Fentanyl

Fentanyl Uses, Dosage, Side Effects, Food Interaction and all others data.

Fentanyl is an opioid analgesic. Fentanyl interacts predominately with the opioid mu-receptor but also binds to kappa and delta-type opioid receptors. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, 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.

Fentanyl produces strong analgesia through its activation of opioid receptors. It has a duration of action of several hours and a wider therapeutic index as patients develop tolerance to opioids. Fentanyl is associated with a risk of addiction and abuse and should not be mixed with alcohol or benzodiazepines.

Trade Name Fentanyl
Availability Prescription only
Generic Fentanyl
Fentanyl Other Names Fentanil, Fentanila, Fentanilo, Fentanyl, Fentanyl CII, Fentanylum, Phentanyl
Related Drugs Buprenex, Subutex, aspirin, acetaminophen, tramadol, trazodone, duloxetine, hydroxyzine, naproxen, Tylenol
Weight 50mcg/ml, , 50µg/ml, 100mcg/inh, 300mcg/inh, 400mcg/inh, 0, 05mg/ml
Type Injection, Solution, Transdermal, Buccal Tablet, Sublingual Spray, Sublingual Tablet, Buccal/sublingual, Nasal Spray, Nasal
Formula C22H28N2O
Weight Average: 336.4705
Monoisotopic: 336.220163528
Protein binding

Fentanyl is 80-85% bound to plasma proteins. In one study, a 0.1µg/L solution of fentanyl was 77.9±1.1% bound to human serum albumin and 12.0±5.4% bound to α-1 acid glycoprotein. A 0.1µg/L solution of norfentanyl, the primary metabolite of fentanyl, was 7.62±1.2% bound to human serum albumin and 7.24±1.9% bound to α-1 acid glycoprotein.

Groups Approved, Illicit, Investigational, Vet approved
Therapeutic Class Opioid analgesics
Manufacturer Renata Limited, Hameln Pharma Ltd, Macarthys Laboratories Ltd T, A Martindale Pharmaceuticals, Kimia Farma
Available Country Bangladesh, United Kingdom, Saudi Arabia, United States, Netherlands, Indonesia
Last Updated: September 19, 2023 at 7:00 am
Fentanyl
Fentanyl

Uses

Fentanyl is used for the management of breakthrough pain in patients with cancer who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. Patients considered opioid tolerant are those who are taking at least 60 mg of oral morphine/day, at least 25 mcg of transdermal Fentanyl/hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.

Fentanyl is also used to associated treatment for these conditions: Cancer Related Pain (Breakthrough Pain), Severe, Chronic Pain, Anesthetic premedication therapy, Anesthetics Agent, General Anesthesia, Induction of anesthesia therapy, Maintenance of anesthesia therapy, Regional Anesthesia, Preanesthetic medication therapy

How Fentanyl works

Fentanyl binds to opioid receptors, especially the mu opioid receptor, which are coupled to G-proteins. Activation of opioid receptors causes GTP to be exchanged for GDP on the G-proteins which in turn down regulates adenylate cyclase, reducing concentrations of cAMP. Reduced cAMP decreases cAMP dependant influx of calcium ions into the cell. The exchange of GTP for GDP results in hyperpolarization of the cell and inhibition of nerve activity.

Dosage

Fentanyl dosage

Oral-

  • Starting Dose: The initial dose of Fentanyl should be 100 mcg.
  • Re-dosing patients within a single episode:  Dosing may be repeated once during a single episode of breakthrough pain if pain is not adequately relieved by one Fentanyl dose. Re-dosing may occur 30 minutes after the start of administration of Fentanyl and the same dosage strength should be used.
  • Increasing the dose:  Titration should be initiated using multiples of the 100 mcg Fentanyl tablet. Patients require to titrate above 100 mcg can be instructed to use two 100 mcg tablets (one on each side of the mouth in the buccal cavity). If this dose is not successful in controlling the breakthrough pain episode, the patient may be instructed to place two 100 mcg tablets on each side of the mouth in the buccal cavity (total of four 100 mcg tablets). Titrate above 400 mcg by 200 mcg increments bearing in mind using more than 4 tablets simultaneously has not been studied and it is important to minimize the number of strengths available to patients at any time to prevent confusion and possible overdose. To reduce the risk of overdose during titration, patients should have only one strength of Fentanyl tablet available at any one time.
  • Dosage Adjustment: Generally, the dose of Fentanyl should be increased when patients require more than one dose per breakthrough pain episode for several consecutive episodes.

