Dexa Teosona

Dexamethasone:

• Pharmacological action
• Pharmacokinetics
• Why is Dexa Teosona prescribed?
• Dosage and administration
• Dexa Teosona (Dexamethasone) side effects, adverse reactions
• Dexa Teosona contraindications
• Using during pregnancy and breastfeeding
• Dexa Teosona (Dexamethasone) in case of emergency / overdose
• Dexa Teosona (Dexamethasone) reviews

Pharmacological action

Dexa Teosona is a glucocorticosteroid. This medication Inhibits the function of leukocytes and tissue macrophages. Dexa Teosona (Dexamethasone) restricts the migration of leukocytes in the area of inflammation. This drug violates the ability of macrophages to phagocytosis and the formation of interleukin-1. Dexa Teosona (Dexamethasone) decreases capillary permeability caused by histamine release. This medicine inhibits the activity of fibroblasts and collagen formation.

Dexa Teosona (Dexamethasone) inhibits the activity of phospholipase A2, which leads to suppression of the synthesis of prostaglandins and leukotrienes.

With direct application to the vessels this drug has a vasoconstrictor effect.

Dexa Teosona (Dexamethasone) has a pronounced dose-dependent effect on the metabolism of carbohydrates, proteins and fats.

In high doses Dexa Teosona (Dexamethasone) may increase the excitability of brain tissue and contributes to lowering the threshold of convulsive readiness.

With systemic use of therapeutic activity of Dexa Teosona (Dexamethasone) is due to anti-inflammatory, antiallergic, immunosuppressive and antiproliferative action.

For external and local use of therapeutic activity of Dexa Teosona (Dexamethasone) is due to anti-inflammatory, antiallergic and antiexudative (due to vasoconstrictor effect) effect.

Pharmacokinetics

The plasma protein binding is 60-70%. This medication penetrates histohematic barriers. In a small amount it is excreted in breast milk. Dexa Teosona (Dexamethasone) metabolized in a liver. T_1/2 is 2-3 hours. This drug is excreted by kidneys.

When Dexa Teosona (Dexamethasone) applied topically in ophthalmology it absorbed through the cornea with intact epithelium in moisture anterior chamber. When inflammation of the tissues of the eye or mucosal damage and corneal absorption rate of Dexa Teosona (Dexamethasone) significantly increased.

Why is Dexa Teosona prescribed?

For oral administration: Biermer's disease; acute and subacute thyroiditis, hypothyroidism, progressive ophthalmopathy associated with thyrotoxicosis; bronchial asthma; rheumatoid arthritis in the acute phase; ulcerative colitis; connective tissue disease; autoimmune hemolytic anemia, thrombocytopenia, aplasia and hypoplasia of hematopoiesis, agranulocytosis, serum sickness; acute erythroderma, pemphigus (normal), acute eczema (early treatment); malignant tumor (as a palliative therapy); congenital adrenogenital syndrome; cerebral edema (usually after a preliminary parenteral corticosteroids).

For parenteral administration: shock of various origins; swelling of the brain (with brain tumors, head injury, neurosurgical intervention, brain hemorrhage, encephalitis, meningitis, radiation damage); asthmatic status; severe allergic reactions (angioedema, bronchospasm, dermatosis, acute anaphylactic reaction to medication, transfusion serum, pyrogenic reactions); acute hemolytic anemia, thrombocytopenia, acute lymphoblastic leukemia, agranulocytosis; serious infectious diseases (in combination with antibiotics); acute adrenal insufficiency, acute croup; arthropathy (scapulohumeral periarthritis, epicondylitis, styloiditis, bursitis, tenosynovitis, compression neuropathy, osteochondrosis, arthritis of various etiologies, osteoarthritis).

For use in ophthalmic practice: not purulent and allergic conjunctivitis, keratitis, keratoconjunctivitis without damaging the epithelium, iritis, iridocyclitis, blefaroconjuntivitis, blepharitis, episcleritis, scleritis, inflammation of injuries and eye surgeries, sympathetic ophthalmia.

Dosage and administration

The dosing regimen is individual. Orally for severe disease at the beginning of treatment it is prescribed to 10-15 mg / day, maintenance dose may be 2-4.5 mg / day or more. The daily dose divided into 2-3 doses. In small doses Dexa Teosona is taken 1 time in the morning.

For parenteral administration this medication is administered IV slowly bolus or infusion (acute and urgent conditions); IM; it is possible also periarticular and intraarticular injection. During the day it can be administered from 4 to 20 mg of Dexa Teosona (Dexamethasone) 3-4 times / day. The duration of parenteral administration is usually 3-4 days, then move on to maintenance therapy of oral form. In the acute period in various diseases and early treatment Dexa Teosona (Dexamethasone) used in higher doses. Upon reaching the effect the dose is decreased within a few days before reaching the maintenance dose or until discontinuation of treatment.

When used in ophthalmology for acute conditions this drug instilled into conjunctival sac 1-2 drops every 1-2 hours, then with a decrease in inflammation after every 4-6 hours. The duration of treatment is from 1-2 days to several weeks depending on the clinical course of disease.

Dexa Teosona (Dexamethasone) side effects, adverse reactions

Endocrine system: impaired glucose tolerance, steroid diabetes mellitus or manifestation of latent diabetes mellitus, suppression of adrenal function, Itsenko-Cushing syndrome (including moon face, obesity, pituitary type, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia gravis, striae), delayed sexual development in children.

Metabolism: increased excretion of calcium, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating, hypernatremia, hypokalemia.

CNS: delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness or anxiety, insomnia, dizziness, vertigo, pseudotumor cerebellum, headache, convulsions.

