Theospirex retard

Package leaflet: Information for the patient

Theospirex retard
150 mg, prolonged-release coated tablets
Theophyllinum anhydricum
Please read carefully the entire leaflet before using the medicine, as it contains
important information for the patient.

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

Table of contents of the leaflet

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

1. What Theospirex retard is and what it is used for

Theospirex retard is a medicine containing anhydrous theophylline in the form of prolonged-release coated tablets.
The medicine exerts a relaxing effect on 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, increases urine excretion, and reduces edema.
Indications for use:

• Prevention of bronchial spasms in bronchial asthma and chronic obstructive pulmonary disease (COPD).

Warning!
Medicines containing prolonged-release theophylline are not intended for immediate treatment of asthmatic status (severe asthma attack) or respiratory disorders caused by acute bronchospasm.
Theophyllines should not be used as first-line treatment for asthma in children.

2. Important information before using Theospirex retard

When not to use Theospirex retard

• 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 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 years of age.

Warnings and precautions
Before starting treatment with Theospirex retard, discuss with your doctor:

• if the patient has hypertension,
• if the patient has unstable angina pectoris,
• in case of risk of cardiac arrhythmias (including tachyarrhythmias),
• if the patient has hypertrophic obstructive cardiomyopathy (a heart muscle disorder),
• if the patient has hyperthyroidism,
• if the patient has gastric or duodenal ulcer disease,
• if the patient has impaired kidney and/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 periods and in elderly patients.
Theospirex retard must not be used during acute asthma attacks or in asthmatic conditions.
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 retard must not be used in children under 6 years of age.
Other pharmaceutical forms of the medicine are available that are more suitable for children under 6 years of age.
Detailed information on the use of this medicine in children and adolescents is provided in section 3, "How to use Theospirex retard".

Theospirex retard and other medicines
Inform your doctor or pharmacist about all medicines currently used, recently used, or planned for use.
In particular, inform about the use of any of the following medicines, as Theospirex retard may alter their effects and increase the risk of adverse reactions:

• Theospirex retard 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 bronchial spasms, caffeine, and similar substances.
• Theophylline increases renal excretion of lithium salts (used in the treatment of mania or depression), reduces their absorption and blood concentration.
• Cardiac glycosides (drugs stimulating heart function): By positively affecting the force and duration of myocardial contraction, theophylline may enhance the effects of cardiac glycosides and lead to conduction disturbances in the heart muscle.
• Theophylline may reduce the effectiveness of β-adrenolytic drugs (used, among others, in hypertension treatment), adenosine (used in cardiac arrhythmias), benzodiazepines (anxiolytic, sedative, hypnotic, anticonvulsant drugs), and pancuronium (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) concurrently, the seizure threshold may be lowered.
• Administration of halothane (an agent used in general anesthesia) in patients treated with theophylline may cause severe cardiac arrhythmias.

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

• cimetidine (used in the treatment of gastric and duodenal ulcer disease),
• allopurinol (reduces blood and urinary uric acid levels, prevents formation of calcium oxalate stones in urinary tract, prevents urate deposits 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 (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 (prevents blood clot formation),
• calcium channel blockers (verapamil, diltiazem) used in heart diseases,
• vilazodone (antidepressant). In such cases, the doctor may recommend reducing the dose of Theospirex retard.

Alcohol increases blood theophylline concentration; therefore, alcoholic beverages must not be consumed during treatment with Theospirex retard.
Inform your doctor about medicines that may decrease the effect of Theospirex retard 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 gastric and duodenal ulcer disease),
• sulfinpyrazone (increases urinary excretion of uric acid, used in gout),
• herbal products containing St. John's wort ( Hypericum perforatum ). If the patient is using any of the above medicines concurrently, the doctor may recommend increasing the dose of Theospirex retard.

Theospirex retard with food and drink
A diet low in carbohydrates (sugars) and high in protein, parenteral nutrition, and consumption of large amounts of grilled beef reduce the amount of theophylline in the body and weaken its effect.
A diet high in carbohydrates and low in protein 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 benefits to the mother outweigh risks to the fetus.
Theophylline crosses the placental barrier and may cause adverse effects in the fetus.
The degree of theophylline binding to plasma proteins and its clearance may decrease during pregnancy progression. Dose reduction may be necessary to avoid adverse effects.
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
The 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 blood.

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.

3. How to use Theospirex retard

This medicine should always be used exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.

The theophylline dose should be individually adjusted based on the drug's efficacy and the patient's tolerance. Dosing is best determined after measuring theophylline serum concentration (therapeutic concentration range: 8 – 20 μg/ml). Monitoring serum theophylline levels is particularly recommended in cases of adverse reactions or inadequate response to treatment.

If the patient has previously been treated with theophylline or its derivatives, this should be taken into account when determining the initial dose, which should be appropriately reduced. The dose should be calculated based on lean body mass, as theophylline does not penetrate into adipose tissue.

Dosage

The maintenance dose of theophylline in adults is approximately 11 to 13 mg/kg body weight, corresponding to a total daily dose of up to 900 mg (6 tablets).

• Adults and adolescents over 16 years of age (8 to 12 mg/kg body weight per day): 300 mg theophylline (2 tablets) every 12 hours (morning and evening).
• Adolescents aged 13 to 16 years (8 to 15 mg/kg body weight per day): 225 to 300 mg theophylline (1\½ to 2 tablets) every 12 hours (morning and evening).
• Children aged 10 to 12 years (11 to 15 mg/kg body weight per day): 225 mg theophylline (1\½ tablets) every 12 hours (morning and evening).
• Children aged 6 to 9 years (10 to 17 mg/kg body weight per day): 150 mg theophylline (1 tablet) every 12 hours (morning and evening).

