Aminophylline BP 25mg/1ml(2ml) Solution for Injection in Prefilled Syringe Taj Pharma

1. Name of the medicinal product

Aminophylline BP 25mg/1ml(2ml) Solution for Injection in Prefilled Syringe Taj Pharma.

2. Qualitative and quantitative composition

Aminophylline BP 25mg/1ml Solution for Injection in Prefilled Syringe
Each ml contains:
Aminophylline Ph Eur                          25mg

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Prefilled syringe

4. Clinical particulars

4.1 Therapeutic indications

Disease of the cardiovascular system (e.g. an adjunct in the treatment of pulmonary edema or paroxysmal nocturnal dyspnea caused by left ventricular heart failure), reversible airways obstruction including status asthmaticus and acute bronchospasm.

4.2 Posology and method of administration

Aminophylline Injection BP may be given by slow intravenous injection or intravenous infusion in glucose injection or sodium chloride injection.

Aminophylline has a narrow therapeutic index, therefore cautious dosage determination is essential. Therapeutic serum concentrations of theophylline are considered to range from 10 to 20 mcg/ml and levels greater than 20 mcg/ml are often associated with toxic effects. A range of 5 to 15 mcg/ml may be effective, and associated with fewer adverse effects.

The dosage should be titrated for each individual and adjusted with caution. Serum theophylline levels should be monitored to ensure that they remain within the therapeutic range. During therapy, patients should be monitored carefully for signs of toxicity.

Elimination of theophylline in children younger than 6 months of age, especially in neonates, appears to be reduced. Because of this variation in metabolism the use of Aminophylline injection in children under 6 months of age is not recommended.

Use in patients NOT currently receiving theophylline preparations

To minimize adverse effects, IV Aminophylline should be administered slowly, at a rate not exceeding 25mg Aminophylline per minute, up to a dose of 250-500mg (5mg/kg). If patients experience acute adverse effects while loading doses are being infused, the infusion may be stopped for 5-10 minutes or administered at a slower rate.

Approximate IV Aminophylline Maintenance Doses

n.b. The use of Aminophylline IV in children under 6 months of age is not recommended.

GroupMaintenance Dose
Children 6 months to 9 years of age1mg/kg/hour
Children 10-16 years of age and young adult smokers0.8mg/kg/hour
Otherwise healthy non-smoking adults0.5mg/kg/hour
Elderly patients0.3mg/kg/hour

Use in patients currently receiving theophylline preparations

In patients who are currently receiving theophylline preparations, the time, route of administration and dosage form of the patient’s last dose should be determined where possible and considered in determining a loading dose. Loading doses are based on the expectation that 0.5mg/kg (lean body weight) of theophylline will result in a 1 microgram/ml increase in serum theophylline concentration. Therefore, in patients currently receiving theophylline preparations, the loading dose should be deferred until a serum theophylline concentration can be attained or the clinician must carefully select a dose based on the potential benefits and risks.

Subsequently, the approximate IV aminophylline maintenance doses described above may be considered.

4.3 Contraindications

Aminophylline injection should not be used in patients hypersensitive to ethylenediamine or those allergic to the theophyllines, caffeine or theobromine.

Aminophylline should not be administered concomitantly with other xanthine drugs. When therapeutic doses of Aminophylline and/or theophylline are administered simultaneously by more that one route or in more than one preparation, the hazard of serious toxicity is increased.

The use of Aminophylline IV in children under 6 months of age is not recommended.

The use of Aminophylline is contraindicated in patients with acute porphyria.

4.4 Special warnings and precautions for use

Intravenous Aminophylline must be administered very slowly to prevent dangerous central nervous system and cardiovascular side-effects due to direct stimulating effect of Aminophylline.

Aminophylline has a narrow therapeutic index and serum levels should be monitored regularly, particularly during initiation of therapy.

Aminophylline injection should be administered cautiously to patients over 55 years of age.