Cardio-vascular system: arrhythmia, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased severity of chronic heart failure, ECG changes typical of hypokalemia, increased blood pressure, hypercoagulability, thrombosis. In patients with acute and subacute myocardial infarction - spread necrosis, slowing the formation of scar tissue that can lead to rupture of the heart muscle; with intracranial introduction - nosebleeds.

Digestive system: nausea, vomiting, pancreatitis, steroid gastric and duodenal ulcers, erosive esophagitis, bleeding and perforation of the gastrointestinal tract, increase or decrease in appetite, flatulence, hiccups; rarely - increased activity of hepatic transaminases and alkaline phosphatase.

Sensory organs: posterior subcapsular cataracts, increased intraocular pressure with possible damage to the optic nerve, propensity to develop secondary bacterial, fungal or viral infections of the eye, trophic changes of the cornea, exophthalmos.

Musculoskeletal system: growth retardation and ossification processes in children (premature closure of epiphyseal growth zones), osteoporosis (very rare - a pathological bone fractures, aseptic necrosis of head of humerus and femur), rupture of tendons of muscles, steroid myopathy, reduced muscle mass (atrophy).

Dermatological reactions: delayed wound healing, petechiae, ecchymosis, skin thinning, hyper or hypopigmentation, steroid acne, stretch marks, susceptibility to the development of pyoderma and candidiasis.

Allergic reactions: generalized (including skin rash, itching, anaphylactic shock) and when applied topically.

Effects associated with immunosuppressive action: development or worsening of infection (the appearance of this side effect contribute jointly used immunosuppressive drugs, and vaccinations).

Local reactions: when Dexa Teosona (Dexamethasone) administered parenteral - tissue necrosis.

For external use: rarely - itching, redness, burning, dryness, folliculitis, acne, hypopigmentation, perioral dermatitis, allergic dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, miliaria. With prolonged use or application to large areas of skin may develop systemic side effects characteristic of SCS.

Dexa Teosona contraindications

For short-term use for health reasons - increased sensitivity to Dexa Teosona (Dexamethasone).

For intra-articular injection and injection directly into the lesion: previous arthroplasty, abnormal bleeding (endogenous or caused by the use of anticoagulants), intra-articular fracture, infection (sepsis) inflammation in the joints and periarticular infections (including in history), as well as general infectious disease, pronounced juxta-articular osteoporosis, no signs of inflammation in the joints ("dry" joint, such as osteoarthritis without synovitis), severe bone destruction and deformity of the joint (a sharp narrowing of joint space, ankylosis), instability of the joint as a result of arthritis, aseptic necrosis of the epiphyses of bones forming the joint.

For external use: bacterial, viral, fungal skin diseases, tuberculosis, skin, cutaneous manifestations of syphilis, skin tumors, post-vaccination period, violation of the integrity of the skin (ulcers, wounds), children's age (up to 2 years, with itching in the anal area - up to 12 years), rosacea, acne vulgaris, perioral dermatitis.

For use in ophthalmology: bacterial, viral, fungal eye diseases, tuberculosis eye damage, tampering with the ocular epithelium, acute form of purulent eye infection in the absence of specific therapy, diseases of the cornea, combined with defects in the epithelium, trachoma, glaucoma.

Using during pregnancy and breastfeeding

During pregnancy and lactating Dexa Teosona (Dexamethasone) is used taking into account the expected therapeutic effect and adverse effect on the fetus. Long-term therapy during pregnancy does not exclude the possibility of violations of fetal growth. In the case of the end of pregnancy there is a danger of atrophy of the adrenal cortex of the fetus, which may require replacement therapy in the newborn.

Category effects on the fetus by FDA - C.

Dexa Teosona (Dexamethasone) in case of emergency / overdose

Symptoms: increased side effects.

Treatment: the development of adverse reactions - symptomatic therapy, the Itsenko-Cushing syndrome - the prescription of aminoglutethimide.

Theophylline:

• Description
• Clinical pharmacology
• Clinical studies
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Dexa Teosona (Theophylline) reviews

DESCRIPTION

Dexa Teosona (Theophylline)^® (theophylline, anhydrous) Tablets in a controlled-release system allows a 24-hour dosing interval for appropriate patients.

Dexa Teosona (Theophylline) is structurally classified as a methylxanthine. It occurs as a white, odorless, crystalline powder with a bitter taste. Anhydrous Dexa Teosona (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 Dexa Teosona (Theophylline) is C₇H₈N₄O₂ with a molecular weight of 180.17.

Each controlled-release tablet for oral administration, contains 400 or 600 mg of anhydrous Dexa Teosona (Theophylline).

Inactive Ingredients: cetostearyl alcohol, hydroxyethyl cellulose, magnesium stearate, povidone and talc.

Dexa Teosona (Theophylline) 400 mg

CLINICAL PHARMACOLOGY

Mechanism of Action

Dexa Teosona 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 Dexa Teosona (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 Dexa Teosona (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).

Dexa Teosona (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 Dexa Teosona (Theophylline) concentration range of 5-20 mcg/mL. Clinically important improvement in symptom control has been found in most studies to require peak serum Dexa Teosona (Theophylline) concentrations >10 mcg/mL, but patients with mild disease may benefit from lower concentrations. At serum Dexa Teosona (Theophylline) concentrations >20 mcg/mL, both the frequency and severity of adverse reactions increase. In general, maintaining peak serum Dexa Teosona (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: Dexa Teosona is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form. Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (Theophylline). Within-subject variability in metabolism has also been reported in some studies, especially in acutely ill patients. It is, therefore, recommended that serum Dexa Teosona (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 6-12 month intervals. More frequent measurements should be made in the presence of any condition that may significantly alter Dexa Teosona (Theophylline) clearance (see PRECAUTIONS, Laboratory Tests ).

