Theospirex

Package leaflet: Information for the patient

Caution! Please keep the leaflet. Information on the immediate packaging is in a foreign language.
Theospirex
20 mg/ml
injection/infusion solution
Theophyllinum
Please read the entire leaflet carefully before using this medicine, as it contains
important information for the patient.

• Keep this leaflet to be able to read it again if necessary.
• If you have any questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

1. What Theospirex is and what it is used for
2. Important information before using Theospirex
3. How to use Theospirex
4. Possible side effects
5. How to store Theospirex
6. Contents of the pack and other information

1. What Theospirex is and what it is used for

Theospirex is a medicine containing theophylline, which acts as a relaxant of smooth muscles
of the bronchi, bronchioles, and blood vessels, and inhibits the release of mediators from cells
involved in inflammatory reactions.
The medicine also exerts a positive effect on the force and duration of cardiac muscle contraction and increases urine excretion.
Indication: treatment of acute and severe bronchospasm in chronic respiratory diseases:

• bronchial asthma, status asthmaticus,
• chronic obstructive pulmonary disease.

Theophyllines should not be used as first-line therapy for asthma in children.

2. 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 recently suffered a myocardial infarction,
• if the patient is in shock or collapse,
• if the patient has acute cardiac arrhythmias,
• if the patient has severe liver disease,
• if the patient has pulmonary edema,
• if the patient has a predisposition to seizures,
• if the patient has epilepsy,
• if the child is under 6 months of age.

Page 1 of 9
Warnings and precautions
Before starting treatment with Theospirex, discuss this with your doctor, pharmacist, or
nurse:

• if the patient has hypertension,
• if the patient has unstable angina pectoris,
• if the patient has a tendency to cardiac arrhythmias (including tachyarrhythmias),
• if the patient has hypertrophic obstructive cardiomyopathy (a heart muscle disease),
• if the patient has hyperthyroidism,
• if the patient has peptic ulcer disease of the stomach or duodenum,
• if the patient has impaired kidney or liver function,
• 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 concurrently taking drugs that inhibit theophylline metabolism (including immediately after discontinuation of such drugs). 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 an acute illness
associated with fever, dose reduction may be necessary to avoid toxicity.
Children and adolescents
Theospirex must not be used in children under 6 months of age.
Detailed information on the use of this medicine in children and adolescents is provided in section

3. "How to use Theospirex".

Theospirex and other medicines
You must tell your doctor or pharmacist about all medicines currently used or recently used, as well as any medicines the patient intends to use.
In particular, inform about the use of any of the following medicines, as Theospirex may alter their effects and increase the risk of adverse reactions:

• Theospirex must not be used concomitantly with other preparations containing xanthines and their derivatives.
• Ephedrine. Theophylline potentiates the effect of ephedrine.
• Theophylline potentiates the effect of sympathomimetics (such as salbutamol, formoterol) used in the treatment of bronchospasm, caffeine, and similar substances.
• Theophylline increases renal excretion of lithium salts (used in the treatment of mania or depression), reduces its absorption, and lowers its blood concentration.
• Cardiac glycosides (heart-stimulating drugs). By positively affecting the force and duration of myocardial contraction, theophylline may enhance the effects of cardiac glycosides and lead to disturbances in myocardial conduction.
• Theophylline may reduce the effectiveness of β-adrenolytic drugs (used, among others, in the treatment of hypertension), adenosine (used in cardiac arrhythmias), benzodiazepines (drugs with anxiolytic, sedative, hypnotic, anticonvulsant effects), and pancuronium (a drug used during general anesthesia to facilitate intubation and skeletal muscle relaxation during surgical procedures).
• Theophylline enhances the effect of diuretics.
• There is evidence that in patients receiving ketamine (a fast-acting anesthetic) simultaneously, the seizure threshold may be lowered.

Page 2 of 9

• The use of halothane (an agent used for general anesthesia) in patients treated with theophylline may cause severe cardiac arrhythmias.

