DRUGS & SUPPLEMENTS
Asthma 23 D
Asthma 23 D usesAsthma 23 D consists of Belladonna, Caffeine-Naphthylacetic Sodium, Ephedrine Hydrochloride, Papaverine Hydrochloride, Theophylline.
FOR YOUR PROTECTION, DO NOT USE IF SEAL OVER MOUTH OF BOTTLE IS BROKEN OR MISSING. CAPUSLES ARE SEALED WITH A RED GELATIN BAND
(in each capsule)
Asthma 23 D (Ephedrine Hydrochloride) Sulfate USP, 25 mg
For temporary relief of shortness of breath, tightness of chest, and wheezing due to bronchial asthma. For the temporary relief of bronchial asthma. Eases breathing for asthma patients by reducing spasms of bronchial muscles.
Do not use this product unless a diagnosis of asthma has been made by a doctor. Do not use this product if you have heart disease, high blood pressure, thyroid disease, diabetes, or difficulty in urination due to enlargement of the prostate gland unless directed by a doctor. Do not use this product if you have ever been hospitalized for asthma or if you are taking and prescription drug for asthma or if you are taking and prescription drug for asthma unless directed by a doctor.
Drug Interaction precaution
Do not use if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson’s disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor of pharmacist before taking this product.
Ask a doctor before use if you have
high blood pressure
trouble urinating due to an enlarged prostate gland
When using this product
Do not use more than directed. Nervousness, tremor, sleeplessness, nausea or loss of appetite may occur. Do not continue to use this product, but seek medical assistance immediately if symptoms are not relieved within 1 hour or become worse, consult your doctor.
Stop use and ask a doctor if
Symptoms are not relieved within 1 hour or become worse. Nervousness, tremor or sleeplessness become worse. Some users of this product may experience nervousness, tremor, sleeplessness, nausea, and loss of appetite. If these symptoms persist or become worse, consult your doctor.
If pregnant or breast-feeding
ask a health professional before use.
Keep out of reach of children.
In case of overdose, get medical help or contact a Poison Control Center right away.
Store at 20-25°C (68-77°F). Protect from light and moisture. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. You may report side effects to FDA at 1-800-FDA-1088.
Colloidal Silicon Dioxide, Corn Starch, Magnesium Stearate. Capsule shell contains: FD&C Red #3 and Gelatin.
West-ward Pharmaceutical Corp.
Eatontown, N.J. 07724
This product is to be used by or under the direction of a physician.
Each vial contains a sufficient amount to permit withdrawal and administration of the volume specified on the label.
Asthma 23 D (Papaverine Hydrochloride), USP, is the hydrochloride of an alkaloid obtained from opium or prepared synthetically. It belongs to the benzylisoquinoline group of alkaloids. It does not contain a phenanthrene group as do morphine and codeine.
Asthma 23 D (Papaverine Hydrochloride), USP, is 6,7-dimethoxy-1- veratrylisoquinoline hydrochloride and contains, on the dried basis, not less than 98.5% of C20H21NO4-HCI. The molecular weight is 375.85. The structural formula is as shown.
Asthma 23 D (Papaverine Hydrochloride) occurs as white crystals or white crystalline powder. One gram dissolves in about 30 mL of water and in 120 mL of alcohol. It is soluble in chloroform and practically insoluble in ether.
Asthma 23 D (Papaverine Hydrochloride) Injection, USP, is a clear, colorless to pale-yellow solution.
Asthma 23 D (Papaverine Hydrochloride), for parenteral administration, is a smooth-muscle relaxant that is available in vials containing 30 mg/mL. Each vial also contains edetate disodium 0.005%. The 10 mL vials also contain chlorobutanol 0.5% as a preservative. pH may be adjusted with sodium citrate and/or citric acid.
The most characteristic effect of papaverine is relaxation of the tonus of all smooth muscle, especially when it has been spasmodically contracted. Asthma 23 D (Papaverine Hydrochloride) apparently acts directly on the muscle itself. This relaxation is noted in the vascular system and bronchial musculature and in the gastrointestinal, biliary and urinary tracts.
The main actions of papaverine are exerted on cardiac and smooth muscle. Papaverine relaxes various smooth muscles, especially those of larger arteries; this relaxation may be prominent if spasm exists. The antispasmodic effect is a direct one and unrelated to muscle innervation, and the muscle still responds to drugs and other stimuli causing contraction. Papaverine has minimal actions on the central nervous system, although very large doses tend to produce some sedation and sleepiness in some patients. In certain circumstances, mild respiratory stimulation can be observed, but this is therapeutically inconsequential. Papaverine stimulates respiration by acting on carotid and aortic body chemoreceptors.