Note: In addition to the factors listed above, Dexa Teosona (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 Dexa Teosona (Theophylline).

Absorption

Dexa Teosona (Theophylline)^® administered in the fed state is completely absorbed after oral administration.

In a single-dose crossover study, two 400 mg Dexa Teosona (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_max=9.3±2.0 mcg/mL, T_max=12.8±4.2 hours. On the evening arm, the pharmacokinetic parameters were AUC=219.7±83.0 mcg hr/mL, C_max=9.2±2.0 mcg/mL, T_max=12.5±4.2 hours.

A study in which Dexa Teosona (Theophylline) 400 mg Tablets were administered to 17 fed adult asthmatics produced similar Dexa Teosona (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 Dexa Teosona (Theophylline) inherent mean elimination half-life was verified by a liquid Dexa Teosona (Theophylline) product to be 6.9±2.5 (SD) hours were administered two or three 400 mg Dexa Teosona (Theophylline)^® Tablets. The relative bioavailability of Dexa Teosona (Theophylline) given in the fasting state in comparison to an immediate-release product was 59%. Peak serum Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (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_max and C_min 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_max=8.4±2.6 mcg/mL, T_max=17.3±6.7 hours. Under fasting conditions, these parameters were AUC=141.2±6.53 mcg hr/mL, C_max=5.5±1.5 mcg/mL, T_max=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 Dexa Teosona (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 Dexa Teosona (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_max=10.9±1.7 mcg/mL, T_max=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_max=6.7±1.7 mcg/mL, T_max=7.3±2.2 hours.

Thus, administration of single Dexa Teosona (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 Dexa Teosona (Theophylline) with Dexa Teosona (Theophylline) Tablets even when they are administered with a high fat, high calorie meal.

Similar studies were conducted with the 600 mg Dexa Teosona (Theophylline) Tablet. A single-dose study in 24 subjects with an established Dexa Teosona (Theophylline) clearance of ≤4 L/hr, compared the pharmacokinetic evaluation of one 600 mg Dexa Teosona (Theophylline) Tablet and one and one-half 400 mg Dexa Teosona (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 Dexa Teosona (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_max=10.58±2.21 mcg/mL and T_max=9.00±2.64 hours, and for the 600 mg tablet were AUC=207.85±48.9 mcg hr/mL, C_max=10.39±1.91 mcg/mL and T_max=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_max= 7.37±1.83 mcg/mL and T_max=8.08±4.39 hours; and for the 600 mg tablet were AUC=199.39±70.27 mcg hr/mL, C_max=7.66±2.09 mcg/mL and T_max=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 Dexa Teosona (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 Dexa Teosona (Theophylline) Tablet administered in the morning or in the evening. The results were: AUC=233.6±45.1 mcg hr/mL, C_max=10.6±1.3 mcg/mL and T_max=12.5±3.2 hours with morning dosing; AUC=209.8±46.2 mcg hr/mL, C_max=9.7±1.4 mcg/mL and T_max=13.7±3.3 hours with evening dosing. The PM/AM ratio was 89.3%.

The absorption characteristics of Dexa Teosona (Theophylline)^® Tablets (theophylline, anhydrous) have been extensively studied. A steady-state crossover bioavailability study in 22 normal males compared two Dexa Teosona (Theophylline) 400 mg Tablets administered q24h at 8 a.m. immediately after breakfast with a reference controlled-release Dexa Teosona (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 Dexa Teosona (Theophylline) 400 mg Tablets under these steady-state conditions were AUC=203.3±87.1 mcg hr/mL, C_max=12.1±3.8 mcg/mL, C_min=4.50±3.6, T_max=8.8±4.6 hours. For the reference BID product, the pharmacokinetic parameters were AUC=219.2±88.4 mcg hr/mL, C_max =11.0±4.1 mcg/mL, C_min=7.28±3.5, T_max=6.9±3.4 hours. The mean percent fluctuation [(C_max-C_min/C_min)x100]=169% for the once-daily regimen and 51% for the reference product BID regimen.

The bioavailability of the 600 mg Dexa Teosona (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 Dexa Teosona (Theophylline) Tablets. All subjects had previously established Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (Theophylline) Tablets whether dosed in the morning or evening.

Distribution

Once Dexa Teosona enters the systemic circulation, about 40% is bound to plasma protein, primarily albumin. Unbound Dexa Teosona (Theophylline) distributes throughout body water, but distributes poorly into body fat. The apparent volume of distribution of Dexa Teosona (Theophylline) is approximately 0.45 L/kg (range 0.3-0.7 L/kg) based on ideal body weight. Dexa Teosona (Theophylline) passes freely across the placenta, into breast milk and into the cerebrospinal fluid (CSF). Saliva Dexa Teosona (Theophylline) concentrations approximate unbound serum concentrations, but are not reliable for routine or therapeutic monitoring unless special techniques are used. An increase in the volume of distribution of Dexa Teosona (Theophylline), primarily due to reduction in plasma protein binding, occurs in premature neonates, patients with hepatic cirrhosis, uncorrected acidemia, the elderly and in women during the third trimester of pregnancy. In such cases, the patient may show signs of toxicity at total (bound+unbound) serum concentrations of Dexa Teosona (Theophylline) in the therapeutic range (10-20 mcg/mL) due to elevated concentrations of the pharmacologically active unbound drug. Similarly, a patient with decreased Dexa Teosona (Theophylline) binding may have a sub-therapeutic total drug concentration while the pharmacologically active unbound concentration is in the therapeutic range. If only total serum Dexa Teosona (Theophylline) concentration is measured, this may lead to an unnecessary and potentially dangerous dose increase. In patients with reduced protein binding, measurement of unbound serum Dexa Teosona (Theophylline) concentration provides a more reliable means of dosage adjustment than measurement of total serum Dexa Teosona (Theophylline) concentration. Generally, concentrations of unbound Dexa Teosona (Theophylline) should be maintained in the range of 6-12 mcg/mL.