Injection-

  • Fentanyl injection can be administered intravenously either as a bolus or by infusion & by intramuscular route also. The dose of fentanyl should be individualized according to age, body weight, physical status, underlying pathological condition, use of other drugs and type of surgery and anesthesia.
  • Doses in excess of 200mcg are for use in anesthesia only. As a premedicant, 1-2 ml fentanyl may be given intramuscularly 45 minutes before induction of anesthesia. After IV administration in unpremedicated adult patients, 2ml fentanyl may be expected to provide sufficient analgesia for 10-20 minutes in surgical procedures involving low pain intensity. 10 ml fentanyl injected as a bolus gives analgesia lasting about one hour. The analgesia produced is sufficient for surgery involving moderately painful procedures. Giving a dose of 50mcglkg fentanyl will provide intense analgesia for some four to six hours, for intensely stimulating surgery.
  • Fentanyl may also be given as an infusion. In ventilated patients, a loading dose of fentanyl may be given as a fast infusion of approximately 1 mcg/kg/min for the first 10 minutes followed by an infusion of approximately 0.1 mcg/kg/min. Alternatively the loading dose of fentanyl may be given as a bolus. Infusion rates should be titrated to individual patient response; lower infusion rates may be adequate. Unless it is planned to ventilate post operatively, the infusion should be terminated at about 40 minutes before the end of surgery.
  • Lower infusion rates, e.g. 0.05-0.08 mcg/kg/min. are necessary if spontaneous ventilation .is to be maintained. Higher infusion rates (up to 3 mcg/kg/min) have been used in cardiac surgery. Fentanyl is chemically incompatible with the induction agents thiopentone & methohexitone because of wide differences in pH
  • Use in elderly and debilitated patients: It is wise to reduce the dosage in the elderly and debilitated patients. The effect of the initial dose should be taken into account in determining supplemental doses.

Transdermal-

Intractable chronic pain:

  • Adult: Patches deliver fentanyl in doses that range from: 12-100 mcg/hr. Doses should be individually titrated based on previous use of opioids. Opioid-naive patients: Initially, ≤25 mcg/hr; it is recommended to initially titrate w/ low doses of short-acting opioids before starting fentanyl patches. Patients receiving a strong opioid analgesic: Initial dose should be based on the previous 24-hr opioid requirements. During transfer to fentanyl patches, previous opioid treatment should be phased out gradually. If patient requires doses >100 mcg/hr, >1 patch may be used; consider alternative or additional therapy if doses >300 mcg/hr are required. Replace patch every 72 hr and apply the new patch to a different site; avoid using the same area of skin for a few days.
  • Elderly: Dose reduction may be needed.

Tablet Administration: Patients should remove the tablet from the blister strip and immediately place the entire tablet in the buccal cavity (above a rear molar, between the upper cheek and gum). Patients should not attempt to split the tablet. The tablet should not be chewed or swallowed, as this will result in lower plasma concentrations than when taken as directed. The tablet should be left between the cheek and gum until it has disintegrated, which usually takes approximately 14-25 minutes. After 30 minutes, if remnants from the tablet remain, they may be swallowed with a glass of water.

Side Effects

As with other narcotic analgesics, the most common serious adverse reactions reported to occur with Fentanyl are respiratory depression, apnoea, muscular rigidity, myoclonic movements, and bradycardia. Respiratory depression is more likely to occur with intravenous administration if a dose is given too rapidly and it rarely occurs with intramuscular administration.

Toxicity

Fentanyl has an intravenous LD50 of 2.91mg/kg in rats, an oral LD50 of 18mg/kg in rats and 368mg/kg in mice. The LD50 in humans is not known.

Symptoms of overdose include respiratory depression, somnolence, stupor, coma, skeletal muscle flaccidity, cold and clammy skin, pupillary constriction, pulmonary edema, bradycardia, hypotension, airway obstruction, atypical snoring, and death. In case of overdose, patients should receive naloxone or nalmefene to reverse the action of the opioids as well as supportive measures to maintain the airway or advanced life support in the case of cardiac arrest.

Precaution

Opioid analgesics impair the mental and/or physical ability required for the performance of potentially dangerous tasks (e.g. driving a car or operating machinery). Patients taking Fentanyl should be warned of these dangers and should be counseled accordingly. The use of concomitant CNS active drugs requires special patient care and observation.

Chronic pulmonary disease: Fentanyl should be titrated with caution in patients with chronic obstructive pulmonary disease or pre-existing medical conditions predisposing them to respiratory depression. 

Head injuries and increased intracranial pressure: Opioids may obscure the clinical course of a patient with a head injury and should be used only if clinically warranted.

Cardiac disease: Intravenous Fentanyl may produce bradycardia. Therefore, Fentanyl should be used with caution in patients with bradyarrhythmias.

Hepatic or renal disease: Fentanyl should be used with caution because of the hepatic metabolism and renal excretion of Fentanyl.

Interaction

Co-administration of different antifungals, macrolide antibiotics, CNS depressant drugs like ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, and nefazadone may enhance or prolong the effects of Fentanyl. The concomitant use of amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, and verapamil with Fentanyl may also result in an increase in Fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.