Lower serum theophylline concentrations occur in tobacco smokers.
When using drugs that affect serum theophylline concentration, the dose should be adjusted accordingly.
Inform your doctor about medicines that may increase the effect of Theospirex and raise the risk of adverse reactions:

• cimetidine (a drug used in the treatment of peptic ulcer disease of the stomach and duodenum),
• allopurinol (a drug that reduces blood and urinary uric acid levels, inhibits formation of calcium oxalate stones in the urinary tract, and prevents deposition of urate crystals in muscles and kidneys),
• fluoroquinolone antibiotics (enoxacin, lomefloxacin, ciprofloxacin, norfloxacin, ofloxacin). Frequent monitoring of theophylline concentration is recommended in patients treated with these 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 (a selective serotonin reuptake inhibitor antidepressant),
• interferon-α (a drug used in cancer treatment),
• isoniazid (a drug used in prevention and treatment of tuberculosis),
• methotrexate (a drug used in cancer treatment),
• mexiletine and propafenone (drugs used in cardiac arrhythmias),
• rofecoxib (a drug used in pain treatment in rheumatic diseases),
• propranolol (a drug used, among others, in hypertension),
• ticlopidine (a drug that inhibits platelet aggregation and release of platelet clotting factors, preventing arterial thrombosis),
• calcium channel blockers (verapamil, diltiazem),
• viloxazine (an antidepressant drug). In such cases, the doctor may recommend reducing the theophylline dose.

Alcohol increases theophylline blood concentration; therefore, alcoholic beverages should not be consumed during treatment with Theospirex.
Inform your doctor about medicines that may decrease the effect of Theospirex and reduce its efficacy:

• aminoglutethimide (a drug used in the treatment of certain prostate cancers),
• carbamazepine (a drug used in epilepsy treatment),
• isoprenaline (a drug used in bronchial asthma),
• phenobarbital (an antiepileptic drug),
• phenytoin (an anticonvulsant drug),
• 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 urinary excretion of uric acid, used in gout),
• herbal preparations containing St. John's wort ( Hypericum perforatum ). If theophylline is administered concomitantly with any of these drugs, the doctor may recommend increasing the theophylline dose.

Theospirex with food and drink
A low-carbohydrate (low-sugar), high-protein diet, parenteral nutrition, and consumption of large amounts of grilled beef reduce theophylline levels in the body and weaken its effect.
Page 3 of 9
A high-carbohydrate, low-protein diet may lead to increased theophylline levels in the body, enhanced effects, and increased risk of adverse reactions.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult a doctor or pharmacist before using this medicine.
Pregnancy
The safety of theophylline use during pregnancy has not been established, as adequate studies have not been conducted.
Theophylline crosses the placental barrier and may cause adverse effects in the fetus.
Theophylline should not be used during pregnancy, especially during the first three months, unless absolutely necessary. In the second and third trimesters, theophylline may be used only when the benefits to the mother outweigh the risks to the fetus.
The degree of theophylline binding to plasma proteins and its clearance may decrease during pregnancy. Dose reduction may be necessary to avoid adverse effects.
The use of theophylline in late pregnancy may inhibit uterine contractility. Close monitoring of newborns exposed to theophylline in late pregnancy is recommended to detect any potential adverse effects.
Breastfeeding
This medicine should not be used during breastfeeding.
Theophylline passes into breast milk and may cause adverse effects in breastfed infants. Its concentration in the milk of a nursing mother may reach 60–90% of the drug concentration in maternal blood.
Driving and operating machinery
Theophylline may affect the ability to drive and operate machinery. Caution is advised due to the possibility of experiencing drowsiness and dizziness.
Theospirex for injection/infusion solution 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 impaired renal function and in patients controlling dietary sodium intake.

3. How to use Theospirex

This medicine should always be used exactly as directed by the physician. If in doubt, consult a
physician, pharmacist, or nurse.
General instructions
Theospirex may be administered intravenously:

• by slow intravenous injection (approximately 6 minutes per vial, into a suitably large vein),
• by short intravenous infusion (approximately 10 minutes per vial as a single solution),
• by continuous intravenous infusion.

