Fentanyl nasal spray
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Nasal spray containing fentanyl
Drugs List
Therapeutic Indications
Uses
Management of breakthrough cancer pain in patients receiving opiates
Dosage
Fentanyl nasal spray should only be administered to patients taking at least 60 mg of oral morphine daily, at least 25 micrograms of transdermal fentanyl per hour, at least 30 mg oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.
Treatment should be initiated by and remain under the supervision of a physician experienced in the management of opioid therapy. Physicians should bear in mind the potential of abuse of fentanyl.
Adults
The maximum daily dose is treatment of up to four breakthrough pain episodes, each with no more than two actuations. (Some manufacturers recommend that actuations should be separated by at least 10 minutes; see manufacturers' information for administration instructions.) Patients should wait at least 4 hours before treating another breakthrough pain episode with fentanyl nasal spray during both titration and maintenance therapy.
Titration:
Patients must be carefully monitored during the titration process and should be individually titrated to the dose that provides adequate analgesia with tolerable adverse drug reactions.
Before titration occurs, background persistent pain should be controlled by chronic opioid therapy and no more than four episodes of breakthrough pain should occur per day.
The initial dose should be one actuation of 50 micrograms or one actuation of 100 micrograms in one nostril. If adequate analgesia is not obtained, a second actuation of the same strength may be administered, following manufacturer's guidance. If adequate pain relief is not achieved, the next highest strength should be considered for the next episode.
The maximum single dose is 800 micrograms (one 400 microgram actuation in each nostril)
Maintenance:
Once the dose has been established, the patient should be maintained on this strength of fentanyl nasal spray.
Dose adjustment:
Generally, the maintenance dose should be increased when a patient requires more than one dose per breakthrough pain episode for several consecutive episodes. Dose adjustment of the background opioid therapy may be required if the patient consistently presents with more than four breakthrough pain episodes in 24 hours. Fentanyl nasal spray should then be re-evaluated and re-titrated as necessary. Any dose re-titration must be monitored by a health professional.
If adverse reactions are intolerable or persistent, the strength should be reduced or treatment with fentanyl nasal spray replaced by other analgesics.
Discontinuation:
Fentanyl nasal spray should be discontinued immediately if the patient no longer experiences breakthrough episodes. The treatment for persistent background pain should not be altered. Discontinuation of all opioid therapy should be carefully monitored and gradual downward opioid titration used to avoid the possibility of abrupt withdrawal effects.
Elderly
(See Dosage; Adult)
Use with caution in elderly patients, particularly during titration, as they may have a reduced clearance, prolonged half-life and higher sensitivity to fentanyl. Observe elderly and debilitated patients for signs of fentanyl toxicity and reduce dose if necessary.
Patients with Renal Impairment
Use with caution in patients with moderate to severe renal impairment.
The Renal Drug Handbook recommends the following dosage guidance for fentanyl:
Mild renal impairment (GFR 20 to 50 ml/minute) - dose as in normal renal function
Moderate renal impairment (GFR 10 to 20 ml/minute) - 75% of normal dose, titrate according to response
Severe renal impairment (GFR <10 ml/minute) - 50% of normal dose, titrate according to response
Additional Dosage Information
The dose of fentanyl nasal spray for breakthrough pain is independent of the daily maintenance dose of opioid.
Contraindications
Children under 18 years
Opioid-naive patients
Previous facial radiotherapy
Recurrent epistaxis
Risk of paralytic ileus
Within 2 weeks of discontinuing MAOIs
Coma
Head trauma
Raised intracranial pressure
Severe obstructive pulmonary disease
Severe respiratory depression
Precautions and Warnings
Cachexia
Debilitation
Elderly
Impaired consciousness
Tobacco smoking
Adrenal insufficiency
Alcoholism
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Bradyarrhythmia
Breastfeeding
Chronic obstructive pulmonary disease
Diabetes mellitus
Epileptic disorder
History of drug misuse
History of psychiatric disorder
Hypotension
Hypothyroidism
Hypovolaemia
Inflammatory bowel disease
Moderate hepatic impairment
Moderate renal impairment
Myasthenia gravis
Pregnancy
Respiratory depression
Not suitable for acute pain relief
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
Treatment to be initiated and supervised by a specialist
Some formulations contain hydroxybenzoate
Consider alternate therapy if nasal discomfort or recurrent epistaxis occur
Monitor for signs of tolerance and dependence
Monitor patient closely during titration of dose
Monitor patient for signs and symptoms of respiratory depression
Potential for drug abuse
Tolerance and dependence may occur
When used with SSRIs, risk of Serotonin syndrome
Consider dose reduction if sleep-related breathing disorders occur
Increased risk of central sleep apnoea and sleep-related hypoxemia
Prolonged use at high doses may result in hyperalgesia
May affect results of some laboratory tests
Discontinue if serotonin syndrome develops
Consider dose reduction or alternative opioid in cases of hyperalgesia
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise that effects are potentiated by CNS depressants (including alcohol)
Pregnancy and Lactation
Pregnancy
Use fentanyl with caution in pregnancy.