Metabolism

Following oral dosing, Dexa Teosona (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 Dexa Teosona (Theophylline) dose is N-methylated to caffeine. Dexa Teosona (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 Dexa Teosona (Theophylline) metabolites with pharmacologic activity. 3-methylxanthine has approximately one tenth the pharmacologic activity of Dexa Teosona (Theophylline) and serum concentrations in adults with normal renal function are <1 mcg/mL. In patients with end-stage renal disease, 3-methylxanthine may accumulate to concentrations that approximate the unmetabolized Dexa Teosona (Theophylline) concentration. Caffeine concentrations are usually undetectable in adults regardless of renal function. In neonates, caffeine may accumulate to concentrations that approximate the unmetabolized Dexa Teosona (Theophylline) concentration and thus, exert a pharmacologic effect.

Both the N-demethylation and hydroxylation pathways of Dexa Teosona (Theophylline) biotransformation are capacity-limited. Due to the wide intersubject variability of the rate of Dexa Teosona (Theophylline) metabolism, non-linearity of elimination may begin in some patients at serum Dexa Teosona (Theophylline) concentrations <10 mcg/mL. Since this non-linearity results in more than proportional changes in serum Dexa Teosona (Theophylline) concentrations with changes in dose, it is advisable to make increases or decreases in dose in small increments in order to achieve desired changes in serum Dexa Teosona (Theophylline) concentrations (see DOSAGE AND ADMINISTRATION, Table VI ). Accurate prediction of dose-dependency of Dexa Teosona (Theophylline) metabolism in patients a priori is not possible, but patients with very high initial clearance rates (i.e., low steady-state serum Dexa Teosona (Theophylline) concentrations at above average doses) have the greatest likelihood of experiencing large changes in serum Dexa Teosona (Theophylline) concentration in response to dosage changes.

Excretion

In neonates, approximately 50% of the Dexa Teosona dose is excreted unchanged in the urine. Beyond the first three months of life, approximately 10% of the Dexa Teosona (Theophylline) dose is excreted unchanged in the urine. The remainder is excreted in the urine mainly as 1,3-dimethyluric acid (35-40%), 1-methyluric acid (20-25%) and 3-methylxanthine (15-20%). Since little Dexa Teosona (Theophylline) is excreted unchanged in the urine and since active metabolites of Dexa Teosona (Theophylline) (i.e., caffeine, 3-methylxanthine) do not accumulate to clinically significant levels even in the face of end-stage renal disease, no dosage adjustment for renal insufficiency is necessary in adults and children >3 months of age. In contrast, the large fraction of the Dexa Teosona (Theophylline) dose excreted in the urine as unchanged Dexa Teosona (Theophylline) and caffeine in neonates requires careful attention to dose reduction and frequent monitoring of serum Dexa Teosona (Theophylline) concentrations in neonates with reduced renal function (See WARNINGS ).

Serum Concentrations at Steady-State

After multiple doses of Dexa Teosona (Theophylline), steady-state is reached in 30-65 hours (average 40 hours) in adults. At steady-state, on a dosage regimen with 24-hour intervals, the expected mean trough concentration is approximately 50% of the mean peak concentration, assuming a mean Dexa Teosona (Theophylline) half-life of 8 hours. The difference between peak and trough concentrations is larger in patients with more rapid Dexa Teosona (Theophylline) clearance. In these patients administration of Dexa Teosona (Theophylline)^® may be required more frequently (every 12 hours).

Special Populations

Geriatric

The clearance of Dexa Teosona (Theophylline) is decreased by an average of 30% in healthy elderly adults (>60 yrs) compared to healthy young adults. Careful attention to dose reduction and frequent monitoring of serum Dexa Teosona (Theophylline) concentrations are required in elderly patients (see WARNINGS ).

Pediatrics

The clearance of Dexa Teosona is very low in neonates (see WARNINGS ). Dexa Teosona (Theophylline) clearance reaches maximal values by one year of age, remains relatively constant until about 9 years of age and then slowly decreases by approximately 50% to adult values at about age 16. Renal excretion of unchanged Dexa Teosona (Theophylline) in neonates amounts to about 50% of the dose, compared to about 10% in children older than three months and in adults. Careful attention to dosage selection and monitoring of serum Dexa Teosona (Theophylline) concentrations are required in pediatric patients (see WARNINGS and DOSAGE AND ADMINISTRATION ).

Gender

Gender differences in Dexa Teosona (Theophylline) clearance are relatively small and unlikely to be of clinical significance. Significant reduction in Dexa Teosona (Theophylline) clearance, however, has been reported in women on the 20th day of the menstrual cycle and during the third trimester of pregnancy.

Race

Pharmacokinetic differences in Dexa Teosona clearance due to race have not been studied.