The therapeutic serum concentration of theophylline is 10 to 20 μg/ml (56 to 112 μmol/l).
Theophylline concentrations exceeding 20 μg/ml (112 μmol/l) may be toxic.
Due to considerable individual differences in theophylline pharmacokinetics and its narrow
therapeutic range, the dosage must be individualized.
Serum theophylline concentrations should be monitored.
This is particularly recommended in cases where there is an increased risk of exceeding the
therapeutic concentration, such as dose adjustments or switching to a different theophylline
preparation. Theospirex for intravenous administration contains theophylline as the active
substance, while intravenous theophylline in other commonly used medicines is usually
formulated in combination with ethylenediamine (as so-called aminophylline). Although the
pharmacokinetic profiles of both medicines appear similar when given in equivalent doses
(expressed in terms of theophylline), it cannot be excluded that switching from one medicine to
the other may result in slightly different theophylline concentrations compared to ongoing therapy.
Therefore, after switching medicines, theophylline concentration measurement is recommended.
Dosage
The dose should be calculated based on lean body mass (adipose tissue constitutes 12% in children
and 22% in adults), as theophylline does not distribute into adipose tissue. Theophylline may be
administered via intermittent or continuous intravenous infusion at a rate of 5 to 10 mg/minute, over
a period of no less than one hour. Theophylline should not be administered at a rate exceeding
25 mg/minute.
The required theophylline concentration, achieved after the initial dose, is maintained by means of a
maintenance dose based on the current serum theophylline concentration.
The total dose (the dose refers to anhydrous theophylline – 1 vial = 200 mg anhydrous theophylline)
should be determined according to the following scheme:
Patients not previously treated with theophylline:

Patients not currently receiving other medications containing theophylline:

In case it is not possible to monitor the drug concentration in the blood, the daily dose should not be exceeded and must be calculated according to the following scheme:
Patient groups Maximum daily dose
Children aged 2 to 9 years 24 mg/kg body weight, not exceeding 900 mg
Children aged 10 to 12 years 20 mg/kg body weight, not exceeding 900 mg
Children aged 13 to 16 years 18 mg/kg body weight, not exceeding 900 mg
Adults and adolescents over 16 years 13 mg/kg body weight, not exceeding 900 mg
Children under 6 months
Theospirex must not be used in children under 6 months of age.
Page 5 of 9
Method of administration
Intravenous injection
Inject 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 a suitable infusion solution.
Intravenous drip infusion
Administer in 250 ml of a suitable infusion solution. The duration of the infusion may be determined according to the dosing scheme above, but may be modified according to individual needs.
In the treatment of young children, consider reducing the volume of infusion fluids.
After administration of injection or infusion, the patient should remain at rest under supervision for a short period. If there is information about prior administration of drugs containing methylxanthines or if such administration is suspected, the injection or infusion should be carried out under special supervision, and if intolerance occurs, 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.
Use of a higher dose of Theospirex than recommended
Symptoms of overdose
Symptoms of theophylline overdose may occur when serum theophylline concentration exceeds 20 µg/ml and become more severe at higher concentrations.
Typically, tachycardia (increased heart rate) appears first, followed by gastrointestinal symptoms (nausea, vomiting, vomiting with blood, stomach pain, diarrhea), central nervous system stimulation (anxiety, headache, insomnia, dizziness), excessive thirst, tinnitus, palpitations, and cardiac arrhythmias. Excessive sweating and muscle tremors may also occur.
In cases of significant overdose (plasma theophylline concentration exceeding 25 µg/ml), seizures, circulatory failure, hyperthermia (elevated body temperature), severe cardiac arrhythmias including ventricular arrhythmias, and even cardiac arrest and death may occur.
In patients with increased sensitivity to theophylline, severe symptoms of overdose may occur even when plasma theophylline concentration is below 20 µg/ml.
Management in case of overdose
If any symptoms of overdose occur, contact a doctor or the emergency department of the nearest hospital immediately. In case of life-threatening symptoms, emergency medical services must be called immediately.
In case of mild overdose symptoms:
Discontinue the drug and measure theophylline plasma concentration. If treatment is resumed, the dose should be appropriately reduced.
If central nervous system symptoms occur (e.g., anxiety and seizures):

• administer intravenous diazepam 0.1–0.3 mg/kg body weight, maximum 15 mg. If overdose symptoms are potentially life-threatening:

• monitor vital functions and maintain airway patency,

• administer oxygen,

• if necessary, administer intravenous fluids to increase plasma volume,

Page 6 of 9

• monitor and, if necessary, correct fluid and electrolyte imbalances,
• perform hemoperfusion (see below).