Children are particularly susceptible to the effects of theophylline and care is required when administrating aminophylline to children. There have been reports of seizures in children with theophylline plasma levels within the accepted therapeutic range. Alternative treatment should be considered in patients with a history of seizure activity and, if Aminophylline Injection is used in such patients, they should be carefully observed for possible signs of central stimulation.

Caution is also advised in patients undergoing influenza immunisation or who have active influenza infection or acute febrile illness.

Aminophylline should be given with caution to patients with cardiac failure, chronic obstructive pulmonary disease, renal or hepatic dysfunction and in chronic alcoholism since clearance of Aminophylline is decreased.

Theophylline clearance may be increased in smokers and in those regularly exposed to tobacco smoke.

During regular therapy serum potassium levels must be monitored. This is essential during combination therapy with beta2-agonists, corticosteroids or diuretics, or in the presence of hypoxia.

Aminophylline should be used with caution in patients with peptic ulcer, hyperthyroidism, glaucoma, diabetes mellitus, severe hypoxaemia, hypertension, compromised cardiac or circulatory function and epilepsy, as these conditions may be exacerbated.

Aminophylline should not be administered concurrently with other xanthine medications.

4.5 Interaction with other medicinal products and other forms of interaction

The following drugs may increase plasma theophylline concentrations:

  • Fluvoxamine

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

  • Cimetidine
  • Macrolide antibiotics (e.g. erythromycin, clarithromycin)
  • Quinolone antibiotics (e.g. ciprofloxacin, norfloxacin)
  • Fluconazole
  • Isoniazid
  • Propranolol
  • Allopurinol (high doses e.g. 600 mg daily)
  • Oral contraceptives
  • Mexiletine, propafenone
  • Calcium channel blockers, diltiazem, verapamil
  • St John’s Wort (Hypericum perforatum)
  • Disulfiram
  • Interferon alfa, influenza vaccine
  • Methotrexate
  • Zafirlukast
  • Thyroid hormones

The following drugs may decrease plasma theophylline concentrations:

  • Rifampicin
  • Antiepileptics (e.g. carbamazepine, phenytoin, primidone, phenobarbitone)
  • Ritonavir
  • Aminoglutethimide
  • Sulfinpyrazone

Other interactions:

Xanthines

Concurrent use of other xanthine derivatives, including theophylline and pentoxifylline are contraindicated due to the risk of toxicity.

Lithium

Aminophylline increases the excretion of lithium and may decrease its therapeutic effectiveness.

Benzodiazepines: Theophylline may reduce the effects of benzodiazepines

Quinolones

Increased risk of convulsions.

General anaesthetics

Increased risk of convulsions with ketamine; increased risk of arrhythmias with halothane

Pancuronium

Resistance to neuromuscular block with pancuronium has been reported in patients receiving aminophylline.

Sympathomimetics

Aminophylline may exhibit synergistic toxicity with ephedrine and other sympathomimetics and concurrent use may dispose the patient to cardiac arrhythmias.

Beta2-adrenergic agonists

Increased risk of cardiac arrhythmias (see also hypokalaemia).

Beta-blockers

Antagonism of bronchodilator effects.

Cardiac glycosides

The direct stimulatory effect of Aminophylline on the myocardium may enhance the sensitivity and toxic potential of the cardiac glycosides.

Adenosine

The anti-arrhythmic effect of adenosine is antagonised by theophylline

Leukotriene antagonists

In clinical trials co-administration with theophylline resulted in decreased plasma levels of zafirlukast, by approximately 30%, but with no effect on plasma theophylline levels. However, during post-marketing surveillance, there have been rare cases of patients experiencing increased theophylline levels when co-administered zafirlukast (see above).

Doxapram

Increased CNS stimulation.

Hypokalaemia

The hypokalaemic effects of beta2-adrenergic agonists may be potentiated by concomitant treatment with aminophylline. There is an increased risk of hypokalaemia when theophylline derivatives are given with corticosteroids or diuretics (see 4.4 Special warnings and precautions for use).

