Theophylline (Anhydrous)
THEOPHYLLINE (ANHYDROUS)- theophylline anhydrous tablet, extended release
Golden State Medical Supply, Inc.
DESCRIPTION
Theophylline (anhydrous) extended-release tablets in a controlled-release system allows a 24-hour dosing interval for appropriate patients.
Theophylline, USP 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 C 7 H 8 N 4 O 2 with a molecular weight of 180.17. Each extended-release tablet for oral administration, contains 400 mg or 600 mg of anhydrous theophylline.
Inactive ingredients: glyceryl behenate, silicified microcrystalline cellulose, silicon dioxide, and magnesium stearate.
CLINICAL PHARMACOLOGY
Mechanism of Action
Theophylline has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects). While the mechanisms of action of theophylline are not known with certainty, studies in animals suggest that 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.
Serum Concentration-Effect Relationship
Bronchodilation occurs over the serum theophylline concentration range of 5 to 20 mcg/mL. Clinically important improvement in symptom control has been found in most studies to require peak serum theophylline concentrations > 10 mcg/mL, but patients with mild disease may benefit from lower concentrations. At serum theophylline concentrations > 20 mcg/mL, both the frequency and severity of adverse reactions increase. In general, maintaining peak serum theophylline concentrations between 10 and 15 mcg/mL will achieve most of the drug’s potential therapeutic benefit while minimizing the risk of serious adverse events.
Pharmacokinetics
Overview
Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form. Theophylline does not undergo any appreciable pre-systemic elimination, distributes freely into fat-free tissues and is extensively metabolized in the liver.
The pharmacokinetics of theophylline vary widely among similar patients and cannot be predicted by age, sex, body weight or other demographic characteristics. In addition, certain concurrent illnesses and alterations in normal physiology (See Table I) and co-administration of other drugs (See Table II) can significantly alter the pharmacokinetic characteristics of theophylline. Within-subject variability in metabolism has also been reported in some studies, especially in acutely ill patients. It is, therefore, recommended that serum theophylline concentrations be measured frequently in acutely ill patients (e.g., at 24-hr intervals) and periodically in patients receiving long-term therapy, e.g., at 6 to 12 month intervals. More frequent measurements should be made in the presence of any condition that may significantly alter theophylline clearance (see PRECAUTIONS, Laboratory Tests).
Note: In addition to the factors listed above, theophylline clearance is increased and half-life decreased by low carbohydrate/high protein diets, parenteral nutrition, and daily consumption of charcoal-broiled beef. A high carbohydrate/low protein diet can decrease the clearance and prolong the half-life of theophylline. | ||
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Population Characteristics | Total Body Clearance † Mean (Range) ‡ (mL/kg/min) | Half-Life Mean (Range) ‡ (hr) |
Age | ||
Premature neonates postnatal age 3 to 15 days postnatal age 25 to 57 days |
0.29 (0.09 to 0.49) 0.64 (0.04 to 1.2) |
30 (17 to 43) 20 (9.4 to 30.6) |
Term infants postnatal age 1 to 2 days postnatal age 3 to 30 weeks |
NR § NR § |
25.7 (25 to 26.5) 11 (6 to 29) |
Children 1 to 4 years 4 to 12 years 13 to 15 years 6 to 17 years |
1.7 (0.5 to 2.9) 1.6 (0.8 to 2.4) 0.9 (0.48 to 1.3) 1.4 (0.2 to 2.6) |
3.4 (1.2 to 5.6) NR § NR § 3.7 (1.5 to 5.9) |
Adults (16 to 60 years) otherwise healthy non-smoking asthmatics |
0.65 (0.27 to 1.03) |
8.7 (6.1 to 12.8) |
Elderly (> 60 years) non-smokers with normal cardiac, liver, and renal function |
0.41 (0.21 to 0.61) |
9.8 (1.6 to 18) |
Concurrent illness or altered physiological state | ||
Acute pulmonary edema | 0.33 ¶ (0.07 to 2.45) | 19 ¶ (3.1 to 82) |
COPD-> 60 years, stable non-smoker > 1 year |
0.54 (0.44 to 0.64) |
11 (9.4 to 12.6) |
COPD with cor pulmonale | 0.48 (0.08 to 0.88) | NR § |
Cystic fibrosis (14 to 28 years) | 1.25 (0.31 to 2.2) | 6.0 (1.8 to 10.2) |
Fever associated with acute viral respiratory illness (children 9 to 15 years) |
NR § |
7.0 (1.0 to 13) |
Liver disease cirrhosis acute hepatitis cholestasis |
0.31 ¶ (0.1 to 0.7) 0.35 (0.25 to 0.45) 0.65 (0.25 to 1.45) |
32 ¶ (10 to 56) 19.2 (16.6 to 21.8) 14.4 (5.7 to 31.8) |
Pregnancy 1st trimester 2nd trimester 3rd trimester |
NR § NR § NR § |
8.5 (3.1 to 13.9) 8.8 (3.8 to 13.8) 13.0 (8.4 to 17.6) |
Sepsis with multi-organ failure | 0.47 (0.19 to 1.9) | 18.8 (6.3 to 24.1) |
Thyroid disease hypothyroid hyperthyroid |
0.38 (0.13 to 0.57) 0.8 (0.68 to 0.97) |
11.6 (8.2 to 25) 4.5 (3.7 to 5.6) |
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