Drug information of fentanyl

Mechanism of effect

Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase.

 Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Fentanyl's analgesic activity is, most likely, due to its conversion to morphine.

Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hypopolarization and reduced neuronal excitability.

Pharmacodynamic

Fentanyl exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Fentanyl may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized.

 In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Fentanyl depresses the respiratory centers, depresses the cough reflex, and constricts the pupils.

Pharmacokinetics

• Bioavailability: 50%
• Onset: IV, immediate; IM, 7-15 min
• Duration: IV, 0.5-1 hr; IM, 1-2 hr
• Peak plasma time: IV (≤100 mcg), 30-60 min; IM, 1-2 hr
• Concentration: 0.2-2 ng/mL (adverse effects occur at >2 ng/mL) 
• Protein bound: 80-85%
• Vd: 4-6 L/kg 
• Metabolism:Metabolized in liver by CYP3A4 
• Half-life: 2-4 hr
• Total plasma clearance: 8.3 mL/min/kg
• Excretion: Urine (75%), feces (9%) 

Drug indications

Pain

Dosage

Adult

Surgery Premedication

50-100 mcg/dose IM or slow IV 30-60 min prior to surgery

Adjunct to regional anesthesia: 25-100 mcg/dose slow IV over 1-2 min

General Anesthesia

Minor surgical procedures: 0.5-2 mcg/kg/dose IV

Major surgery: 2-20 mcg/kg/dose initially; 1-2 mcg/kg/hr maintenance infusion IV; discontinue infusion 30-60 min prior to end of surgery

Adjunct to general anesthesia (rarely used): 20-50 mcg/kg/dose IV

Pediatric

Continuous Sedation/Analgesia

0.5-2 mcg/kg/hr; titrate to desired effect

Adjunct Anesthesia

<2 years: Safety and efficacy not established

>2 years: 2-3 mcg/kg IV/IM q1-2hr PRN

Drug contraindications

Hypersensitivity to this drug

Side effects

depression , Anxiety , Diarrhea , nausea , Headache , dry mouth , dizziness , vomiting , Seizures , flushing , vertigo , asthenia , urticaria , cardiac arrhythmias , dyspepsia , sinusitis , fever , Injection-site reaction , anorexia , Tremor , urinary retention , flatulence , sweating , lethargy , hallucinations , difficulty urinating , tiredness , Restlessness , shortness of breath , Abdominal pain , Rash , rhinitis , Angina pectoris , Syncope , Myocardial Infarction , urinary retention , oliguria

Interactions

Spiramycin , Oxecarbazepin , Propofol , Succinylcholine , Sibutramine , Methocarbamol , Atracurium , Amiodarone , Aprepitant , Etomidate , Erythromycin , Itraconazole , Estazolam , Ceritinib , conivaptan , Iloperidone , Tasimelteon , Ramelteon , Secobarbital , Apalutamide , Temazepam , Doxylamine , Nicardipine , Delavirdine , Alvimopan , Butorphanol , Butabarbital , Fosphenytoin , Idelalisib , Rocuronium , brigatinib , Triazolam , Tipranavir , Indinavir , Ticagrelor , Hydrocodone , Zaleplon , Loxapine , Butalbital and Acetaminophen , Fosamprenavir , Enflurane , Eluxadoline , Lopinavir , Sufentanil , fospropofol , Pancuronium , morphine , meperidine , Nefazodone , saquinavir , nelfinavir , Pentobarbital , Amobarbital , Remifentanil , Levorphanol , Oxycodone , safinamide , Ketamine , Desflurane , Prochlorperazine , Quinidine , Grapefruit , isocarboxazid , escitalopram , Atazanavir , Vecuronium , Linezolid , Buprenorphine , Phenelzine , Voriconazole , Ketoconazole , Clarithromycin , Chlorpromazine , Clozapine , Bicalutamide , Lidocaine , Methadon , Metronidazole , Haloperidol , Verapamil , Venlafaxine , Fluphenazine , Fluoxetine , Fluconazole , Phenobarbital , Lapatinib , Loperamide , Selegiline , Sevo flurane , Citalopram , Cis atracurium , Cyclosporine , Flurazepam , Thioridazine , Doxycycline , Desipramine , Zolpidem , Cimetidine , Sertraline , Pimozide , Tetracycline , Tramadol , Tranylcypromine , Trifluoperazine , Thiothixene , Isoflurane , Isoniazid , Imatinib , Paroxetine , Perfenazine , Posaconazole , Darunavir , Tapentadol , methylene blue , rasagiline , codeine , Pentazocine , dronedarone , ritonavir , Zileuton , Adalimumab , Mifepristone , Palonosetron , Succinylcholine Chloride , Methohexital , Chloral hydrate , lumacaftor and Ivacaftor , Etravirine , Desvenlafaxine , Mibefradil , Dexfenfluramine , Molindone , cobicistat , Letermovir , Asenapine , Paraldehyde , Acetaminophen and benzhydrocodone , tedizolid , Crizotinib , Troleandomycin , Dasatinib

Alerts

Black Box Warnings

Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death; assess each patient’s risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions

Life-threatening respiratory depression

Accidental ingestion

Neonatal opioid withdrawal syndrome

• Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts

Risks from concomitant use with benzodiazepines or other CNS depressants

• Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to minimum required; follow patients for signs and symptoms of respiratory depression and sedation

Pregnancy level

C

Related drugs

Tramadol , Methadon , Buprenorphine , Tapentadol , Levorphanol , propoxyphene , morphine , meperidine , codeine , Hydrocodone , Butorphanol , Opium , Pethidine , Remifentanil , Oxycodone , Pentazocine , Sufentanil , Alfentanil