UNIPHYL- theophylline anhydrous tablet

Uniphyl by

Drug Labeling and Warnings

Uniphyl by is a Prescription medication manufactured, distributed, or labeled by Purdue Pharmaceutical Products LP, Purdue Pharma LP, The PF Laboratories Inc.. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

Concurrent Diseases

  •   Acute pulmonary edema
  •   Congestive heart failure
  •   Cor-pulmonale
  •   Fever; ≥102° for 24 hours or more; or lesser temperature elevations for longer periods
  •   Hypothyroidism
  •   Liver disease; cirrhosis, acute hepatitis
  •   Reduced renal function in infants <3 months of age
  •   Sepsis with multi-organ failure
  •   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 corticosteroids 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).

  • PRECAUTIONS

    General

    Careful consideration of the various interacting drugs and physiologic conditions that can alter theophylline clearance and require dosage adjustment should occur prior to initiation of theophylline therapy, prior to increases in theophylline dose, and during follow up (see WARNINGS). The dose of theophylline selected for initiation of therapy should be low and, if tolerated, increased slowly over a period of a week or longer with the final dose guided by monitoring serum theophylline concentrations and the patient’s clinical response (see DOSAGE AND ADMINISTRATION, Table V).

    Monitoring Serum Theophylline Concentrations

    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:

    1. When initiating therapy to guide final dosage adjustment after titration.
    2. Before making a dose increase to determine whether the serum concentration is sub-therapeutic in a patient who continues to be symptomatic.
    3. Whenever signs or symptoms of theophylline toxicity are present.
    4. Whenever there is a new illness, worsening of a chronic illness or a change in the patient’s treatment regimen that may alter theophylline clearance (e.g., fever >102°F sustained for ≥24 hours, hepatitis, or drugs listed in Table II are added or discontinued).

    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.

    Effects on Laboratory Tests

    As a result of its pharmacological effects, theophylline at serum concentrations within the 10-20 mcg/mL range modestly increases plasma glucose (from a mean of 88 mg% to 98 mg%), uric acid (from a mean of 4 mg/dL to 6 mg/dL), free fatty acids (from a mean of 451 µEq/L to 800 µEq/L, total cholesterol (from a mean of 140 vs 160 mg/dL), HDL (from a mean of 36 to 50 mg/dL), HDL/LDL ratio (from a mean of 0.5 to 0.7), and urinary free cortisol excretion (from a mean of 44 to 63 mcg/24 hr). Theophylline at serum concentrations within the 10-20 mcg/mL range may also transiently decrease serum concentrations of triiodothyronine (144 before, 131 after one week and 142 ng/dL after 4 weeks of theophylline). The clinical importance of these changes should be weighed against the potential therapeutic benefit of theophylline in individual patients.

    Information for Patients

    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 Table II). 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® Tablets can be taken once a day in the morning or evening. It is recommended that Uniphyl be taken with meals. Patients should be advised that if they choose to take Uniphyl 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 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 Tablets may pass an intact matrix tablet in the stool or via colostomy. These matrix tablets usually contain little or no residual theophylline.

