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Theophylline in Dextrose Viaflex

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Theophylline 5% Dextrose Injection Viaflex

Indications
Dosage
How Supplied

INDICATIONS

Intravenous theophylline is indicated as an adjunct to inhaled beta-2 selective agonists and systemically administered corticosteroids for the treatment of acute exacerbations of the symptoms and reversible airflow obstruction associated with asthma and other chronic lung diseases, e.g., emphysema and chronic bronchitis.

DOSAGE AND ADMINISTRATION

General Considerations

The steady-state peak serum theophylline concentration is a function of the infusion rate and the rate of theophylline clearance in the individual patient. Because of marked individual differences in the rate of theophylline clearance, the dose required to achieve a serum theophylline concentration in the 10-20 mcg/mL range varies fourfold among otherwise similar patients in the absence of factors known to alter theophylline clearance. For a given population there is no single theophylline dose that will provide both safe and effective serum concentrations for all patients. Administration of the median theophylline dose required to achieve a therapeutic serum theophylline concentration in a given population may result in either sub-therapeutic or potentially toxic serum theophylline concentrations in individual patients. The dose of theophylline must be individualized on the basis of peak serum theophylline concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk of adverse effects.

When theophylline is used as an acute bronchodilator, the goal of obtaining a therapeutic serum concentration is best accomplished with an intravenous loading dose. Because of rapid distribution into body fluids, the serum concentration (C) obtained from an initial loading dose (LD) is related primarily to the volume of distribution (V), the apparent space into which the drug diffuses:

C = LD/V

If a mean volume of distribution of about 0.5 L/kg is assumed (actual range is 0.3 to 0.7 L/kg), each mg/kg (ideal body weight) of theophylline administered as a loading dose over 30 minutes results in an average 2 mcg/mL increase in serum theophylline concentration. Therefore, in a patient who has received no theophylline in the previous 24 hours, a loading dose of intravenous theophylline of 4.6 mg/kg, calculated on the basis of ideal body weight and administered over 30 minutes, on average, will produce a maximum post-distribution serum concentration of 10 mcg/mL with a range of 6-16 mcg/mL. When a loading dose becomes necessary in the patient who has already received theophylline, estimation of the serum concentration based upon the history is unreliable, and an immediate serum level determination is indicated. The loading dose can then be determined as follows:

D = (Desired C - Measured C)(V)

where D is the loading dose, C is the serum theophylline concentration, and V is the volume of distribution. The mean volume of distribution can be assumed to be 0.5 L/kg and the desired serum concentration should be conservative (e.g., 10 mcg/mL) to allow for the variability in the volume of distribution. A loading dose should not be given before obtaining a serum theophylline concentration if the patient has received any theophylline in the previous 24 hours.

A serum concentration obtained 30 minutes after an intravenous loading dose, when distribution is complete, can be used to assess the need for and size of subsequent loading doses, if clinically indicated, and for guidance of continuing therapy. Once a serum concentration of 10 to 15 mcg/mL has been achieved with the use of a loading dose(s), a constant intravenous infusion is started. The rate of administration is based upon mean pharmacokinetic parameters for the population and calculated to achieve a target serum concentration of 10 mcg/mL (see Table VI). For example, in nonsmoking adults, initiation of a constant intravenous theophylline infusion of 0.4 mg/kg/hr at the completion of the loading dose, on average, will result in a steady-state concentration of 10 mcg/ mL with a range of 7-26 mcg/mL. The mean and range of steady-state serum concentrations are similar when the average child (age 1 to 9 years) is given a loading dose of 4.6 mg/kg theophylline followed by a constant intravenous infusion of 0.8 mg/kg/ hr. Since there is large interpatient variability in theophylline clearance, serum concentration will rise or fall when the patient's clearance is significantly different from the mean population value used to calculate the initial infusion rate. Therefore, a second serum concentration should be obtained one expected half-life after starting the constant infusion (e.g., approximately 4 hours for children age 1 to 9 and 8 hours for nonsmoking adults; See Table II for the expected half-life in additional patient populations) to determine if the concentration is accumulating or declining from the post loading dose level. If the level is declining as a result of a higher than average clearance, an additional loading dose can be administered and/or the infusion rate increased. In contrast, if the second sample demonstrates a higher level, accumulation of the drug can be assumed, and the infusion rate should be decreased before the concentration exceeds 20 mcg/mL. An additional sample is obtained 12 to 24 hours later to determine if further adjustments are required and then at 24-hour intervals to adjust for changes, if they occur. This empiric method, based upon mean pharmacokinetic parameters, will prevent large fluctuations in serum concentration during the most critical period of the patient's course.

In patients with cor pulmonale, cardiac decompensation, or liver dysfunction, or in those taking drugs that markedly reduce theophylline clearance (e.g., cimetidine), the initial theophylline infusion rate should not exceed 17 mg/hr unless serum concentrations can be monitored at 24-hour intervals. In these patients, 5 days may be required before steady-state is reached.

Theophylline distributes poorly into body fat, therefore, mg/kg dose should be calculated on the basis of ideal body weight. Table VI contains initial theophylline infusion rates following an appropriate loading dose recommended for patients in various age groups and clinical circumstances. Table VII contains recommendations for final theophylline dosage adjustment based upon serum 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 theophylline concentration.

Table VI : Initial theophylline infusion rates following an appropriate loading dose.

