL, C=10.39±1.91 mcg/mL and T=9.58±1.86 hours. Under fasted conditions the pharmacokinetic results for the one and one-half 400 mg tablets were AUC=191.85 ±51.1 mcg hr/mL, C= 7.37±1.83 mcg/mL and T=8.08±4.39 hours; and for the 600 mg tablet were AUC=199.39±70.27 mcg hr/mL, C=7.66±2.09 mcg/mL and T=9.67±4.89 hours.
In this study the mean fed/fasted ratios for the one and one-half 400 mg tablets and the 600 mg tablet were about 112% and 104%, respectively.
In another study, the bioavailability of the 600 mg Uniphyl (Theophylline) Tablet was examined with morning and evening administration. This single-dose, crossover study in 22 healthy males was conducted under fed (standard high fat diet) conditions. The results demonstrated no clinically significant difference in the bioavailability of the 600 mg Uniphyl (Theophylline) Tablet administered in the morning or in the evening. The results were: AUC=233.6±45.1 mcg hr/mL, C=10.6±1.3 mcg/mL and T=12.5±3.2 hours with morning dosing; AUC=209.8±46.2 mcg hr/mL, C=9.7±1.4 mcg/mL and T=13.7±3.3 hours with evening dosing. The PM/AM ratio was 89.3%.
The absorption characteristics of Uniphyl (Theophylline) Tablets (theophylline, anhydrous) have been extensively studied. A steady-state crossover bioavailability study in 22 normal males compared two Uniphyl (Theophylline) 400 mg Tablets administered q24h at 8 a.m. immediately after breakfast with a reference controlled-release theophylline product administered BID in fed subjects at 8 a.m. immediately after breakfast and 8 p.m. immediately after dinner (769 calories, consisting of 97 grams carbohydrates, 33 grams protein and 27 grams fat).
The pharmacokinetic parameters for Uniphyl (Theophylline) 400 mg Tablets under these steady-state conditions were AUC=203.3±87.1 mcg hr/mL, C=12.1±3.8 mcg/mL, C=4.50±3.6, T=8.8±4.6 hours. For the reference BID product, the pharmacokinetic parameters were AUC=219.2±88.4 mcg hr/mL, C =11.0±4.1 mcg/mL, C=7.28±3.5, T=6.9±3.4 hours. The mean percent fluctuation [(C-C/C)x100]=169% for the once-daily regimen and 51% for the reference product BID regimen.
The bioavailability of the 600 mg Uniphyl (Theophylline) Tablet was further evaluated in a multiple dose, steady-state study in 26 healthy males comparing the 600 mg Tablet to one and one-half 400 mg Uniphyl (Theophylline) Tablets. All subjects had previously established theophylline clearances of ≤4 L/hr and were dosed once-daily for 6 days under fed conditions. The results showed no clinically significant difference between the 600 mg and one and one-half 400 mg Uniphyl (Theophylline) Tablet regimens. Steady-state results were:
The bioavailability ratio for the 600/400 mg tablets was 98.8%. Thus, under all study conditions the 600 mg tablet is bioequivalent to one and one-half 400 mg tablets.
Studies demonstrate that as long as subjects were either consistently fed or consistently fasted, there is similar bioavailability with once-daily administration of Uniphyl (Theophylline) Tablets whether dosed in the morning or evening.
Following oral dosing, theophylline does not undergo any measurable first-pass elimination. In adults and children beyond one year of age, approximately 90% of the dose is metabolized in the liver. Biotransformation takes place through demethylation to 1-methylxanthine and 3-methylxanthine and hydroxylation to 1,3-dimethyluric acid. 1-methylxanthine is further hydroxylated, by xanthine oxidase, to 1-methyluric acid. About 6% of a theophylline dose is N-methylated to caffeine. Theophylline demethylation to 3-methylxanthine is catalyzed by cytochrome P-450 1A2, while cytochromes P-450 2E1 and P-450 3A3 catalyze the hydroxylation to 1,3-dimethyluric acid. Demethylation to 1-methylxanthine appears to be catalyzed either by cytochrome P-450 1A2 or a closely related cytochrome. In neonates, the N-demethylation pathway is absent while the function of the hydroxylation pathway is markedly deficient. The activity of these pathways slowly increases to maximal levels by one year of age.