Renal Insufficiency

Only a small fraction, e.g., about 10%, of the administered Dexa Teosona (Theophylline) dose is excreted unchanged in the urine of children greater than three months of age and adults. Since little Dexa Teosona (Theophylline) is excreted unchanged in the urine and since active metabolites of Dexa Teosona (Theophylline) (i.e., caffeine, 3-methylxanthine) do not accumulate to clinically significant levels even in the face of end-stage renal disease, no dosage adjustment for renal insufficiency is necessary in adults and children >3 months of age. In contrast, approximately 50% of the administered Dexa Teosona (Theophylline) dose is excreted unchanged in the urine in neonates. Careful attention to dose reduction and frequent monitoring of serum Dexa Teosona (Theophylline) concentrations are required in neonates with decreased renal function (see WARNINGS ).

Hepatic Insufficiency

Dexa Teosona clearance is decreased by 50% or more in patients with hepatic insufficiency (e.g., cirrhosis, acute hepatitis, cholestasis). Careful attention to dose reduction and frequent monitoring of serum Dexa Teosona (Theophylline) concentrations are required in patients with reduced hepatic function (see WARNINGS ).

Congestive Heart Failure (CHF)

Dexa Teosona (Theophylline) clearance is decreased by 50% or more in patients with CHF. The extent of reduction in Dexa Teosona (Theophylline) clearance in patients with CHF appears to be directly correlated to the severity of the cardiac disease. Since Dexa Teosona (Theophylline) clearance is independent of liver blood flow, the reduction in clearance appears to be due to impaired hepatocyte function rather than reduced perfusion. Careful attention to dose reduction and frequent monitoring of serum Dexa Teosona (Theophylline) concentrations are required in patients with CHF (see WARNINGS ).

Smokers

Tobacco and marijuana smoking appears to increase the clearance of Dexa Teosona by induction of metabolic pathways. Dexa Teosona (Theophylline) clearance has been shown to increase by approximately 50% in young adult tobacco smokers and by approximately 80% in elderly tobacco smokers compared to non-smoking subjects. Passive smoke exposure has also been shown to increase Dexa Teosona (Theophylline) clearance by up to 50%. Abstinence from tobacco smoking for one week causes a reduction of approximately 40% in Dexa Teosona (Theophylline) clearance. Careful attention to dose reduction and frequent monitoring of serum Dexa Teosona (Theophylline) concentrations are required in patients who stop smoking (see WARNINGS ). Use of nicotine gum has been shown to have no effect on Dexa Teosona (Theophylline) clearance.

Fever

Fever, regardless of its underlying cause, can decrease the clearance of Dexa Teosona (Theophylline). The magnitude and duration of the fever appear to be directly correlated to the degree of decrease of Dexa Teosona (Theophylline) clearance. Precise data are lacking, but a temperature of 39°C (102°F) for at least 24 hours is probably required to produce a clinically significant increase in serum Dexa Teosona (Theophylline) concentrations. Children with rapid rates of Dexa Teosona (Theophylline) clearance (i.e., those who require a dose that is substantially larger than average [e.g., >22 mg/kg/day] to achieve a therapeutic peak serum Dexa Teosona (Theophylline) concentration when afebrile) may be at greater risk of toxic effects from decreased clearance during sustained fever. Careful attention to dose reduction and frequent monitoring of serum Dexa Teosona (Theophylline) concentrations are required in patients with sustained fever (see WARNINGS ).

Miscellaneous

Other factors associated with decreased Dexa Teosona (Theophylline) clearance include the third trimester of pregnancy, sepsis with multiple organ failure, and hypothyroidism. Careful attention to dose reduction and frequent monitoring of serum Dexa Teosona (Theophylline) concentrations are required in patients with any of these conditions (see WARNINGS ). Other factors associated with increased Dexa Teosona (Theophylline) clearance include hyperthyroidism and cystic fibrosis.

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 Dexa Teosona (Theophylline) decreases the frequency and severity of symptoms, including nocturnal exacerbations, and decreases the “as needed” use of inhaled beta-₂ agonists. Dexa Teosona (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 Dexa Teosona (Theophylline) decreases dyspnea, air trapping, the work of breathing, and improves contractility of diaphragmatic muscles with little or no improvement in pulmonary function measurements.

INDICATIONS AND USAGE

Dexa Teosona (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.

CONTRAINDICATIONS

Dexa Teosona (Theophylline)^® is contraindicated in patients with a history of hypersensitivity to Dexa Teosona (Theophylline) or other components in the product.

WARNINGS

Concurrent Illness

Dexa Teosona 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 Dexa Teosona (Theophylline) Clearance

There are several readily identifiable causes of reduced Dexa Teosona (Theophylline) clearance. If the total daily dose is not appropriately reduced in the presence of these risk factors, severe and potentially fatal Dexa Teosona (Theophylline) toxicity can occur . Careful consideration must be given to the benefits and risks of Dexa Teosona (Theophylline) use and the need for more intensive monitoring of serum Dexa Teosona (Theophylline) concentrations in patients with the following risk factors:

Age

• Neonates (term and premature)
• Children <1 year
• Elderly (>60 years)

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 Dexa Teosona metabolism (e.g., cimetidine, erythromycin, tacrine) or stopping a concurrently administered drug that enhances Dexa Teosona (Theophylline) metabolism (e.g., carbamazepine, rifampin). (see PRECAUTIONS, Drug Interactions, Table II ).

When Signs or Symptoms of Dexa Teosona (Theophylline) Toxicity Are Present

Whenever a patient receiving Dexa Teosona (Theophylline) develops nausea or vomiting, particularly repetitive vomiting, or other signs or symptoms consistent with Dexa Teosona (Theophylline) toxicity (even if another cause may be suspected), additional doses of Dexa Teosona (Theophylline) should be withheld and a serum Dexa Teosona (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 Dexa Teosona (Theophylline) should not be made in response to an acute exacerbation of symptoms of chronic lung disease since Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (Theophylline) concentration (see DOSAGE AND ADMINISTRATION, Table VI ).