Papaverine relaxes the smooth musculature of the larger blood vessels, including the coronary, cerebral, peripheral, and pulmonary arteries. This action is particularly evident when such vessels are in spasm, induced reflexly or by drugs, and it provides the basis for the clinical use of papaverine in peripheral or pulmonary arterial embolism.
Experimentally in dogs, the alkaloid has been shown to cause fairly marked and long-lasting coronary vasodilatation and an increase in coronary blood flow. However, it also appears to have a direct inotropic effect and, when increased mechanical activity coincides with decreased systemic pressure, increases in coronary blood flow may not be sufficient to prevent brief periods of hypoxic myocardial depression.
Papaverine is effective by all routes of administration. A considerable fraction of the drug localizes in fat deposits and in the liver, with the remainder being distributed throughout the body. It is metabolized in the liver. About 90% of the drug is bound to plasma protein. Although estimates of its biologic half-life vary widely, reasonably constant plasma levels can be maintained with oral administration at 6 hour intervals. The drug is excreted in the urine in an inactive form.
INDICATIONS AND USAGE
Papaverine is recommended in various conditions accompanied by spasm of smooth muscle, such as vascular spasm associated with acute myocardial infarction (coronary occlusion), angina pectoris, peripheral and pulmonary embolism, peripheral vascular disease in which there is a vasospastic element, or certain cerebral angiospastic states; and visceral spasm, as in ureteral, biliary, or gastrointestinal colic.
Intravenous injection of papaverine is contraindicated in the presence of complete atrioventricular heart block. When conduction is depressed, the drug may produce transient ectopic rhythms of ventricular origin, either premature beats or paroxysmal tachycardia.
Asthma 23 D (Papaverine Hydrochloride) is not indicated for the treatment of impotence by intracorporeal injection. The intracorporeal injection of Asthma 23 D (Papaverine Hydrochloride) has been reported to have resulted in persistent priapism requiring medical and surgical intervention.
Asthma 23 D Injection, USP, should not be added to Lactated Ringer’s Injection, because precipitation would result.
Asthma 23 D (Papaverine Hydrochloride) should be used with caution in patients with glaucoma. The medication should be discontinued if hepatic hypersensitivity with gastrointestinal symptoms, jaundice, or eosinophilia becomes evident or if liver function test values become altered.
Pregnancy Category C - No teratogenic effects were observed in rats when Asthma 23 D (Papaverine Hydrochloride) was administered subcutaneously as a single agent. It is not known whether papaverine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Asthma 23 D (Papaverine Hydrochloride) should be given to a pregnant woman only if clearly needed.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Asthma 23 D is administered to a nursing woman.
Safety and effectiveness in children have not been established.
The following side effects have been reported: general discomfort, nausea, abdominal discomfort, anorexia, constipation or diarrhea, skin rash, malaise, vertigo, headache, intensive flushing of the face, perspiration, increase in the depth of respiration, increase in heart rate, a slight rise in blood pressure, and excessive sedation.
Hepatitis, probably related to an immune mechanism, has been reported infrequently. Rarely, this has progressed to cirrhosis.
DRUG ABUSE AND DEPENDENCE
Drug dependence resulting from the abuse of many of the selective depressants, including Asthma 23 D (Papaverine Hydrochloride), has been reported.
Signs and Symptoms –
The symptoms of toxicity from Asthma 23 D often result from vasomotor instability and include nausea, vomiting, weakness, central nervous system depression, nystagmus, diplopia, diaphoresis, flushing, dizziness, and sinus tachycardia. In large overdoses, papaverine is a potent inhibitor of cellular respiration and a weak calcium antagonist. Following an oral overdose of 15 g, metabolic acidosis with hyperventilation, hyperglycemia, and hypokalemia have been reported. No information on toxic serum concentrations is available.
Following intravenous overdosing in animals, seizures, tachyarrhythmias, and ventricular fibrillation have been reported. The oral median lethal dose in rats is 360 mg/kg.
To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physician’s Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.
Protect the patient’s airway and support ventilation and perfusion. Meticulously monitor vital signs, blood gases, blood chemistry values, and other variables.
If convulsions occur, consider diazepam, phenytoin, or phenobarbital. If the seizures are refractory, general anesthesia with thiopental or halothane and paralysis with a neuromuscular blocking agent may be necessary.
For hypotension, consider intravenous fluids, elevation of the legs, and an inotropic vasopressor, such as dopamine or norepinephrine (levarterenol). Theoretically, calcium gluconate may be helpful in treating some of the toxic cardiovascular effects of papaverine; monitor the ECG and plasma calcium concentrations.
Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of Asthma 23 D (Papaverine Hydrochloride).
DOSAGE AND ADMINISTRATION
Asthma 23 D (Papaverine Hydrochloride) may be administered intravenously or intramuscularly. The intravenous route is recommended when an immediate effect is desired, but the drug must be injected slowly over the course of 1 or 2 minutes to avoid uncomfortable or alarming side effects.