4.6 Fertility, pregnancy and lactation

Pregnancy

It is not known whether theophyllines can cause foetal harm when administered to pregnant women. Although the safe use of theophylline during pregnancy has not been established relative to potential risk to the foetus, theophyllines have been used during pregnancy without teratogenicity or other adverse foetal effect. Because of the risk of uncontrolled asthma, their safety during pregnancy when clearly needed is generally not seriously questioned. As with other drugs, aminophylline should only be used during pregnancy if considered essential by the physician. Theophylline crosses the placenta.

Breast-feeding

Theophylline is distributed into milk and may occasionally induce irritability or other signs of toxicity in nursing infants, and therefore should not be used if the mother is breast-feeding her infant.

Fertility

Animal reproduction studies have not been performed with theophyllines.

4.7 Effects on ability to drive and use machines

None known.

4.8 Undesirable effects

Adverse events are usually a consequence of gastrointestinal irritation, stimulation of the central nervous system and effects on the cardiovascular system. Hypotension, arrhythmias and convulsions may follow intravenous injection, particularly if the injection is too rapid, and sudden deaths have been reported. Severe toxicity may occur without preceding milder symptoms (see also 4.9 Overdose).

Immune system disorders:

Hypersensitivity reactions (see also Skin and subcutaneous tissue disorders).

Metabolism and nutrition disorders:

Metabolic disturbances such as hypokalaemia, hypophosphataemia, and hyponatraemia may occur.

Nervous system/Psychiatric disorders:

Headache, insomnia, confusion, restlessness, hyperventilation, anxiety, vertigo/dizziness, tremor. Higher doses may lead to maniacal behaviour, delirium and convulsions.

Eye disorders:

Visual disturbances.

Cardiac disorders:

Palpitations, tachycardia, cardiac arrhythmias, hypotension.

Gastrointestinal disorders:

Nausea, vomiting, abdominal pain, diarrhoea, gastro-oesophageal reflux, gastrointestinal bleeding.

Skin and subcutaneous tissue disorders:

Rash, maculo-papular rash, erythema, pruritus, urticaria, exfoliative dermatitis.

General/Administration site reactions:

Higher doses may result in hyperthermia and extreme thirst.

Reporting of suspected 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. Healthcare professionals are asked to report any suspected adverse reactions.

4.9 Overdose

Aminophylline has a narrow 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.

Fatalities in adults have occurred during IV Aminophylline administration in large doses in patients with renal, hepatic or cardiovascular complications or where the injection has been given rapidly.

Symptoms
Tachycardia, in the absence of hypoxia, fever or administration of sympathomimetic drugs, may be an indication of theophylline toxicity.

Gastro-intestinal symptoms:

Anorexia, nausea, vomiting, diarrhoea, and haematemesis.

Neurological symptoms:

Restlessness, insomnia, irritability, headache, agitation, hallucinations, extreme thirst, slight fever, dilated pupils, and tinnitus. Seizures may occur even without preceding symptoms of toxicity and often result in death. Coma may develop in very severe cases.

Cardiovascular symptoms:

Palpitations, arrhythmias, hypotension, supraventricular and ventricular arrhythmias may occur.

Metabolic symptoms:

Hypokalaemia can develop rapidly and may be severe. Hyperglycaemia, albuminuria, hyperthermia, hypomagnesaemia, hypophosphataemia, hypercalcaemia, respiratory alkalosis and metabolic acidosis may also occur. Rhabdomyolysis may also occur.

Treatment

Treatment of overdosage is supportive and symptomatic. Serum theophylline and potassium levels should be monitored. Repeated oral administration of activated charcoal enhances the elimination of theophylline from the body even after intravenous administration. Aggressive antiemetic therapy may be required to allow administration and retention of activated charcoal.

Seizures may be treated with IV diazepam 0.1-0.3mg/kg up to 10mg. Restoration of fluid and electrolytes balance is necessary. Hypokalaemia should be corrected by intravenous infusion of potassium chloride. Sedation with diazepam may be required in agitated patients.