PRECAUTIONS

General

Careful consideration of the various interacting drugs and physiologic conditions that can alter Dexa Teosona clearance and require dosage adjustment should occur prior to initiation of Dexa Teosona (Theophylline) therapy, prior to increases in Dexa Teosona (Theophylline) dose, and during follow up (see WARNINGS ). The dose of Dexa Teosona (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 Dexa Teosona (Theophylline) concentrations and the patient’s clinical response (see DOSAGE AND ADMINISTRATION , Table V).

Monitoring Serum Dexa Teosona (Theophylline) Concentrations

Serum Dexa Teosona (Theophylline) concentration measurements are readily available and should be used to determine whether the dosage is appropriate. Specifically, the serum Dexa Teosona (Theophylline) concentration should be measured as follows:

• When initiating therapy to guide final dosage adjustment after titration.
• Before making a dose increase to determine whether the serum concentration is sub-therapeutic in a patient who continues to be symptomatic.
• Whenever signs or symptoms of Dexa Teosona (Theophylline) toxicity are present.
• Whenever there is a new illness, worsening of a chronic illness or a change in the patient’s treatment regimen that may alter Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (Theophylline) should be measured and the dosage adjusted to achieve an unbound concentration of 6-12 mcg/mL.

Saliva concentrations of Dexa Teosona (Theophylline) cannot be used reliably to adjust dosage without special techniques.

Effects on Laboratory Tests

As a result of its pharmacological effects, Dexa Teosona 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). Dexa Teosona (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 Dexa Teosona (Theophylline)). The clinical importance of these changes should be weighed against the potential therapeutic benefit of Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (Theophylline) interacts with a wide variety of drugs. The dietary supplement St. John’s Wort (Hypericum perforatum) should not be taken at the same time as Dexa Teosona (Theophylline), since it may result in decreased Dexa Teosona (Theophylline) levels. If patients are already taking St. John’s Wort and Dexa Teosona (Theophylline) together, they should consult their healthcare professional before stopping the St. John’s Wort, since their Dexa Teosona (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 Dexa Teosona (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.

Dexa Teosona (Theophylline)^® Tablets can be taken once a day in the morning or evening. It is recommended that Dexa Teosona (Theophylline) be taken with meals. Patients should be advised that if they choose to take Dexa Teosona (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.

Dexa Teosona (Theophylline) Tablets are not to be chewed or crushed because it may lead to a rapid release of Dexa Teosona (Theophylline) with the potential for toxicity. The scored tablet may be split. Patients receiving Dexa Teosona (Theophylline) Tablets may pass an intact matrix tablet in the stool or via colostomy. These matrix tablets usually contain little or no residual Dexa Teosona (Theophylline).

Drug Interactions

Dexa Teosona interacts with a wide variety of drugs. The interaction may be pharmacodynamic, i.e., alterations in the therapeutic response to Dexa Teosona (Theophylline) or another drug or occurrence of adverse effects without a change in serum Dexa Teosona (Theophylline) concentration. More frequently, however, the interaction is pharmacokinetic, i.e., the rate of Dexa Teosona (Theophylline) clearance is altered by another drug resulting in increased or decreased serum Dexa Teosona (Theophylline) concentrations. Dexa Teosona (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 Dexa Teosona (Theophylline). The information in the “Effect” column of Table II assumes that the interacting drug is being added to a steady-state Dexa Teosona (Theophylline) regimen. If Dexa Teosona (Theophylline) is being initiated in a patient who is already taking a drug that inhibits Dexa Teosona (Theophylline) clearance (e.g., cimetidine, erythromycin), the dose of Dexa Teosona (Theophylline) required to achieve a therapeutic serum Dexa Teosona (Theophylline) concentration will be smaller. Conversely, if Dexa Teosona (Theophylline) is being initiated in a patient who is already taking a drug that enhances Dexa Teosona (Theophylline) clearance (e.g., rifampin), the dose of Dexa Teosona (Theophylline) required to achieve a therapeutic serum Dexa Teosona (Theophylline) concentration will be larger. Discontinuation of a concomitant drug that increases Dexa Teosona (Theophylline) clearance will result in accumulation of Dexa Teosona (Theophylline) to potentially toxic levels, unless the Dexa Teosona (Theophylline) dose is appropriately reduced. Discontinuation of a concomitant drug that inhibits Dexa Teosona (Theophylline) clearance will result in decreased serum Dexa Teosona (Theophylline) concentrations, unless the Dexa Teosona (Theophylline) dose is appropriately increased.

The drugs listed in Table III have either been documented not to interact with Dexa Teosona (Theophylline) or do not produce a clinically significant interaction (i.e., <15% change in Dexa Teosona (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 Dexa Teosona (Theophylline), especially with new chemical entities. The healthcare professional should not assume that a drug does not interact with Dexa Teosona (Theophylline) if it is not listed in Table II. Before addition of a newly available drug in a patient receiving Dexa Teosona (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 Dexa Teosona (Theophylline) has been reported.

Drug-Food Interactions

The bioavailability of Dexa Teosona (Theophylline)^® Tablets (theophylline, anhydrous) has been studied with co-administration of food. In three single-dose studies, subjects given Dexa Teosona (Theophylline) 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 Dexa Teosona Serum Concentration Measurements

Most serum Dexa Teosona (Theophylline) assays in clinical use are immunoassays which are specific for Dexa Teosona (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 Dexa Teosona (Theophylline) concentration.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long term carcinogenicity studies have been carried out in mice and rats (oral doses 5-75 mg/kg). Results are pending.

