Theospirex

Package leaflet: Information for the patient

Warning! Keep the package leaflet, information on the outer packaging in a foreign language!
Theospirex
20 mg/ml, solution for injection/infusion
Theophyllinum
Please read carefully all the information in this leaflet before using the medicine, as it contains
important information for the patient.

• Keep this leaflet so that you can 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 another person, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

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 by relaxing the smooth muscles of the bronchi, bronchioles, and blood vessels, and inhibits the release of mediators from cells involved in inflammatory reactions.
The medicine also positively affects the force and duration of cardiac muscle contraction and increases urine excretion.
Indications:

• 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. 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 recently suffered a myocardial infarction,
• if the patient is experiencing shock or collapse,
• if the patient has acute cardiac arrhythmia,
• 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.

Warnings and precautions
Before starting treatment with Theospirex, discuss with your doctor, pharmacist, or nurse:

• if the patient has hypertension,
• if the patient has unstable angina pectoris,
• if the patient has a tendency towards cardiac arrhythmias (including tachyarrhythmias),
• if the patient has hypertrophic obstructive cardiomyopathy (a heart muscle disorder),
• 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 using 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 acute illness accompanied by 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
Inform your doctor or pharmacist about all medicines currently used, recently used, or planned for use.

In particular, inform your doctor 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 concurrently with other xanthine-containing preparations 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 bronchospasm, caffeine, and similar substances.
• Theophylline increases renal excretion of lithium salts (used in the treatment of mania or depression), reduces their absorption, and lowers their blood concentration.
• Cardiac glycosides (drugs that stimulate heart function). By positively affecting myocardial contractility and contraction duration, theophylline may enhance the effects of cardiac glycosides and lead to disturbances in cardiac conduction.
• Theophylline may reduce the effectiveness of β-adrenergic blockers (used, among others, in hypertension treatment), adenosine (used in cardiac arrhythmias), benzodiazepines (drugs with anxiolytic, sedative, hypnotic, and 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.
• Evidence suggests that in patients receiving ketamine (a fast-acting anesthetic), the seizure threshold may be lowered.
• Administration of halothane (a general anesthetic) 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, appropriate dose adjustments are necessary.

Inform your doctor about medicines that may increase the effect of Theospirex and raise the risk of adverse reactions:

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

Alcohol increases theophylline blood concentration; therefore, alcoholic beverages must not be consumed during treatment with Theospirex.

Inform your doctor about medicines that may decrease the effect of Theospirex and reduce its efficacy:

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

Theospirex with food and drink
A low-carbohydrate, high-protein diet, parenteral nutrition, and consumption of large amounts of grilled beef reduce theophylline levels in the body and weaken its effect.
A high-carbohydrate, low-protein diet may increase theophylline levels in the body, enhance its effects, and increase the risk of adverse reactions.

Pregnancy and breastfeeding
If the patient is pregnant, 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.
Plasma protein binding and clearance of theophylline may decrease during pregnancy progression. Dose reduction may be necessary to avoid adverse effects.
Theophylline use 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
Theospirex must not be used during breastfeeding.
Theophylline passes into breast milk and may cause adverse effects in breastfed infants. Its concentration in breast milk may reach 60–90% of the maternal blood concentration.

Driving and operating machinery
Theophylline may affect the ability to drive and operate machinery. Caution is advised due to the possibility of drowsiness and dizziness.

Theospirex 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 on a controlled sodium diet.

3. How to use Theospirex

This medicine should always be used as directed by the physician. In case of doubt, consult a
physician, pharmacist, or nurse.
General recommendations
Theospirex may be administered intravenously:

• intravenously as a slow injection (approximately 6 minutes per ampoule, into a sufficiently large vein),
• as a short intravenous infusion (approximately 10 minutes per ampoule in a single solution),
• or as an intravenous drip infusion.

The therapeutic serum theophylline concentration ranges from 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 concentration 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 changes in the type of theophylline
preparation used. Theospirex for intravenous administration contains theophylline as the active
substance, whereas intravenous theophylline commonly used in other medicines is most often
formulated in combination with ethylenediamine (as so-called aminophylline). Although the
pharmacokinetic profiles of both medicines appear similar when administered in equivalent doses
(expressed in terms of theophylline), it cannot be excluded that switching from one medicine to
another may result in slightly different serum theophylline concentrations compared to those
achieved during prior 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), since 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 adjusted according to the current serum theophylline concentration.
The total dose (the dose refers to anhydrous theophylline – 1 ampoule = 200 mg 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 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 of age 13 mg/kg body weight, not exceeding 900 mg
Children under 6 months of age
Theospirex must not be used in children under 6 months of age.
Administration method
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 the need to reduce the volume of fluids administered in the infusion.
After administration of injection or infusion, the patient should remain at rest under supervision for a short period of time. If there is information about prior administration of drugs containing methylxanthines or if such administration is suspected, the injection or infusion should be performed 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 blood concentration exceeds 20 μg/ml and become more severe with higher concentrations.
Typically, tachycardia (accelerated heart rate) occurs 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 exceeds 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 physician or the emergency department of the nearest hospital immediately. In case of life-threatening symptoms, call emergency services immediately.
In case of mild overdose symptoms:
Discontinue administration of 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 diazepam intravenously at a dose of 0.1–0.3 mg/kg body weight, maximum 15 mg.

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

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

In case of life-threatening cardiac arrhythmias:

• in patients not suffering from asthma, administer propranolol intravenously: 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 administered instead of propranolol in these patients.
In very severe cases of poisoning, when the above management is 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 because theophylline is metabolized sufficiently quickly.
Missed dose of Theospirex
Do not administer a double dose to compensate for a missed dose.
Discontinuation of Theospirex
If you have any further doubts regarding the use of this medicine, consult your physician or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The following adverse effects may occur during treatment with Theospirex:

Gastrointestinal disorders:
Very common (in more than 1 in 10 patients): irritation of the gastrointestinal mucosa, nausea, vomiting, epigastric pain, diarrhoea, loss of appetite, anorexia. Haematemesis has been reported with theophylline. Gastroesophageal reflux may worsen at night due to oesophageal sphincter relaxation.

Central nervous system and psychiatric disorders:
Very common (in more than 1 in 10 patients): stimulation of the central nervous system; headache, irritability, restlessness, insomnia, dizziness, hyperreflexia, limb tremors, and seizures.

Cardiac disorders:
Very common (in more than 1 in 10 patients): cardiac arrhythmias, tachycardia, extrasystoles, 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 urine output due to theophylline's diuretic effect; proteinuria of varying degrees and increased erythrocytes 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 rashes 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 serum uric acid concentration.

Adverse effects 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, signs of toxic effects may occur, such as seizures, sudden drop in blood pressure, ventricular arrhythmias, and severe gastrointestinal symptoms (including gastrointestinal bleeding).

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse effects can be reported directly to the Department for Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting adverse effects helps to provide more information on the safety of this medicine.

5. How to store Theospirex

Keep the medicine out of the sight and reach of children.
There are no special requirements regarding 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 stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the packaging 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.
• The other components 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 packed in OPC glass ampoules (type I), each containing 10 ml of solution, placed 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 Parallel Importer.
Marketing Authorisation 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:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Repackaged in:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Austrian Marketing Authorisation Number (country of export): 1-18867
Parallel Import Authorisation Number: 211/25

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 discolorations, 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 tested.
Solvents for theophylline should not be mixed directly in the same syringe, as this may cause precipitation or chemical changes in the resulting solution.
Interactions of theophylline with other drugs should also be taken into account.