    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.*
    DrugType of InteractionEffect**
    *Refer to PRECAUTIONS, Drug Interactions for further information regarding table.
    **Average effect on steady-state theophylline concentration or other clinical effect for pharmacologic interactions. Individual patients may experience larger changes in serum theophylline concentration than the value listed.
    AdenosineTheophylline blocks adenosine receptors.Higher doses of adenosine may be required to achieve desired effect.
    AlcoholA single large dose of alcohol (3 mL/kg of whiskey) decreases theophylline clearance for up to 24 hours.30% increase
    AllopurinolDecreases theophylline clearance at allopurinol doses ≥600 mg/day.25% increase
    AminoglutethimideIncreases theophylline clearance by induction of microsomal enzyme activity.25% decrease
    CarbamazepineSimilar to aminoglutethimide.30% decrease
    CimetidineDecreases theophylline clearance by inhibiting cytochrome P450 1A2.70% increase
    CiprofloxacinSimilar to cimetidine.40% increase
    ClarithromycinSimilar to erythromycin.25% increase
    DiazepamBenzodiazepines 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.
    DisulfiramDecreases theophylline clearance by inhibiting hydroxylation and demethylation.50% increase
    EnoxacinSimilar to cimetidine.300% increase
    EphedrineSynergistic CNS effects.Increased frequency of nausea, nervousness, and insomnia.
    ErythromycinErythromycin metabolite decreases theophylline clearance by inhibiting cytochrome P450 3A3.35% increase. Erythromycin steady-state serum concentrations decrease by a similar amount.
    EstrogenEstrogen containing oral contraceptives decrease theophylline clearance in a dose-dependent fashion. The effect of progesterone on theophylline clearance is unknown.30% increase
    FlurazepamSimilar to diazepam.Similar to diazepam.
    FluvoxamineSimilar to cimetidine.Similar to cimetidine.
    HalothaneHalothane sensitizes the myocardium to catecholamines, theophylline increases release of endogenous catecholamines.Increased risk of ventricular arrhythmias.
    Interferon, human recombinant alpha-ADecreases theophylline clearance.100% increase
    Isoproterenol (IV)Increases theophylline clearance.20% decrease
    KetaminePharmacologicMay lower theophylline seizure threshold.
    LithiumTheophylline increases renal lithium clearance.Lithium dose required to achieve a therapeutic serum concentration increased an average of 60%.
    LorazepamSimilar to diazepam.Similar to diazepam.
    Methotrexate (MTX)Decreases theophylline clearance.20% increase after low dose MTX, higher dose MTX may have a greater effect.
    MexiletineSimilar to disulfiram.80% increase
    MidazolamSimilar to diazepam.Similar to diazepam.
    MoricizineIncreases theophylline clearance.25% decrease
    PancuroniumTheophylline may antagonize non-depolarizing neuromuscular blocking effects; possibly due to phosphodiesterase inhibition.Larger dose of pancuronium may be required to achieve neuromuscular blockade.
    PentoxifyllineDecreases theophylline clearance.30% increase
    Phenobarbital (PB)Similar to aminoglutethimide.25% decrease after two weeks of concurrent PB.
    PhenytoinPhenytoin increases theophylline clearance by increasing microsomal enzyme activity. Theophylline decreases phenytoin absorption.Serum theophylline and phenytoin concentrations decrease about 40%.
    PropafenoneDecreases theophylline clearance and pharmacologic interaction.40% increase. Beta-2 blocking effect may decrease efficacy of theophylline.
    PropranololSimilar to cimetidine and pharmacologic interaction.100% increase. Beta-2 blocking effect may decrease efficacy of theophylline.
    RifampinIncreases theophylline clearance by increasing cytochrome P450 1A2 and 3A3 activity.20-40% decrease
    St. John’s Wort (Hypericum Perforatum) Decrease in theophylline plasma concentrations.Higher doses of theophylline may be required to achieve desired effect. Stopping St. John’s Wort may result in theophylline toxicity.
    SulfinpyrazoneIncreases theophylline clearance by increasing demethylation and hydroxylation. Decreases renal clearance of theophylline.20% decrease
    TacrineSimilar to cimetidine, also increases renal clearance of theophylline.90% increase
    ThiabendazoleDecreases theophylline clearance.190% increase
    TiclopidineDecreases theophylline clearance.60% increase
    TroleandomycinSimilar to erythromycin.33-100% increase depending on troleandomycin dose.
    VerapamilSimilar to disulfiram.20% increase
    TABLE III. Drugs that have been documented not to interact with theophylline or drugs that produce no clinically significant interaction with theophylline. *
    *Refer to PRECAUTIONS, Drug Interactions for information regarding table.
    albuterol, systemic and inhaledmebendazole
    amoxicillinmedroxyprogesterone
    ampicillin, with or without
       sulbactam    		methylprednisolone
    metronidazole
    atenololmetoprolol
    azithromycinnadolol
    caffeine, dietary ingestionnifedipine
    cefaclornizatidine
    co-trimoxazole (trimethoprim and
    sulfamethoxazole)    		norfloxacin
    ofloxacin
    diltiazemomeprazole
    dirithromycinprednisone, prednisolone
    enfluraneranitidine
    famotidinerifabutin
    felodipineroxithromycin
    finasteridesorbitol (purgative doses do not inhibit
    hydrocortisonetheophylline absorption)
    isofluranesucralfate
    isoniazidterbutaline, systemic
    isradipineterfenadine
    influenza vaccinetetracycline
    ketoconazoletocainide
    lomefloxacin 

    Drug-Food Interactions

    The bioavailability of Uniphyl® Tablets (theophylline, anhydrous) has been studied with co-administration of food. In three single-dose studies, subjects given Uniphyl 400 mg or 600 mg Tablets with a standardized high-fat meal were compared to fasted conditions. Under fed conditions, the peak plasma concentration and bioavailability were increased; however, a precipitous increase in the rate and extent of absorption was not evident (see Pharmacokinetics, Absorption). The increased peak and extent of absorption under fed conditions suggests that dosing should be ideally administered consistently either with or without food.