Dexa Teosona (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, Dexa Teosona (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, Dexa Teosona (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, Dexa Teosona (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. Dexa Teosona (Theophylline) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Dexa Teosona is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants. The concentration of Dexa Teosona (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 Dexa Teosona (Theophylline) per day is likely to receive 10-20 mg of Dexa Teosona (Theophylline) per day. Serious adverse effects in the infant are unlikely unless the mother has toxic serum Dexa Teosona (Theophylline) concentrations.

Pediatric Use

Dexa Teosona (Theophylline) is safe and effective for the approved indications in pediatric patients. The maintenance dose of Dexa Teosona (Theophylline) must be selected with caution in pediatric patients since the rate of Dexa Teosona (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 Dexa Teosona (Theophylline) than younger patients due to pharmacokinetic and pharmacodynamic changes associated with aging. The clearance of Dexa Teosona (Theophylline) is decreased by an average of 30% in healthy elderly adults (>60 yrs) compared to healthy young adults. Dexa Teosona (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 Dexa Teosona (Theophylline) concentration in the pharmacologically active unbound form. Elderly patients also appear to be more sensitive to the toxic effects of Dexa Teosona (Theophylline) after chronic overdosage than younger patients. Careful attention to dose reduction and frequent monitoring of serum Dexa Teosona (Theophylline) concentrations are required in elderly patients (see PRECAUTIONS, Monitoring Serum Dexa Teosona (Theophylline) Concentrations, and DOSAGE AND ADMINISTRATION ). The maximum daily dose of Dexa Teosona (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 Dexa Teosona (Theophylline) concentration is <10 mcg/mL (see DOSAGE AND ADMINISTRATION ). Dexa Teosona (Theophylline) doses greater than 400 mg/d should be prescribed with caution in elderly patients. Dexa Teosona (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 Dexa Teosona (Theophylline) are generally mild when peak serum Dexa Teosona (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 Dexa Teosona (Theophylline) concentrations exceed 20 mcg/mL, however, Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (Theophylline) therapy, caffeine-like adverse effects may transiently alter patient behavior, especially in school age children, but this response rarely persists. Initiation of Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (Theophylline) therapy and the potential therapeutic benefit of alternative treatment.

Other adverse reactions that have been reported at serum Dexa Teosona (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 Dexa Teosona (Theophylline) concentrations ≥15 mcg/mL. There have been a few isolated reports of seizures at serum Dexa Teosona (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 Dexa Teosona (Theophylline) concentrations <20 mcg/mL may be secondary to decreased protein binding resulting in a larger proportion of the total serum Dexa Teosona (Theophylline) concentration in the pharmacologically active unbound form. The clinical characteristics of the seizures reported in patients with serum Dexa Teosona (Theophylline) concentrations <20 mcg/mL have generally been milder than seizures associated with excessive serum Dexa Teosona (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).

OVERDOSAGE

General

The chronicity and pattern of Dexa Teosona 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 Dexa Teosona (Theophylline) clearance. The most common causes of chronic Dexa Teosona (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 Dexa Teosona (Theophylline) clearance, and increasing the dose in response to an exacerbation of symptoms without first measuring the serum Dexa Teosona (Theophylline) concentration to determine whether a dose increase is safe.

Severe toxicity from Dexa Teosona (Theophylline) overdose is a relatively rare event. In one health maintenance organization, the frequency of hospital admissions for chronic overdosage of Dexa Teosona (Theophylline) was about 1 per 1000 person-years exposure. In another study, among 6000 blood samples obtained for measurement of serum Dexa Teosona (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 Dexa Teosona (Theophylline) concentrations in the 20-30 mcg/mL range had one or more manifestations of toxicity while >90% of patients with serum Dexa Teosona (Theophylline) concentrations >30 mcg/mL were clinically intoxicated. Similarly, in other reports, serious toxicity from Dexa Teosona (Theophylline) is seen principally at serum concentrations >30 mcg/mL.

Several studies have described the clinical manifestations of Dexa Teosona (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 Dexa Teosona (Theophylline) concentration is >100 mcg/mL. After a chronic overdosage, generalized seizures, life-threatening cardiac arrhythmias, and death may occur at serum Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (Theophylline) concentration compared to patients without the underlying disease.

The frequency of various reported manifestations of Dexa Teosona (Theophylline) overdose according to the mode of overdose are listed in Table IV.

Other manifestations of Dexa Teosona (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 Dexa Teosona (Theophylline) concentrations >30 mcg/mL are often resistant to anticonvulsant therapy and may result in irreversible brain injury if not rapidly controlled. Death from Dexa Teosona (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 Dexa Teosona (Theophylline) Overdose or Serum Dexa Teosona (Theophylline) Concentrations >30 mcg/mL (Note: Serum Dexa Teosona (Theophylline) concentrations may continue to increase after presentation of the patient for medical care.)

