Theophylline Extended Release Tablets 300mg Taj Pharma

Theophylline Extended Release Tablets 300mg Taj Pharma

1. Name of the medicinal product

Theophylline Extended-Release Tablets 100mg Taj Pharma
Theophylline Extended Release Tablets 200mg Taj Pharma
Theophylline Extended Release Tablets 300mg Taj Pharma
Theophylline Extended Release Tablets 400mg Taj Pharma

2. Qualitative and quantitative composition

Each tablet contains
Theophylline                       100mg
Excipients                             q.s

Theophylline                       200mg
Excipients                             q.s

Theophylline                       300mg
Excipients                             q.s

Theophylline                       400mg
Excipients                             q.s

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Prolonged release tablet.

4. Clinical particulars

4.1 Therapeutic indications

For the treatment and prophylaxis of bronchospasm associated with asthma, chronic obstructive pulmonary disease and chronic bronchitis. Also indicated for the treatment of left ventricular and congestive cardiac failure.

Theophylline tablets are indicated for use in adults and children aged 6 years and above.

Theophylline should not be used as first drug of choice in the treatment of asthma in children.

4.2 Posology and method of administration

Posology

Adults and the elderly

The usual maintenance dose is 200mg 12 hourly. This may be titrated to either 300mg or 400mg dependent on the therapeutic response.

Paediatric population aged 6 years and above

The usual paediatric maintenance dose is 9mg/kg twice daily. Some children with chronic asthma require and tolerate much higher doses (10-16mg/kg twice daily).

Clearance is increased in children compared to values observed in adult subjects. The rapid clearance observed in children decreases towards adult values in late teens. Therefore, lower dosages (based on usual adult dose) may be required for adolescents.

Theophylline tablets should not be used in children below 6 years of age. Other dosage forms are available that are more suitable for children aged less than 6 years.

Theophylline distributes poorly into body fat, thereforemg/kg doses should be calculated on the basis of lean (ideal) bodyweight.

Plasma theophylline concentrations should ideally be maintained between 5 and 12 micrograms/ml. A plasma level of 5 micrograms/ml probably represents the lower level of clinical effectiveness. Significant adverse reactions are usually seen at plasma theophylline levels greater than 20 micrograms/ml. Monitoring of plasma theophylline concentrations may be required when:

• higher dosages are prescribed;
• patients have co-morbidities resulting in impaired clearance;
• theophylline is co-administered with medication that reduces theophylline clearance.

Patients vary in their response to xanthines and it may be necessary to titrate the dose on an individual basis.

It may be appropriate to administer a larger evening or morning dose in some patients, in order to achieve optimum therapeutic effect when symptoms are most severe e.g. at the time of the ‘morning dip’ in lung function.

In patients whose night time or day time symptoms persist despite other therapy and who are not currently receiving theophylline, then the total daily requirement of Theophylline tablets (as specified above) may be added to their treatment regimen as either a single evening or morning dose.

Method of administration

Oral.

These tablets must be swallowed whole and not broken, crushed or chewed as doing so may lead to a rapid release of theophylline with the potential for toxicity.

Missed dose

If a patient forgets to take a dose but remembers within 4 hours of the time the dose was due to be taken, the tablets can be taken straight away. The next dose should be taken at the normal time. Beyond 4 hours the prescriber may need to consider alternative treatment until the next dose is due.

4.3 Contraindications

Hypersensitivity to xanthines or any of the excipients listed in section 6.1.

Patients with porphyria.

Concomitant administration with ephedrine in children less than 6 years of age (or less than 22 kg).

Theophylline is contraindicated in children under 6 months of age.

4.4 Special warnings and precautions for use

The patient’s response to therapy should be carefully monitored – worsening of asthma symptoms requires medical attention.

Due to potential decreased theophylline clearance, dose reduction and monitoring of serum theophylline concentrations may be required in elderly patients and patients with:

• cardiac disease
• hepatic disease
• exacerbations of lung disease
• hypothyroidism
• fever
• viral infections

Due to potential increased theophylline clearance, dose increase and monitoring of serum theophylline concentrations may be required in patients with hyperthyroidism (and when starting acute hyperthyroidism treatment) and cystic fibrosis.

Theophylline may:

• act as a gastrointestinal tract irritant and increase gastric secretion, therefore caution should be exercised in patients with peptic ulcers;
• exacerbate cardiac arrhythmias and therefore caution should be exercised in patients with cardiac disorders;
• exacerbate frequency and duration of seizures and therefore caution should be exercised in patients with history of seizures and alternative treatment considered.

