Fentanyl


Generic Medicine Info
Indications and Dosage
Buccal
Breakthrough cancer pain
Adult: In patients already receiving and tolerant to opioid treatment: As loz: Initially, 200 mcg over 15 minutes for an episode of breakthrough pain, may repeat once after 15 minutes if needed; wait for at least 4 hours before treating another episode. As tab: Initially, 100 mcg for an episode, may repeat once after 30 minutes if needed; wait for at least 4 hours before treating another episode. As film: Initially, 200 mcg for an episode; wait for at least 2 hours before treating another episode. All subsequent doses must be individually titrated according to patient response (refer to respective detailed product guideline).
Child: In patients already receiving and tolerant to opioid treatment: ≥16 years As loz: Same as adult dose.
Elderly: Dose reduction may be needed. 

Intramuscular
Premedication before anaesthesia
Adult: 50-100 mcg may be given 30-60 minutes prior to induction of anaesthesia or surgery.
Elderly: Dose reduction may be needed.

Intramuscular
Postoperative pain
Adult: 50-100 mcg, may be repeated in 1-2 hours, if necessary.
Elderly: Dose reduction may be needed.

Intravenous
Adjunct to general anaesthesia
Adult: Patients with spontaneous respiration: Initially, 50-200 mcg followed by 50 mcg. Patients with assisted ventilation: Initially, 300-3,500 mcg, followed by 100-200 mcg supplemental dose depending on patient response. Loading dose via infusion: Approx 1 mcg/kg/min given for the 1st 10 minutes, followed by infusion of 0.1 mcg/kg/min. Alternatively, loading dose may be given as a bolus. Titrate infusion rates according to patient response.
Child: 2-11 years Patients with spontaneous respiration: Initially, 1-3 mcg/kg, followed by 1-1.25 mcg/kg supplemental dose. Patients with assisted ventilation: Initially, 1-3 mcg/kg, followed by 1-1.25 mcg/kg supplemental dose. 12-17 years Same as adult dose.
Elderly: Dose reduction may be needed.

Nasal
Breakthrough cancer pain
Adult: In patients already receiving and tolerant to opioid therapy: As spray: Initially, 50 mcg or 100 mcg (1 spray) into 1 nostril for an episode of breakthrough pain, may repeat once after 10; wait for at least 2 or 4 hours before treating another episode. Titrate subsequent doses according to response up to max 4 episodes treated daily (refer to detailed product guideline).
Elderly: Dose reduction may be needed.

Parenteral
Adjunct to regional anaesthesia
Adult: 50-100 mcg via IM or slow IV inj over 1-2 minutes, when additional analgesia is needed.
Elderly: Dose reduction may be needed.

Sublingual
Breakthrough cancer pain
Adult: In patients already receiving and tolerant to opioid therapy: As tab: Initially, 100 mcg for an episode of breakthrough pain, may repeat once after 30 minutes if needed; wait for at least 2-4 hours before treating another episode. As spray: Initially, 100 mcg for an episode of breakthrough pain, may repeat once after 30 minutes if necessary; wait for at least 4 hours before treating another episode. All subsequent doses must be individually titrated according to patient response (refer to respective detailed product guideline).
Elderly: Dose reduction may be needed. 

Transdermal
Intractable chronic pain
Adult: As patch releasing 12-100 mcg/hour: Opioid-naive patients: Initially, 12 mcg/hour, up to 25 mcg/hour; it is recommended to initially titrate with low doses of short-acting opioids before starting fentanyl patches. Opioid-tolerant patients: Initial doses are based on previous 24-hour opioid requirements (refer to detailed product guideline). During transfer to fentanyl patches, previous opioid treatment should be phased out gradually. May apply >1 patch for doses >100 mcg/hour; consider additional or alternative therapy for doses >300 mcg/hour. Patch may be worn continuously for up to 72 hours.
Child: Opioid-tolerant patients: 2-16 years Initial doses are based on previous 24-hour opioid requirements (refer to detailed product guideline). Doses must be individually titrated in increments of 12 mcg/hour at 3-days intervals until balance between analgesic efficacy and tolerability is achieved; ≥16 years Same as adult dose.
Elderly: Opioid-naive patients: Initially, 12 mcg/hour, considered only if benefits outweighs the risks. Patients already receiving and tolerant to opioid treatment Dose reduction may be needed. Alternatively, consider use of non-opioid analgesics.
Special Patient Group
Cachectic or debilitated patients: Dose reduction may be needed.