    The Effect of Other Drugs on Theophylline Serum Concentration Measurements

    Most serum theophylline assays in clinical use are immunoassays which are specific for theophylline. Other xanthines such as caffeine, dyphylline, and pentoxifylline are not detected by these assays. Some drugs (e.g., cefazolin, cephalothin), however, may interfere with certain HPLC techniques. Caffeine and xanthine metabolites in neonates or patients with renal dysfunction may cause the reading from some dry reagent office methods to be higher than the actual serum theophylline concentration.

    Carcinogenesis, Mutagenesis, and Impairment of Fertility

    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, in vivo and in vitro 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 B6C3F1 mice at oral doses of 120, 270 and 500 mg/kg (approximately 1.0-3.0 times the human dose on a mg/m2 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 B6C3F1 mice at oral doses of 40-300 mg/kg (approximately 2.0 times the human dose on a mg/m2 basis). At the high dose, systemic toxicity was observed in both species including decreases in testicular weight.

    Pregnancy: Teratogenic Effects: Category C

    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/m2 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/m2 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/m2 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/m2 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/m2 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/m2 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.

    Nursing Mothers

    Theophylline is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants. The concentration of theophylline in breast milk is about equivalent to the maternal serum concentration. An infant ingesting a liter of breast milk containing 10-20 mcg/mL of theophylline per day is likely to receive 10-20 mg of theophylline per day. Serious adverse effects in the infant are unlikely unless the mother has toxic serum theophylline concentrations.

    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

    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 decreased 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 PRECAUTIONS: 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. Theophylline should be prescribed with caution in elderly male patients with pre-existing partial outflow obstruction, such as prostatic enlargement, due to the risk of urinary retention.

  • 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 abdominal pain, agitation, anaphylactic reaction, anaphylactoid reaction, anxiety, cardiac arrhythmias, diarrhea, dizziness, fine skeletal muscle tremors, gastric irritation, gastroesophageal reflux, hyperuricemia, irritability, palpitations, pruritus, rash, sinus tachycardia, restlessness, transient diuresis, urinary retention and urticaria. 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 symptom
    Sign/SymptomAcute OverdoseChronic Overdosage
    (Large Single Ingestion)(Multiple Excessive Doses)
    Study 1Study 2Study 1Study 2
    (n=157)(n=14)(n=92)(n=102)
    *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;119:1161-67), data were prospectively collected from 249 consecutive cases of theophylline toxicity referred to a regional poison center for consultation. In the second study (Study #2—Sessler, Am J Med 1990;88:567-76), data were retrospectively collected from 116 cases with serum theophylline concentrations >30 mcg/mL among 6000 blood samples obtained for measurement of serum theophylline concentrations in three emergency departments. Differences in the incidence of manifestations of theophylline toxicity between the two studies may reflect sample selection as a result of study design (e.g., in Study #1, 48% of the patients had acute intoxications versus only 10% in Study #2) and different methods of reporting results.
    **NR=Not reported in a comparable manner.
    AsymptomaticNR**0NR**6
    Gastrointestinal
    Vomiting73933061
    Abdominal PainNR**21NR**12
    DiarrheaNR**0NR**14
    HematemesisNR**0NR**2
    Metabolic/Other
    Hypokalemia85794443
    Hyperglycemia98NR**18NR**
    Acid/base disturbance342195
    RhabdomyolysisNR**7NR**0
    Cardiovascular
    Sinus tachycardia1008610062
    Other supraventricular    
    tachycardias2211214
    Ventricular premature beats3211019
    Atrial fibrillation or flutter1NR**12NR**
    Multifocal atrial tachycardia0NR**2NR**
    Ventricular arrhythmias with
    hemodynamic instability    		714400
    Hypotension/shockNR**21NR**8
    Neurologic    
    NervousnessNR**64NR**21
    Tremors38291614
    DisorientationNR**7NR**11
    Seizures514145
    Death321104
  • 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 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.

    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.)