In case of life-threatening cardiac arrhythmias:

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

Warning:
In patients with bronchial asthma, propranolol may cause severe bronchospasm; therefore, verapamil should be used instead of propranolol in these patients.
In very severe cases of poisoning, when the above measures are ineffective and in patients with very high plasma theophylline concentrations, rapid and complete detoxification can be achieved by hemoperfusion or hemodialysis. In most cases, this is not necessary, as theophylline is metabolized sufficiently quickly.
Missed dose of Theospirex
Do not take a double dose to make up for a missed dose.
Discontinuation of Theospirex
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although they do not
occur in everyone.
The following adverse reactions may occur during treatment with Theospirex:
Gastrointestinal disorders:
Very common (in more than 1 in 10 patients): gastrointestinal mucosal irritation, nausea, vomiting, epigastric pain, diarrhoea, loss of appetite, anorexia. Haematemesis (vomiting of blood) has been reported with theophylline. Gastro-oesophageal reflux may worsen at night due to oesophageal sphincter relaxation.
Nervous system disorders and psychiatric disorders:
Very common (in more than 1 in 10 patients): central nervous system stimulation; headache, irritability, restlessness, insomnia, dizziness, increased reflexes, limb tremors and convulsions.
Cardiac disorders:
Very common (in more than 1 in 10 patients): cardiac arrhythmias, tachycardia, extrasystoles and ventricular arrhythmias, palpitations.
Respiratory, thoracic and mediastinal disorders:
Very common (in more than 1 in 10 patients): increased respiratory rate.
Vascular disorders:
Very common (in more than 1 in 10 patients): hypotension.
Renal and urinary disorders:
Very common (in more than 1 in 10 patients): increased urinary excretion due to theophylline's diuretic effect; proteinuria of varying degrees and increased erythrocyte count in urine may occur. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has also been observed.
Immune system disorders:
Uncommon (in less than 1 in 100 but more than 1 in 1,000 patients): hypersensitivity reactions such as urticaria, generalized pruritus, angioedema—i.e., allergic reactions including skin reactions and sudden swelling of the skin and mucous membranes (e.g., throat or tongue), breathing difficulties and (or) itching and rash.
Investigations:
Very common (in more than 1 in 10 patients): increased serum glucose concentration, (decreased blood potassium concentration), increased serum creatinine concentration, changes in blood electrolyte concentrations, increased blood uric acid concentration.
Adverse symptoms may be more pronounced in individuals hypersensitive to theophylline or in cases of overdose (plasma theophylline concentration greater than 20 mg/L).
In particular, when plasma theophylline concentration exceeds 25 mg/L, toxic effects may occur, such as convulsions, sudden drop in blood pressure, ventricular arrhythmias, and severe gastrointestinal symptoms (including gastrointestinal bleeding).
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions 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
Reporting adverse reactions helps to provide more information on the safety of this medicine.

5. How to store Theospirex

Keep this medicine out of the sight and reach of children.
Store below 25°C. Keep in the original packaging to protect from light.
Do not use this medicine after the expiry date stated on the container. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Theospirex contains

• The active substance is theophylline. One ml of solution contains 20 mg of theophylline. One ampoule (10 ml) contains 200 mg of theophylline.

Page 8 of 9

• The other ingredients are: water for injections, glycine and sodium hydroxide.

What Theospirex looks like and contents of the pack
Theospirex is a colourless and clear solution.
Theospirex is supplied in ampoules made of colourless glass OPC, each containing 10 ml of solution, packed in a cardboard box.
The pack contains 5 ampoules with 10 ml of solution each.
For further information, please contact the marketing authorisation holder or the parallel importer.
Marketing authorisation holder in Hungary, country of export:
Gebro Pharma GmbH, Bahnhofbichl 13, 6391 Fieberbrunn, Austria
Manufacturer:
Gebro Pharma GmbH, Bahnhofbichl 13, 6391 Fieberbrunn, Austria
Parallel importer:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Repackaged by:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Marketing authorisation number in Hungary, country of export: OGYI-T-4246/03
Parallel import authorisation number: 158/25

Information intended exclusively for healthcare professionals:

Recommendations for preparation of infusion solution:
When mixing Theospirex with another solution, particular attention should be paid to possible discoloration, turbidity, and precipitation in the resulting solution.
Theospirex may be mixed with the following solutions:

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

Theospirex should not be mixed with other solutions unless their chemical compatibility with theophylline has been established.
Solvents for theophylline should not be mixed directly in the same syringe, as this may cause precipitation or chemical changes in the resulting solution.
Potential interactions of theophylline with other drugs should also be taken into account.
Page 9 of 9