Drugs List

Therapeutic Indications

Uses

Analgesia & sedation in mechanically ventilated adult ITU patients
Analgesic agent during induction and/or maintenance of general anaesthesia

Dosage

Due to the complexity and specialist nature of using anaesthesia, specific dosing information on this agent is not included.

When using this agent, specialist literature, national guidelines and trust policies should be consulted to ensure appropriate dosage and assessment of all relevant patient factors.

Administration

Remifentanil is for intravenous use only. It should be administered over not less than 30 seconds when given by bolus injection.

Remifentanil must be given via a dedicated IV line or by a calibrated infusion device into a fast flowing IV line. This line should be connected at, or close to, the venous cannula and primed, to minimise the potential dead space. Remifentanil may be given by manually controlled infusion or by target controlled infusion (TCI) with an approved infusion device incorporating the Minto pharmacokinetic model with covariates for age and lean body mass.

Avoid inadvertent administration due to drug remaining in IV lines/cannulae. There may be sufficient amounts of remifentanil remaining in the IV line/cannulae to cause respiratory depression, apnoea, or muscle rigidity if the line is flushed with other fluids. Avoid obstruction or disconnection of lines. This may be avoided by flushing the lines after use or administering remifentanil via a fast flowing IV line or via a dedicated IV line that is removed following remifentanil administration.

Contraindications

Risk of paralytic ileus
Acute respiratory depression
Chronic obstructive pulmonary disease
Coma
Head trauma
Raised intracranial pressure

Precautions and Warnings

Children under 1 year
Debilitation
Obesity
Patients over 65 years
Adrenal insufficiency
Alcoholism
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Breastfeeding
Cardiogenic shock
Gastrointestinal obstruction
Hepatic impairment
Hypotension
Hypothyroidism
Hypovolaemia
Inflammatory bowel disease
Myasthenia gravis
Opioid dependence
Pregnancy
Renal impairment
Respiratory impairment
Seizures
Urethral stricture

Advise ability to drive/operate machinery may be affected by side effects
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Use in combination with anaesthetics/sedatives, as appropriate
A patent airway and adequate oxygenation must be maintained
Avoid inadvertent administration due to drug remaining in IV lines/cannulae
Excess muscle rigidity: Administer neuromuscular blocker and/or hypnotic.
Give analgesic, if needed post-op, well in advance of stopping anaesthetic
Resuscitation facilities must be immediately available
To be administered by anaesthetist or a doctor trained in intensive care
May cause respiratory depression
Monitor post operative patients for respiratory and other side effects
Tolerance and dependence may occur
Use only when equipment adequate for cardiac/respiratory monitoring/support
Discontinue or reduce rate in muscle rigidity
Avoid abrupt withdrawal
Consider reducing initial dose in the elderly
In obese patients dosing should be based on ideal weight
Not licensed for all indications in all age groups
Advise patient to avoid alcohol during treatment

No residual opioid activity will be present within 5 to 10 minutes after discontinuation due to the very rapid offset of action. For patients in whom post-operative pain is anticipated, analgesics should be administered prior to discontinuation of remifentanil, allowing sufficient time to reach their maximal effect. When other opioid agents are administered as part of the regimen for transition to alternative analgesia, the patient must be carefully monitored, and the benefit of providing adequate post-operative analgesia must always be balanced against the potential risk of respiratory depression. Common post-operative effects associated with recovery from general anaesthesia may occur earlier following the discontinuation. Where reported re-introduction and tapering of infusion has been beneficial.

Reduced dosages are advised in patients with adrenocortical insufficiency, hypothyroidism or who are debilitated.
Debilitated, hypovolaemic and elderly patients may be more sensitive to the cardiovascular effects of remifentanil.

The possibility of tolerance, hyperalgesia and associated haemodynamic changes should be considered when remifentanil is used in intensive care.

Patients with severe hepatic impairment may have an increased risk of developing respiratory depression; they should be closely monitored and the dose titrated accordingly.

Pregnancy and Lactation

Pregnancy

Use remifentanil with caution in pregnancy.

There are no adequate and well-controlled studies in pregnant women. The short duration of remifentanil and its rapid metabolism by the foetus may lessen the potential effects which are seen with all opioid analgesics (Briggs 2011). There are insufficient data to recommend remifentanil for use during labour, delivery and caesarean section. Remifentanil crosses the placental barrier and fentanyl analogues can cause respiratory depression in the neonate. Animals studies have shown some reproductive toxicity but teratogenic effects were not seen in rats or rabbits.