    1. While simultaneously instituting treatment, contact a regional poison center to obtain updated information and advice on individualizing the recommendations that follow.
    2. Institute supportive care, including establishment of intravenous access, maintenance of the airway, and electrocardiographic monitoring.
    3. Treatment of seizures Because of the high morbidity and mortality associated with theophylline-induced seizures, treatment should be rapid and aggressive. Anticonvulsant therapy should be initiated with an intravenous benzodiazepine, e.g., diazepam, in increments of 0.1-0.2 mg/kg every 1-3 minutes until seizures are terminated. Repetitive seizures should be treated with a loading dose of phenobarbital (20 mg/kg infused over 30-60 minutes). Case reports of theophylline overdose in humans and animal studies suggest that phenytoin is ineffective in terminating theophylline-induced seizures. The doses of benzodiazepines and phenobarbital required to terminate theophylline-induced seizures are close to the doses that may cause severe respiratory depression or respiratory arrest; the healthcare professional should therefore be prepared to provide assisted ventilation. Elderly patients and patients with COPD may be more susceptible to the respiratory depressant effects of anticonvulsants. Barbiturate-induced coma or administration of general anesthesia may be required to terminate repetitive seizures or status epilepticus. General anesthesia should be used with caution in patients with theophylline overdose because fluorinated volatile anesthetics may sensitize the myocardium to endogenous catecholamines released by theophylline. Enflurane appears less likely to be associated with this effect than halothane and may, therefore, be safer. Neuromuscular blocking agents alone should not be used to terminate seizures since they abolish the musculoskeletal manifestations without terminating seizure activity in the brain.
    4. Anticipate Need for Anticonvulsants In patients with theophylline overdose who are at high risk for theophylline-induced seizures, e.g., patients with acute overdoses and serum theophylline concentrations >100 mcg/mL or chronic overdosage in patients >60 years of age with serum theophylline concentrations >30 mcg/mL, the need for anticonvulsant therapy should be anticipated. A benzodiazepine such as diazepam should be drawn into a syringe and kept at the patient’s bedside and medical personnel qualified to treat seizures should be immediately available. In selected patients at high risk for theophylline-induced seizures, consideration should be given to the administration of prophylactic anticonvulsant therapy. Situations where prophylactic anticonvulsant therapy should be considered in high risk patients include anticipated delays in instituting methods for extracorporeal removal of theophylline (e.g., transfer of a high risk patient from one healthcare facility to another for extracorporeal removal) and clinical circumstances that significantly interfere with efforts to enhance theophylline clearance (e.g., a neonate where dialysis may not be technically feasible or a patient with vomiting unresponsive to antiemetics who is unable to tolerate multiple-dose oral activated charcoal). In animal studies, prophylactic administration of phenobarbital, but not phenytoin, has been shown to delay the onset of theophylline-induced generalized seizures and to increase the dose of theophylline required to induce seizures (i.e., markedly increases the LD50). Although there are no controlled studies in humans, a loading dose of intravenous phenobarbital (20 mg/kg infused over 60 minutes) may delay or prevent life-threatening seizures in high risk patients while efforts to enhance theophylline clearance are continued. Phenobarbital may cause respiratory depression, particularly in elderly patients and patients with COPD.
    5. Treatment of cardiac arrhythmias Sinus tachycardia and simple ventricular premature beats are not harbingers of life-threatening arrhythmias, they do not require treatment in the absence of hemodynamic compromise, and they resolve with declining serum theophylline concentrations. Other arrhythmias, especially those associated with hemodynamic compromise, should be treated with antiarrhythmic therapy appropriate for the type of arrhythmia.
    6. Gastrointestinal decontamination Oral activated charcoal (0.5 g/kg up to 20 g and repeat at least once 1-2 hours after the first dose) is extremely effective in blocking the absorption of theophylline throughout the gastrointestinal tract, even when administered several hours after ingestion. If the patient is vomiting, the charcoal should be administered through a nasogastric tube or after administration of an antiemetic. Phenothiazine antiemetics such as prochlorperazine or perphenazine should be avoided since they can lower the seizure threshold and frequently cause dystonic reactions. A single dose of sorbitol may be used to promote stooling to facilitate removal of theophylline bound to charcoal from the gastrointestinal tract. Sorbitol, however, should be dosed with caution since it is a potent purgative which can cause profound fluid and electrolyte abnormalities, particularly after multiple doses. Commercially available fixed combinations of liquid charcoal and sorbitol should be avoided in young children and after the first dose in adolescents and adults since they do not allow for individualization of charcoal and sorbitol dosing. Ipecac syrup should be avoided in theophylline overdoses. Although ipecac induces emesis, it does not reduce the absorption of theophylline unless administered within 5 minutes of ingestion and even then is less effective than oral activated charcoal. Moreover, ipecac induced emesis may persist for several hours after a single dose and significantly decrease the retention and the effectiveness of oral activated charcoal.
    7. Serum Theophylline Concentration Monitoring The serum theophylline concentration should be measured immediately upon presentation, 2-4 hours later, and then at sufficient intervals, e.g., every 4 hours, to guide treatment decisions and to assess the effectiveness of therapy. Serum theophylline concentrations may continue to increase after presentation of the patient for medical care as a result of continued absorption of theophylline from the gastrointestinal tract. Serial monitoring of serum theophylline serum concentrations should be continued until it is clear that the concentration is no longer rising and has returned to non-toxic levels.
    8. General Monitoring Procedures Electrocardiographic monitoring should be initiated on presentation and continued until the serum theophylline level has returned to a non-toxic level. Serum electrolytes and glucose should be measured on presentation and at appropriate intervals indicated by clinical circumstances. Fluid and electrolyte abnormalities should be promptly corrected. Monitoring and treatment should be continued until the serum concentration decreases below 20 mcg/mL.
    9. Enhance clearance of theophylline Multiple-dose oral activated charcoal (e.g., 0.5 mg/kg up to 20 g, every two hours) increases the clearance of theophylline at least twofold by adsorption of theophylline secreted into gastrointestinal fluids. Charcoal must be retained in, and pass through, the gastrointestinal tract to be effective; emesis should therefore be controlled by administration of appropriate antiemetics. Alternatively, the charcoal can be administered continuously through a nasogastric tube in conjunction with appropriate antiemetics. A single dose of sorbitol may be administered with the activated charcoal to promote stooling to facilitate clearance of the adsorbed theophylline from the gastrointestinal tract. Sorbitol alone does not enhance clearance of theophylline and should be dosed with caution to prevent excessive stooling which can result in severe fluid and electrolyte imbalances. Commercially available fixed combinations of liquid charcoal and sorbitol should be avoided in young children and after the first dose in adolescents and adults since they do not allow for individualization of charcoal and sorbitol dosing. In patients with intractable vomiting, extracorporeal methods of theophylline removal should be instituted (see OVERDOSAGE, Extracorporeal Removal).