Patients with fever (transdermal patch): Dose reduction may be needed.
Renal Impairment
Intravenous
Adjunct to general anaesthesia
Dose reduction may be needed.

Intramuscular
Premedication before anaesthesia; Postoperative pain
Dose reduction may be needed.

Parenteral
Adjunct to regional anaesthesia
Dose reduction may be needed.

Transdermal
Intractable chronic pain
Opioid-naive patients: Initially, 12 mcg/hour. Opioid-tolerant patients: Mild to moderate: Reduce dose by 50%.
Hepatic Impairment
Intravenous
Adjunct to general anaesthesia
Dose reduction may be needed.

Intramuscular
Premedication before anaesthesia; Postoperative pain
Dose reduction may be needed.

Parenteral
Adjunct to regional anaesthesia
Dose reduction may be needed.

Transdermal
Intractable chronic pain
Opioid-naive patients: Initially, 12 mcg/hour, considered only if benefits outweighs the risks. Opioid-tolerant patients: Mild to moderate: Reduce dose by 50%.
Incompatibility
IM/IV: Incompatible with thiopental Na, methohexital Na.
Contraindications
Transdermal patch/buccal tab/nasal spray/lozenge/SL spray: Significant respiratory depression, acute or severe bronchial asthma in unmonitored setting or in the absence of resuscitative equipment; gastrointestinal obstruction including paralytic ileus, management of acute pain; mild, or post-operative pain; non-opioid tolerant patient. Nasal spray: Previous facial radiotherapy, recurrent episodes of epistaxis.
Special Precautions
Patient with risk factors for sleep-disordered breathing (e.g. heart failure, obesity); hypovolaemia, hypotension, CV disease, acute MI, previous/pre-existing bradycardia, bradyarrhythmia, non-severe COPD, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, acute abdominal conditions, chronic constipation, thyroid dysfunction, adrenal insufficiency, Addison’s disease, biliary tract dysfunction, acute pancreatitis; impaired consciousness or coma, head injury, intracranial lesion, brain tumour, increased intracranial pressure, delirium tremens, mental health conditions (e.g. depression, anxiety disorders, post-traumatic stress disorder), toxic psychosis, history of seizure disorders, myasthenia gravis, prostatic hyperplasia, urinary stricture, history of drug abuse or acute alcoholism; mouth wounds, oral mucositis (sublingual); fever (patch). Cachectic or debilitated patients. Avoid abrupt withdrawal. Renal and hepatic impairment. Children and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Severe hypotension, including orthostatic hypotension and syncope; secondary hypogonadism (long-term use), bradycardia, CNS depression, seizures, non-epileptic (myo)clonic movements, constriction of sphincter of Oddi, elevated intracranial pressure, hyperalgesia (high doses), increased sleep-related disorders (e.g. central sleep apnoea, hypoxaemia), decreased bowel motility, tolerance, physical or psychological dependence, withdrawal symptoms, anaphylaxis, hypersensitivity; muscular rigidity, including thoracic muscles (rapid IV infusion).
Blood and lymphatic system disorders: Anaemia, neutropenia.
Cardiac disorders: Tachycardia, palpitation, arrhythmia, dyspnoea.
Ear and labyrinth disorders: Vertigo.
Eye disorders: Blurred or double vision.
Gastrointestinal disorders: Nausea, vomiting, throat irritation, constipation, dysgeusia, abdominal pain, stomatitis, dry mouth, diarrhoea, dyspepsia, toothache, oral candidiasis.
General disorders and administration site conditions: Pyrexia, asthenia, fatigue, chills, lethargy, application site reactions (e.g. pain, erythema, irritation, ulcer, bleeding).
Injury, poisoning and procedural complications: Fall, postoperative confusion.
Investigations: Weight decreased.
Metabolism and nutrition disorders: Anorexia, peripheral oedema, dehydration.
Musculoskeletal and connective tissue disorders: Myalgia, backpain, muscle spasms.
Nervous system disorders: Headache, dizziness, tremor, sedation, paraesthesia.
Psychiatric disorders: Somnolence, depression, anxiety, insomnia, confusional state, hallucination.
Renal and urinary disorders: Urinary retention.
Respiratory, thoracic and mediastinal disorders: Pharyngolaryngeal pain, laryngospasm, bronchospasm.
Skin and subcutaneous tissue disorders: Hyperhidrosis, rash, pruritus, allergic dermatitis.
Vascular disorders: Flushing, hypertension; venous pain (IM/IV).
Potentially Fatal: Respiratory depression, serotonin syndrome, neonatal withdrawal syndrome (long-term use during pregnancy), adrenal insufficiency.
Buccal/Epidural/IM/IV/Nasal/Parenteral/PO/SL/Transdermal: C