Use with caution in patients with severe hypertension or chronic alcoholism.

Caution should be exercised in elderly males with pre-existing partial urinary tract obstruction, such as prostatic enlargement, due to risk of urinary retention.

Particular care is advised in patients suffering from severe asthma who require acute theophylline administration. It is recommended that serum theophylline concentrations are monitored in such situations.

In case of insufficient effect of the recommended dose and in case of adverse events, theophylline plasma concentration should be monitored.

4.5 Interaction with other medicinal products and other forms of interaction

The following increase clearance of theophylline and it may therefore be necessary to increase dosage to ensure a therapeutic effect: aminoglutethimide, carbamazepine, isoprenaline, phenytoin, rifampicin, ritonavir, sulphinpyrazone, barbiturates and hypericum perforatum (St John’s Wort).

Smoking and alcohol consumption can also increase clearance of theophylline.

The following reduce clearance and a reduced dosage may therefore be necessary to avoid side-effects: aciclovir, allopurinol, carbimazole, cimetidine, clarithromycin, diltiazem, disulfiram, erythromycin, fluconazole, interferon, isoniazid, methotrexate, mexiletine, nizatidine, pentoxifylline, propafenone, propranolol, thiabendazole, verapamil and oral contraceptives (see section 4.9).

Theophylline has been shown to interact with some quinolone antibiotics including ciprofloxacin and enoxacin which may result in elevated plasma theophylline levels.

The concomitant use of theophylline and fluvoxamine should usually be avoided. Where this is not possible, patients should have their theophylline dose reduced and plasma theophylline should be monitored closely.

Factors such as viral infections, liver disease and heart failure also reduce theophylline clearance (see section 4.9). There are conflicting reports concerning the potentiation of theophylline by influenza vaccine and physicians should be aware that interaction may occur resulting in increased serum theophylline levels. A reduction of dosage may also be necessary in elderly patients. Thyroid disease or associated treatment may alter theophylline plasma levels.

Concurrent administration of theophylline may:

• inhibit the effect of adenosine receptor agonists (adenosine, regadenoson, dipyridamol) and may reduce their toxicity when used for cardiac perfusion scanning;
• oppose the sedatory effect of benzodiazepines;
• result in the occurrence of arrhythmias with halothane;
• result in thrombocytopenia with lomustine;
• increase urinary lithium clearance.

Therefore these drugs should be used with caution.

Theophylline may decrease steady state phenytoin levels.

Hypokalaemia resulting from beta₂ agonist therapy, steroids, diuretics and hypoxia may be potentiated by xanthines. Particular care is advised in patients suffering from severe asthma who require hospitalisation. It is recommended that serum potassium concentrations are monitored in such situations.

Care should be taken in its concomitant use with β-adrenergic agonists, glucagon and other xanthines drugs, as these will potentiate the effects of theophylline.

Co-administration with ketamine may cause reduced convulsive threshold; with doxapram may cause increased CNS stimulation.

The incidence of toxic effects may be enhanced by the concomitant use of ephedrine.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no adequate data from well controlled studies of the use of theophylline in pregnant women. Theophylline has been reported to give rise to teratogenic effects in mice, rats and rabbits (see section 5.3). The potential risk for humans is unknown. Theophylline should not be administered during pregnancy unless clearly necessary.

Breastfeeding

Theophylline is secreted in breast milk, and may be associated with irritability in the infant, therefore it should only be given to breast feeding women when the anticipated benefits outweigh the risk to the child.

4.7 Effects on ability to drive and use machines

Theophylline tablets have no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

The following adverse drug reactions have been reported in the post-marketing setting for theophylline. Frequencies of “not known” have been assigned as accurate frequencies cannot be estimated from the available clinical trial data.

* Please refer to section 4.4 as theophylline may induce urinary retention in elderly males with pre-existing partial urinary tract obstruction.

Reporting of adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

Theophylline has a low therapeutic index. Theophylline toxicity is most likely to occur when serum concentrations exceed 20 micrograms/ml and becomes progressively more severe at higher serum concentrations.

Over 3 g could be serious in an adult (40mg/kg in a child). The fatal dose may be as little as 4.5 g in an adult (60mg/kg in a child), but is generally higher.

Symptoms

Warning: Serious symptoms may develop as long as 12 hours after overdosage with extended release formulations.

Alimentary symptoms: Nausea, vomiting (which is often severe), epigastric pain and haematemesis. Consider pancreatitis if abdominal pain persists.