Parenteral administration of Asthma 23 D (Papaverine Hydrochloride) in doses of 1 to 4 mL is repeated every 3 hours as indicated. In the treatment of cardiac extrasystoles, 2 doses may be given 10 minutes apart.
Asthma 23 D (Papaverine Hydrochloride) Injection, USP, 30 mg/mL
0517-4002-25 2 mL Vial packaged in boxes of 25
0517-4010-01 10 mL Multiple Dose Vial* packaged individually
*The 10 mL Multiple Dose Vial contains chlorobutanol 0.5% as a preservative.
Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).
PROTECT FROM LIGHT. RETAIN IN CARTON UNTIL TIME OF USE.
SHIRLEY, NY 11967
Asthma 23 D (Theophylline)® (theophylline, anhydrous) Tablets in a controlled-release system allows a 24-hour dosing interval for appropriate patients.
Asthma 23 D (Theophylline) is structurally classified as a methylxanthine. It occurs as a white, odorless, crystalline powder with a bitter taste. Anhydrous Asthma 23 D (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 Asthma 23 D (Theophylline) is C7H8N4O2 with a molecular weight of 180.17.
Each controlled-release tablet for oral administration, contains 400 or 600 mg of anhydrous Asthma 23 D (Theophylline).
Inactive Ingredients: cetostearyl alcohol, hydroxyethyl cellulose, magnesium stearate, povidone and talc.
Mechanism of Action
Asthma 23 D 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 Asthma 23 D (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 Asthma 23 D (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).
Asthma 23 D (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 Asthma 23 D (Theophylline) concentration range of 5-20 mcg/mL. Clinically important improvement in symptom control has been found in most studies to require peak serum Asthma 23 D (Theophylline) concentrations >10 mcg/mL, but patients with mild disease may benefit from lower concentrations. At serum Asthma 23 D (Theophylline) concentrations >20 mcg/mL, both the frequency and severity of adverse reactions increase. In general, maintaining peak serum Asthma 23 D (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.
Overview: Asthma 23 D is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form. Asthma 23 D (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 Asthma 23 D (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 Asthma 23 D (Theophylline). Within-subject variability in metabolism has also been reported in some studies, especially in acutely ill patients. It is, therefore, recommended that serum Asthma 23 D (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 Asthma 23 D (Theophylline) clearance (see PRECAUTIONS, Laboratory Tests ).
Note: In addition to the factors listed above, Asthma 23 D (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 Asthma 23 D (Theophylline).
Asthma 23 D (Theophylline)® administered in the fed state is completely absorbed after oral administration.
In a single-dose crossover study, two 400 mg Asthma 23 D (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, Cmax=9.3±2.0 mcg/mL, Tmax=12.8±4.2 hours. On the evening arm, the pharmacokinetic parameters were AUC=219.7±83.0 mcg hr/mL, Cmax=9.2±2.0 mcg/mL, Tmax=12.5±4.2 hours.
A study in which Asthma 23 D (Theophylline) 400 mg Tablets were administered to 17 fed adult asthmatics produced similar Asthma 23 D (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 Asthma 23 D (Theophylline) inherent mean elimination half-life was verified by a liquid Asthma 23 D (Theophylline) product to be 6.9±2.5 (SD) hours were administered two or three 400 mg Asthma 23 D (Theophylline)® Tablets. The relative bioavailability of Asthma 23 D (Theophylline) given in the fasting state in comparison to an immediate-release product was 59%. Peak serum Asthma 23 D (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 Asthma 23 D (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 Asthma 23 D (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 Asthma 23 D (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, Cmax and Cmin 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, Cmax=8.4±2.6 mcg/mL, Tmax=17.3±6.7 hours. Under fasting conditions, these parameters were AUC=141.2±6.53 mcg hr/mL, Cmax=5.5±1.5 mcg/mL, Tmax=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 Asthma 23 D (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 Asthma 23 D (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, Cmax=10.9±1.7 mcg/mL, Tmax=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, Cmax=6.7±1.7 mcg/mL, Tmax=7.3±2.2 hours.
Thus, administration of single Asthma 23 D (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 Asthma 23 D (Theophylline) with Asthma 23 D (Theophylline) Tablets even when they are administered with a high fat, high calorie meal.