Patient Counseling Information
This drug may cause dizziness, somnolence, and blurred vision, if affected, do not drive or operate machinery. Do not switch between brands or dosage forms unless instructed by your doctor. Transdermal patch: Avoid exposing the application site and surrounding area to direct external heat sources (e.g. heating pad, tanning lamp, hot tub, sauna).
Monitoring Parameters
Monitor blood pressure, heart rate, respiratory and mental status, pain relief; LFTs at baseline and as clinically indicated; respiratory depression within the 1st 24-72 hours after treatment initiation and dose increases. Assess for signs and symptoms of misuse, abuse or addiction, hypogonadism, hypoadrenalism.
Overdosage
Symptoms: Hypothermia, decreased muscle tonus, bradycardia, hypotension, deep sedation, altered mental status, loss of consciousness, lethargy, ataxia, convulsions, coma, respiratory depression, distress, and failure. Management: Supportive treatment. Immediately remove patch, loz, sublingual or buccal film/tab. Stimulate patient physically or verbally. May administer naloxone to treat respiratory depression for opioid-naive individuals if necessary; IV neuromuscular blockers for muscle rigidity; parenteral fluid therapy for severe or persistent hypotension. Establish and maintain patent airway, body temperature, and fluid intake.
Drug Interactions
Enhanced CNS depressants effects with Na oxybate. Reduced analgesic effects and induce withdrawal symptoms with partial opioid agonists/antagonists (e.g. buprenorphine, nalbuphine, pentazocine). Reduced plasma levels and efficacy with CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenytoin), and oxymetazoline. May reduce the efficacy of diuretics. Increased risk of urinary retention and severe constipation with anticholinergics. May increase the terminal half-life and reduce the clearance of midazolam. May increase the plasma concentrations of etomidate. Induced extrapyramidal symptoms with neuroleptics.
Potentially Fatal: May cause profound sedation, respiratory depression, coma and death with benzodiazepines or other CNS depressants (e.g. non-benzodiazepine sedative/hypnotics, anxiolytics, tranquilisers, muscle relaxants, general anaesthetics). Increased risk of serotonin syndrome with SSRIs, serotonin norepinephrine reuptake inhibitors, MAOIs, triptans, TCAs, lithium. Increased plasma concentrations leading to increased or prolonged adverse reactions which may cause potentially fatal respiratory depression when used with CYP3A4 inhibitors (e.g. ritonavir, ketoconazole, erythromycin, diltiazem, verapamil).
Food Interaction
Enhanced depressants effects with alcohol. Increased risk of serotonin syndrome with St. John’s wort. Increased plasma levels with grapefruit juice.
Action
Description: Fentanyl is an opioid agonist analgesic that predominantly interacts with opioid μ-receptors in the CNS. It increases pain threshold, alters pain reception, and inhibits the ascending pain pathways by binding to stereospecific receptors at several sites within the CNS.
Onset: Analgesic effect: 7-8 minutes (IM); almost immediate (IV); 6 hours (transdermal patch on initial placement); 5-15 minutes (transmucosal).
Duration: 1-2 hours (IM); 0.5-1 hour (IV).
Pharmacokinetics:
Absorption: Transmucosal: Rapidly absorbed from buccal and nasal mucosa; the remainder is swallowed and slowly absorbed from the gastrointestinal tract. Bioavailability: 71% (buccal film); 65% (buccal tab); approx 50% (loz); 76% (sublingual spray); 54% (sublingual tab); approx 89% (intranasal spray); 92% (transdermal patch). Time to peak plasma concentration: 0.75-4 hours (buccal film); 20-240 minutes (buccal tab); 20-480 minutes (loz); 15-21 minutes (intranasal spray); 10-120 minutes (sublingual spray); 15-240 minutes (sublingual tab); 20-72 hours (transdermal patch).
Distribution: Rapidly redistributed into muscles and fat; present in CSF. Crosses the placenta and enters breast milk. Volume of distribution: 4-6 L/kg. Plasma protein binding: 79-87%, mainly to α-1 acid glycoprotein; albumin and erythrocytes.
Metabolism: Rapidly and extensively metabolised in the liver by CYP3A4 isoenzyme via N-dealkylation to norfentanyl and hydroxylation to form other inactive metabolites.
Excretion: Via urine (75%, primarily as metabolites; <7-10% as unchanged drug); faeces (approx 9%). Elimination half-life: 2-4 hours (IV); approx 14 hours (buccal film); 3-14 hours dose dependent (transmucosal); 20-27 hours (transdermal patch); 15-25 hours (intranasal spray).
Chemical Structure

