Theospirex retard 300 mg

Patient Information Leaflet

Theospirex retard 300 mg
300 mg, prolonged-release coated tablets
Theophyllinum anhydricum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for the patient.

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

Leaflet Contents

1. What Theospirex retard 300 mg is and what it is used for
2. What you need to know before taking Theospirex retard 300 mg
3. How to take Theospirex retard 300 mg
4. Possible side effects
5. How to store Theospirex retard 300 mg
6. Contents of the pack and other information

1. What Theospirex retard 300 mg is and what it is used for

Theospirex retard 300 mg is a medicine containing 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.
It also has a positive effect on the force and duration of cardiac muscle contraction, increases urine excretion,
and reduces oedema.
Indications:

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

Warning!
Theophylline preparations with prolonged release 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 therapy for asthma in children.

2. Important information before using Theospirex retard 300 mg

When not to use Theospirex retard 300 mg

• 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 arrhythmia,
• 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 300 mg, consult your doctor if:

• the patient has hypertension,
• the patient has unstable angina pectoris,
• there is a risk of cardiac arrhythmia (including tachyarrhythmia),
• the patient has hypertrophic obstructive cardiomyopathy (a heart muscle disease),
• the patient has hyperthyroidism,
• the patient has gastric or duodenal ulcer disease,
• the patient has impaired kidney and/or liver function,
• the patient has porphyria,
• the patient has heart failure,
• the patient has cor pulmonale,
• the patient has glaucoma,
• the patient has diabetes,
• the patient has prolonged fever,
• the patient has viral infections,
• the patient is concurrently using drugs that inhibit theophylline metabolism (including immediately after discontinuation of such drugs).

This medicine should be used with caution during vaccination periods and in elderly patients.
Theospirex retard 300 mg must not be used during acute asthma attacks or asthmatic conditions.
Fever reduces the rate of theophylline elimination from the body. In acute illness associated with fever, dose reduction may be necessary to avoid toxicity.

Children and adolescents
Theospirex retard 300 mg must not be used in children under 6 years of age.
Other pharmaceutical forms of this 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 300 mg".

Theospirex retard 300 mg and other medicines
Inform your doctor or pharmacist about all medicines currently used, recently used, or planned for use.
In particular, inform your doctor if any of the following medicines are being used, as Theospirex retard 300 mg may alter their effects and increase the risk of adverse reactions:

• Theospirex retard 300 mg must not be used concomitantly with other preparations containing xanthines and their derivatives.
• Ephedrine: theophylline potentiates the effect of ephedrine.
• Theophylline enhances the action 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 blood concentration.
• Cardiac glycosides (medicines stimulating heart function). 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 (anxiolytic, sedative, hypnotic, anticonvulsant medicines), and pancuronium (used during general anesthesia to facilitate intubation and skeletal muscle relaxation during surgical procedures).
• Theophylline enhances the action of diuretics.
• There is evidence that in patients receiving ketamine (a fast-acting anesthetic) concomitantly, the seizure threshold may be lowered.
• The use of halothane (an agent used in general anesthesia) in patients treated with theophylline may cause severe cardiac arrhythmias.

Lower serum theophylline concentrations occur in tobacco smokers.
When using medicines that affect serum theophylline concentration, the dose should be adjusted accordingly.
Inform your doctor about medicines that may increase the effect of Theospirex retard 300 mg and increase the risk of adverse reactions:

• cimetidine (used in the treatment of gastric and duodenal ulcer disease),
• allopurinol (reduces uric acid levels in blood and urine, inhibits formation of calcium oxalate stones in urinary tract, 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 (used in the treatment of alcohol dependence),
• estrogens (hormonal medicines 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,
• viloxazine (an antidepressant). In such cases, the doctor may recommend reducing the dose of Theospirex retard 300 mg.

Alcohol increases theophylline blood concentration; therefore, alcoholic beverages must not be consumed during treatment with Theospirex retard 300 mg.
Inform your doctor about medicines that may decrease the effect of Theospirex retard 300 mg and reduce its efficacy:

• aminoglutethimide (used in the treatment of certain prostate cancers),
• carbamazepine (used in epilepsy treatment),
• isoprenaline (used in bronchial asthma),
• phenobarbital (antiepileptic medicine),
• phenytoin (anticonvulsant),
• primidone (antiepileptic),
• rifampicin (used in tuberculosis),
• sucralfate (used in gastric and duodenal ulcer disease),
• sulfinpyrazone (increases urinary excretion of uric acid, used in gout),
• herbal medicines containing St John's wort ( Hypericum perforatum ). If the patient is taking any of the above medicines concomitantly, the doctor may recommend increasing the dose of Theospirex retard 300 mg.