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 remifentanil with caution in breastfeeding.

It is not known whether remifentanil is excreted in human milk. However, fentanyl analogues are excreted in human milk and remifentanil-related material was found in rat milk after dosing with remifentanil. Due to its kinetics, short half life and poor oral availability, it is unlikely remifentanil will product clinically relevant levels in human breast milk (Hale 2010). No paediatric concerns have been reported via milk. Contact a physician if the baby shows signs of increased sleepiness, difficulty breastfeeding/breathing or limpness (LactMed). Most sources recommend avoiding breastfeeding for 24 hours after administration. An alternative drug may be preferred if the mother requires prolonged administration in the early postpartum period (LactMed).

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

Aches
Agitation
Anaphylaxis
Apnoea
Asystole
Atrioventricular block
Bradycardia
Cardiac arrest
Cardiovascular depression
Constipation
Convulsions
Dependence
Hypersensitivity reactions
Hypertension
Hypotension
Hypoxia
Nausea
Post-operative pain
Post-operative shivering
Pruritus
Respiratory depression
Sedation
Skeletal muscle rigidity
Tachycardia
Tolerance
Vomiting

Presentation

All formulations of remifentanil

Drugs List

Therapeutic Indications

Uses

Analgesia & sedation in mechanically ventilated adult ITU patients
Analgesic agent during induction and/or maintenance of general anaesthesia

Dosage

Due to the complexity and specialist nature of using anaesthesia, specific dosing information on this agent is not included.

When using this agent, specialist literature, national guidelines and trust policies should be consulted to ensure appropriate dosage and assessment of all relevant patient factors.

Administration

Remifentanil is for intravenous use only. It should be administered over not less than 30 seconds when given by bolus injection.

Remifentanil must be given via a dedicated IV line or by a calibrated infusion device into a fast flowing IV line. This line should be connected at, or close to, the venous cannula and primed, to minimise the potential dead space. Remifentanil may be given by manually controlled infusion or by target controlled infusion (TCI) with an approved infusion device incorporating the Minto pharmacokinetic model with covariates for age and lean body mass.

Avoid inadvertent administration due to drug remaining in IV lines/cannulae. There may be sufficient amounts of remifentanil remaining in the IV line/cannulae to cause respiratory depression, apnoea, or muscle rigidity if the line is flushed with other fluids. Avoid obstruction or disconnection of lines. This may be avoided by flushing the lines after use or administering remifentanil via a fast flowing IV line or via a dedicated IV line that is removed following remifentanil administration.

Contraindications

Risk of paralytic ileus
Acute respiratory depression
Chronic obstructive pulmonary disease
Coma
Head trauma
Raised intracranial pressure

Precautions and Warnings

Children under 1 year
Debilitation
Obesity
Patients over 65 years
Adrenal insufficiency
Alcoholism
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Breastfeeding
Cardiogenic shock
Gastrointestinal obstruction
Hepatic impairment
Hypotension
Hypothyroidism
Hypovolaemia
Inflammatory bowel disease
Myasthenia gravis
Opioid dependence
Pregnancy
Renal impairment
Respiratory impairment
Seizures
Urethral stricture

Advise ability to drive/operate machinery may be affected by side effects
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Use in combination with anaesthetics/sedatives, as appropriate
A patent airway and adequate oxygenation must be maintained
Avoid inadvertent administration due to drug remaining in IV lines/cannulae
Excess muscle rigidity: Administer neuromuscular blocker and/or hypnotic.
Give analgesic, if needed post-op, well in advance of stopping anaesthetic
Resuscitation facilities must be immediately available
To be administered by anaesthetist or a doctor trained in intensive care
May cause respiratory depression
Monitor post operative patients for respiratory and other side effects
Tolerance and dependence may occur
Use only when equipment adequate for cardiac/respiratory monitoring/support
Discontinue or reduce rate in muscle rigidity
Avoid abrupt withdrawal
Consider reducing initial dose in the elderly
In obese patients dosing should be based on ideal weight
Not licensed for all indications in all age groups
Advise patient to avoid alcohol during treatment

No residual opioid activity will be present within 5 to 10 minutes after discontinuation due to the very rapid offset of action. For patients in whom post-operative pain is anticipated, analgesics should be administered prior to discontinuation of remifentanil, allowing sufficient time to reach their maximal effect. When other opioid agents are administered as part of the regimen for transition to alternative analgesia, the patient must be carefully monitored, and the benefit of providing adequate post-operative analgesia must always be balanced against the potential risk of respiratory depression. Common post-operative effects associated with recovery from general anaesthesia may occur earlier following the discontinuation. Where reported re-introduction and tapering of infusion has been beneficial.