Patient population Age Theophylline infusion rate (mg/kg/hr)*†
Neonates Postnatal age up to 24 days 1 mg/kg q12h/‡
Postnatal age beyond 24 days 1.5 mg/kg q 12h/‡
Infants 6-52 weeks old mg/kg/hr = (0.008) (age in weeks) + 0.21
Young children 1-9 years 0.8
Older children 9-12 years 0.7
Adolescents (cigarette or marijuana smokers) 12-16 years 0.7
Adolescents (nonsmokers) 12-16 years 0.5§
Adults (otherwise healthy nonsmokers) 16-60 years 0.4§
Elderly >60 years 0.3¶
Cardiac decompensation, cor pulmonale, liver dysfunction, sepsis with multi-organ failure, or shock   0.2¶
* To achieve a target concentration of 10 mcg/mL. Use ideal body weight for obese patients.
† Lower initial dosage may be required for patients receiving other drugs that decrease theophylline clearance (e.g., cimetidine).
To achieve a target concentration of 7.5 mcg/mL for neonatal apnea.
Not to exceed 900 mg/day, unless serum levels indicate the need for a larger dose.
¶ Not to exceed 400 mg/day, unless serum levels indicate the need for a larger dose.

Table VII : Final dosage adjustment guided by serum theophylline concentration.

Peak Serum Concentration Dosage Adjustment
<9.9 mcg/mL If symptoms are not controlled and current dosage is tolerated, increase infusion rate about 25%. Recheck serum concentration after 12 hours in children and 24 hours in adults for further dosage adjustment.
10 to 14.9 mcg/mL If symptoms are controlled and current dosage is tolerated, maintain infusion rate and recheck serum concentration at 24 hour 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 infusion rate to provide greater margin of safety even if current dosage is tolerated.*
20-24.9 mcg/mL Decrease infusion rate by 25% even if no adverse effects are present. Recheck serum concentration after 12 hours in children and 24 hours in adults to guide further dosage adjustment.
25-30 mcg/mL Stop infusion for 12 hours in children and 24 hours in adults and decrease subsequent infusion rate at least 25% even if no adverse effects are present. Recheck serum concentration after 12 hours in children and 24 hours in adults to guide further dosage adjustment. If symptomatic, stop infusion and consider whether overdose treatment is indicated (see recommendations for chronic OVERDOSAGE).
> 30 mcg/mL Stop the infusion and treat overdose as indicated (see recommendations for chronic OVERDOSAGE). If theophylline is subsequently resumed, decrease infusion rate by at least 50% and recheck serum concentration after 12 hours in children and 24 hours in adults to guide further dosage adjustment.
*Dose reduction and/or serum theophylline concentration measurement is indicated whenever adverse effects are present, physiologic abnormalities that can reduce theophylline clearance occur (e.g., sustained fever), or a drug that interacts with theophylline is added or discontinued (see WARNINGS).

Many intravenous theophylline products are supplied as aminophylline where ethylenediamine is added to solubilize theophylline. Ethylenediamine is not required for solubility of premixed Theophylline and 5% Dextrose Injection. Each milligram of aminophylline dihydrate contains approximately 0.8 milligrams of theophylline anhydrous. Equivalent doses of premixed Theophylline and 5% Dextrose Injection can be determined by multiplying those doses specified as aminophylline dihydrate by 0.8.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible. All injections in VIAFLEX Plus plastic containers are intended for intravenous administration using sterile equipment.

Because dosages of this drug are titrated to response, no additives should be made to Theophylline and 5% Dextrose Injections.

HOW SUPPLIED

Theophylline in 5% Dextrose Injection, USP in VIAFLEX Plus plastic container is available as follows:

Code Size (mL) NDC Product Name
2B0896 50 0338-0445-41 200 mg Theophylline in 5% Dextrose Injection, USP
2B0897 100 0338-0443-48 200 mg Theophylline in 5% Dextrose Injection, USP
2B0887 100 0338-0445-48 400 mg Theophylline in 5% Dextrose Injection, USP
2B0882 250 0338-0441-02 400 mg Theophylline in 5% Dextrose Injection, USP
2B0883 500 0338-0439-03 400 mg Theophylline in 5% Dextrose Injection, USP
2B0884 1000 0338-0437-04 400 mg Theophylline in 5% Dextrose Injection, USP
2B0872 250 0338-0444-02 800 mg Theophylline in 5% Dextrose Injection, USP
2B0873 500 0338-0441-03 800 mg Theophylline in 5% Dextrose Injection, USP
2B0874 1000 0338-0439-04 800 mg Theophylline in 5% Dextrose Injection, USP

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. It is recommended the product be stored at room temperature (25°C); brief exposure up to 40°C does not adversely affect the product.

Caution: Federal (USA) law prohibits dispensing without prescription.

DIRECTIONS FOR USE OF VIAFLEX PLUS PLASTIC CONTAINER

Warning: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is completed.

To Open

Tear overwrap down side at slit and remove solution container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. Check for minute leaks by squeezing inner bag firmly. If leaks are found, discard solution as sterility may be impaired. Do not add supplementary medication.

Preparation for Administration
  1. Suspend container from eyelet support.
  2. Remove plastic protector from outlet port at bottom of container.
  3. Attach administration set. Refer to complete directions accompanying set.

Baxter Healthcare Corporation, Deerfield, IL 60015, USA. Rev. March 2008. FDA revision date: 10/17/2008

Last reviewed on RxList: 2/10/2009
This monograph has been modified to include the generic and brand name in many instances.

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