Theospirex

Leaflet accompanying the packaging: patient information

Warning! Keep the leaflet! Information on the immediate packaging in a foreign language.

Theospirex, 20 mg/ml, solution for injection/infusion

Theophylline

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet so that you can read it again if necessary.
• In case of any doubts, you should consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Theospirex and what is it used for
• 2. Important information before using Theospirex
• 3. How to use Theospirex
• 4. Possible side effects
• 5. How to store Theospirex
• 6. Package contents and other information

1. What is Theospirex and what is it used for

Theospirex is a medicine that contains theophylline, which has a bronchodilating effect on the smooth muscles of the bronchi, bronchioles, and blood vessels, and also inhibits the release of mediators from cells involved in inflammatory reactions.
The medicine also has a positive effect on the strength and duration of cardiac muscle contraction, as well as increasing urine excretion.

Indication for use:

treatment of acute and severe bronchospasm in chronic respiratory diseases:

• bronchial asthma, asthmatic condition,
• chronic obstructive pulmonary disease.

Theophylline should not be used as a first-line treatment for asthma in children.

2. Important information before using Theospirex

When not to use Theospirex

• if the patient is allergic to theophylline, theophylline derivatives, or other xanthine derivatives, or to any of the other ingredients of this medicine (listed in section 6),
• if the patient has had a recent myocardial infarction,
• if the patient has had shock or collapse,
• if the patient has acute arrhythmias,
• if the patient has severe liver disease,
• if the patient has pulmonary edema,
• if the patient has a tendency to seizures,
• if the patient has epilepsy,
• if the child is under 6 months old.

Warnings and precautions

Before starting treatment with Theospirex, the patient should discuss it with their doctor, pharmacist, or nurse:

• if the patient has hypertension,
• if the patient has unstable angina pectoris,
• if the patient has a tendency to arrhythmias (including arrhythmias with rapid heart rate),
• if the patient has hypertrophic cardiomyopathy with outflow obstruction (heart muscle disease),
• if the patient has hyperthyroidism,
• if the patient has peptic ulcer disease of the stomach and duodenum,
• if the patient has renal and hepatic impairment,
• if the patient has porphyria,
• if the patient has heart failure,
• if the patient has cor pulmonale,
• if the patient has glaucoma,
• if the patient has diabetes,
• if the patient has prolonged fever,
• if the patient has viral infections,
• if the patient is taking drugs that slow down theophylline metabolism (including during the period immediately after their withdrawal).

The medicine should be used with caution during vaccination and in elderly patients.
Fever reduces the rate of theophylline elimination from the body. In case of acute illness with fever, it may be necessary to reduce the dose to avoid toxicity.

Children and adolescents

Theospirex should not be used in children under 6 months old.
Detailed information on the use of the medicine in children and adolescents is presented in section

• 3. "How to use Theospirex".

Theospirex and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
In particular, they should inform about the use of any of the following medicines, as Theospirex may change their effect and increase the risk of side effects:

• Theospirex should not be used concomitantly with other preparations containing xanthines and their derivatives.
• Ephedrine. Theophylline enhances the effect of ephedrine.
• Theophylline enhances the effect of sympathomimetics (such as salbutamol, formoterol) used in the treatment of bronchospastic conditions, caffeine, and similar substances.
• Theophylline increases the renal excretion of lithium salts (used in the treatment of mania or depression), reduces its absorption, and concentration in the blood.
• Digitalis glycosides (drugs that stimulate heart function). Through its positive effect on the strength and duration of cardiac muscle contraction, theophylline may enhance the effect of digitalis glycosides and lead to conduction disorders in the heart muscle.
• Theophylline may weaken the effect of beta-adrenergic blockers (drugs used, among others, in the treatment of hypertension), adenosine (a drug used in arrhythmias), benzodiazepines (drugs with anxiolytic, sedative, hypnotic, anticonvulsant effects), and pancuronium (a drug used during general anesthesia to facilitate intubation and muscle relaxation during surgical procedures).
• Theophylline enhances the effect of diuretics.
• There is evidence that in people receiving ketamine (a rapidly acting anesthetic) at the same time, the seizure threshold may be lowered.
• The use of halothane (a general anesthetic) in patients treated with theophylline may cause severe arrhythmias.