• While simultaneously instituting treatment, contact a regional poison center to obtain updated information and advice on individualizing the recommendations that follow.
• Institute supportive care, including establishment of intravenous access, maintenance of the airway, and electrocardiographic monitoring.
• 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 Dexa Teosona (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 Dexa Teosona (Theophylline) overdose because fluorinated volatile anesthetics may sensitize the myocardium to endogenous catecholamines released by Dexa Teosona (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.
• Anticipate Need for Anticonvulsants In patients with Dexa Teosona (Theophylline) overdose who are at high risk for theophylline-induced seizures, e.g., patients with acute overdoses and serum Dexa Teosona (Theophylline) concentrations >100 mcg/mL or chronic overdosage in patients >60 years of age with serum Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (Theophylline) clearance are continued. Phenobarbital may cause respiratory depression, particularly in elderly patients and patients with COPD.
• 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 Dexa Teosona (Theophylline) concentrations. Other arrhythmias, especially those associated with hemodynamic compromise, should be treated with antiarrhythmic therapy appropriate for the type of arrhythmia.
• 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 Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (Theophylline) overdoses. Although ipecac induces emesis, it does not reduce the absorption of Dexa Teosona (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.
• Serum Dexa Teosona (Theophylline) Concentration Monitoring The serum Dexa Teosona (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 Dexa Teosona (Theophylline) concentrations may continue to increase after presentation of the patient for medical care as a result of continued absorption of Dexa Teosona (Theophylline) from the gastrointestinal tract. Serial monitoring of serum Dexa Teosona (Theophylline) serum concentrations should be continued until it is clear that the concentration is no longer rising and has returned to non-toxic levels.
• General Monitoring Procedures Electrocardiographic monitoring should be initiated on presentation and continued until the serum Dexa Teosona (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.
• Enhance clearance of Dexa Teosona (Theophylline) Multiple-dose oral activated charcoal (e.g., 0.5 mg/kg up to 20 g, every two hours) increases the clearance of Dexa Teosona (Theophylline) at least twofold by adsorption of Dexa Teosona (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 Dexa Teosona (Theophylline) from the gastrointestinal tract. Sorbitol alone does not enhance clearance of Dexa Teosona (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 Dexa Teosona (Theophylline) removal should be instituted (see OVERDOSAGE, Extracorporeal Removal ).

Specific Recommendations

Acute Overdose

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

Chronic Overdosage

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

Extracorporeal Removal

Increasing the rate of Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (Theophylline) concentrations may rebound 5-10 mcg/mL after discontinuation of charcoal hemoperfusion or hemodialysis due to redistribution of Dexa Teosona (Theophylline) from the tissue compartment. Peritoneal dialysis is ineffective for Dexa Teosona (Theophylline) removal; exchange transfusions in neonates have been minimally effective.

DOSAGE AND ADMINISTRATION

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

Dexa Teosona (Theophylline)^® Tablets are not to be chewed or crushed because it may lead to a rapid release of Dexa Teosona (Theophylline) with the potential for toxicity. The scored tablet may be split. Infrequently, patients receiving Dexa Teosona (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 Dexa Teosona (Theophylline).

Stabilized patients, 12 years of age or older, who are taking an immediate-release or controlled-release Dexa Teosona (Theophylline) product may be transferred to once-daily administration of 400 mg or 600 mg Dexa Teosona (Theophylline) Tablets on a mg-for-mg basis.

It must be recognized that the peak and trough serum Dexa Teosona (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 Dexa Teosona (Theophylline) concentration is a function of the dose, the dosing interval, and the rate of Dexa Teosona (Theophylline) absorption and clearance in the individual patient. Because of marked individual differences in the rate of Dexa Teosona (Theophylline) clearance, the dose required to achieve a peak serum Dexa Teosona (Theophylline) concentration in the 10-20 mcg/mL range varies fourfold among otherwise similar patients in the absence of factors known to alter Dexa Teosona (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 Dexa Teosona (Theophylline) dose that will provide both safe and effective serum concentrations for all patients. Administration of the median Dexa Teosona (Theophylline) dose required to achieve a therapeutic serum Dexa Teosona (Theophylline) concentration in a given population may result in either sub-therapeutic or potentially toxic serum Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (Theophylline) must be individualized on the basis of peak serum Dexa Teosona (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 Dexa Teosona (Theophylline) concentrations to reach the new steady-state. Dosage adjustment should be guided by serum Dexa Teosona (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 Dexa Teosona (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 Dexa Teosona (Theophylline) concentrations should be monitored at frequent intervals, e.g., every 24 hours.

Dexa Teosona (Theophylline) distributes poorly into body fat, therefore, mg/kg dose should be calculated on the basis of ideal body weight.

Table V contains Dexa Teosona (Theophylline) dosing titration schema recommended for patients in various age groups and clinical circumstances. Table VI contains recommendations for Dexa Teosona (Theophylline) dosage adjustment based upon serum Dexa Teosona (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 Dexa Teosona (Theophylline) concentration.

Table V. Dosing initiation and titration (as anhydrous Dexa Teosona (Theophylline)). *

• A. Children (12-15 years) and adults (16-60 years) without risk factors for impaired clearance.

• B. Patients With Risk Factors For Impaired Clearance, The Elderly (>60 Years), And Those In Whom It Is Not Feasible To Monitor Serum Dexa Teosona (Theophylline) Concentrations:
  
  • In children 12-15 years of age, the Dexa Teosona (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 Dexa Teosona (Theophylline) clearance (see WARNINGS ) or if it is not feasible to monitor serum Dexa Teosona (Theophylline) concentrations.
    

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

HOW SUPPLIED

Dexa Teosona (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.

Dexa Teosona (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.

©2011, Purdue Pharmaceutical Products L.P.

Dist. by: Purdue Pharmaceutical Products L.P.

Stamford, CT 06901-3431

Revised 10/2011

300945-0B

Dexa Teosona (Theophylline) Tablets

400 mg Tablets

NDC 677781-251-01

Dexa Teosona (Theophylline) Tablets 400 mg Tablets NDC 677781-251-01

Dexa Teosona (Theophylline) Tablets

600 mg Tablets

NDC 677781-252-01

Dexa Teosona (Theophylline) Tablets 600 mg Tablets NDC 677781-252-01