Similar studies were conducted with the 600 mg Asthma 23 D (Theophylline) Tablet. A single-dose study in 24 subjects with an established Asthma 23 D (Theophylline) clearance of ≤4 L/hr, compared the pharmacokinetic evaluation of one 600 mg Asthma 23 D (Theophylline) Tablet and one and one-half 400 mg Asthma 23 D (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 Asthma 23 D (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, Cmax=10.58±2.21 mcg/mL and Tmax=9.00±2.64 hours, and for the 600 mg tablet were AUC=207.85±48.9 mcg hr/mL, Cmax=10.39±1.91 mcg/mL and Tmax=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, Cmax= 7.37±1.83 mcg/mL and Tmax=8.08±4.39 hours; and for the 600 mg tablet were AUC=199.39±70.27 mcg hr/mL, Cmax=7.66±2.09 mcg/mL and Tmax=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 Asthma 23 D (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 Asthma 23 D (Theophylline) Tablet administered in the morning or in the evening. The results were: AUC=233.6±45.1 mcg hr/mL, Cmax=10.6±1.3 mcg/mL and Tmax=12.5±3.2 hours with morning dosing; AUC=209.8±46.2 mcg hr/mL, Cmax=9.7±1.4 mcg/mL and Tmax=13.7±3.3 hours with evening dosing. The PM/AM ratio was 89.3%.
The absorption characteristics of Asthma 23 D (Theophylline)® Tablets (theophylline, anhydrous) have been extensively studied. A steady-state crossover bioavailability study in 22 normal males compared two Asthma 23 D (Theophylline) 400 mg Tablets administered q24h at 8 a.m. immediately after breakfast with a reference controlled-release Asthma 23 D (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 Asthma 23 D (Theophylline) 400 mg Tablets under these steady-state conditions were AUC=203.3±87.1 mcg hr/mL, Cmax=12.1±3.8 mcg/mL, Cmin=4.50±3.6, Tmax=8.8±4.6 hours. For the reference BID product, the pharmacokinetic parameters were AUC=219.2±88.4 mcg hr/mL, Cmax =11.0±4.1 mcg/mL, Cmin=7.28±3.5, Tmax=6.9±3.4 hours. The mean percent fluctuation [(Cmax-Cmin/Cmin)x100]=169% for the once-daily regimen and 51% for the reference product BID regimen.
The bioavailability of the 600 mg Asthma 23 D (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 Asthma 23 D (Theophylline) Tablets. All subjects had previously established Asthma 23 D (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 Asthma 23 D (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 Asthma 23 D (Theophylline) Tablets whether dosed in the morning or evening.
Once Asthma 23 D enters the systemic circulation, about 40% is bound to plasma protein, primarily albumin. Unbound Asthma 23 D (Theophylline) distributes throughout body water, but distributes poorly into body fat. The apparent volume of distribution of Asthma 23 D (Theophylline) is approximately 0.45 L/kg (range 0.3-0.7 L/kg) based on ideal body weight. Asthma 23 D (Theophylline) passes freely across the placenta, into breast milk and into the cerebrospinal fluid (CSF). Saliva Asthma 23 D (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 Asthma 23 D (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 Asthma 23 D (Theophylline) in the therapeutic range (10-20 mcg/mL) due to elevated concentrations of the pharmacologically active unbound drug. Similarly, a patient with decreased Asthma 23 D (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 Asthma 23 D (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 Asthma 23 D (Theophylline) concentration provides a more reliable means of dosage adjustment than measurement of total serum Asthma 23 D (Theophylline) concentration. Generally, concentrations of unbound Asthma 23 D (Theophylline) should be maintained in the range of 6-12 mcg/mL.
Following oral dosing, Asthma 23 D (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 Asthma 23 D (Theophylline) dose is N-methylated to caffeine. Asthma 23 D (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 Asthma 23 D (Theophylline) metabolites with pharmacologic activity. 3-methylxanthine has approximately one tenth the pharmacologic activity of Asthma 23 D (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 Asthma 23 D (Theophylline) concentration. Caffeine concentrations are usually undetectable in adults regardless of renal function. In neonates, caffeine may accumulate to concentrations that approximate the unmetabolized Asthma 23 D (Theophylline) concentration and thus, exert a pharmacologic effect.
Both the N-demethylation and hydroxylation pathways of Asthma 23 D (Theophylline) biotransformation are capacity-limited. Due to the wide intersubject variability of the rate of Asthma 23 D (Theophylline) metabolism, non-linearity of elimination may begin in some patients at serum Asthma 23 D (Theophylline) concentrations <10 mcg/mL. Since this non-linearity results in more than proportional changes in serum Asthma 23 D (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 Asthma 23 D (Theophylline) concentrations (see DOSAGE AND ADMINISTRATION, Table VI ). Accurate prediction of dose-dependency of Asthma 23 D (Theophylline) metabolism in patients a priori is not possible, but patients with very high initial clearance rates (i.e., low steady-state serum Asthma 23 D (Theophylline) concentrations at above average doses) have the greatest likelihood of experiencing large changes in serum Asthma 23 D (Theophylline) concentration in response to dosage changes.