A lower concentration of theophylline in the blood occurs in tobacco smokers.
In case of taking medicines that affect the concentration of theophylline in blood serum, the dose should be adjusted accordingly.
The patient should inform about the use of medicines that may enhancethe effect of Theospirex and increase the risk of its side effects:

• cimetidine (a drug used in the treatment of peptic ulcer disease of the stomach and duodenum),
• allopurinol (a drug that reduces the content of uric acid in the blood and urine, inhibiting the formation of urate stones in the urinary tract, preventing the deposition of urate deposits in muscles and kidneys),
• fluoroquinolone antibiotics (enoxacin, lomefloxacin, ciprofloxacin, norfloxacin, ofloxacin). It is recommended to frequently monitor theophylline levels in patients treated with such antibiotics.
• macrolide antibiotics (erythromycin, clarithromycin),
• disulfiram (a drug used in the treatment of alcohol dependence),
• estrogens (hormonal drugs used, among others, in hormone replacement therapy),
• fluvoxamine (an antidepressant from the group of selective serotonin reuptake inhibitors),
• interferon-alpha (a drug used in the treatment of cancer),
• isoniazid (a drug used in the prevention and treatment of tuberculosis),
• methotrexate (a drug used in the treatment of cancer),
• mexiletine and propafenone (drugs used in arrhythmias),
• rofecoxib (a drug used in the treatment of pain in rheumatic diseases),
• propranolol (a drug used, among others, in hypertension),
• ticlopidine (a drug that inhibits platelet aggregation and the release of platelet clotting factors, preventing the formation of arterial thrombi),
• calcium channel blockers (verapamil, diltiazem),
• viloxazine (an antidepressant). In such cases, the doctor may recommend reducing the dose of theophylline.

Alcohol causes an increase in theophylline concentration in the blood, so during treatment with Theospirex, drinks containing alcohol should not be consumed.
The patient should inform about the use of medicines that may weakenthe effect of Theospirex and reduce its effectiveness:

• aminoglutethimide (a drug used in the treatment of certain prostate cancers),
• carbamazepine (a drug used in the treatment of epilepsy),
• isoprenaline (a drug used in bronchial asthma),
• phenobarbital (an antiepileptic drug),
• phenytoin (a drug with anticonvulsant effects),
• primidone (an antiepileptic drug),
• rifampicin (a drug used in tuberculosis),
• sucralfate (a drug used in peptic ulcer disease of the stomach and duodenum),
• sulfinpyrazone (a drug that increases the excretion of uric acid in the urine, used in gout),
• drugs containing St. John's wort (Hypericum perforatum). If theophylline is administered concomitantly with any of these drugs, the doctor may recommend increasing the dose of theophylline.

Theospirex with food and drink

A diet low in carbohydrates (sugars) and high in protein, as well as parenteral nutrition, and consuming large amounts of grilled beef can reduce the amount of theophylline in the body and weaken its effect.
A diet high in carbohydrates and low in protein may lead to an increase in the amount of theophylline in the body, enhancement of its effect, and an increased risk of side effects.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, suspects that they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before using this medicine.
Pregnancy
The safety of theophylline use during pregnancy has not been established, as no adequate studies have been conducted.
Theophylline crosses the placental barrier and may cause side effects in the fetus.
Theophylline should not be used during pregnancy, especially in the first three months, unless it is absolutely necessary. In the second and third trimesters of pregnancy, theophylline can be used only when the benefits to the mother outweigh the risk to the fetus.
The degree of theophylline binding to plasma proteins and clearance may decrease during pregnancy. It may be necessary to reduce the dose to avoid side effects.
The use of theophylline in the late stages of pregnancy may inhibit uterine contractions. It is recommended to closely monitor newborns exposed to theophylline in the late stages of pregnancy to detect any possible objective symptoms caused by its effects.
Breastfeeding
The medicine should not be used during breastfeeding.
Theophylline passes into breast milk and during breastfeeding may cause side effects in breastfed infants. Its concentration in breast milk of a nursing mother may be 60-90% of the concentration of this medicine in the blood.

Driving and using machines

Theophylline may affect the ability to drive and use machines. Caution should be exercised due to the possibility of drowsiness and dizziness.

Theospirex in the form of a solution for injection/infusion contains sodium.

Each 10 ml ampoule contains 1.19 mmol (or 27.31 mg) of sodium. This should be taken into account in patients with reduced renal function and in patients controlling their sodium intake.

3. How to use Theospirex

This medicine should always be used as directed by the doctor. In case of doubts, the patient should consult their doctor, pharmacist, or nurse.

General recommendations

Theospirex can be administered intravenously:

• intravenously in slow injection (about 6 minutes/ampoule, into a sufficiently large vein),
• in a short intravenous infusion (about 10 minutes/ampoule in one solution),
• in intravenous drip infusion.

The therapeutic concentration of theophylline in serum is 10 to 20 μg/ml (56 to 112 μmol/l).
Theophylline at a concentration higher than 20 μg/ml (112 μmol/l) may be toxic.
Due to significant individual differences in theophylline pharmacokinetics and the narrow therapeutic range, the medicine should be dosed individually.
Theophylline concentration in serum should be monitored.
This recommendation is particularly important in cases where there is an increased risk of exceeding the therapeutic concentration, such as when changing the dose or changing the type of preparation used. Theospirex for intravenous administration contains theophylline as the active substance, and commonly used theophylline for intravenous administration in other medicines usually occurs in the form of a combination with ethylenediamine (as so-called aminophylline). Although the pharmacokinetic profile of both medicines administered in equivalent (in terms of theophylline) doses seems to be similar, it cannot be ruled out that changing one medicine to another may result in achieving theophylline concentrations that are slightly different from those occurring during previous therapy, therefore, after changing the medicine, it is recommended to determine the theophylline concentration.