Food Interaction

  • Avoid alcohol.

[Major] GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including fentanyl.

Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills.

In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Consumption of grapefruit juice during treatment with oral transmucosal formulations of fentanyl may result in increased plasma concentrations of fentanyl, which is primarily metabolized by CYP450 3A4 isoenzyme in the liver and intestine.

Certain compounds present in grapefruit are known to inhibit CYP450 3A4 and may increase the bioavailability of swallowed fentanyl (reportedly up to 75% of a dose) and

The clinical significance is unknown.

In 12 healthy volunteers, consumption of 250 mL regular-strength grapefruit juice the night before and 100 mL double-strength grapefruit juice one hour before administration of oral transmucosal fentanyl citrate (600 or 800 mcg lozenge) did not significantly affect fentanyl pharmacokinetics, overall extent of fentanyl-induced miosis (miosis AUC), or subjective self-assessment of various clinical effects compared to control.

However, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

The possibility of significant interaction in some patients should be considered.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with fentanyl.

Any history of alcohol or illicit drug use should be considered when prescribing fentanyl, and therapy initiated at a lower dosage if necessary.

Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension.

Due to a high degree of interpatient variability with respect to grapefruit juice interactions, patients treated with fentanyl should preferably avoid the consumption of grapefruit and grapefruit juice.

In addition, patients receiving transdermal formulations of fentanyl should be cautioned that drug interactions and drug effects may be observed for a prolonged period beyond removal of the patch, as significant amounts of fentanyl are absorbed from the skin for 17 hours or more after the patch is removed.

Volume of Distribution

The intravenous volume of distribution is 4L/kg (3-8L/kg). The oral volume of distribution is 25.4L/kg. In hepatically impaired patients, the intravenous volume of distribution ranges from 0.8-8L/kg.

Fentanyl crosses the blood brain barrier and the placenta.

Elimination Route

Fentanyl sublingual tablets are 54% bioavailable, transmucosal lozenges are 50% bioavailable, buccal tablets are 65% bioavailable, sublingual spray is 76% bioavailable, and nasal spray is 20% more bioavailable than transmucosal (or approximately 64% bioavailable).

Fentanyl transmucosal lozenges reach a Cmax of 0.4±0.1ng/mL for a 200µg dose and 2.5±0.6ng/mL for a 1600µg dose with a Tmax of 20-40 minutes. The AUC was 172±96ng*min/mL for a 200µg dose and 1508±1360ng*min/mL for a 1600µg dose.

Fentanyl sublingual spray reached a Cmax of 0.20±0.06ng/mL for a 100µg dose and 1.61±0.60ng/mL for an 800µg dose with a Tmax of 0.69-1.25 hours, decreasing as the dose increased. The AUC was 1.25±0.67ng*h/mL for a 100µg dose and 10.38±3.70ng*h/mL for a 800µg dose.

Fentanyl transdermal systems reached a Cmax of 0.24±0.20ng/mL with a Tmax of 3.6±1.3h for a 25µg/h dose. The AUC was 0.42±0.35ng/mL*h.

Fentanyl nasal spray reaches a Cmax of 815±301pg/mL with a Tmax of less than 1 hour for a 200µg/100µL dose. The AUC was 3772pg*h/mL.

Half Life

The half life of fentanyl is 7 hours. The half life of fentanyl sublingual spray is 5-12 hours.

Clearance

Total plasma clearance of fentanyl is 0.5L/hr/kg (0.3-0.7L/hr/kg) or 42L/hr. Following an intravenous dose, surgical patients displayed a clearance of 27-75L/h, hepatically impaired patients displayed a clearance of 3-80L/h, and renally impaired patients displayed a clearance of 30-78L/h.

Elimination Route

Within 72 hours, 75% of a dose of fentanyl is excreted in the urine with Label,15,19

Pregnancy & Breastfeeding use

Pregnancy category C. There are no adequate and well-controlled studies in pregnant women. Fentanyl should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Fentanyl is excreted in human milk; therefore Fentanyl should not be used in nursing women because of the possibility of sedation and/or respiratory depression in their infants.

Contraindication

Fentanyl is contraindicated in the management of acute or postoperative pain. Fentanyl Citrate must not be used in opioid non-tolerant patients. Fentanyl is contraindicated in patients with known intolerance or hypersensitivity to any of its components or the drug Fentanyl.

Acute Overdose

In insufficient overdosage, Fentanyl would produce narcosis, marked skeletal muscle rigidity. Cardio-respiratory depression and cyanosis may also occur. In the presence of hypoventilation or apnoea, oxygen should be administered and respiration should be assisted. A specific narcotic antagonist, such as naloxane, should be available for use as indicated to manage respiratory depression.