Chemical Structure Image
Fentanyl

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3345, Fentanyl. https://pubchem.ncbi.nlm.nih.gov/compound/Fentanyl. Accessed Feb. 23, 2021.

Storage
Buccal tab/film/loz, sublingual tab/spray: Store between 20-25°C. Protect from moisture. Do not freeze. Nasal spray: Store at 25°C. Protect from light. Do not freeze. Transdermal patch, IM/IV: Store between 15-30°C. Protect from light. Follow recommended procedures for handling, administration, and disposal. Keep out of the reach of children.
MIMS Class
ATC Classification
N01AH01 - fentanyl ; Belongs to the class of opioid anesthetics. Used as general anesthetics.
N02AB03 - fentanyl ; Belongs to the class of phenylpiperidine derivative opioids. Used to relieve pain.
References
Abstral 300 mcg Sublingual Tablets (Kyowa Kirin Ltd). MHRA. https://products.mhra.gov.uk. Accessed 19/03/2020.

Actiq 200 mcg Compressed Lozenge with Integral Oromucosal Applicator (Teva Pharma B.V.). MHRA. https://products.mhra.gov.uk. Accessed 19/03/2020.

Anon. Fentanyl. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 19/03/2020.

Buckingham R (ed). Fentanyl. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 19/03/2020.

Duragesic Patch (Janssen Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 19/03/2020.

Durogesic DTrans 75 mcg/hour Transdermal Patch (Janssen-Cilag Limited). MHRA. https://products.mhra.gov.uk. Accessed 19/03/2020.

Effentora Buccal Tablets (Teva B.V.). European Medicines Agency [online]. Accessed 19/03/2020.

Fentanyl (Briggs Drugs in Pregnancy and Lactation). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 19/01/2021.

Fentanyl Citrate Lozenge (Teva Pharmaceuticals USA, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 19/03/2020.

Fentanyl Citrate Solution for Injection (Hospira Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 19/03/2020.

Fentanyl Hexal Mat Transdermal Patch (IMEKS Pharma Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 19/03/2020.

Instanyl Nasal Spray, Solution (Takeda Pharma A/S). European Medicines Agency [online]. Accessed 19/03/2020.

Lazanda Nasal Spray (West Therapeutic Development LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 19/03/2020.

Onsolis Buccal Film (BioDelivery Sciences, International, Inc.). U.S. FDA. https://www.fda.gov. Accessed 19/03/2020.

Sublimaze (Piramal Critical Care Limited). MHRA. https://products.mhra.gov.uk. Accessed 19/03/2020.

Subsys Sublingual Spray (Insys Therapeutics, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 19/03/2020.

Disclaimer: This information is independently developed by MIMS based on Fentanyl from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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