    Specific Recommendations

    Acute Overdose

    1. Serum Concentration >20<30 mcg/mL
      1. Administer a single dose of oral activated charcoal.
      2. Monitor the patient and obtain a serum theophylline concentration in 2-4 hours to insure that the concentration is not increasing.
    2. Serum Concentration >30<100 mcg/mL
      1. Administer multiple dose oral activated charcoal and measures to control emesis.
      2. Monitor the patient and obtain serial theophylline concentrations every 2-4 hours to gauge the effectiveness of therapy and to guide further treatment decisions.
      3. Institute extracorporeal removal if emesis, seizures, or cardiac arrhythmias cannot be adequately controlled (see OVERDOSAGE, Extracorporeal Removal).
    3. Serum Concentration>100 mcg/mL
      1. Consider prophylactic anticonvulsant therapy.
      2. Administer multiple-dose oral activated charcoal and measures to control emesis.
      3. Consider extracorporeal removal, even if the patient has not experienced a seizure (see OVERDOSAGE, Extracorporeal Removal).
      4. Monitor the patient and obtain serial theophylline concentrations every 2-4 hours to gauge the effectiveness of therapy and to guide further treatment decisions.

    Chronic Overdosage

    1. Serum Concentration >20<30 mcg/mL (with manifestations of theophylline toxicity)
      1. Administer a single dose of oral activated charcoal.
      2. Monitor the patient and obtain a serum theophylline concentration in 2-4 hours to insure that the concentration is not increasing.
    2. Serum Concentration >30 mcg/mL in patients <60 years of age
      1. Administer multiple-dose oral activated charcoal and measures to control emesis.
      2. Monitor the patient and obtain serial theophylline concentrations every 2-4 hours to gauge the effectiveness of therapy and to guide further treatment decisions.
      3. Institute extracorporeal removal if emesis, seizures, or cardiac arrhythmias cannot be adequately controlled (see OVERDOSAGE, Extracorporeal Removal).
    3. Serum Concentration >30 mcg/mL in patients ≥ 60 years of age
      1. Consider prophylactic anticonvulsant therapy.
      2. Administer multiple-dose oral activated charcoal and measures to control emesis.
      3. Consider extracorporeal removal even if the patient has not experienced a seizure (see OVERDOSAGE, Extracorporeal Removal).
      4. Monitor the patient and obtain serial theophylline concentrations every 2-4 hours to gauge the effectiveness of therapy and to guide further treatment decisions.