In neonates, approximately 50% of the Asthma 23 D dose is excreted unchanged in the urine. Beyond the first three months of life, approximately 10% of the Asthma 23 D (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 Asthma 23 D (Theophylline) is excreted unchanged in the urine and since active metabolites of Asthma 23 D (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 Asthma 23 D (Theophylline) dose excreted in the urine as unchanged Asthma 23 D (Theophylline) and caffeine in neonates requires careful attention to dose reduction and frequent monitoring of serum Asthma 23 D (Theophylline) concentrations in neonates with reduced renal function (See WARNINGS ).
|Drug||Type of Interaction||Effect**|
|*Refer to PRECAUTIONS, Drug Interactions for further information regarding table.|
|**Average effect on steady-state Asthma 23 D (Theophylline) concentration or other clinical effect for pharmacologic interactions. Individual patients may experience larger changes in serum Asthma 23 D (Theophylline) concentration than the value listed.|
|Adenosine||Asthma 23 D (Theophylline) blocks adenosine receptors.||Higher doses of adenosine may be required to achieve desired effect.|
|Alcohol||A single large dose of alcohol (3 mL/kg of whiskey) decreases Asthma 23 D (Theophylline) clearance for up to 24 hours.||30% increase|
|Allopurinol||Decreases Asthma 23 D (Theophylline) clearance at allopurinol doses ≥600 mg/day.||25% increase|
|Aminoglutethimide||Increases Asthma 23 D (Theophylline) clearance by induction of microsomal enzyme activity.||25% decrease|
|Carbamazepine||Similar to aminoglutethimide.||30% decrease|
|Cimetidine||Decreases Asthma 23 D (Theophylline) clearance by inhibiting cytochrome P450 1A2.||70% increase|
|Ciprofloxacin||Similar to cimetidine.||40% increase|
|Clarithromycin||Similar to erythromycin.||25% increase|
|Diazepam||Benzodiazepines increase CNS concentrations of adenosine, a potent CNS depressant, while Asthma 23 D (Theophylline) blocks adenosine receptors.||Larger diazepam doses may be required to produce desired level of sedation. Discontinuation of Asthma 23 D (Theophylline) without reduction of diazepam dose may result in respiratory depression.|
|Disulfiram||Decreases Asthma 23 D (Theophylline) clearance by inhibiting hydroxylation and demethylation.||50% increase|
|Enoxacin||Similar to cimetidine.||300% increase|
|Ephedrine||Synergistic CNS effects.||Increased frequency of nausea, nervousness, and insomnia.|
|Erythromycin||Erythromycin metabolite decreases Asthma 23 D (Theophylline) clearance by inhibiting cytochrome P450 3A3.||35% increase. Erythromycin steady-state serum concentrations decrease by a similar amount.|
|Estrogen||Estrogen containing oral contraceptives decrease Asthma 23 D (Theophylline) clearance in a dose-dependent fashion. The effect of progesterone on Asthma 23 D (Theophylline) clearance is unknown.||30% increase|
|Flurazepam||Similar to diazepam.||Similar to diazepam.|
|Fluvoxamine||Similar to cimetidine.||Similar to cimetidine.|
|Halothane||Halothane sensitizes the myocardium to catecholamines, Asthma 23 D (Theophylline) increases release of endogenous catecholamines.||Increased risk of ventricular arrhythmias.|
|Interferon, human recombinant alpha-A||Decreases Asthma 23 D (Theophylline) clearance.||100% increase|
|Isoproterenol (IV)||Increases Asthma 23 D (Theophylline) clearance.||20% decrease|
|Ketamine||Pharmacologic||May lower Asthma 23 D (Theophylline) seizure threshold.|
|Lithium||Asthma 23 D (Theophylline) increases renal lithium clearance.||Lithium dose required to achieve a therapeutic serum concentration increased an average of 60%.|
|Lorazepam||Similar to diazepam.||Similar to diazepam.|
|Methotrexate (MTX)||Decreases Asthma 23 D (Theophylline) clearance.||20% increase after low dose MTX, higher dose MTX may have a greater effect.|
|Mexiletine||Similar to disulfiram.||80% increase|
|Midazolam||Similar to diazepam.||Similar to diazepam.|
|Moricizine||Increases Asthma 23 D (Theophylline) clearance.||25% decrease|
|Pancuronium||Asthma 23 D (Theophylline) may antagonize non-depolarizing neuromuscular blocking effects; possibly due to phosphodiesterase inhibition.||Larger dose of pancuronium may be required to achieve neuromuscular blockade.|
|Pentoxifylline||Decreases Asthma 23 D (Theophylline) clearance.||30% increase|
|Phenobarbital (PB)||Similar to aminoglutethimide.||25% decrease after two weeks of concurrent PB.|
|Phenytoin||Phenytoin increases Asthma 23 D (Theophylline) clearance by increasing microsomal enzyme activity. Asthma 23 D (Theophylline) decreases phenytoin absorption.||Serum Asthma 23 D (Theophylline) and phenytoin concentrations decrease about 40%.|
|Propafenone||Decreases Asthma 23 D (Theophylline) clearance and pharmacologic interaction.||40% increase. Beta-2 blocking effect may decrease efficacy of Asthma 23 D (Theophylline).|
|Propranolol||Similar to cimetidine and pharmacologic interaction.||100% increase. Beta-2 blocking effect may decrease efficacy of Asthma 23 D (Theophylline).|
|Rifampin||Increases Asthma 23 D (Theophylline) clearance by increasing cytochrome P450 1A2 and 3A3 activity.||20-40% decrease|