Theospirex retard 300 mg 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.
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.
Theophylline use in late pregnancy may inhibit uterine contractility. Close monitoring of neonates 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 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. Exercise caution due to the possibility of drowsiness and dizziness.

This medicine contains less than 1 mmol (23 mg) of sodium per maximum daily dose, meaning the medicine is considered "sodium-free".

3. How to use Theospirex retard 300 mg

This medicine should always be used as directed by the physician. 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 to the treatment. Dosing is best determined after measuring serum theophylline
concentrations (therapeutic range: 8 – 20 μg/ml). Monitoring serum theophylline levels is
recommended, especially if adverse reactions occur or if the response to treatment is inadequate.
If the patient has previously used theophylline or its derivatives, this should be taken into account
when determining the initial dose, which may need to be appropriately reduced. The dose should be
calculated based on lean body mass, as theophylline does not distribute into adipose tissue.

Dosage
The maintenance daily dose of theophylline in adults is approximately 11 to 13 mg/kg body weight.
This corresponds to a total daily dose of 900 mg (3 tablets).

• Adults and adolescents over 16 years of age (8 to 12 mg/kg body weight per day): 300 mg theophylline (1 tablet) every 12 hours (morning and evening).
• Children over 6 years of age (10 to 15 mg/kg body weight per day): 150 mg theophylline (half a tablet) every 12 hours (morning and evening).

If there is insufficient improvement after three days of treatment, the dose may be gradually
increased by half a tablet:

• in children: up to a daily dose of 20 mg/kg body weight
• in adults: up to a daily dose of 15 mg/kg body weight

If serum drug concentration monitoring is not possible, the following maximum daily doses
should not be exceeded:

• in children aged 6 to 9 years: 600 mg (2 tablets),
• in children aged over 9 to 12 years: 750 mg (2 and a half tablets),
• in adolescents over 12 years of age and adults: 900 mg (3 tablets).

When maintaining doses above these maximum levels is necessary, monitoring of serum theophylline
concentrations is recommended.
If a theophylline preparation with immediate release is to be replaced by one with modified release,
a reduction in the total daily dose may be required.
When switching from one theophylline-containing medicine to another, the physician should
monitor treatment by measuring serum theophylline concentrations.

Children under 6 years of age
Theospirex retard 300 mg should not be used in children under 6 years of age.

Smoking tobacco
Smokers require a higher dose of theophylline, adjusted for body weight, compared to non-smoking
adults due to faster theophylline elimination. Special caution is required when adjusting the dose
in patients who are quitting smoking, as their serum theophylline concentrations may be elevated
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), fever unresponsive to treatment, elderly patients, those taking certain medications (see
section 2. "Theospirex retard 300 mg and other medicines"), and those consuming large amounts of
alcohol. 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 impaired liver and/or kidney function
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.

Method of administration
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 should not be chewed or crushed.

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

Use of a higher than recommended dose of Theospirex retard 300 mg
Symptoms of overdose
Symptoms of theophylline overdose may occur when serum concentrations exceed 20 μg/ml and
become more severe at higher levels.
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 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 overdose symptoms may occur even
when serum theophylline concentrations are below 20 μg/ml.

Management in case of overdose
If any symptoms of overdose occur, contact a doctor or the nearest hospital emergency department immediately. In life-threatening situations, emergency medical services should be called immediately.
In cases of mild overdose symptoms:
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):

• 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,
• monitor and, if needed, correct fluid and electrolyte imbalances,
• consider hemoperfusion (see below).

In life-threatening cardiac arrhythmias:

• in patients without 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 serum 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 retard 300 mg
Do not take a double dose to make up for a missed dose.

Discontinuation of Theospirex retard 300 mg
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 not everyone experiences them.
The following adverse effects may occur during treatment with Theospirex retard 300 mg:

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. 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, hyperreflexia, limb tremor, 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 (rapid breathing).

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 output due to theophylline's diuretic effect; proteinuria of varying degree, increased erythrocyte count in urine may occur. 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 blood potassium concentration, increased serum creatinine concentration, changes in blood electrolyte concentrations, increased blood uric acid concentration.

Adverse effects may be more pronounced in individuals hypersensitive to theophylline or in cases of overdose (serum theophylline concentration greater than 20 mg/l). In particular, when serum theophylline concentration exceeds 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 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 of Adverse Drug Reactions 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
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of this medicine.

5. How to store Theospirex retard 300 mg

Keep this 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 stated month.
Medicines must not be disposed of via the sewage system 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 300 mg contains

• The active substance is anhydrous theophylline. One prolonged-release coated tablet contains 300 mg of anhydrous theophylline.
• The 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), indigo carmine (E132), macrogol 4000, macrogol 6000.

What Theospirex retard 300 mg looks like and contents of the pack
Blue, elongated coated tablets, with a score line on both sides.

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