Search The Medical Knowledge Base

Drug Details

Fentanyl citrate

• Drug Class Description
  Narcotic analgesics (opiates / opioids).
• Generic Name
  Generic
• Presentation
  Injection, fentanyl citrate 100 microgram (2mL), 500 microgram (10mL).
• Description
  Clear, colourless, sterile solution for injection in ampoules.
• Indications
  

  Fentanyl citrate is a narcotic analgesic. In low doses it is used to provide analgesia during short surgical procedures and as a premedicant. In higher doses it is employed as an analgesic/respiratory depressant in patients who need assisted ventilation. In combination with a neuroleptic drug, fentanyl is employed as part of the technique of neuroleptanalgesia. Fentanyl citrate is also used in the treatment of severe pain, such as that of myocardial infarction.

• Adult Dosage
  

  Routes of administration:

  Fentanyl should be given only in an environment where the airway can be controlled and by personnel who can control the airway.

  Intravenous and Intramuscular routes. Fentanyl Injection can be administered to both adults and children via the intravenous route as a bolus or as an infusion. The dose should be individualised according to age, body weight, physical status, any underlying pathological condition, concomitant medication, and type of surgery and anaesthesia. The usual dosage regimen is as follows: 

  	Adults
  	Initial micrograms	Supplemental micrograms
  Spontaneous Respiration Assisted ventilation	50 – 200 300 - 3500	50 100 - 200

  Doses greater than 200 micrograms are solely for use in anaesthesia.

  As a premedicant, 1 - 2ml may be administered intramuscularly before induction of anaesthesia.

  Following intravenous administration in the non-premedicated adult patient, 2ml fentanyl may be anticipated to provide adequate analgesia for 10 – 20 minutes in surgical procedures involving low pain intensity. A bolus of 10ml of fentanyl can be expected to provide analgesia for about one hour. The analgesia produced is generally adequate for surgery involving moderate pain intensity. Administration of 50 microgram/kg will provide intense analgesia for some four to six hours for surgery associated with intense stimulation.

  Fentanyl Injection may also be administered as an intravenous infusion.

  Ventilated patients may be given a loading dose as a fast infusion of approximately 1 microgram/kg/minute for the first 10 minutes, followed by an infusion of approximately 0.1 microgram/kg/minute. Alternatively, the loading dose may be administered as a bolus. The rate of infusion should be titrated to the individual patient response and lower infusion rates may be adequate. The infusion should be discontinued approximately 40 minutes before the end of surgery, unless post-operative ventilation is intended.

  Lower infusion rates, e.g. 0.05 - 0.08 microgram/kg/minute, are required if spontaneous ventilation is to be maintained. Higher infusion rates of up to 3 micrograms/kg/minute have been employed in cardiac surgery.

  It is important when estimating the required dose to assess the likely degree of surgical stimulation, the effect of premedicant drugs, and the duration of the procedure.

  Use in elderly and debilitated patients: It is important to reduce the dosage in the elderly and in debilitated patients. The effect of the initial dose of fentanyl should be considered when determining supplemental dosage.

  Paediatric population

  Children aged 12 to 17 years old- Follow adult dosage:

  Children aged 2 to 11 years old:

  The usual dosage regimen in children is as follows: 

  	Age	Initial	Supplemental
  Spontaneous respiration	2-11 years	1-3 micrograms/kg	1-1.25 micrograms/kg
  Assisted Ventilation	2-11 years	1-3 micrograms/kg	1-1.25 micrograms/kg

  Use in children:

  Analgesia during operation, enhancement of anaesthesia with spontaneous respiration

  Techniques that involve analgesia in a spontaneous breathing child should only be used as part of an anaesthetic technique, or given as part of a sedation/ analgesia technique with experienced personnel in an environment that can manage sudden chest wall rigidity requiring intubation, or apnoea requiring airway support

• Contra Indications
  

  Known hypersensitivity to fentanyl citrate: respiratory depression: obstructive airways disease. Concurrent administration with monoamine oxidase inhibitors or within two weeks of their discontinuation. Known intolerance to fentanyl or other morphinomimetics.

  In patients after operative interventions in the biliary tract.

• Special Precautions
  

  Warnings:

  Repeated use of fentanyl may result in the development of tolerance and dependence.

  Intravenous administration of fentanyl may result in a transient fall in blood pressure, particularly in patients with hypovolaemia, and appropriate measures should be taken to maintain a stable arterial pressure.

  Significant respiratory depression will occur if doses of fentanyl in excess of 200 micrograms are administered. This effect and the other pharmacological effects of fentanyl can be reversed by specific narcotic antagonists, such as naloxone. Since the duration of respiratory depression may outlast the duration of action of the narcotic antagonist, additional doses of the antagonist may be required.

  Bradycardia and possibly asystole may occur in non-atropinised patients and can be antagonised by atropine.

  Muscle rigidity, including rigidity of the thoracic muscles, may occur and may be avoided by adopting the following measures: giving intravenous injection slowly (which is usually sufficient for lower doses), premedicating with a benzodiazepine, administration of a muscle relaxant.

  Precautions:

  Fentanyl should be given only in an environment where the airway can be controlled and by personnel who can control the airway.

  As with all narcotic analgesics, care should be observed when administering fentanyl to patients with myasthenia gravis.

  It is desirable to reduce dosage in the elderly and in debilitated patients.

  Careful dosage titration is required in hypothyroidism, pulmonary disease, decreased respiratory reserve, alcoholism and impaired renal or hepatic function, and prolonged monitoring may be required.