|St. John’s Wort (Hypericum Perforatum)||Decrease in Asthma 23 D (Theophylline) plasma concentrations.||Higher doses of Asthma 23 D (Theophylline) may be required to achieve desired effect. Stopping St. John’s Wort may result in Asthma 23 D (Theophylline) toxicity.|
|Sulfinpyrazone||Increases Asthma 23 D (Theophylline) clearance by increasing demethylation and hydroxylation. Decreases renal clearance of Asthma 23 D (Theophylline).||20% decrease|
|Tacrine||Similar to cimetidine, also increases renal clearance of Asthma 23 D (Theophylline).||90% increase|
|Thiabendazole||Decreases Asthma 23 D (Theophylline) clearance.||190% increase|
|Ticlopidine||Decreases Asthma 23 D (Theophylline) clearance.||60% increase|
|Troleandomycin||Similar to erythromycin.||33-100% increase depending on troleandomycin dose.|
|Verapamil||Similar to disulfiram.||20% increase|
|*Refer to PRECAUTIONS, Drug Interactions for information regarding table.|
|albuterol, systemic and inhaled||mebendazole|
|ampicillin, with or without |
|caffeine, dietary ingestion||nifedipine|
|co-trimoxazole (trimethoprim and |
|finasteride||sorbitol (purgative doses do not inhibit|
|hydrocortisone||Asthma 23 D (Theophylline) absorption)|
The bioavailability of Asthma 23 D (Theophylline)® Tablets (theophylline, anhydrous) has been studied with co-administration of food. In three single-dose studies, subjects given Asthma 23 D (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.
Most serum Asthma 23 D (Theophylline) assays in clinical use are immunoassays which are specific for Asthma 23 D (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 Asthma 23 D (Theophylline) concentration.
Long term carcinogenicity studies have been carried out in mice and rats (oral doses 5-75 mg/kg). Results are pending.
Asthma 23 D (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, Asthma 23 D (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, Asthma 23 D (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.
In studies in which pregnant mice, rats and rabbits were dosed during the period of organogenesis, Asthma 23 D (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. Asthma 23 D (Theophylline) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Asthma 23 D is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants. The concentration of Asthma 23 D (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 Asthma 23 D (Theophylline) per day is likely to receive 10-20 mg of Asthma 23 D (Theophylline) per day. Serious adverse effects in the infant are unlikely unless the mother has toxic serum Asthma 23 D (Theophylline) concentrations.
Asthma 23 D (Theophylline) is safe and effective for the approved indications in pediatric patients. The maintenance dose of Asthma 23 D (Theophylline) must be selected with caution in pediatric patients since the rate of Asthma 23 D (Theophylline) clearance is highly variable across the pediatric age range (see CLINICAL PHARMACOLOGY, Table I, WARNINGS, and DOSAGE AND ADMINISTRATION, Table V ).
Elderly patients are at a significantly greater risk of experiencing serious toxicity from Asthma 23 D (Theophylline) than younger patients due to pharmacokinetic and pharmacodynamic changes associated with aging. The clearance of Asthma 23 D (Theophylline) is decreased by an average of 30% in healthy elderly adults (>60 yrs) compared to healthy young adults. Asthma 23 D (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 Asthma 23 D (Theophylline) concentration in the pharmacologically active unbound form. Elderly patients also appear to be more sensitive to the toxic effects of Asthma 23 D (Theophylline) after chronic overdosage than younger patients. Careful attention to dose reduction and frequent monitoring of serum Asthma 23 D (Theophylline) concentrations are required in elderly patients (see PRECAUTIONS, Monitoring Serum Asthma 23 D (Theophylline) Concentrations, and DOSAGE AND ADMINISTRATION ). The maximum daily dose of Asthma 23 D (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 Asthma 23 D (Theophylline) concentration is <10 mcg/mL (see DOSAGE AND ADMINISTRATION ). Asthma 23 D (Theophylline) doses greater than 400 mg/d should be prescribed with caution in elderly patients. Asthma 23 D (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 associated with Asthma 23 D (Theophylline) are generally mild when peak serum Asthma 23 D (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 Asthma 23 D (Theophylline) concentrations exceed 20 mcg/mL, however, Asthma 23 D (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 Asthma 23 D (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 Asthma 23 D (Theophylline) therapy, caffeine-like adverse effects may transiently alter patient behavior, especially in school age children, but this response rarely persists. Initiation of Asthma 23 D (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 Asthma 23 D (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 Asthma 23 D (Theophylline) therapy and the potential therapeutic benefit of alternative treatment.