Propranolol may be administered intravenously to reverse extreme tachycardia, hypokalaemia and hyperglycaemia provided the patient does not suffer from asthma.

In general, theophylline is metabolised rapidly and haemodialysis is not warranted. In patients with congestive heart failure or liver disease, haemodialysis may increase theophylline clearance by as much as 2-fold.

Charcoal haemoperfusion should be considered if:

  • Ileus/ intestinal obstruction prevents administration of multiple dose activated charcoal.
  • Plasma theophylline concentration > 80mg/L (acute) or > 60mg/L (chronic). In infants under 6 months of age or the elderly, charcoal haemoperfusion should be considered at theophylline concentrations >40 mg/L. Clinical features rather than theophylline concentration are the best guide for treatment.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Aminophylline is a soluble derivative of theophylline and is given for its theophylline activity. Aminophylline relaxes smooth muscle and relieves bronchial spasm. It stimulates the myocardium and reduces venous pressure in congestive heart failure, leading to a marked increase in cardiac output. It has stimulant effect on respiration, and also a diuretic action of short duration.

5.2 Pharmacokinetic properties

None stated.

5.3 Preclinical safety data
No further information other than that which is included in the Summary of Product Characteristics.

6. Pharmaceutical particulars

6.1 List of excipients

Ethylenediamine Ph. Eur.

Water for Injections Ph. Eur.

6.2 Incompatibilities

Aminophylline injection is not stable in solutions having a pH of substantially less than 8, however, the drug appears to be relatively stable in large volume parenteral solutions over a wide pH range (3.5-8.6) if Aminophylline concentrations do not exceed 40mg per ml. The activity of alkali-sensitive drugs will be reduced by Aminophylline, these drugs should not be added to IV fluids containing Aminophylline.

6.3 Shelf life

36 months.

6.4 Special precautions for storage

None stated.

6.5 Nature and contents of container

10ml Prefilled Syringes, packed in cardboard cartons.

6.6 Special precautions for disposal and other handling

Use as directed by a physician.

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

 

Aminophylline BP 25mg/1ml(2ml) Solution for Injection in Prefilled Syringe Taj Pharma

Important information about your medicine

  • Your doctor or nurse will give you the injection
  • If this injection causes you any problems talk to your doctor, nurse or pharmacist
  • Please tell your doctor or pharmacist, if you have any other medical conditions or have an allergy to any of the ingredients of this medicine
  • Please tell your doctor or pharmacist, if you are taking any other medicines
  • Read all of this leaflet carefully before you start using this medicine because it contains important information for In some circumstances this may not be possible and this leaflet will be kept in a safe place should you wish to read it.
  • Keep this leaflet. You may need to read it again
  • If you have any further questions, ask your doctor, pharmacist or
  • This medicine has been prescribed for you Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
  • If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section
What is in this leaflet
  1. What Aminophylline Prefilled Syringe is and what it is used for
  2. What you need to know before you use Aminophylline Prefilled Syringe
  3. How to use Aminophylline Prefilled Syringe
  4. Possible side effects
  5. How to store Aminophylline Prefilled Syringe
  6. Contents of the pack and other information

1. What Aminophylline Prefilled Syringe is and what it is used for

Aminophylline Prefilled Syringe belongs to a group of medicines known as xanthines, which can stimulate breathing. It is used to treat breathing difficulties associated with:

  • heart failure
  • reversible airway obstruction, as in acute asthma or acute spasm of the airways (bronchial spasm).

2. What you need to know before you use Aminophylline Prefilled Syringe

Do NOT use Aminophylline Prefilled Syringe:

  • if you are sensitive or allergic to Aminophylline Prefilled Syringe ethylenediamine, theophylline, caffeine or theobromine or any of the other ingredients in this injection.
  • if you are taking similar medicines e.g. theophylline or Aminophylline tablets.
  • if you have Porphyria (a condition that affects your blood).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Aminophylline Prefilled Syringe:

  • if you have a peptic ulcer
  • if you have an overactive thyroid
  • if you have pressure in the eyes (known asglaucoma)
  • if you are a diabetic
  • if you are epileptic
  • if you have high blood pressure or heart disease
  • if you have low blood oxygen
  • if you suffer from poor circulation
  • if you have heart or lung failure
  • if you have chronic bronchitis
  • if you are a smoker or you are regularly exposed to tobacco smoke.
  • if you have liver or kidney disease
  • if you have an alcohol problem
  • if you have flu or have recently had a flu injection or you have a fever.

