Theophylline
Theophylline: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. For violations of liver function
- 11. Drug interactions
- 12. Analogs
- 13. Terms and conditions of storage
- 14. Terms of dispensing from pharmacies
- 15. Reviews
- 16. Price in pharmacies
Latin name: Theophylline
ATX code: R03DA04
Active ingredient: Theophylline (Theophylline)
Producer: JSC Valenta Pharmaceuticals, Russia
Description and photo update: 2019-12-08
Theophylline is a purine derivative; antispasmodic and bronchodilating agent.
Release form and composition
Theophylline dosage form is prolonged-release tablets: flat-cylindrical, white with a yellowish tinge; 100 mg tablets - with bevelling, 200 and 300 mg tablets - with beveled and scored (10 pcs. in blisters, in a cardboard box 2, 3 or 5 packs; 20, 30 or 50 pcs. in polymer cans, in cardboard box 1 can).
Active ingredient: theophylline, in 1 tablet - 100, 200 or 300 mg.
Additional components: Kollidon SR (polyvinyl acetate, povidone, sodium lauryl sulfate, silicon dioxide), calcium stearate, microcrystalline cellulose.
Pharmacological properties
Pharmacodynamics
Theophylline is a purine-derived antispasmodic drug. It blocks the work of adenosine receptors and is a phosphodiesterase inhibitor. The substance has a pronounced bronchodilator effect caused by a direct effect on the muscles of the bronchi.
Theophylline acts as a stabilizer of the mast cell membrane, slows down the release of mediators of allergic reactions, increases mucociliary clearance, stimulates diaphragmatic contractions, and normalizes the function of the intercostal and respiratory muscles. Improving the respiratory function, the drug provides full saturation of blood with oxygen and a decrease in the level of carbon dioxide in it, as well as activates the respiratory center and helps to increase ventilation of the lungs during hypokalemia.
Theophylline intensifies cardiac activity, increases heart rate and strength, improves coronary blood flow and increases myocardial oxygen demand. When it is taken, the tone of the blood vessels (mainly the vessels of the kidneys, skin and brain) decreases, the pulmonary vascular resistance decreases, the pressure in the pulmonary circulation returns to normal. The drug activates renal blood flow and has a moderate diuretic effect, as well as expands the lumen of the biliary tract located outside the liver.
The active ingredient is released from the tablets rather slowly, which allows reaching the therapeutic concentration of theophylline in the blood 3-5 hours after oral administration. This level remains practically constant for 10-12 hours, so that the content of the active substance in the blood plasma, which has a therapeutic effect, is observed when the drug is taken 2 times a day.
Pharmacokinetics
Theophylline is fairly well absorbed from the gastrointestinal tract, with bioavailability ranging from 88 to 100%. The maximum concentration in blood plasma is reached 6 hours after ingestion.
Theophylline binds to plasma proteins by about 60%. It crosses the placental barrier and is found in breast milk. The substance is metabolized in the liver by 90% with the direct participation of several cytochrome P 450 enzymes (the main one among them is CYP1A2). The most important metabolites are 3-methylxanthine and 1,3-dimethyl uric acid.
Metabolites are excreted through the kidneys, and the proportion of the unchanged active component is about 7-13%. The half-life in nonsmoking patients is 6-12 hours, and in smoking patients it is significantly shortened and is equal to 4-5 hours. In patients with liver cirrhosis, alcoholism and renal failure, the half-life is prolonged. The total clearance decreases in patients with chronic heart or hepatic failure, severe respiratory failure, with viral infectious diseases, high fever and in patients over 55 years of age.
Indications for use
- broncho-obstructive syndrome of any genesis: chronic obstructive pulmonary disease (chronic obstructive bronchitis, pulmonary emphysema), bronchial asthma (as the main drug for exercise-induced asthma, as an additional remedy for other forms of the disease);
- sleep apnea;
- pulmonary hypertension and cor pulmonale;
- edematous syndrome of renal genesis (as part of combination therapy).
Contraindications
- epilepsy;
- severe tachyarrhythmias;
- severe arterial hypertension or hypotension;
- retinal hemorrhage;
- hemorrhagic stroke;
- bleeding from the gastrointestinal tract;
- peptic ulcer and 12 duodenal ulcer;
- gastritis with high acidity;
- children under 12 years old;
- lactation (or you should stop breastfeeding);
- hypersensitivity to the components of the drug, including other xanthine derivatives (for example, pentoxifylline, caffeine, theobromine).