Most experience of fentanyl exposure has been with dose forms other than the nasal spray.
Placental transfer of fentanyl has been demonstrated in the first and second trimesters, and at term, and is detectable in foetal blood. The potential risk for humans is unknown, but there are no reports of teratogenic effects or congenital defects. Animal studies have found that fentanyl is not teratogenic in rats, but impaired fertility and embryotoxic effects were seen at intravenous doses only 0.3 times the human dose.
The manufacturer does not recommend the use of fentanyl during labour and delivery due to the risk of respiratory depression in the foetus or neonate. However, studies using parenteral preparations have shown that the risk of neonatal respiratory depression is small, and fentanyl seems to be less frequently associated with maternal nausea, vomiting or prolonged sedation. Studies comparing intravenous fentanyl with no analgesia during labour found no statistical differences in the neonates in terms of changes in respiratory rate, heart rate, blood pressure, adaptive capacity, neurologic evaluation and overall assessment.
There is some concern, as with any opioid analgesic, that long-term use during pregnancy may cause withdrawal symptoms in the neonate. Mild withdrawal symptoms, without apparent long-term effects were observed in an infant after long-term high-dose maternal treatment with a transdermal fentanyl patch. The neonate should be observed closely for withdrawal syndrome. Schaefer concludes that fentanyl can be used during every phase of pregnancy.
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 fentanyl with caution in breastfeeding.
Most experience of fentanyl exposure has been with dose forms other than the nasal spray.
Fentanyl is excreted into breast milk, and the manufacturer warns this may cause respiratory depression and sedation in the infant. However, studies have shown that, due to the low oral bioavailability of fentanyl, the amounts the infant is exposed to are so small they are not expected to cause clinically significant adverse effects. No toxic effects have been described following exposure.
LactMed states that when fentanyl is used during labour or for a short time postpartum, it is not necessary to discard milk or enforce a waiting period before resuming breastfeeding; it can resume as soon as the mother is sufficiently recovered to nurse her child. There is no published experience with repeated doses of fentanyl during lactation - in these cases other agents may be preferred, especially in newborn or premature infants.
Infants should be monitored for drowsiness, adequate weight gain and developmental milestones, especially in younger, exclusively breastfed infants. Consider limiting maternal intake of fentanyl and supplementing with a non-narcotic analgesic if necessary. A physician should be contacted immediately if the infant experiences difficulty in breastfeeding, breathing difficulties or limpness. As with any opiate analgesic, fentanyl should only be used for short periods during breastfeeding, and particular care should be taken with infants with a tendency towards apnoea because of the risk of respiratory depression.
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
Abdominal pain
Agitation
Amnesia
Anorexia
Anuria
Anxiety
Apnoea
Arrhythmias
Arthralgia
Asystole
Ataxia
Attention disturbances
Biliary spasm
Bradycardia
Cardiovascular disturbances
Circulatory depression
Confusion
Constipation
Cyanosis
Delirium
Dependence
Depersonalisation
Depression
Diarrhoea
Difficulty in micturition
Disorientation
Dizziness
Drowsiness
Dry mouth
Dysaesthesia
Dysarthria
Dysgeusia
Dyspepsia
Dysphagia
Dysphoria
Dyspnoea
Epistaxis
Euphoria
Fasciculation
Flushing
Gastro-intestinal perforation
Haemoptysis
Hallucinations
Headache
Hot flushes
Hyperhidrosis
Hypotension
Hypoventilation
Inco-ordination
Insomnia
Laryngospasm
Lymphoedema
Malaise
Miosis
Mood changes
Motion sickness
Mouth ulcers
Muscle rigidity
Muscle weakness
Myoclonus
Nasal symptoms
Nasal ulceration
Nasopharyngitis
Nausea
Oedema
Palpitations
Paraesthesia
Paralytic ileus
Pneumonia
Postural hypotension
Proteinuria
Pruritus
Psychosis
Pyrexia
Rash
Reduced platelet count
Respiratory depression
Rhinorrhoea
Sedation
Seizures
Sexual dysfunction
Shock
Skin pain
Sleep disturbances
Somnolence
Stomatitis
Sweating
Tachycardia
Thirst
Throat irritation
Tremor
Ureteric spasm
Urinary retention
Urticaria
Vasodilatation
Vertigo
Visual disturbances
Vomiting
Effects on Laboratory Tests
Fentanyl use may result in positive doping tests.
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: June 2016
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 Accessed on 20 April 2016.
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.
Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications Accessed on 16 June 2016.
Summary of Product Characteristics: Instanyl 50 mcg, 100mcg, 200mcg nasal spray, solution in single dose container. Takeda UK Ltd. Revised May 2021.
Summary of Product Characteristics: Pecfent 100 micrograms, 400micrograms/spray nasal solution. Kyowa Kirin Ltd. Revised April 2021.
The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.
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
Fentanyl Last revised: 02 June 2016
Last accessed: 16 June 2016
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
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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