Caffeine and 3-methylxanthine are the only theophylline metabolites with pharmacologic activity. 3-methylxanthine has approximately one tenth the pharmacologic activity of theophylline and serum concentrations in adults with normal renal function are
Both the N-demethylation and hydroxylation pathways of theophylline biotransformation are capacity-limited. Due to the wide intersubject variability of the rate of theophylline metabolism, non-linearity of elimination may begin in some patients at serum theophylline concentrations
(see for mean clearance and half-life values)
Uniphyl (Theophylline) Clinical Studies
In patients with chronic asthma, including patients with severe asthma requiring inhaled corticosteroids or alternate-day oral corticosteroids, many clinical studies have shown that theophylline decreases the frequency and severity of symptoms, including nocturnal exacerbations, and decreases the “as needed” use of inhaled beta- agonists. Theophylline has also been shown to reduce the need for short courses of daily oral prednisone to relieve exacerbations of airway obstruction that are unresponsive to bronchodilators in asthmatics.
In patients with chronic obstructive pulmonary disease (COPD), clinical studies have shown that theophylline decreases dyspnea, air trapping, the work of breathing, and improves contractility of diaphragmatic muscles with little or no improvement in pulmonary function measurements.
Uniphyl (Theophylline) Indications And Usage
Theophylline is 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.
Uniphyl (Theophylline) Contraindications
Uniphyl (Theophylline) is contraindicated in patients with a history of hypersensitivity to theophylline or other components in the product.
Uniphyl (Theophylline) Warnings
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)
There are several readily identifiable causes of reduced theophylline clearance. 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:
When Signs or Symptoms of Theophylline Toxicity Are Present
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 beta-selective agonists and systemically administered corticosteroids in this circumstance and increases the risk of adverse effects. A 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 ).
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 ).
Uniphyl (Theophylline) Precautions
Serum theophylline concentration measurements are readily available and should be used to determine whether the dosage is appropriate. Specifically, the serum theophylline concentration should be measured as follows:
To guide a dose increase, the blood sample should be obtained at the time of the expected peak serum theophylline concentration; 12 hours after an evening dose or 9 hours after a morning dose at steady-state. For most patients, steady-state will be reached after 3 days of dosing when no doses have been missed, no extra doses have been added, and none of the doses have been taken at unequal intervals. A trough concentration (i.e., at the end of the dosing interval) provides no additional useful information and may lead to an inappropriate dose increase since the peak serum theophylline concentration can be two or more times greater than the trough concentration with an immediate-release formulation. If the serum sample is drawn more than 12 hours after the evening dose, or more than 9 hours after a morning dose, the results must be interpreted with caution since the concentration may not be reflective of the peak concentration. In contrast, when signs or symptoms of theophylline toxicity are present, a serum sample should be obtained as soon as possible, analyzed immediately, and the result reported to the healthcare professional without delay. In patients in whom decreased serum protein binding is suspected (e.g., cirrhosis, women during the third trimester of pregnancy), the concentration of unbound theophylline should be measured and the dosage adjusted to achieve an unbound concentration of 6-12 mcg/mL.
Saliva concentrations of theophylline cannot be used reliably to adjust dosage without special techniques.
The patient (or parent/caregiver) should be instructed to seek medical advice whenever nausea, vomiting, persistent headache, insomnia or rapid heartbeat occurs during treatment with theophylline, even if another cause is suspected. The patient should be instructed to contact their healthcare professional if they develop a new illness, especially if accompanied by a persistent fever, if they experience worsening of a chronic illness, if they start or stop smoking cigarettes or marijuana, or if another healthcare professional adds a new medication or discontinues a previously prescribed medication. Patients should be informed that theophylline interacts with a wide variety of drugs (see ). The dietary supplement St. John’s Wort (Hypericum perforatum) should not be taken at the same time as theophylline, since it may result in decreased theophylline levels. If patients are already taking St. John’s Wort and theophylline together, they should consult their healthcare professional before stopping the St. John’s Wort, since their theophylline concentrations may rise when this is done, resulting in toxicity. Patients should be instructed to inform all healthcare professionals involved in their care that they are taking theophylline, especially when a medication is being added or deleted from their treatment. Patients should be instructed to not alter the dose, timing of the dose, or frequency of administration without first consulting their healthcare professional. If a dose is missed, the patient should be instructed to take the next dose at the usually scheduled time and to not attempt to make up for the missed dose.