Neurological symptoms: Restlessness, hypertonia, exaggerated limb reflexes, convulsions, seizures. Coma may develop in very severe cases.

Cardiovascular symptoms: Hypotension. Sinus tachycardia is common. Ectopic beats and supraventricular and ventricular tachycardia may follow.

Metabolic symptoms: Hypokalaemia due to shift of potassium from plasma into cells is common, can develop rapidly and may be severe. Hyperglycaemia, hypomagnesaemia and metabolic acidosis may also occur. Rhabdomyolysis may also occur.

Management

Activated charcoal or gastric lavage should be considered if a significant overdose has been ingested within 1-2 hours. Repeated doses of activated charcoal given by mouth can enhance theophylline elimination. Measure the plasma potassium concentration urgently, repeat frequently and correct hypokalaemia. BEWARE! If large amounts of potassium have been given, serious hyperkalaemia may develop during recovery. If plasma potassium is low, then the plasma magnesium concentration should be measured as soon as possible.

In the treatment of ventricular arrhythmias, proconvulsant antiarrhythmic agents such as lignocaine (lidocaine) should be avoided because of the risk of causing or exacerbating seizures.

Measure the plasma theophylline concentration regularly when severe poisoning is suspected, until concentrations are falling. Vomiting should be treated with an antiemetic such as metoclopramide or ondansetron.

Tachycardia with an adequate cardiac output is best left untreated. Beta-blockers may be given in extreme cases but not if the patient is asthmatic. Control isolated convulsions with intravenous diazepam. Exclude hypokalaemia as a cause.

Particularly in the setting of theophylline overdose induced convulsions, efficacy of some anticonvulsant drugs, such as benzodiazepines, may be reduced through suspected pharmacodynamic interactions.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs for obstructive airways diseases, xanthines

ATC code: R03D A04

Theophylline is a bronchodilator. In addition it affects the function of a number of cells involved in the inflammatory processes associated with asthma and chronic obstructive airways disease. Of most importance may be enhanced suppressor T-lymphocyte activity and reduction of eosinophil and neutrophil function. These actions may contribute to an anti-inflammatory prophylactic activity in asthma and chronic obstructive airways disease.

Theophylline stimulates the myocardium and produces a diminution of venous pressure in congestive heart failure leading to marked increase in cardiac output.

5.2 Pharmacokinetic properties

Absorption

Following oral administration, theophylline is efficiently absorbed and is associated with an absolute bioavailability approximating 100%. Following oral administration of Theophylline tablets, the delivery of theophylline is controlled and, at steady state, peak concentrations are typically seen after approximately 5 hours.

An effective plasma concentration is considered to be 5-12 micrograms/ml, although plasma concentrations up to 20 micrograms/ml may be necessary to achieve efficacy in some cases. Do not exceed 20 micrograms/ml.

Distribution and protein binding.

Theophylline is distributed through all body compartments; approximately 60% is bound to plasma proteins.

An effective plasma concentration is considered to be 5-12 micrograms/ml, although plasma concentrations up to 20 micrograms/ml may be necessary to achieve efficacy in some cases. Do not exceed 20 micrograms/ml.

Biotransformation

Theophylline is metabolised in the liver to 1, 3-dimethyl uric acid and 3-methylxanthine.

Elimination

Theophylline and its metabolites are excreted mainly in the urine. Approximately 10% is excreted unchanged. The mean elimination half life associated with Theophylline tablets is approximately 7 hours.

Factors affecting clearance

The predominant factors which alter theophylline clearance are: age, body weight, diet, smoking habits, other drugs and cardiorespiratory or hepatic disease. Clearance is increased in children compared to values observed in adult subjects. Clearance decreases towards adult values in late teens.

Linearity

Studies involving extended-release Theophylline tablets have demonstrated approximately dose-proportional pharmacokinetics across the 200-600mg dose range.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology and repeated dose toxicity.

Genotoxicity and carcinogenicity

In vitro and in vivo assays have shown both positive and negative genotoxic results for theophylline. However, oral theophylline administered daily to rats and mice for 2 years did not show carcinogenicity. Therefore, it is unlikely that theophylline poses a carcinogenic risk in humans.

Reproductive and developmental toxicity

Theophylline has been shown to have effects upon the male reproductive system in rodents, but at doses considered in excess of the maximum human dose indicating little relevance to clinical use.