If the clinical response is unsatisfactory, the daily dose should be gradually increased every 3 days by approximately 25% until clinical improvement is achieved or until the maximum daily dose is reached, as follows:

• Adults and adolescents over 16 years: 13 mg/kg body weight per day
• Adolescents aged 13 to 16 years: 18 mg/kg body weight per day
• Children aged 10 to 12 years: 20 mg/kg body weight per day
• Children aged 6 to 9 years: 24 mg/kg body weight per day

If monitoring of blood drug concentration is not possible, the daily dose should not exceed:

• In children aged 6 to 9 years: 600 mg (4 tablets)
• In children aged over 9 to 12 years: 750 mg (5 tablets)
• In adolescents over 12 years and adults: 900 mg (6 tablets)

When it is necessary to maintain doses higher than those listed above, monitoring of serum theophylline concentration is recommended.

If a theophylline preparation with unmodified release is to be replaced by one with modified release, a reduction in the total daily dose may be necessary.

When switching from one theophylline-containing medicine to another, the physician should monitor treatment by measuring serum theophylline concentration.

Children under 6 years of age

Theospirex retard must not be used in children under 6 years of age.

Smoking

Smokers require a higher dose of theophylline (adjusted for body weight) than non-smoking adult patients, due to faster theophylline elimination.

Particular caution is required when adjusting the dose in patients who are in the process of quitting smoking, as their serum theophylline concentration may be increased compared to non-smokers.

Special patient groups

Theophylline elimination is generally slower in patients with heart failure, severe hypoxia, chronic obstructive pulmonary disease, pneumonia, acute pulmonary edema, viral infections (especially influenza), treatment-resistant fever, in elderly patients, in patients taking certain medications (see section 2. "Theospirex retard and other medicines"), and in individuals consuming large amounts of alcohol. Therefore, these patients require lower theophylline doses, and particular caution should be exercised when considering dose increases.

Reduced theophylline elimination has also been reported after influenza and tuberculosis vaccinations. In such cases, a reduction in theophylline dose may be necessary.

Patients with hepatic and/or renal impairment

Theophylline elimination is very frequently slower in patients with liver dysfunction.

In patients with severe renal impairment, accumulation of theophylline metabolites may occur. Therefore, lower doses should be used in these patients, and particular caution is required when increasing the dose.

Administration method

The tablets should be taken orally, after meals.

Individual doses should be taken at regular intervals throughout the day. When the medicine is administered twice daily, doses are usually taken in the morning and evening.

The tablets may be divided into two equal parts along the score line.

The tablets must not be chewed or crushed.

Duration of treatment

The duration of treatment is determined by the physician according to the type, severity, and course of the disease.

Use of a higher than recommended dose of Theospirex retard

Symptoms of overdose

Symptoms of theophylline overdose may occur when serum 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 (serum theophylline concentration greater 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 serum theophylline concentration is below 20 μg/ml.

Management in case of overdose

If any symptoms of overdose occur, contact your doctor or the nearest hospital emergency department immediately. In case of life-threatening symptoms, emergency medical services must be called immediately.

In cases of mild overdose:

Discontinue the drug and measure serum theophylline concentration. If treatment is resumed, the dose should be appropriately reduced.

If central nervous system symptoms occur (e.g. anxiety, seizures):

• intravenous diazepam 0.1–0.3 mg/kg body weight, maximum 15 mg, should be administered.

If overdose symptoms are potentially life-threatening:

• vital functions should be monitored and airway patency maintained,
• oxygen should be administered,
• intravenous fluids to increase plasma volume should be given if necessary,
• fluid and electrolyte imbalances should be monitored and corrected as needed,
• hemoperfusion should be considered (see below).

In case of life-threatening cardiac arrhythmias:

• in patients without asthma, intravenous propranolol should be administered: 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 serum theophylline concentrations, rapid and complete detoxification can be achieved by hemoperfusion or hemodialysis. However, this is rarely necessary, as theophylline is metabolized sufficiently quickly in most cases.

Missed dose of Theospirex retard

Do not take a double dose to make up for a missed dose.

Discontinuation of Theospirex retard

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although they
do not occur in every individual.
The following adverse effects may occur during treatment with Theospirex retard:
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 after theophylline has been reported. 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): central nervous system stimulation: headache, irritability, restlessness, insomnia, dizziness, increased reflexes, tremor of limbs, 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): tachypnoea.
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 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, urticaria, generalized pruritus, angioedema – allergic reactions such as 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 serum 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 or pharmacist. Adverse effects can be reported directly to the Department of Monitoring 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
Email: [email protected]
Reporting adverse effects helps to gather more information on the safety of the medicine.

5. How to store Theospirex retard

Keep the medicine out of the sight and reach of children.
Store below 25°C.
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 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 retard contains

• The active substance is anhydrous theophylline. One prolonged-release tablet contains 150 mg of anhydrous theophylline.
• Other ingredients are: ammonio methacrylate copolymer (type B) (Eudragit RSPO), povidone 25, talc, magnesium stearate, purified water, hypromellose HPMC 5-6, hypromellose HPMC 2910, titanium dioxide (E171), triacetin, macrogol 6000.

What Theospirex retard looks like and contents of the pack
White, round coated tablets, with a score line on both sides, smooth surface, without
damage, spots or chipping.
The tablets are packed in aluminium/PVC blisters, placed in a cardboard box.
The pack contains 50 tablets (5 blisters with 10 tablets each).
Marketing Authorisation Holder and Manufacturer
Biofarm Sp. z o.o.
Wałbrzyska Street 13
60-198 Poznań
Tel.: +48 61 66 51 500
Fax: +48 61 66 51 505