Other medicines and Aminophylline Prefilled Syringe :

Tell your doctor, pharmacist or nurse if you are taking, have recently taken, or might take any other medicines, including medicines obtained without a prescription. This is especially important with the following medicines as they may interact with your Aminophylline Prefilled Syringe :

  • Aminophylline or theophylline
  • Antibiotics (e.g.erythromycin or ciprofloxacin).
  • Medicines for your heart (e.g. digoxin, propranolol, diltiazem)
  • Medicines for the prevention of gout (Allopurinol and Sulfinpyrazone)
  • Disulfiram (a medicine for an alcohol problem)
  • Oral Contraceptives
  • Medicines for epilepsy (e.g. carbamazepine, phenytoin)
  • Medicines to thin your blood (e.g. warfarin)
  • Any medicines that you may have bought yourself including St John’s Wort (a medicine for depression) or medicines for colds and nasal congestion
  • Lithium (a medicine to regulate your moods)
  • Fluvoxamine (a medicine for depression)
  • Benzodiazepines (e.g. diazepam)
  • Cimetidine (a medicine for stomach ulcers)
  • Antiviral medicines (e.g. ritonavir)
  • A recent flu vaccination
  • Medicines to treat tuberculosis (e.g.isoniazid, rifampicin)
  • Fluconazole (a medicine to treat fungal infections)
  • Corticosteroids (medicines used to treat inflammation in your body e.g. in asthma)
  • Zafirlukast (a medicine for asthma).
  • Thyroid hormones

Pregnancy and breast feeding:

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines:

You should not  drive  or  use  machinery  if you are affected by the administration of Aminophylline Prefilled Syringe .

3. How to use Aminophylline Prefilled Syringe

Your nurse or doctor will give you the injection.

Your doctor will decide the correct dosage for you and how and when the injection will be given.

Since the injection will be given to you by a doctor or nurse, it is unlikely that you will be given too much. If you think you have been given too much, you feel thirsty, have ringing in your ears or feel palpitations you must tell the person giving you the injection.

4. Possible side effects

Like   all medicines, Aminophylline   Prefilled Syringe can cause side effects, although not everybody gets them. The following unwanted side effects have been reported for aminophylline injection:

  • Allergic reactions involving rash and redness and flakiness of the skin
  • Feeling sick or being sick,
  • Stomach bleeding, heartburn and diarrhoea
  • Visual disorders
  • Sleeplessness, headache
  • Anxiety, confusion, restlessness
  • Fast breathing
  • Spinning sensation
  • Higher doses may lead to maniacal behaviour, delirium and convulsions
  • Low levels of potassium, phosphate or salt in the blood
  • Palpitations (a sensation of your heart beating)
  • Fever and extreme thirst

Your doctor will monitor your blood to see if this medicine is causing you any problems.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse: This includes any possible side effects not listed in this leaflet. You can also report side effects directly. By reporting side effects, you can help provide more information on the safety of this medicine.

5.How to store Aminophylline Prefilled Syringe

Your injection will be stored at less than 25°C and protected from light. The nurse or doctor will check that the injection is not past its expiry date before giving you the injection.

6. Contents of the pack and other information

What Aminophylline Prefilled Syringe contains:

The active ingredient is aminophylline (theophylline – ethylenediamine). Each 1 ml of solution contains 25 mg aminophylline.

The other ingredient is Sterile Water for Prefilled Syringes

What Aminophylline Prefilled Syringe looks like and contents of the pack:

Aminophylline Prefilled Syringe is supplied in 10 ml.

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