Theophylline is used with caution in the following cases:
- gastroesophageal reflux;
- bleeding from the gastrointestinal tract in a recent history;
- a history of gastric ulcer and 12 duodenal ulcer;
- hepatic and / or renal failure;
- frequent ventricular premature beats;
- hypertrophic obstructive cardiomyopathy;
- common vascular atherosclerosis;
- chronic heart failure;
- severe coronary insufficiency (angina pectoris, acute phase of myocardial infarction);
- hypertrophy of the prostate;
- increased convulsive readiness;
- uncontrolled hypothyroidism or thyrotoxicosis;
- prolonged hyperthermia;
- pregnancy (especially the first trimester and the last weeks);
- elderly age.
Instructions for the use of Theophylline: method and dosage
Theophylline extended-release tablets should be taken orally with a sufficient amount of liquid.
The average daily dose for adolescents over 12 years of age and adults is 300 mg (at the rate of 10-15 mg / kg) 2 times a day at 12-hour intervals. If necessary, a single dose of 500 mg at bedtime is possible (for patients with predominantly night and morning attacks) or 300 mg 3 times a day.
For non-smoking adult patients weighing 60 kg or more, the recommended initial dose is 200 mg (in the evening), then 200 mg 2 times a day.
Smoking adults weighing less than 60 kg are prescribed 200 mg in the morning and 400 mg in the evening, with a body weight of more than 60 kg - 300 mg in the morning and 600 mg in the evening.
It is recommended to start treatment with Theophylline with small doses, which are gradually increased by 100-200 mg every 1-2 days until the maximum therapeutic effect is achieved. In case of poor tolerance of the drug, the dose should be reduced.
The specific dosage is determined by the doctor depending on the type of disease, the patient's age and body weight.
When large doses are prescribed, treatment should be carried out under the control of the concentration of theophylline in the blood. The average therapeutic concentration should be 0.01–0.015 mg / ml. If the check reveals a concentration of 0.02–0.025 mg / ml, the daily dose of the drug must be reduced by 10%, if 0.025–0.03 mg / ml - by 25%, if more than 0.03 mg / ml - 2 times. Repeated control of the concentration of theophylline in the blood is carried out after 3 days. If the concentration is too low, the dose is increased by 25% every 3 days. If, when taking the drug in high doses, the patient's condition is stable, monitoring should be carried out every 6-12 months.
Recommended maintenance daily doses of Theophylline: for patients weighing less than 60 kg - 400 mg, with a body weight of more than 60 kg - 600 mg.
In the presence of liver dysfunction or diseases of the cardiovascular system, the doses are adjusted: for patients weighing less than 60 kg, 200 mg per day is prescribed, and for patients weighing more than 60 kg - 400 mg per day. A decrease in the daily dose is also required for the elderly, patients with viral infections, severe liver and heart disease.
For children weighing up to 30 kg, Theophylline is prescribed in a daily dose of 10–20 mg / kg and divided into 2 doses.
Side effects
- from the cardiovascular system: lowering blood pressure, increasing the frequency of angina attacks, arrhythmias, palpitations, cardialgia, tachycardia (including in the fetus if the drug is taken by a woman in the third trimester of pregnancy);
- from the digestive system: heartburn, nausea, exacerbation of peptic ulcer disease, vomiting, diarrhea, gastroesophageal reflux, gastralgia; with long-term treatment - decreased appetite;
- from the nervous system: irritability, headache, anxiety, insomnia, tremors, dizziness, agitation;
- allergic reactions: itching, skin rashes, fever;
- others: hypoglycemia, hematuria, albuminuria, flushing, increased urine output, tachypnea, increased sweating, chest pain.
The severity of side effects usually decreases with a decrease in the dose of Theophylline.
Overdose
Overdose symptoms include anxiety, motor agitation, insomnia, tremors, convulsions, photophobia, hyperemia of the skin of the face, tachypnea, ventricular arrhythmias, tachycardia, decreased appetite, gastralgia, nausea, vomiting (including blood-borne bleeding), gastrointestinal, diarrhea.
