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Aminophylline Injection Bp 250mg/10ml

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SUMMARY OF PRODUCT CHARACTERISTICS

1.    NAME OF THE MEDICINAL PRODUCT

Aminophylline Injection BP 250 mg in 10 ml

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Theophylline BP 2.11% w/v.

Ethylene Diamine, Anhydrous BP 0.523% w/v

3.    PHARMACEUTICAL FORM

Solution for injection.

4.    CLINICAL PARTICULARS

4.1    Therapeutic indications

Reversible airways obstruction.

Status asthmaticus.

4.2    Posology and method of administration

By slow intravenous injection or infusion (using 5% Glucose, 0.9% Sodium Chloride or Sodium Lactate, Compound Injection)

Do not give as a bolus injection if the patient is already receiving oral theophylline. Injection should be interrupted if adverse effects develop.

Monitor plasma theophylline levels, especially if the patient is already receiving oral theophylline, to ensure that they are maintained within the therapeutic range. However adverse reactions may occur even within this range.

Dosage should be individualised and adjusted according to plasma-theophylline concentrations.

Adults and the elderly Initially:


250- 500 mg (5 mg / kg) given over a 20 minute period by slow IV injection.

Children. 6 months to 9 years

1 mg/kg/hour by IV infusion.


Maintenance :

Children. 10 years to 16 years

Maintenance :


Children. 6 months to 16 years


Initially:


5 mg / kg given over a 20 minute period by slow IV Infusion.


800 micrograms /kg/hour by IV infusion.

4.3 Contraindications

Sensitivity to Theophylline or Ethylene Diamine. Acute porphyria. Concomitant administration with ephedrine in children.

4.4 Special warnings and precautions for use

The drug has a narrow therapeutic index and serum levels should be monitored regularly, particularly during the initiation of therapy. During regular therapy serum potassium levels must be monitored. This is essential during combination therapy with p2 agonists, corticosteroids or diuretics, or in the presence of hypoxia as serious hypokalaemia may result.

Aminophylline should be given with caution to patients with peptic ulceration, hyperthyroidism, hypertension, fever, hepatic impairment, cardiac arrhythmias, cardiovascular disease, or epilepsy as these may be made worse.

Theophylline clearance may be decreased in patients having heart failure, pulmonary oedema, hepatic dysfunction, cirrhosis, acute febrile illness, severe hypoxia, chronic lung disease, viral infections, drugs that inhibit its metabolism and in the neonate and the elderly - toxic accumulation may occur. Theophylline clearance is increased in smokers, chronic alcoholism and by drugs that induce its metabolism.

Herbal preparations containing St John’s wort (Hypericum perforatum) should not be used while taking theophylline due to the risk of decreased plasma concentrations and reduced clinical effects of theophylline.

4.5 Interactions with other medicinal products and other forms of interaction

The following drugs may increase plasma theophylline concentrations:

■    Cimetidine, nizatidine.

■    Antibiotics including ciprofloxacin, norfloxacin, clarithromycin, erythromycin, troleandomycin,

■    Isoniazid

■    Antifungals such as fluconazole and ketoconazole.

■    Viloxazine.

■    Combined oral contraceptives, Oestrogens.

■    Carbimazole.

■    Thiabendazole.

■    Calcium channel blockers (diltiazem, verapamil and possibly others)

■    Anti-arrhythmics: Mexiletine, propafenone

■    Allopurinol.

■    Analgesics such as Rofecoxib.

■    Cytotoxics such as methotrexate.

■    Oxpentifylline

■    Other xanthines

■    Disulfiram.

■    Interferon alfa.

■    Influenza vaccine.

■    Leukotriene Antagonist: Zafirlukast.

The following drugs may reduce plasma theophylline concentrations:

■    Anticonvulants including carbamazepine, phenytoin, phenobarbitone and primidone.

■    Rifampicin.

■    Ritonavir.

■    Aminoglutethimide.

■    Sulfinpyrazone.

■    Barbiturates.

■    Tobacco.

Other interactions:

■    P2 Agonists, corticosteroids and diuretics: potential for hypokalaemia.

■    P-Blockers such as Propanolol: antagonism of bronchodilation.

■    Doxapram: increased CNS stimulation.

■    Adrenocorticoids glucocorticoids and mineralocorticoids: concurrent use with aminophylline and sodium chloride may result in hypernatremia .

■    Lithium: lithium excretion is accelerated.

■    Anaesthetics: increased risk of arrhythmias with halothane and increased risk of convulsions with ketamine.

■    Theophylline antagonises anti-arrhythmic effects of adenosine.

■    Benzodiazepine: effects reduced by theophylline.

In cases of hypoxia: hypokalaemia may be potentiated.

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.

Particular care is advised in severe asthma.

Plasma concentrations of theophylline can be reduced by concomitant use of the herbal preparation St John’s wort (Hypericum perforatum). This is due to induction of drug metabolising enzymes by St John’s wort. Herbal preparations containing St John’s wort should therefore not be combined with theophylline. The inducing effect may persist for at least 2 weeks after cessation of treatment with St John’s wort. If a patient is already taking St John’s wort check theophylline levels and stop St John’s wort. Theophylline levels may increase on stopping St John’s wort. The dose of theophylline may need adjusting.

4.6 Pregnancy and lactation

Theophylline crosses the placental barrier and is excreted in breast milk. It should only be used during pregnancy or breast feeding if no alternative treatment is available and then only with extreme caution.

4.7 Effects on ability to drive and use machines

None known.

4.8 Undesirable effects

Nausea and gastro-intestinal disturbance. CNS stimulation, palpitations, tachycardia, arrhythmias, insomnia, flushing, dizziness, anxiety, restlessness, headache or convulsions. Hypotension can result if the rate of injection is too rapid.

4.9 Overdose

Over 3g could be serious in adults (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:

Alimentary features: Nausea, vomiting (which is often severe), epigastric pain, and haematemesis. Consider pancreatitis in very severe cases.

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

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

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

Management: Treatment should be supportive and symptomatic, and must be started immediately. 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 levels are 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 concentrations 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.

5.    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Theophylline is a bronchodilator. It directly relaxes smooth muscle of the bronchial airways and pulmonary blood vessels to release bronchospasm and increase flow rates and vital capacity.

It is also a respiratory stimulant and is believed to act by increasing the sensitivity to carbon dioxide.

5.2    Pharmacokinetic properties

Aminophylline releases theophylline in vivo.

Theophylline has a T of about 4 hours in children and about 9 hours in adults.

Therapeutic levels are between 10 - 20 micrograms / ml of serum.

It is metabolised by the liver to caffeine.

About 10% theophylline is excreted unchanged.

5.3    Preclinical safety data

No additional pre-clinical data of relevance to the prescriber is available.

6.    PHARMACEUTICAL PARTICULARS

6.1


List of excipients

Water for Injections BP

6.2    Incompatibilities

Aminophylline injection should not be mixed with any other intravenous additive.

6.3    Shelf life

24 months.

6.4    Special precautions for storage

Protect from light.

6.5    Nature and contents of container

10 ml in type 1 colourless neutral glass ampoules. Fusion sealed.

6.6    Instructions for use/handling

None stated.

7.    MARKETING AUTHORISATION HOLDER

Macarthys Laboratories Ltd t/a Martindale Pharmaceuticals

Bampton Road

Harold Hill

Romford

RM3 8UG

8.    MARKETING AUTHORISATION NUMBER

PL 01883/6167R

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

9.


10.


First authorised    November 1989

Renewal    November 1994

DATE OF REVISION OF TEXT

November 2004