openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 1 matching rows.
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 infusion rate 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 less than 1 year Elderly (greater than 60 years) Concurrent Diseases Acute pulmonary edema Congestive heart failure Cor-pulmonale Fever; greater than or equal to 102°F for 24 hours or more; or lesser temperature elevations for longer periods Hypothyroidism Liver disease; cirrhosis, acute hepatitis Reduced renal function in infants less than 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), the intravenous infusion should be stopped and a serum theophylline concentration measured immediately . Dosage Increases Increases in the dose of intravenous theophylline should not be made in response to an acute exacerbation of symptoms unless the steady-state serum theophylline concentration is less than 10 mcg/mL. 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 infusion rate increases to about 25% of the previous infusion rate will reduce the risk of unintended excessive increases in serum theophylline concentration (see DOSAGE AND ADMINISTRATION, Table VI ). Solutions containing dextrose without electrolytes should not be administered simultaneously with blood through the same infusion set because of the possibility of agglomeration of erythrocytes. The intravenous administration of these solutions may cause fluid overloading resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. Because dosages of these drugs are titrated to response (see DOSAGE AND ADMINISTRATION ), no additives should be made to Theophylline in 5% Dextrose Injection USP.
ADVERSE REACTIONS Adverse reactions associated with theophylline are generally mild when serum theophylline concentrations are less than 20 mcg/mL and mainly consist of transient caffeine-like adverse effects such as nausea, vomiting, headache, and insomnia. When 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 ). Other adverse reactions that have been reported at serum theophylline concentrations less than 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 greater than or equal to 15 mcg/mL. There have been a few isolated reports of seizures at serum theophylline concentrations less than 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 less than 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 less than 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). There have been reports of non-convulsive status epilepticus in patients receiving theophylline, and this possibility should be considered in patients with abnormal central nervous system function and a history of theophylline administration. Hypercalcemia has been reported in a patient with hyperthyroid disease at therapeutic theophylline concentrations (see OVERDOSAGE ). Table IV. Manifestations of theophylline toxicity. These data are derived from two studies in patients with serum theophylline concentrations greater than 30 mcg/mL. In the first study (Study #1 - Shanon, Ann lntern 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 greater than 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. Percentage of patients reported with sign or symptom 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 NR = Not reported in a comparable manner. 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 with 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 Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia.
adverse reactions table
<table><col/><col/><col/><col/><col/><tbody><tr><td align="center" colspan="5" styleCode=" Botrule"><content styleCode="bold"> Table IV. Manifestations of theophylline toxicity.<footnote ID="FOOT_2604">These data are derived from two studies in patients with serum theophylline concentrations greater than 30 mcg/mL. In the first study (Study #1 - Shanon, Ann lntern 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 greater than 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 (<content styleCode="italics">e.g.</content>, in Study #1, 48% of the patients had acute intoxications versus only 10% in Study #2) and different methods of reporting results.</footnote></content></td></tr><tr><td align="center"> </td><td align="center" colspan="2"> <content styleCode="bold">Percentage of patients reported with sign or symptom</content></td><td align="center"> </td><td align="center"> </td></tr><tr><td align="center"> </td><td align="center" colspan="2"> <content styleCode="bold">Acute Overdose (Large Single Ingestion)</content></td><td align="center" colspan="2"> <content styleCode="bold">Chronic Overdosage (Multiple Excessive Doses)</content></td></tr><tr><td align="center" styleCode=" Botrule"> <content styleCode="bold">Sign/Symptom</content></td><td align="center" styleCode=" Botrule"><content styleCode="bold">Study 1 (n=157)</content></td><td align="center" styleCode=" Botrule"><content styleCode="bold">Study 2 (n=14)</content></td><td align="center" styleCode=" Botrule"><content styleCode="bold">Study 1 (n=92)</content></td><td align="center" styleCode=" Botrule"><content styleCode="bold">Study 2 (n=102)</content></td></tr><tr><td><content styleCode="underline">Asymptomatic </content></td><td align="center">NR<footnote ID="FOOT_2605">NR = Not reported in a comparable manner.