Dosage

The dose should be calculated based on the lean body mass (fat tissue in children accounts for 12%, in adults 22%), as theophylline is not distributed to fat tissue. Theophylline can be administered in intermittent or continuous intravenous infusion at a rate of 5 to 10 mg/minute, for a period of not less than one hour. Theophylline should not be administered at a rate greater than 25 mg/minute.
The required theophylline concentration, achieved after administration of the initial dose, is maintained using a maintenance dose based on the current theophylline concentration in the blood serum.
The total dose (the dose refers to anhydrous theophylline - 1 ampoule = 200 mg of anhydrous theophylline) should be determined according to the following scheme:
Patients not previously treated with theophylline:

Patients not currently receiving other theophylline-containing medicines:

In case of inability to monitor the drug concentration in the blood, the daily dose should not be exceeded, which should be calculated according to the following scheme:
Patient groups
Maximum daily dose
Children aged 2 to 9 years
24 mg/kg body weight, not more than 900 mg
Children aged 10 to 12 years
20 mg/kg body weight, not more than 900 mg
Children aged 13 to 16 years
18 mg/kg body weight, not more than 900 mg
Adults and adolescents over 16 years old
13 mg/kg body weight, not more than 900 mg
Children under 6 months old
Theospirex should not be used in children under 6 months old.

Method of administration

Intravenous injection
Administer slowly, over at least 6 minutes, into a sufficiently large vein.
Short intravenous infusion
Administer intravenously over 20-30 minutes, in 50-100 ml of an appropriate infusion solution.
Intravenous drip infusion
Administer in 250 ml of an appropriate infusion solution. The duration of the infusion can be determined according to the above dosage scheme. However, it can be modified according to individual needs.
In the treatment of small children, it is recommended to consider the need to reduce the volume of fluids administered in the infusion.
After injection or infusion, the patient should remain at rest for a short time, under supervision. In case of information about previous administration of methylxanthine-containing drugs or suspicion of such administration, the injection or infusion should be performed under special supervision, and in case of intolerance, it should be discontinued.

Duration of treatment

The duration of treatment depends on the type, severity, and course of the disease and is determined by the attending physician.

Using a higher dose of Theospirex than recommended

Symptoms of overdose
Symptoms of theophylline overdose may occur if its concentration in the blood serum is higher than 20 μg/ml and are more severe at higher concentrations.
Usually, tachycardia (rapid heart rate) occurs first, followed by gastrointestinal symptoms (nausea, vomiting, vomiting with blood, stomach pain, diarrhea), central nervous system stimulation (anxiety, headaches, insomnia, dizziness), excessive thirst, tinnitus, palpitations, and arrhythmias. Excessive sweating and muscle tremors may also occur.
In case of significant overdose (theophylline concentration in the blood is higher than 25 μg/ml), seizures, circulatory failure, hyperthermia (elevated body temperature), severe arrhythmias, including ventricular arrhythmias, and even cardiac arrest and death may occur.
In patients with increased sensitivity to theophylline, severe overdose symptoms may occur even when the theophylline concentration in the blood is less than 20 μg/ml.
Procedure in case of overdose

In case of any symptoms of overdose, the patient should immediately contact their doctor or the emergency department of the nearest hospital. In case of life-threatening symptoms, emergency services should be called immediately.

In case of mild overdose symptoms:
The administration of the medicine should be discontinued and the theophylline concentration in the blood serum should be determined. If treatment is resumed, the dose should be reduced accordingly.
If symptoms from the central nervous system occur (e.g., anxiety and seizures):

• diazepam should be administered intravenously at a dose of 0.1-0.3 mg/kg body weight, up to a maximum of 15 mg.

If overdose symptoms are potentially life-threatening, the following should be done:

• monitor vital functions and maintain airway patency,
• administer oxygen,
• if necessary, administer intravenous fluids to increase blood volume,
• monitor and correct, if necessary, fluid and electrolyte deficiencies,
• perform hemoperfusion (see below).

In case of life-threatening arrhythmias:

• in patients who do not have asthma, propranolol should be administered intravenously: 1 mg in adults; 0.02 mg/kg body weight in children. The dose can be repeated every 5-10 minutes until a normal heart rhythm is restored, up to a maximum dose of 0.1 mg/kg body weight.