    Extracorporeal Removal

    Increasing the rate of theophylline clearance by extracorporeal methods may rapidly decrease serum concentrations, but the risks of the procedure must be weighed against the potential benefit. Charcoal hemoperfusion is the most effective method of extracorporeal removal, increasing theophylline clearance up to sixfold, but serious complications, including hypotension, hypocalcemia, platelet consumption and bleeding diatheses may occur. Hemodialysis is about as efficient as multiple-dose oral activated charcoal and has a lower risk of serious complications than charcoal hemoperfusion. Hemodialysis should be considered as an alternative when charcoal hemoperfusion is not feasible and multiple-dose oral charcoal is ineffective because of intractable emesis. Serum theophylline concentrations may rebound 5-10 mcg/mL after discontinuation of charcoal hemoperfusion or hemodialysis due to redistribution of theophylline from the tissue compartment. Peritoneal dialysis is ineffective for theophylline removal; exchange transfusions in neonates have been minimally effective.

  • DOSAGE AND ADMINISTRATION

    Uniphyl® 400 or 600 mg Tablets can be taken once a day in the morning or evening. It is recommended that Uniphyl be taken with meals. Patients should be advised that if they choose to take Uniphyl 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® 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 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 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.

    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). Healthcare providers should instruct patients and caregivers 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 dosage adjustments in order to decrease the risk of potentially serious adverse events associated with unexpected large increases in serum theophylline concentration.

    Table V. Dosing initiation and titration (as anhydrous theophylline). *

  •   A. Children (12-15 years) and adults (16-60 years) without risk factors for impaired clearance.
    •          Titration Step         Children <45 kg   Children >45 kg and adults
    1If caffeine-like adverse effects occur, then consideration should be given to a lower dose and titrating the dose more slowly (see ADVERSE REACTIONS).
  • 1. Starting Dosage
    		• 12-14 mg/kg/day up to a maximum of 300 mg/day admin. QD*300-400 mg/day1 admin. QD*
  • 2. After 3 days, if tolerated, increase dose to:
    		• 16 mg/kg/day up to a maximum of 400 mg/day admin. QD*400-600 mg/day1 admin. QD*
  • 3. After 3 more days, if tolerated, and if needed increase dose to:
    		• 20 mg/kg/day up to a maximum of 600 mg/day admin. QD*As with all theophylline products, doses greater than 600 mg should be titrated according to blood level (see Table VI)
  •   B. Patients With Risk Factors For Impaired Clearance, The Elderly (>60 Years), And Those In Whom It Is Not Feasible To Monitor Serum Theophylline Concentrations:

  •   In children 12-15 years of age, the theophylline dose should not exceed 16 mg/kg/day up to a maximum of 400 mg/day in the presence of risk factors for reduced theophylline clearance (see WARNINGS) or if it is not feasible to monitor serum theophylline concentrations.

  •   In adolescents ≥16 years and adults, including the elderly, the theophylline dose should not exceed 400 mg/day in the presence of risk factors for reduced theophylline clearance (see WARNINGS) or if it is not feasible to monitor serum theophylline concentrations.

    • *Patients with more rapid metabolism clinically identified by higher than average dose requirements, should receive a smaller dose more frequently (every 12 hours) to prevent breakthrough symptoms resulting from low trough concentrations before the next dose.