</footnote></td><td align="center"> 0</td><td align="center"> NR<footnoteRef IDREF="FOOT_2605"/></td><td align="center">6</td></tr><tr><td><content styleCode="underline">Gastrointestinal </content></td><td align="center"> </td><td align="center"> </td><td align="center"> </td><td align="center"/></tr><tr><td> Vomiting</td><td align="center">73</td><td align="center"> 93</td><td align="center"> 30</td><td align="center">61</td></tr><tr><td> Abdominal Pain</td><td align="center">NR<footnoteRef IDREF="FOOT_2605"/> </td><td align="center"> 21</td><td align="center">NR<footnoteRef IDREF="FOOT_2605"/> </td><td align="center">12</td></tr><tr><td> Diarrhea </td><td align="center">NR<footnoteRef IDREF="FOOT_2605"/></td><td align="center">0 </td><td align="center">NR<footnoteRef IDREF="FOOT_2605"/> </td><td align="center">14</td></tr><tr><td> Hematemesis </td><td align="center">NR<footnoteRef IDREF="FOOT_2605"/></td><td align="center">0</td><td align="center">NR<footnoteRef IDREF="FOOT_2605"/></td><td align="center">2</td></tr><tr><td><content styleCode="underline">Metabolic/Other</content> </td><td align="center"> </td><td align="center"> </td><td align="center"> </td><td align="center"> </td></tr><tr><td> Hypokalemia </td><td align="center">85</td><td align="center">79</td><td align="center">44</td><td align="center">43</td></tr><tr><td> Hyperglycemia </td><td align="center">98</td><td align="center"> NR<footnoteRef IDREF="FOOT_2605"/></td><td align="center">18</td><td align="center">NR<footnoteRef IDREF="FOOT_2605"/></td></tr><tr><td> Acid/base disturbance </td><td align="center">34</td><td align="center">21</td><td align="center">9</td><td align="center">5</td></tr><tr><td> Rhabdomyolysis </td><td align="center">NR<footnoteRef IDREF="FOOT_2605"/></td><td align="center">7</td><td align="center"> NR<footnoteRef IDREF="FOOT_2605"/></td><td align="center">0</td></tr><tr><td><content styleCode="underline">Cardiovascular </content></td><td align="center"> </td><td align="center"> </td><td align="center"> </td><td align="center"> </td></tr><tr><td> Sinus tachycardia </td><td align="center">100</td><td align="center">86 </td><td align="center"> 100</td><td align="center">62</td></tr><tr><td> Other supraventricular tachycardias </td><td align="center"> 2</td><td align="center"> 21</td><td align="center"> 12</td><td align="center"> 14</td></tr><tr><td> Ventricular premature beats </td><td align="center">3</td><td align="center"> 21</td><td align="center">10</td><td align="center">19</td></tr><tr><td> Atrial fibrillation or flutter </td><td align="center">1</td><td align="center">NR<footnoteRef IDREF="FOOT_2605"/> </td><td align="center"> 12</td><td align="center">NR<footnoteRef IDREF="FOOT_2605"/></td></tr><tr><td> Multifocal atrial tachycardia </td><td align="center">0</td><td align="center">NR<footnoteRef IDREF="FOOT_2605"/> </td><td align="center">2</td><td align="center">NR<footnoteRef IDREF="FOOT_2605"/></td></tr><tr><td> Ventricular arrhythmias with hemodynamic instability </td><td align="center"> 7</td><td align="center"> 14 </td><td align="center"> 40 </td><td align="center"> 0</td></tr><tr><td> Hypotension/shock </td><td align="center">NR<footnoteRef IDREF="FOOT_2605"/></td><td align="center">21</td><td align="center">NR<footnoteRef IDREF="FOOT_2605"/> </td><td align="center">8</td></tr><tr><td><content styleCode="underline"> Neurologic</content></td><td align="center"> </td><td align="center"> </td><td align="center"> </td><td align="center"> </td></tr><tr><td> Nervousness </td><td align="center">NR<footnoteRef IDREF="FOOT_2605"/></td><td align="center">64</td><td align="center"> NR<footnoteRef IDREF="FOOT_2605"/></td><td align="center">21</td></tr><tr><td> Tremors </td><td align="center"> 38</td><td align="center">29</td><td align="center">16 </td><td align="center">14</td></tr><tr><td> Disorientation</td><td align="center">NR<footnoteRef IDREF="FOOT_2605"/></td><td align="center">7</td><td align="center"> NR<footnoteRef IDREF="FOOT_2605"/></td><td align="center">11 </td></tr><tr><td> Seizures</td><td align="center">5</td><td align="center"> 14</td><td align="center">14</td><td align="center">5</td></tr><tr><td><content styleCode="underline">Death</content></td><td align="center">3</td><td align="center">21</td><td align="center">10</td><td align="center">4</td></tr></tbody></table>