Several embryofetal developmental studies in rats, mice and rabbits have demonstrated developmental effects independent from maternal toxicity at high doses of theophylline. Therefore, theophylline should be considered to have the potential for developmental toxicity in humans.

6. Pharmaceutical particulars

6.1 List of excipients

Hydroxyethylcellulose, Povidone (K25), Cetostearyl Alcohol

Macrogol 6000, Talc, Magnesium Stearate

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

Three years

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

Blister packs consisting of aluminium foil sealed to 250 µm PVC with a PVdC coating of at least 40 gsm thickness, containing 56 tablets.

6.6 Special precautions for disposal and other handling

No special requirements.

7.Manufactured in india by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Theophylline Extended Release Tablets 100mg, 200mg, 300mg, 400mg Taj Pharma

Package leaflet: Information for the user

Theophylline 100mg 200mg, 300mg and 400mg prolonged-release tablets

Theophylline

Read all of this leaflet carefully because it contains important information for you.

This medicine is available without prescription. However you still need to take Theophylline tablets carefully to get the best results from them.

• Keep this leaflet. You may need to read it again.
• Ask your pharmacist if you need more information or advice.
• You must contact a doctor if your symptoms worsen or do not improve.
• If any of the side effects become serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

1. What Theophyllinetablets are and what they are used for
   2. Before you take Theophyllinetablets
   3. How to take Theophylline tablets
   4. Possible side effects
   5. How to store Theophylline tablets
   6. Further information
2. What Theophyllinetablets are and what they are used for

These tablets are used to treat asthma, long-term breathing difficulties such as chronic obstructive pulmonary disease and chronic bronchitis, and are sometimes used to treat heart failure.

They contain the active ingredient theophylline which belongs to a group of medicines called bronchodilators. Bronchodilators help stop you wheezing and being breathless. Theophylline also reduces swelling in the lungs of asthma patients and relieves the feeling of ‘tightness’ in their chest.

2. Before you take Theophyllinetablets

Do not take Theophylline tablets if you:

• are allergic (hypersensitive) to theophylline, aminophylline or any of the other ingredients of the tablets (see section 6 ‘Further Information’);
• have porphyria (a rare disease of the blood pigments).

Take special care with Theophylline tablets

Before treatment with these tablets tell your doctor or pharmacist if you:

• have high blood pressure or any other heart problems;
• have an over-active thyroid gland (hyperthyroidism);
• have a stomach ulcer;
• have liver problems;
• suffer from seizures, fits or convulsions;
• are unwell with a high temperature or fever;
• have a viral infection;
• are addicted to alcohol;
• are male and have difficulty in passing urine (for instance due to an enlarged prostate gland);
• smoke, as smoking may alter the way your tablets work.

Children under six years of age should not take these tablets.

Taking other medicines

Tell your doctor or pharmacist if you are taking:

• certain other medicines to treat asthma or breathing conditions that contain theophylline, aminophylline, salbutamol, terbutaline or salmeterol, as you may need additional monitoring;
• steroids;
• diuretics to increase urine production;
• oral contraceptives;
• a herbal remedy called St John’s Wort (also known as Hypericum perforatum);
• aminoglutethimide, methotrexate or lomustine to treat cancer;
• carbamazepine or phenytoin to treat seizures, fits or convulsions;
• medicines known as barbiturates to help you sleep;
• adenosine, moracizine, diltiazem, isoprenaline, mexiletine, propafenone, propranolol, verapamil or beta blockers to treat high blood pressure and other heart problems;
• oxpentifylline to treat diseased blood vessels;
• medicines known as benzodiazepines, which are used as a sedative or to treat anxiety;
• sulphinpyrazone or allopurinol to treat gout;
• carbimazole to treat problems with your thyroid gland;
• cimetidine or nizatidine to treat stomach ulcers, indigestion or heartburn;
• certain antibiotics such as ciprofloxacin, clarithromycin, erythromycin, norfloxacin, ofloxacin;
• fluconazole to treat fungal infections;
• rifampicin or isoniazid to treat tuberculosis;
• ritonavir to treat HIV;
• medicines known as interferons, which you may be taking to treat conditions such as herpes, cancer, leukaemia or hepatitis;
• thiabendazole to treat worms such as threadworms;
• viloxazine, fluvoxamine or lithium to treat depression;
• doxapram to stimulate breathing;
• disulfiram to treat alcoholism.