    TABLE VI. Dosage adjustment guided by serum theophylline concentration.
    Peak Serum
    Concentration    		Dosage Adjustment
    ¶Dose reduction and/or serum theophylline concentration measurement is indicated whenever adverse effects are present physiologic abnormalities that can reduce theophylline clearance occur (e.g. sustained fever), or a drug that interacts with theophylline is added or discontinued (see WARNINGS).
    <9.9 mcg/mLIf symptoms are not controlled and current dosage is tolerated, increase dose about 25%. Recheck serum concentration after three days for further dosage adjustment.
    10-14.9 mcg/mLIf symptoms are controlled and current dosage is tolerated, maintain dose and recheck serum concentration at 6-12 month intervals.¶ If symptoms are not controlled and current dosage is tolerated consider adding additional medication(s) to treatment regimen.
    15-19.9 mcg/mLConsider 10% decrease in dose to provide greater margin of safety even if current dosage is tolerated. ¶
    20-24.9 mcg/mLDecrease dose by 25% even if no adverse effects are present. Recheck serum concentration after 3 days to guide further dosage adjustment.
    25-30 mcg/mLSkip next dose and decrease subsequent doses at least 25% even if no adverse effects are present. Recheck serum concentration after 3 days to guide further dosage adjustment. If symptomatic, consider whether overdose treatment is indicated (see recommendations for chronic overdosage).
    >30 mcg/mLTreat overdose as indicated (see recommendations for chronic overdosage). If theophylline is subsequently resumed, decrease dose by at least 50% and recheck serum concentration after 3 days to guide further dosage adjustment.
  • HOW SUPPLIED

    Uniphyl® (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, 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.

  • SPL UNCLASSIFIED SECTION

    ©2011, Purdue Pharmaceutical Products L.P.

    Dist. by: Purdue Pharmaceutical Products L.P.
    Stamford, CT 06901-3431

    Revised 10/2011

    300945-0B

  • PRINCIPAL DISPLAY PANEL

    Uniphyl Tablets
    400 mg Tablets
    NDC: 677781-251-01

    Uniphyl Tablets 400 mg Tablets NDC: <a href=/NDC/677781-251-0>677781-251-0</a>1
  • PRINCIPAL DISPLAY PANEL

    Uniphyl Tablets
    600 mg Tablets
    NDC: 677781-252-01

    Uniphyl Tablets 600 mg Tablets NDC: <a href=/NDC/677781-252-0>677781-252-0</a>1
  • INGREDIENTS AND APPEARANCE
    UNIPHYL 
    theophylline anhydrous tablet
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 67781-251
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    theophylline anhydrous (UNII: 0I55128JYK) (theophylline anhydrous - UNII:0I55128JYK) theophylline anhydrous400 mg
    Inactive Ingredients
    Ingredient NameStrength
    cetostearyl alcohol (UNII: 2DMT128M1S)  
    hydroxyethyl cellulose (2000 CPS at 1%) (UNII: S38J6RZN16)  
    magnesium stearate (UNII: 70097M6I30)  
    povidone (UNII: FZ989GH94E)  
    talc (UNII: 7SEV7J4R1U)  
    Product Characteristics
    ColorWHITE (WHITE) Score2 pieces
    ShapeROUND (ROUND) Size11mm
    FlavorImprint Code PF;U;400
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 67781-251-01100 in 1 BOTTLE
    2NDC: 67781-251-05500 in 1 BOTTLE
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA08757109/01/1982
    UNIPHYL 
    theophylline anhydrous tablet
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 67781-252
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    theophylline anhydrous (UNII: 0I55128JYK) (theophylline anhydrous - UNII:0I55128JYK) theophylline anhydrous600 mg
    Inactive Ingredients
    Ingredient NameStrength
    cetostearyl alcohol (UNII: 2DMT128M1S)  
    hydroxyethyl cellulose (2000 CPS at 1%) (UNII: S38J6RZN16)  
    magnesium stearate (UNII: 70097M6I30)  
    povidone (UNII: FZ989GH94E)  
    talc (UNII: 7SEV7J4R1U)  
    Product Characteristics
    ColorWHITE (WHITE) Score2 pieces
    ShapeRECTANGLE (RECTANGLE) Size18mm
    FlavorImprint Code PF;U;600
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 67781-252-01100 in 1 BOTTLE
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA04008606/07/1996
    Labeler - Purdue Pharmaceutical Products LP (138922641)
    Registrant - Purdue Pharma LP (932323652)
    Establishment
    NameAddressID/FEIBusiness Operations
    The PF Laboratories Inc.098258726MANUFACTURE

    • Trademark Results [Uniphyl]

    Mark Image

    Registration | Serial
    Company
    Trademark
    Application Date
    UNIPHYL
    UNIPHYL
    73492602 1332816 Live/Registered
    Purdue Frederick Company; The
    1984-07-30
    UNIPHYL
    UNIPHYL
    73415357 1282995 Dead/Cancelled
    Purdue Frederick Company, The
    1983-04-26
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