Warning

In patients with asthma, propranolol may cause severe bronchospasm, so in these patients, verapamil should be administered instead of propranolol.
In very severe cases of poisoning, when the above procedure is ineffective, and in patients with very high theophylline concentrations in the blood, rapid and complete detoxification can be achieved through hemoperfusion or hemodialysis. In most cases, this is not necessary, as theophylline is metabolized sufficiently quickly.

Missing a dose of Theospirex

A double dose should not be used to make up for a missed dose.

Discontinuing Theospirex

In case of any further doubts related to the use of this medicine, the patient should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
During treatment with Theospirex, the following side effects may occur:
Gastrointestinal disorders:
Very common (in more than 1 in 10 patients): irritation of the mucous membrane of the digestive tract, nausea, vomiting, stomach pain, diarrhea, loss of appetite, anorexia. Bleeding vomiting has been reported after theophylline. Existing gastroesophageal reflux may worsen at night due to the relaxation of the esophageal sphincter.
Nervous system and psychiatric disorders:
Very common (in more than 1 in 10 patients): central nervous system stimulation; headaches, irritability, anxiety, insomnia, dizziness, increased reflexes, tremors of the limbs, and seizures.
Cardiac disorders:
Very common (in more than 1 in 10 patients): arrhythmias, rapid heart rate, extra beats, and ventricular arrhythmias, palpitations.
Respiratory, thoracic, and mediastinal disorders:
Very common (in more than 1 in 10 patients): rapid breathing.
Vascular disorders:
Very common (in more than 1 in 10 patients): decreased blood pressure.
Renal and urinary disorders:
Very common (in more than 1 in 10 patients): increased urine excretion associated with the diuretic effect of theophylline, proteinuria, and hematuria may occur. SIADH (syndrome of inappropriate antidiuretic hormone secretion) has also been observed.
Immune system disorders:
Uncommon (in less than 1 in 100 but more than 1 in 1,000 patients): hypersensitivity reactions, urticaria, generalized itching, angioedema - allergic reactions, such as skin reactions and sudden swelling of the skin and mucous membranes (e.g., throat or tongue), difficulty breathing, and (or) itching and rash.
Diagnostic tests:
Very common (in more than 1 in 10 patients): increased glucose concentration in the blood serum, (decreased potassium concentration in the blood), increased creatinine concentration in the blood serum, changes in electrolyte concentrations in the blood, increased uric acid concentration in the blood.
Side effects may be more severe in people with hypersensitivity to theophylline or in case of overdose (theophylline concentration in the blood serum higher than 20 mg/l).
In particular, when the theophylline concentration in the blood serum is higher than 25 mg/l, symptoms of toxicity, such as seizures, sudden drop in blood pressure, ventricular arrhythmias, and severe gastrointestinal symptoms (including gastrointestinal bleeding), may occur.

Reporting side effects

If any side effects occur, including any side effects not listed in the leaflet, the patient should tell their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Theospirex

The medicine should be stored out of sight and reach of children.
There are no special recommendations for storage temperature. Store in the original packaging to protect from light.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the specified month.
Medicines should not be disposed of via wastewater or household waste containers. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Package contents and other information

What Theospirex contains

• The active substance of the medicine is theophylline. One ml of the solution contains 20 mg of theophylline. One ampoule (10 ml) contains 200 mg of theophylline.
• The other ingredients of the medicine are: water for injections, glycine, and sodium hydroxide.

What Theospirex looks like and what the package contains

Theospirex is a colorless and clear solution.
The medicine is packaged in Type I glass ampoules, each containing 10 ml of the solution, and placed in a cardboard box.
The package contains 5 ampoules of 10 ml of the solution.
For more detailed information, the patient should contact the marketing authorization holder or the parallel importer.

Marketing authorization holder in Austria, the country of export:

Gebro Pharma GmbH
Bahnhofbichl 13
6391 Fieberbrunn, Austria

Manufacturer:

Gebro Pharma GmbH
Bahnhofbichl 13
6391 Fieberbrunn, Austria

Parallel importer:

InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw

Repackaged by:

InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Austrian marketing authorization number:1-18867

Parallel import authorization number: 332/24

Date of leaflet approval: 02.09.2024

[Information about the trademark]
Information intended only for healthcare professionals:

Recommendations for preparing the infusion solution:

In case of mixing Theospirex with another solution, special attention should be paid to possible discoloration, clouding, and precipitation in the resulting solution.
Theospirex can be mixed with the following solutions:

• 0.9% NaCl solution (physiological saline);
• Ringer's solution containing lactate;
• in case of mixing theophylline with glucose solution, a yellow discoloration of the solution may occasionally occur.

The medicine should not be mixed with other solutions unless their chemical compatibility with theophylline has been tested.
Solvents for theophylline should not be mixed directly in the same syringe, as they may cause precipitation or chemical changes in the resulting solution.
It should also be remembered that theophylline interacts with other medicines.