Also tell your doctor or pharmacist if:

• you are going to have an operation, as these tablets may interact with certain anaesthetics such as halothane and ketamine;
• you have recently had, or are going to have a flu injection;
• these tablets have been prescribed for your child and they are also taking a cough medicine or decongestant containing ephedrine.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. If you take these tablets with some other medicines, the effect of these tablets or the other medicine may be changed.

Taking Theophylline tablets with alcohol

Alcohol can alter the way these tablets work. Please consult your doctor if you intend to drink alcohol whilst taking these tablets.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding do not take these tablets until you have talked to your doctor or pharmacist.

Ask your doctor or pharmacist for advice before taking any medicine.

3. How to take Theophyllinetablets

Always take these tablets exactly as your doctor or pharmacist has told you.

Swallow your tablets whole with a glass of water. Do not crush or chew them.

Theophylline tablets are designed to work properly over 12 hours. If a tablet is crushed or chewed the entire 12-hour dose may be absorbed rapidly into your body. This can be dangerous, causing serious problems such as an overdose.

You should take your tablets every 12 hours. For instance, if you take a tablet at 8 o’clock in the morning, you should take your next tablet at 8 o’clock in the evening.

Adults

The usual starting dose for adults is one 200mg tablet every 12 hours. Your doctor may increase your dose to one 300mg or 400mg tablet every 12 hours, depending upon how you respond to treatment. If you are elderly your doctor may suggest a lower dose.

Children

Children over six years of age can take these tablets. The required dose will depend on their weight and the severity of their breathing problems. This should be discussed with your doctor or pharmacist.

Do not exceed the dose recommended by your doctor. You should check with your doctor or pharmacist if you are not sure.

If you take more Theophylline tablets than you should or if someone accidentally swallows your tablets

Call your doctor or hospital straight away. People who have taken an overdose may have stomach pains and feel or be sick. They may also have a fast or irregular heartbeat, feel very restless or have a fit. These symptoms may appear up to 12 hours after the overdose. When seeking medical attention make sure that you take this leaflet and any remaining tablets with you to show the doctor.

If you forget to take Theophylline tablets

If you remember within 4 hours of the time your tablet was due, take your tablet straight away. Take your next tablet at your normal time. If you are more than 4 hours late, please call your doctor or pharmacist for advice. Do not take a double dose to make up for a forgotten tablet.

If you stop taking Theophylline tablets

You will probably take these tablets for a long time. Do not stop taking them unless your doctor tells you to, even if you feel better.

If you have any further questions on the use of these tablets, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, these tablets can cause side effects, although not everybody gets them.

All medicines can cause allergic reactions, although serious allergic reactions have been reported in rare cases. Tell your doctor immediately if you get any sudden wheeziness, difficulties in breathing, swelling of the eyelids, face or lips, rash or itching especially those covering your whole body.

The following side effects have been reported in patients treated with these tablets:

• Feeling sick.
• Headache.
• Vomiting (being sick), abdominal pain, diarrhoea, heartburn or gastrointestinal disorders (e.g. upset stomach).
• Difficulty in sleeping, agitation, anxiety or shaking.
• A fast heart beat or palpitations.
• Dizziness.
• Difficulty in passing urine (especially in men) or passing increased amounts of urine.
• Increased uric acid level in the blood, which could cause painful, swollen joints.
• Seizures, fits or convulsions.
• Rash or itchy skin.

If any of the side effects become serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5. How to store Theophyllinetablets

Keep out of the reach and sight of children.

Do not use any tablets after the expiry date stated on the outer carton and blister pack. EXP 08 2010 means that you should not take the tablets after the last day of that month i.e. August 2010.

Do not store your tablets above 25°C.

Do not take your tablets if they are broken or crushed as this can be dangerous and can lead to serious problems such as overdose.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Further information

What Theophylline tablets contain

The active ingredient is theophylline. Each tablet contains 100mg, 200mg, 300mg or 400mg of theophylline.

The other ingredients are:

• Hydroxyethylcellulose
• Povidone
• Magnesium stearate
• Cetostearyl alcohol
• Macrogol
• Talc

What Theophylline tablets look like and the contents of the pack

The tablets are white and capsule shaped.

In each box there are 56 tablets.

7. Manufactured in india by:
   TAJ PHARMACEUTICALS LTD.
   Mumbai, India
   Unit No. 214.Old Bake House,
   Maharashtra chambers of  Commerce Lane,
   Fort, Mumbai – 400001
   at:Gujarat, INDIA.
   Customer Service and Product Inquiries:
   1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
   Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
   E-mail: tajgroup@tajpharma.com