Drugs List

Therapeutic Indications

Uses

Acute asthma
Acute exacerbation of chronic obstructive airways disease
Left ventricular failure - cardiac failure - cardiac asthma
Reversible airways obstruction

Administration

For administration by slow intravenous injection or intravenous infusion.

Contraindications

Neonates under 1 month
Acute porphyria

Precautions and Warnings

Children aged 1 to 6 months
Febrile disorder
Obesity
Patients over 55 years
Tobacco smoking
Viral infection
Alcoholism
Breastfeeding
Cardiac arrhythmias
Cardiac failure
Cardiovascular disorder
Diabetes mellitus
Epileptic disorder
Glaucoma
Hepatic impairment
History of seizures
Hypertension
Hyperthyroidism
Hypoxia
Peptic ulcer
Pregnancy
Renal impairment

Reduce dose in patients with hepatic impairment
Not licensed for use in children under 6 months
Always administer by slow intravenous injection or infusion
Breastfeeding: Monitor infant for systemic effects of treating the mother
Monitor serum K+ in patients on beta agonists/steroids/diuretics
Monitor serum potassium regularly in severe asthmatic or hypoxic patients
Monitor theophylline level before giving parenteral xanthines
Neonate exposed in utero: Monitor neonate for adverse effects
Plasma level monitoring may be useful: refer to local guidelines
Alcohol increases clearance - higher doses may be required
Dose adjustment required if patient starts/stops smoking during therapy
In obese patients dosing should be based on ideal weight
Advise patient not to take St John's wort concurrently

Pregnancy and Lactation

Pregnancy

Use only if there is no safer alternative or when the disease carries risk for mother and child.

Theophylline crosses the placenta, and newborn infants may have therapeutic serum levels. Transient tachycardia, irritability and vomiting have been reported in new-borns delivered from mothers consuming theophylline. These effects are more likely to occur when maternal serum levels at term are in the high therapeutic range or above (therapeutic range 8microgram/ml to 20microgram/ml). Cord blood levels are approximately 100% of the maternal serum concentration.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use only if essential.

Theophylline has a prolonged half-life in neonates which may cause retention. Milk concentrations are approximately equal to the maternal plasma levels. Estimate generally indicate that less than 1% of dose is absorbed by infant.

One reported case of irritability and fretful sleeping was reported in an infant exposed to breast milk only on days when the mother reported taking theophylline. The average milk concentration of theophylline in this case was 0.7mg/L.

Because very young infants may be more sensitive to levels that would be non-toxic in older infants, less rapidly absorbed theophylline preparations may be advisable for nursing mothers.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Anxiety
Arrhythmias
Behavioural disturbances
CNS stimulation
Confusion
Convulsions
Delirium
Diarrhoea
Dizziness
Erythema
Exfoliative dermatitis
Extreme thirst
Gastric irritation
Gastroesophageal reflux
Gastrointestinal bleeding
Headache
Hypersensitivity reactions
Hyperthermia
Hyperventilation
Hypokalaemia
Hyponatraemia
Hypophosphataemia
Hypotension
Insomnia
Maculopapular rash
Nausea
Palpitations
Pruritus
Rash
Restlessness
Tachycardia
Tremor
Urticaria
Vertigo
Visual disturbances
Vomiting

Presentation

Solution for injection containing aminophylline

Drugs List

Therapeutic Indications

Uses

Acute asthma
Acute exacerbation of chronic obstructive airways disease
Left ventricular failure - cardiac failure - cardiac asthma
Reversible airways obstruction

Dosage

Dose should be carefully individualised and plasma theophylline level monitored.

Plasma theophylline levels should be maintained between 5 and 20micrograms/ml, levels exceeding 20micrograms/ml are often associated with toxic effects. There is a wide individual variability in plasma theophylline clearance at all ages and doses should be adjusted accordingly.

To avoid excessive dosage in obese patients, doses should be calculated on the basis of ideal bodyweight

To be administered by slow IV injection or infusion at a rate not exceeding 25mg per minute to reduce dangerous central nervous system and cardiovascular side-effects.