Other adverse reactions that have been reported at serum Asthma 23 D (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 Asthma 23 D (Theophylline) concentrations ≥15 mcg/mL. There have been a few isolated reports of seizures at serum Asthma 23 D (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 Asthma 23 D (Theophylline) concentrations <20 mcg/mL may be secondary to decreased protein binding resulting in a larger proportion of the total serum Asthma 23 D (Theophylline) concentration in the pharmacologically active unbound form. The clinical characteristics of the seizures reported in patients with serum Asthma 23 D (Theophylline) concentrations <20 mcg/mL have generally been milder than seizures associated with excessive serum Asthma 23 D (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).
|Percentage of patients reported with sign or symptom|
|Sign/Symptom||Acute Overdose||Chronic Overdosage|
|(Large Single Ingestion)||(Multiple Excessive Doses)|
|Study 1||Study 2||Study 1||Study 2|
|*These data are derived from two studies in patients with serum Asthma 23 D (Theophylline) concentrations >30 mcg/mL. In the first study (Study #1-Shanon, Ann Intern Med 1993;119:1161-67), data were prospectively collected from 249 consecutive cases of Asthma 23 D (Theophylline) toxicity referred to a regional poison center for consultation. In the second study (Study #2-Sessler, Am J Med 1990;88:567-76), data were retrospectively collected from 116 cases with serum Asthma 23 D (Theophylline) concentrations >30 mcg/mL among 6000 blood samples obtained for measurement of serum Asthma 23 D (Theophylline) concentrations in three emergency departments. Differences in the incidence of manifestations of Asthma 23 D (Theophylline) toxicity between the two studies may reflect sample selection as a result of study design (e.g., in Study #1, 48% of the patients had acute intoxications versus only 10% in Study #2) and different methods of reporting results.|
|**NR=Not reported in a comparable manner.|
|Ventricular premature beats||3||21||10||19|
|Atrial fibrillation or flutter||1||NR**||12||NR**|
|Multifocal atrial tachycardia||0||NR**||2||NR**|
|Ventricular arrhythmias with |
The chronicity and pattern of Asthma 23 D 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 Asthma 23 D (Theophylline) clearance. The most common causes of chronic Asthma 23 D (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 Asthma 23 D (Theophylline) clearance, and increasing the dose in response to an exacerbation of symptoms without first measuring the serum Asthma 23 D (Theophylline) concentration to determine whether a dose increase is safe.
Severe toxicity from Asthma 23 D (Theophylline) overdose is a relatively rare event. In one health maintenance organization, the frequency of hospital admissions for chronic overdosage of Asthma 23 D (Theophylline) was about 1 per 1000 person-years exposure. In another study, among 6000 blood samples obtained for measurement of serum Asthma 23 D (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 Asthma 23 D (Theophylline) concentrations in the 20-30 mcg/mL range had one or more manifestations of toxicity while >90% of patients with serum Asthma 23 D (Theophylline) concentrations >30 mcg/mL were clinically intoxicated. Similarly, in other reports, serious toxicity from Asthma 23 D (Theophylline) is seen principally at serum concentrations >30 mcg/mL.
Several studies have described the clinical manifestations of Asthma 23 D (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 Asthma 23 D (Theophylline) concentration is >100 mcg/mL. After a chronic overdosage, generalized seizures, life-threatening cardiac arrhythmias, and death may occur at serum Asthma 23 D (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 Asthma 23 D (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 Asthma 23 D (Theophylline) concentration compared to patients without the underlying disease.
The frequency of various reported manifestations of Asthma 23 D (Theophylline) overdose according to the mode of overdose are listed in Table IV.
Other manifestations of Asthma 23 D (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 Asthma 23 D (Theophylline) concentrations >30 mcg/mL are often resistant to anticonvulsant therapy and may result in irreversible brain injury if not rapidly controlled. Death from Asthma 23 D (Theophylline) toxicity is most often secondary to cardiorespiratory arrest and/or hypoxic encephalopathy following prolonged generalized seizures or intractable cardiac arrhythmias causing hemodynamic compromise.
General Recommendations for Patients with Symptoms of Asthma 23 D (Theophylline) Overdose or Serum Asthma 23 D (Theophylline) Concentrations >30 mcg/mL (Note: Serum Asthma 23 D (Theophylline) concentrations may continue to increase after presentation of the patient for medical care.)
Increasing the rate of Asthma 23 D (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 Asthma 23 D (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 Asthma 23 D (Theophylline) concentrations may rebound 5-10 mcg/mL after discontinuation of charcoal hemoperfusion or hemodialysis due to redistribution of Asthma 23 D (Theophylline) from the tissue compartment. Peritoneal dialysis is ineffective for Asthma 23 D (Theophylline) removal; exchange transfusions in neonates have been minimally effective.