Reduced dosages are advised in patients with adrenocortical insufficiency, hypothyroidism or who are debilitated.
Debilitated, hypovolaemic and elderly patients may be more sensitive to the cardiovascular effects of remifentanil.

The possibility of tolerance, hyperalgesia and associated haemodynamic changes should be considered when remifentanil is used in intensive care.

Patients with severe hepatic impairment may have an increased risk of developing respiratory depression; they should be closely monitored and the dose titrated accordingly.

Pregnancy and Lactation

Pregnancy

Use remifentanil with caution in pregnancy.

There are no adequate and well-controlled studies in pregnant women. The short duration of remifentanil and its rapid metabolism by the foetus may lessen the potential effects which are seen with all opioid analgesics (Briggs 2011). There are insufficient data to recommend remifentanil for use during labour, delivery and caesarean section. Remifentanil crosses the placental barrier and fentanyl analogues can cause respiratory depression in the neonate. Animals studies have shown some reproductive toxicity but teratogenic effects were not seen in rats or rabbits.

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 remifentanil with caution in breastfeeding.

It is not known whether remifentanil is excreted in human milk. However, fentanyl analogues are excreted in human milk and remifentanil-related material was found in rat milk after dosing with remifentanil. Due to its kinetics, short half life and poor oral availability, it is unlikely remifentanil will product clinically relevant levels in human breast milk (Hale 2010). No paediatric concerns have been reported via milk. Contact a physician if the baby shows signs of increased sleepiness, difficulty breastfeeding/breathing or limpness (LactMed). Most sources recommend avoiding breastfeeding for 24 hours after administration. An alternative drug may be preferred if the mother requires prolonged administration in the early postpartum period (LactMed).

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

Effects on Ability to Drive and Operate Machinery

This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). When prescribing this medicine: Advise patient the medicine can affect cognitive function and is likely to affect ability to drive. Advise patient not to drive until they know how the medicine affects them.

Side Effects

Aches
Agitation
Anaphylaxis
Apnoea
Asystole
Atrioventricular block
Bradycardia
Cardiac arrest
Cardiovascular depression
Constipation
Convulsions
Dependence
Hypersensitivity reactions
Hypertension
Hypotension
Hypoxia
Nausea
Post-operative pain
Post-operative shivering
Pruritus
Respiratory depression
Sedation
Skeletal muscle rigidity
Tachycardia
Tolerance
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 ).

Further Information

Last Full Review Date: July 2014

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

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, Philadelphia.

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com Accessed on 3 July, 2014.

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications https://www.medicinescomplete.com Accessed on 3 July, 2014.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Summaries of Product Characteristics: Remifentanil 1mg powder for concentrate for solution for injection or infusion. Actavis UK Ltd. July 2012.
Summaries of Product Characteristics: Remifentanil 2mg powder for concentrate for solution for injection or infusion. Actavis UK Ltd. July 2012.
Summaries of Product Characteristics: Remifentanil 5mg powder for concentrate for solution for injection or infusion. Actavis UK Ltd. July 2012.

Summaries of Product Characteristics: Remifentanil 1mg powder for concentrate for solution for injection or infusion. Hospira UK Ltd. June 2013.
Summaries of Product Characteristics: Remifentanil 2mg powder for concentrate for solution for injection or infusion. Hospira UK Ltd. June 2013.
Summaries of Product Characteristics: Remifentanil 5mg powder for concentrate for solution for injection or infusion. Hospira UK Ltd. June 2013.

Summaries of Product Characteristics: Remifentanil powder for concentrate for solution for injection or infusion (1mg, 2mg, 5mg). Teva UK Ltd. Revised February 2010.

Summaries of Product Characteristics: Remifentanil powder for concentrate for solution for injection or infusion (1mg, 2mg, 5mg). Wockhardt UK Ltd. Revised April 2011.

Summary of Product Characteristics: Ultiva Injection. GlaxoSmithKline UK. Revised April 2014.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Remifentanil. Last revised: January 16, 2014. Last accessed: July 8, 2014.

Gov.uk. Government departments. Department for Transport. Publications. Drug driving and medicine: advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at: https://www.gov.uk Last accessed: 6 January 2015 New drug driving offence implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: https://www.mhra.gov.uk Last accessed: 6 January 2015