Storage Condition

Store between 20-25°C. Protect from light.

Innovators Monograph

You find simplified version here Fentanyl

Fentanyl contains Fentanyl see full prescribing information from innovator Fentanyl Monograph, Fentanyl MSDS, Fentanyl FDA label

FAQ

What is Fentanyl used for?

Fentanyl used to treat patients with severe pain or to manage pain after surgery. Fentanyl is also used as a recreational drug, sometimes mixed with heroin, cocaine, or methamphetamine, and its potentially deadly overdose effects can be neutralized by naloxone.

How safe is Fentanyl?

Fentanyl has a risk for abuse and addiction, which can lead to overdose and death. Fentanyl may also cause severe, possibly fatal, breathing problems. Do not use transdermal patches unless you have been regularly using moderate to large amounts of opioid pain medication. Otherwise, it may cause overdose (even death).

How does Fentanyl work?

Fentanyl works by binding to the body's opioid receptors, which are found in areas of the brain that control pain and emotions. Its effects include extreme happiness, drowsiness, nausea, confusion, constipation, sedation, tolerance, addiction, respiratory depression and arrest, unconsciousness, coma, and death.

What are the common side effects of Fentanyl?

Common side effcets of Fentanyl are include:

  • drowsiness
  • stomach pain
  • gas
  • heartburn
  • weight loss
  • difficulty urinating
  • changes in vision
  • anxiety
  • depression
  • unusual thinking
  • unusual dreams
  • difficulty falling asleep or staying asleep
  • dry mouth
  • sudden reddening of the face, neck, or upper chest
  • uncontrollable shaking of a part of the body
  • back pain
  • chest pain
  • pain, sores, or irritation in the mouth in the area where you placed the medication
  • swelling of the hands, arms, feet, ankles, or lower legs

Is Fentanyl safe during pregnancy?

Use of this Fentanyl is not recommended unless the benefit outweighs the risk to the developing fetus.

Is Fentanyl safe during breastfeeding?

Fentanyl are usually small and are not expected to cause any adverse effects in breastfed infants.

Can I drink alcohol with Fentanyl?

While using a Fentanyl patch, you should avoid drinking alcohol. Alcohol and Fentanyl will still interact with your system, regardless of the delivery method of the Fentanyl. The same risks of mixing Fentanyl and alcohol apply in the case of using a patch.

Can I drive after taking Fentanyl?

You should not plan on driving or doing anything that requires you to be awake and alert right after you are treated with this medication.

How many time can I take Fentanyl daily?

Do not use Fentanyl more than four times a day.

How many time can I take Fentanyl daily?

Yes. It does not have any side effects like acidity / gastritis if taken on empty stomach.

How long should Fentanyl be administered?

Onset of action after IV administration of Fentanyl is 3-5 minutes; duration of action is 30-60 minutes. Women should be observed closely for signs of adverse reaction and possible respiratory distress.

How long does Fentanyl stay in my system?

Fentanyl will usually show up on a urine test between 24-72 hours after last use. Hair tests can detect the drug for up to 3 months, and blood tests can detect it between 5 and 48 hours after use depending on the dose.

Who should not take Fentanyl?

You should not use Fentanyl unless you recently used opioid medicine and your body is tolerant to it (ask your doctor if you're not sure). Do not put a fentanyl skin patch on any person who does not have a personal prescription for this medicine. You should not use Fentanyl if you are allergic to it, or if you have: severe asthma or other breathing problems; or a stomach or bowel obstruction (including paralytic ileus).

What happens if I miss a dose?

If you are using the skin patches on a schedule, apply the missed patch as soon as you remember. Continue wearing the patch for up to 72 hours and then apply a new one if needed for pain. Do not wear extra patches to make up a missed dose.

What happens if I overdose?

Seek emergency medical attention. A Fentanyl overdose can be fatal, especially in a child or other person using the medicine without a prescription. Overdose symptoms may include slow breathing and heart rate, severe drowsiness, muscle weakness, cold and clammy skin, pinpoint pupils, and fainting.

Is Fentanyl hard on the heart?

When someone uses an opioid like fentanyl chronically, it can lead to a condition called long Q-T syndrome, where the electrical conduction of the heart is slowed and the heart's natural rhythm is disrupted. This can even happen with short-term opioid use.

Can Fentanyl affect my kidneys?

Direct and indirect effects of anesthesia and surgical stress can affect kidney function.

Can Fentanyl affects my liver?

Although Fentanyl has many serious side effects and has been implicated in deaths from overdose and inadvertent use, it has not been linked to cases of clinically apparent liver injury.

Will Fentanyl affect my fertility?

Fentanyl generally has been shown to lower fertility in men.

*** Taking medicines without doctor's advice can cause long-term problems.
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