Uniphyl (Theophylline) Tablets can be taken once a day in the morning or evening. It is recommended that Uniphyl (Theophylline) be taken with meals. Patients should be advised that if they choose to take Uniphyl (Theophylline) with food it should be taken consistently with food and if they take it in a fasted condition it should routinely be taken fasted. It is important that the product whenever dosed be dosed consistently with or without food.
Uniphyl (Theophylline) Tablets are not to be chewed or crushed because it may lead to a rapid release of theophylline with the potential for toxicity. The scored tablet may be split. Patients receiving Uniphyl (Theophylline) Tablets may pass an intact matrix tablet in the stool or via colostomy. These matrix tablets usually contain little or no residual theophylline.
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.,
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. 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.
Long term carcinogenicity studies have been carried out in mice (oral doses 30-150 mg/kg) and rats (oral doses 5-75 mg/kg). Results are pending.
Theophylline has been studied in Ames salmonella, and cytogenetics, micronucleus and Chinese hamster ovary test systems and has not been shown to be genotoxic.
In a 14 week continuous breeding study, theophylline, administered to mating pairs of B6C3F mice at oral doses of 120, 270 and 500 mg/kg (approximately 1.0-3.0 times the human dose on a mg/m basis) impaired fertility, as evidenced by decreases in the number of live pups per litter, decreases in the mean number of litters per fertile pair, and increases in the gestation period at the high dose as well as decreases in the proportion of pups born alive at the mid and high dose. In 13 week toxicity studies, theophylline was administered to F344 rats and B6C3F mice at oral doses of 40-300 mg/kg (approximately 2.0 times the human dose on a mg/m basis). At the high dose, systemic toxicity was observed in both species including decreases in testicular weight.
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 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 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 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 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 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 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.
Uniphyl (Theophylline) Adverse Reactions
Adverse reactions associated with theophylline are generally mild when peak serum theophylline concentrations are 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 ). In a small percentage of patients (
Other adverse reactions that have been reported at serum theophylline concentrations
Uniphyl (Theophylline) Overdosage
The chronicity and pattern of theophylline overdosage significantly influences clinical manifestations of toxicity, management and outcome. There are two common presentations: (1) , 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) , 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 caregiver 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 overdosage, generalized seizures, life-threatening cardiac arrhythmias, and death may occur at serum theophylline concentrations >30 mcg/mL. The severity of toxicity after chronic overdosage 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. Pre-existing 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.
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.)
Acute Overdose
Chronic Overdosage
Uniphyl (Theophylline) Dosage And Administration
Uniphyl (Theophylline) 400 or 600 mg Tablets can be taken once a day in the morning or evening. It is recommended that Uniphyl (Theophylline) be taken with meals. Patients should be advised that if they choose to take Uniphyl (Theophylline) with food it should be taken consistently with food and if they take it in a fasted condition it should routinely be taken fasted. It is important that the product whenever dosed be dosed consistently with or without food.
Uniphyl (Theophylline) Tablets are not to be chewed or crushed because it may lead to a rapid release of theophylline with the potential for toxicity. The scored tablet may be split. Infrequently, patients receiving Uniphyl (Theophylline) 400 or 600 mg Tablets may pass an intact matrix tablet in the stool or via colostomy. These matrix tablets usually contain little or no residual theophylline.
Stabilized patients, 12 years of age or older, who are taking an immediate-release or controlled-release theophylline product may be transferred to once-daily administration of 400 mg or 600 mg Uniphyl (Theophylline) Tablets on a mg-for-mg basis.
It must be recognized that the peak and trough serum theophylline levels produced by the once-daily dosing may vary from those produced by the previous product and/or regimen.
Uniphyl (Theophylline) How Supplied
Uniphyl (Theophylline) (theophylline, anhydrous) Controlled-Release Tablets 400 mg are supplied in white, opaque plastic, child-resistant bottles containing 100 tablets (NDC 67781-251-01) or 500 tablets (NDC 67781-251-05). Each round, white 400 mg tablet bears the symbol PF on the scored side and U400 on the other side.
Uniphyl (Theophylline) (theophylline, anhydrous) Controlled-Release Tablets 600 mg are supplied in white, opaque plastic, child-resistant bottles containing 100 tablets (NDC 67781-252-01). Each rectangular, concave, white 600 mg tablet bears the symbol PF on the scored side and U 600 on the other side.
Store at 25°C (77°F); excursions permitted between 15°-30°C (59°-86°F).
Dispense in a tight, light-resistant container.
Uniphyl (Theophylline)
Uniphyl (Theophylline)
Uniphyl (Theophylline)