  Patients on prolonged opioid therapy or with a history of opioid abuse may require higher doses of fentanyl.

  Administration of fentanyl during labour may result in neonatal respiratory depression.

  As with all potent opioids, profound analgesia is accompanied by marked respiratory depression, which may persist into or recur in the early postoperative period. It is imperative to ensure that adequate spontaneous breathing has been established and maintained before discharge from the recovery area whenever large doses or infusions of Fentanyl Citrate Injection have been administered.

  Hyperventilation during anaesthesia may alter the patient's response to CO2, thus affecting respiration post-operatively.

  Opioid pre-medication may potentiate or prolong respiratory depressant effects of fentanyl citrate. Resuscitation facilities and opioid antagonists should be readily available.

  Rapid bolus injection of opioids should be avoided in patients with compromised cerebrovascular compliance, as the transient decrease in mean arterial pressure has occasionally been accompanied by a transient reduction of the cerebral perfusion pressure in such patients.

  Paediatric population:

  Techniques that involve analgesia in a spontaneous breathing child should only be used as part of an anaesthetic technique, or given as part of a sedation/ analgesia technique with experienced personnel in an environment that can manage sudden chest wall rigidity requiring intubation, or apnoea requiring airway support.

• Interactions
  

  Effect of other drugs on fentanyl

  The respiratory depressant effect of fentanyl may be enhanced or prolonged by opioid premedication, barbiturates, benzodiazepines, neuroleptics, halogenic gasses, alcohol and other non-selective CNS depressants.

  In patients who have received a CNS depressant, the dose of fentanyl will be less than usual.

  When fentanyl is used in combination with non-vagolytic muscle relaxants, bardycardia and possibly asystole may occur.

  Concomitant use of fentanyl and droperidol can result in higher incidence of hypotension.

  Fentanyl, a high clearance drug, is rapidly and extensively metabolised mainly by CYP3A4. Itraconazole ( a potent CYP3A4 inhibitor ) at 200 mg/day given orally for 4 days had no significant effect on the pharmacokinetics of iv fentanyl.

  Oral ritonavir (one of the most potent CYP3A4 inhibitors) reduced the clearance of iv fentanyl by two thirds; however, peak plasma concentrations after a single dose of fentanyl were not affected.

  When fentanyl is used in a single dose, the concomitant use of potent CYP3A4 inhibitors such as ritonavir requires special patient care and observation.

  Co-administration of fluconazole or voriconazole (moderate CYP3A4 inhibitors) and fentanyl may result in an increased exposure to fentanyl.

  With continuous treatment of fentanyl and concomitant administration of CYP3A4 inhibitors, dose reduction of fentanyl may be required to avoid accumulation of fentanyl, which may increase the risk of prolonged or delayed respiratory depression.

  Pretreatment with, or concurrent administration of, cimetidine may increase plasma levels of fentanyl, when repeated doses of both drugs are used.

  Bradycardia may be intensified by pretreatment with, or concurrent use of, drugs such as beta-blockers, suxamethonium, halothane, vecuronium, which may themselves cause bradycardia.

  Effect of fentanyl on other drugs

  Following the administration of fentanyl, the dose of other CNS depressant drugs should be reduced.

  The total plasma clearance and volume of distribution of etomidate is decreased by a factor 2 to 3 without a change in half-life when administered with fentanyl. Simultaneous administration of fentanyl and intravenous midazolam results in an increase in the terminal plasma half-life and a reduction in the plasma clearance of midazolam. When these drugs are co-administered with fentanyl their dose may need to be reduced.

• Adverse Drug Reactions
  

  The following table displays ADRs that have been reported with the use of fentanyl IV from either clinical trials or postmarketing experiences. The displayed frequency categories use the following convention: Very common ( 1/10); common ( 1/100 to <1/10); uncommon (1/1,000 to <1/100); rare (1/10,000 to <1/1,000); very rare (<1/10,000); and not known (cannot be estimated from the available clinical trial data).

  Table 1: Adverse Drug Reactions 

  System Organ Class	Adverse Drug Reactions
  	Frequency Category
  	Very Common ( 1/10)	Common ( 1/100 to < 1/10)	Uncommon ( 1/1,000 to < 1/100)	Not Known
  Immune System Disorders				Hypersensitivity (such as anaphylactic shock, anaphylactic reaction, urticaria)
  Psychiatric Disorders		Agitation	Euphoric mood
  Nervous System Disorders	Muscle rigidity (which may also involve the thoracic muscles)	Dyskinesia; Sedation; Dizziness	Headache	Convulsions; Loss of consciousness; Myoclonus
  Eye Disorders		Visual disturbance
  Cardiac Disorders		Bradycardia; Tachycardia; Arrhythmia		Cardiac arrest
  Vascular Disorders		Hypotension; Hypertension; Venous pain	Phlebitis; Blood pressure fluctuation
  Respiratory, Thoracic and Mediastinal Disorders		Laryngospasm; Bronchospasm; Apnoea	Hyperventilation; Hiccups	Respiratory depression
  Gastrointestinal Disorders	Nausea; Vomiting
  Skin and Subcutaneous Tissue Disorders		Allergic dermatitis		Pruritus
  General Disorders and Administration Site Conditions			Chills; Hypothermia
  Injury, Poisoning and Procedural Complications		Postoperative confusion	Airway complication of anaesthesia

  When a neuroleptic is used with fentanyl, the following adverse reactions may be observed: chills and/or shivering, restlessness, postoperative hallucinatory episodes and extrapyramidal symptoms.