When very high doses of Theophylline enter the body, patients may experience clouded consciousness, a decrease in blood pressure, epileptoid seizures (children are at risk, and there are no precursors), renal failure, accompanied by myoglobinuria, hypoxia, skeletal muscle necrosis, hypokalemia, hyperglycemia, metabolic acidosis. In this case, the drug is canceled and the stomach is washed. At the next stage, it is recommended to take activated charcoal and laxatives, forced diuresis, intestinal lavage with a mixture of electrolytes and polyethylene glycol, plasma sorption, hemosorption, hemodialysis (its effectiveness is negligible, and peritoneal dialysis is completely ineffective). Symptomatic therapy is also prescribed: for example,with severe nausea and vomiting, ondansetron or metoclopramide is given intravenously.
With the development of a convulsive seizure, it is necessary to monitor the patency of the airways and apply oxygen therapy. To stop the attack, diazepam is injected intravenously at a dose of 0.1–0.3 mg / kg (no more than 10 mg).
special instructions
According to the instructions, Theophylline is not intended for the relief of emergency conditions.
Treatment should be carried out under the control of the concentration of the drug in the blood.
If bronchial asthma can be controlled, there are no side effects, and there are no factors that could lead to a change in the need for a dose of the drug, it is sufficient to measure theophylline concentration every 6–12 months.
During treatment, you should not consume large quantities of caffeinated drinks and foods.
Application during pregnancy and lactation
During pregnancy (especially for the first trimester), Theophylline tablets are prescribed only if the intended benefits to the mother's health significantly outweigh the potential risks to the fetus. Taking the drug in the first trimester and in the last weeks of pregnancy is allowed only under strict indications.
When using Theophylline during lactation, it should be borne in mind that it penetrates into breast milk, therefore, it is recommended to stop breastfeeding during treatment.
For violations of liver function
In severe liver disease, it is necessary to adjust the dose of Theophylline downward.
Drug interactions
- agents that stimulate the central nervous system: their neurotoxicity increases;
- lithium preparations, beta-blockers: their effectiveness decreases;
- glucocorticosteroids: the likelihood of developing their side effects increases;
- mineralocorticosteroids: the risk of developing hypernatremia increases;
- means for general anesthesia: the likelihood of ventricular arrhythmias increases;
- enterosorbents, antidiarrheal drugs: theophylline absorption decreases;
- beta-adrenostimulants, diuretics: their effect is enhanced;
- inducers of microsomal oxidation (oral estrogen-containing contraceptives, sulfinpyrazone, moracizin, carbamazepine, phenytoin, rifampicin, isoniazid, phenobarbital, aminoglutethimide): theophylline clearance increases (an increase in its dose may be required);
- P 450 inhibitors (including macrolide antibiotics, fluoroquinolones, allopurinol, cimetidine, lincomycin), recombinant interferon alfa, influenza vaccine, methotrexate, enoxacin, propafenone, disulfiram, verapamil, ticlopidine, mexrenalietin, possibly iziletin theophylline (dose reduction may be required).
Theophylline should not be administered concurrently with other xanthine derivatives; caution should be used in combination with anticoagulants.
The drug is compatible with antispasmodics.
Analogs
Theophylline analogs are: Aerofillin, Neophyllin, Teofedrin-N, Euphyllin, Teotard, Teopek, Diprofillin, Neo-Teofedrin, Theobromine.
Terms and conditions of storage
Store out of reach of children, dry, protected from light, at temperatures up to 25 ºС.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Theophylline
According to reviews, Theophylline has proven itself as a remedy for the treatment of the cardiovascular and respiratory systems. Doctors often recommend it to patients, but mention of serious side effects is not uncommon. The expediency of prescribing the drug can only be assessed by a specialist with extensive knowledge and rich clinical experience. Thus, Theophylline prolonged-release tablets show excellent results with a long course of treatment, but are poorly suited for relieving acute attacks.
Also, when taking Theophylline, one should take into account the presence of concomitant diseases in the patient and his individual sensitivity to the drug, the patient's history, the combination with other drugs. In this regard, it is recommended to use the drug only after consulting a doctor.
Theophylline price in pharmacies
The price of Theophylline is currently unknown, there are analogues of the drug on sale (Teopek, Kombipek), the cost of which is 250–390 rubles (50 pcs per pack).
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
