Theophylline

Heritage Pharmaceuticals Inc.

Theophylline Extended-Release Tablets Rx only

FULL PRESCRIBING INFORMATION: CONTENTS*

• THEOPHYLLINE DESCRIPTION
• CLINICAL PHARMACOLOGY
• THEOPHYLLINE INDICATIONS AND USAGE
• THEOPHYLLINE CONTRAINDICATIONS
• WARNINGS
• PRECAUTIONS
  • General
  • Effects on Laboratory Tests
  • Information for Patients
  • Drug Interactions
  • Carcinogenesis, Mutagenesis, Impairment of Fertility
  • Pregnancy
  • Nursing Mothers
  • Pediatric Use
  • Geriatric Use
• THEOPHYLLINE ADVERSE REACTIONS
• OVERDOSAGE
• THEOPHYLLINE DOSAGE AND ADMINISTRATION
• HOW SUPPLIED
• PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

FULL PRESCRIBING INFORMATION

THEOPHYLLINE DESCRIPTION

CLINICAL PHARMACOLOGY

Thus, blood samples taken 4 to 8 hours post-dosing should reference the peak serum level for most patients. The mean T_max was 6.2 hours (fasting) and 8.7 hours (with food). The respective AUC (0-inf.) for these treatments were 73.3 mcg x hr/mL and 82.2 mcg x hr/mL, respectively. 

THEOPHYLLINE INDICATIONS AND USAGE

Theophylline extended-release tablets are indicated for the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, e.g., emphysema and chronic bronchitis.

THEOPHYLLINE CONTRAINDICATIONS

WARNINGS

PRECAUTIONS

General

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

Drug Interactions

Carcinogenesis, Mutagenesis, Impairment of Fertility

Pregnancy

Teratogenic Effects

Nursing Mothers

Pediatric Use

Geriatric Use

THEOPHYLLINE ADVERSE REACTIONS

OVERDOSAGE

1.
2.

3.   Treatment of seizures:

4.  Anticipate need for anticonvulsants: but not phenytoin₅₀

5.   Treatment of cardiac arrhythmias:

6.   Gastrointestinal decontamination:

7.   Serum theophylline concentration monitoring:  

8.   General monitoring procedures: Monitoring and treatment should be continued until the serum concentration decreases below 20 mcg/mL. 

9.   Enhance clearance of theophylline: OVERDOSAGE, Extracorporeal Removal  

Specific Recommendations: 
Acute Overdose
Serum Concentration >20<30 mcg/mL




Serum Concentration >30<100 mcg/mL



OVERDOSAGE, Extracorporeal Removal

Serum Concentration >100 mcg/mL



OVERDOSAGE, Extracorporeal Removal


Chronic Overdosage 

Serum Concentration >20<30 mcg/mL (with manifestations of theophylline toxicity)




Serum Concentration >30 mcg/mL in patients <60 years of age 



OVERDOSAGE, Extracorporeal Removal

Serum Concentration >30 mcg/mL in patients > 60 years of age.



OVERDOSAGE, Extracorporeal Removal


Extracorporeal Removal :

THEOPHYLLINE DOSAGE AND ADMINISTRATION

_maxmax CLINICAL PHARMACOLOGY, Drug interactions, Drug-Food Interactions



General considerations: 
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.  

if judged to be clinically indicated PRECAUTIONS, Laboratory Tests  DOSAGE AND ADMINISTRATION, Table VI). WARNINGS . 

WARNINGS  PRECAUTIONS ,


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 (6-15 years) and adults (16-60 years) without risk factors for impaired clearance.

	Titration Step	Children < 45 kg	Children > 45 kg and adults
1	Starting Dosage	12-14 mg/kg/day up to a maximum of  300 mg/day divided Q12 hrs*	300 mg/day divided Q12 hrs*
2	After 3 days,  if tolerated, increase dose to:	16 mg/kg/day up to a maximum of  400 mg/day divided Q12 hrs*	400 mg/day divided Q12 hrs*
3	After 3 more days, if tolerated , increase dose to:	20 mg/kg/day up to a maximum of 600 mg/day divided Q12 hrs*	600 mg/day divided Q12 hrs*

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:

WARNINGS WARNINGS



Table VI.       Dosage adjustment guided by serum theophylline concentration.

Peak Serum Concentration	Dosage Adjustment
<9.9 mcg/mL	If symptoms are not controlled and current dosage is tolerated, increase dose about 25%. Recheck serum concentration after three days for further dosage adjustment.
10 to 14.9 mcg/mL	If 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/mL	Consider 10% decrease in dose to provide greater margin of safety even if current dosage is tolerated.¶
20-24.9 mcg/mL	Decrease dose by 25% even if no adverse effects are present. Recheck serum concentration after 3 days to guide further dosage adjustment.
25-30 mcg/mL	Skip 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/mL	Treat 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.

WARNINGS

Once-Daily Dosing: _minmax­

HOW SUPPLIED

Theophylline Extended-release Tablets:



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Heritage Pharmaceuticals Inc.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

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Theophylline Theophylline TABLET, EXTENDED RELEASE Product Information Product Type Human prescription drug label Item Code (Source) NDC:23155-062 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength THEOPHYLLINE ANHYDROUS THEOPHYLLINE ANHYDROUS 300 mg Inactive Ingredients Ingredient Name Strength HYPROMELLOSES lactose monohydrate MAGNESIUM STEARATE POVIDONE K30 Product Characteristics Color Size Imprint Code Shape WHITE (White to off-White) 14 mm L107 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:23155-062-03 30 in 1 BOTTLE 2 NDC:23155-062-01 100 in 1 BOTTLE 3 NDC:23155-062-05 500 in 1 BOTTLE 4 NDC:23155-062-10 1000 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090430 2010-11-01

Theophylline Theophylline TABLET, EXTENDED RELEASE Product Information Product Type Human prescription drug label Item Code (Source) NDC:23155-063 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength THEOPHYLLINE ANHYDROUS THEOPHYLLINE ANHYDROUS 450 mg Inactive Ingredients Ingredient Name Strength HYPROMELLOSES lactose monohydrate MAGNESIUM STEARATE POVIDONE K30 Product Characteristics Color Size Imprint Code Shape WHITE (White to off-White) 19 mm L108 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:23155-063-03 30 in 1 BOTTLE 2 NDC:23155-063-01 100 in 1 BOTTLE 3 NDC:23155-063-05 500 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090430 2010-11-01