Theospirex

Leaflet attached to the packaging: patient information

Theospirex

20 mg/ml

Solution for injection and intravenous 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 you need to.
• If you have 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. Contents of the packaging 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 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.

Indications for use:

Treatment of acute and severe bronchospasm in chronic respiratory diseases:

• bronchial asthma, asthmatic status,
• 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

Warnings and precautions

Before starting treatment with Theospirex, you should discuss it with your doctor, pharmacist or nurse:

The medicine should be used with caution during vaccination and in the elderly. Fever reduces the rate of theophylline elimination from the body. In the case of an 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

You should tell your doctor or pharmacist about all the medicines you are taking, have recently taken or plan to take.
In particular, you should inform about the use of any of the following medicines, as Theospirex may affect their action and increase the risk of side effects:

• Theospirex should not be used concomitantly with other xanthine and xanthine derivative preparations.
• 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 cardiac arrhythmias), benzodiazepines (drugs with anxiolytic, sedative, hypnotic, anticonvulsant action) and pancuronium (a drug used during general anesthesia to facilitate intubation and relaxation of skeletal muscles 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 (an agent used for general anesthesia) in patients treated with theophylline may cause severe cardiac arrhythmias.

A lower concentration of theophylline in the blood occurs in tobacco smokers.
In the case of using drugs that affect the concentration of theophylline in the blood serum, the dose should be adjusted accordingly.
You should inform about the use of drugs 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 the muscles and kidneys),
• fluoroquinolone antibiotics (enoxacin, lomefloxacin, ciprofloxacin, norfloxacin, ofloxacin). It is recommended to frequently monitor the theophylline concentration 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 tumors),
• isoniazid (a drug used in the prevention and treatment of tuberculosis),
• methotrexate (a drug used in the treatment of tumors),
• mexiletine and propafenone (drugs used in cardiac 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 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 you should not consume alcoholic beverages while using Theospirex.
You should inform about the use of drugs that may weakenthe effect of Theospirex and reduce its effectiveness:

• aminoglutethimide (a drug used in the treatment of certain prostate tumors),
• 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 action),
• 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 low-carbohydrate diet (sugars) and high-protein diet, as well as parenteral nutrition and consumption of large amounts of grilled beef, reduce the amount of theophylline in the body and weaken its effect.
A high-carbohydrate diet and low-protein diet may lead to an increase in the amount of theophylline in the body, enhancement of its effect and increased risk of side effects.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or plan to have a child, you should consult your 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 trimester 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 action.
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 your ability to drive and use machines. You should be careful, due to the possibility of drowsiness and dizziness.

Theospirex in the form of a solution for injection and intravenous 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 exactly as your doctor has told you. If you are not sure, you should ask your 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 large 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 applies particularly to 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 the 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 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 fatty 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 by means of 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 the absence of the possibility of monitoring 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, the need to reduce the volume of fluids administered in the infusion should be considered.
After the injection or infusion, the patient should remain at rest for a short time, under supervision. If there is information about previous administration of methylxanthine or xanthine derivative-containing medicines, or if such a suspicion exists, 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.

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 they become more severe with higher concentrations.
Usually, the first symptom to occur is tachycardia (rapid heart rate), 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 cardiac arrhythmias. Excessive sweating and muscle tremors may also occur.
In the case of significant overdose (theophylline concentration in the blood serum is higher than 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 overdose symptoms may occur even when the theophylline concentration in the blood serum is less than 20 μg/ml.
Procedure in case of overdose

In case of any symptoms of overdose, you should immediately contact a doctor or the emergency department of the nearest hospital. In case of life-threatening symptoms, you should immediately call the emergency services.

In the 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 occur from the central nervous system (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, you should:

• 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,
• use hemoperfusion (see below).

In the case of life-threatening cardiac 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 bronchial 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 serum, rapid and complete detoxification can be achieved by using hemoperfusion or hemodialysis. In most cases, this is not necessary, as theophylline is metabolized sufficiently quickly.

Missing a dose of Theospirex

You should not take a double dose to make up for a missed dose.

Stopping the use of Theospirex

If you have any further doubts about the use of this medicine, you should consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur during treatment with Theospirex:
Gastrointestinal disorders:
Very common (in more than 1 in 10 patients): irritation of the mucous membrane of the digestive tract, nausea, vomiting, abdominal pain, diarrhea, loss of appetite, anorexia. Bleeding vomiting after theophylline has been reported. 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): cardiac arrhythmias, rapid heart rate, extra systoles 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 may occur, and an increase in the number of erythrocytes in the urine. 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 1000 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 the 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, toxic effects may occur, such as seizures, sudden drop in blood pressure, ventricular arrhythmias and severe gastrointestinal symptoms (including gastrointestinal bleeding).

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should tell your doctor, pharmacist or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the 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
e-mail: ndl@urpl.gov.pl
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Theospirex

The medicine should be stored out of the sight and reach of children.
Store in a temperature below 25°C.
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 month stated.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer required. This will help protect the environment.

6. Contents of the packaging 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 pack contains

Theospirex is a colorless and clear solution.
The medicine is packaged in ampoules made of colorless glass, containing 10 ml of the solution, and placed in a cardboard box.
The packaging contains 5 ampoules of 10 ml of the solution.

Marketing authorization holder

Biofarm Sp. z o.o.
ul. Wałbrzyska 13
60-198 Poznań
Tel.: +48 61 66 51 500
Fax: +48 61 66 51 505

Manufacturer

Gebro Pharma GmbH
A-6391 Fieberbrunn
Austria

Date of approval of the leaflet: -------------------------------------------------------------------------------------------------------------------------------------------

Information intended exclusively for healthcare professionals:

Recommendations for preparing the solution for infusion:

In the case of mixing Theospirex with another solution, you should pay particular attention to any discoloration, clouding or 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 the case of mixing theophylline with a glucose solution, a yellow discoloration of the solution may occasionally occur.

The medicine should not be mixed with other solutions if their chemical compatibility with theophylline has not 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.