If patients experience acute adverse effects while loading doses are being infused, the infusion may be stopped for 5 to 10 minutes or administered at a slower rate.

Adults

Elderly

Children

Administration

For administration by slow intravenous injection or intravenous infusion.

Contraindications

Neonates under 1 month
Acute porphyria

Precautions and Warnings

Children aged 1 to 6 months
Febrile disorder
Obesity
Patients over 55 years
Tobacco smoking
Viral infection
Alcoholism
Breastfeeding
Cardiac arrhythmias
Cardiac failure
Cardiovascular disorder
Diabetes mellitus
Epileptic disorder
Glaucoma
Hepatic impairment
History of seizures
Hypertension
Hyperthyroidism
Hypoxia
Peptic ulcer
Pregnancy
Renal impairment

Reduce dose in patients with hepatic impairment
Not licensed for use in children under 6 months
Always administer by slow intravenous injection or infusion
Breastfeeding: Monitor infant for systemic effects of treating the mother
Monitor serum K+ in patients on beta agonists/steroids/diuretics
Monitor serum potassium regularly in severe asthmatic or hypoxic patients
Monitor theophylline level before giving parenteral xanthines
Neonate exposed in utero: Monitor neonate for adverse effects
Plasma level monitoring may be useful: refer to local guidelines
Alcohol increases clearance - higher doses may be required
Dose adjustment required if patient starts/stops smoking during therapy
In obese patients dosing should be based on ideal weight
Advise patient not to take St John's wort concurrently

Pregnancy and Lactation

Pregnancy

Use only if there is no safer alternative or when the disease carries risk for mother and child.

Theophylline crosses the placenta, and newborn infants may have therapeutic serum levels. Transient tachycardia, irritability and vomiting have been reported in new-borns delivered from mothers consuming theophylline. These effects are more likely to occur when maternal serum levels at term are in the high therapeutic range or above (therapeutic range 8microgram/ml to 20microgram/ml). Cord blood levels are approximately 100% of the maternal serum concentration.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use only if essential.

Theophylline has a prolonged half-life in neonates which may cause retention. Milk concentrations are approximately equal to the maternal plasma levels. Estimate generally indicate that less than 1% of dose is absorbed by infant.

One reported case of irritability and fretful sleeping was reported in an infant exposed to breast milk only on days when the mother reported taking theophylline. The average milk concentration of theophylline in this case was 0.7mg/L.

Because very young infants may be more sensitive to levels that would be non-toxic in older infants, less rapidly absorbed theophylline preparations may be advisable for nursing mothers.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Anxiety
Arrhythmias
Behavioural disturbances
CNS stimulation
Confusion
Convulsions
Delirium
Diarrhoea
Dizziness
Erythema
Exfoliative dermatitis
Extreme thirst
Gastric irritation
Gastroesophageal reflux
Gastrointestinal bleeding
Headache
Hypersensitivity reactions
Hyperthermia
Hyperventilation
Hypokalaemia
Hyponatraemia
Hypophosphataemia
Hypotension
Insomnia
Maculopapular rash
Nausea
Palpitations
Pruritus
Rash
Restlessness
Tachycardia
Tremor
Urticaria
Vertigo
Visual disturbances
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

The MHRA have produced 'generic' overdose sections for the top ten drugs for which the NPIS received the greatest number of queries about management of overdose in 2002. This information is attached below:

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

Signs and Symptoms

Warning: Serious features may develop as long as 12 hours after overdosage with sustained release formulations.

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

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.

Metabolic features: 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.

Treatment

Activated charcoal or gastric lavage should be considered if a significant overdose has been ingested within 1 to 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.

Further Information

Last Full Review Date: March 2014

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelph

Summary of Product Characteristics: Aminophylline Injection BP 250mg/10ml. Amdipharm Mercury Company Limited. Revised August 2012.

Summary of Product Characteristics: Aminophylline Injection BP, Hameln Pharmaceuticals Ltd. Revised July 2010.

(Summary of Product Characteristics: Phyllocontin Continus Tablets 225 mg and Phyllocontin Forte Continus Tablets 350 mm. Napp Pharmaceuticals Ltd. Revised March 2014.)

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 20 June 2017