Asthma 23 D ® 400 or 600 mg Tablets can be taken once a day in the morning or evening. It is recommended that Asthma 23 D (Theophylline) be taken with meals. Patients should be advised that if they choose to take Asthma 23 D (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.
Asthma 23 D (Theophylline)® Tablets are not to be chewed or crushed because it may lead to a rapid release of Asthma 23 D (Theophylline) with the potential for toxicity. The scored tablet may be split. Infrequently, patients receiving Asthma 23 D (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 Asthma 23 D (Theophylline).
Stabilized patients, 12 years of age or older, who are taking an immediate-release or controlled-release Asthma 23 D (Theophylline) product may be transferred to once-daily administration of 400 mg or 600 mg Asthma 23 D (Theophylline) Tablets on a mg-for-mg basis.
It must be recognized that the peak and trough serum Asthma 23 D (Theophylline) levels produced by the once-daily dosing may vary from those produced by the previous product and/or regimen.
The steady-state peak serum Asthma 23 D (Theophylline) concentration is a function of the dose, the dosing interval, and the rate of Asthma 23 D (Theophylline) absorption and clearance in the individual patient. Because of marked individual differences in the rate of Asthma 23 D (Theophylline) clearance, the dose required to achieve a peak serum Asthma 23 D (Theophylline) concentration in the 10-20 mcg/mL range varies fourfold among otherwise similar patients in the absence of factors known to alter Asthma 23 D (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 Asthma 23 D (Theophylline) dose that will provide both safe and effective serum concentrations for all patients. Administration of the median Asthma 23 D (Theophylline) dose required to achieve a therapeutic serum Asthma 23 D (Theophylline) concentration in a given population may result in either sub-therapeutic or potentially toxic serum Asthma 23 D (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 Asthma 23 D (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 Asthma 23 D (Theophylline) must be individualized on the basis of peak serum Asthma 23 D (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 Asthma 23 D (Theophylline) concentrations to reach the new steady-state. Dosage adjustment should be guided by serum Asthma 23 D (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 Asthma 23 D (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 Asthma 23 D (Theophylline) concentrations should be monitored at frequent intervals, e.g., every 24 hours.
Asthma 23 D (Theophylline) distributes poorly into body fat, therefore, mg/kg dose should be calculated on the basis of ideal body weight.
Table V contains Asthma 23 D (Theophylline) dosing titration schema recommended for patients in various age groups and clinical circumstances. Table VI contains recommendations for Asthma 23 D (Theophylline) dosage adjustment based upon serum Asthma 23 D (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 Asthma 23 D (Theophylline) concentration.
Table V. Dosing initiation and titration (as anhydrous Asthma 23 D (Theophylline)). *
|Titration Step||Children <45 kg||Children >45 kg and adults|
|1If caffeine-like adverse effects occur, then consideration should be given to a lower dose and titrating the dose more slowly (see ADVERSE REACTIONS ).|
| ||12-14 mg/kg/day up to a maximum of 300 mg/day admin. QD*||300-400 mg/day1 admin. QD*|
| ||16 mg/kg/day up to a maximum of 400 mg/day admin. QD*||400-600 mg/day1 admin. QD*|
| ||20 mg/kg/day up to a maximum of 600 mg/day admin. QD*||As with all Asthma 23 D (Theophylline) products, doses greater than 600 mg should be titrated according to blood level|
*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.
| Peak Serum |
|¶Dose reduction and/or serum Asthma 23 D (Theophylline) concentration measurement is indicated whenever adverse effects are present physiologic abnormalities that can reduce Asthma 23 D (Theophylline) clearance occur (e.g. sustained fever), or a drug that interacts with Asthma 23 D (Theophylline) is added or discontinued (see WARNINGS ).|
|<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.|
|10-14.9 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.|
|>30 mcg/mL||Treat overdose as indicated. If Asthma 23 D (Theophylline) is subsequently resumed, decrease dose by at least 50% and recheck serum concentration after 3 days to guide further dosage adjustment.|
Asthma 23 D (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.
Asthma 23 D (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
Asthma 23 D (Theophylline) Tablets
400 mg Tablets
Asthma 23 D (Theophylline) Tablets 400 mg Tablets NDC 677781-251-01
Asthma 23 D (Theophylline) Tablets
600 mg Tablets
Asthma 23 D (Theophylline) Tablets 600 mg Tablets NDC 677781-252-01
Depending on the reaction of the Asthma 23 D after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Asthma 23 D not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Asthma 23 D addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
There are no reviews yet. Be the first to write one!
The information was verified by Dr. Arunabha Ray, MD Pharmacology