Fentanyl

What is Fentanyl?

• Fentanyl (Abstral; Actiq; Fentora; Onsolis) is an opioid agonist used for management of severe pain and as an adjunct to general anesthesia.
• Fentanyl and its congeners are controlled substances and classified as Schedule II drugs, indicating that they have medical usefulness, but also a high potential for physical and psychological dependency and abuse. Indeed, deaths have been reported due to fentanyl patches and transbuccal formulations either from inadvertent overdose, accidental ingestion (by children for instance) or abuse.

Fentanyl

Fentanyl3Dan2

What are the uses of this medicine?

Fentanyl (Abstral; Actiq; Fentora; Onsolis) is used for:

• analgesic action of short duration during the anesthetic periods, premedication, induction and maintenance, and in the immediate postoperative period (recovery room) as the need arises.
• use as a narcotic analgesic supplement in general or regional anesthesia.
• administration with a neuroleptic as an anesthetic premedication, for the induction of anesthesia and as an adjunct in the maintenance of general and regional anesthesia.
• use as an anesthetic agent with oxygen in selected high risk patients, such as those undergoing open heart surgery or certain complicated neurological or orthopedic procedures.

Other forms of Fentanyl: Alfentanil (al fen’ ta nil) is a structural analogue of fentanyl, which has a very short onset of action (5 to 10 minutes) and is approved for use as an adjunct to general anesthesia.

• Alfentanil is available as a solution for intravenous use in anesthesia generically and under the trade name Alfenta.
• It has similar adverse effects as fentanyl, but is not used for chronic pain management and should be used only by medical personnel trained in the use of intravenous anesthesia.

Remifentanil (rem” i fen’ ta nil) is a structural analogue of fentanyl, but has a very short onset and duration of action with a rapid dissipation of activity even after prolonged infusions.

• Remifentanil is available as a solution under the brand name Ultiva for intravenous use in anesthesia.
• It has similar adverse effects as fentanyl, but is not used for chronic pain management and should be used only by medical personnel trained in the use of intravenous anesthesia.

Sufentanil (soo fen’ ta nil) is a structural analogue of fentanyl, which is 10 times more potent and is generally reserved for anesthesia in patients with opioid tolerance or opioid dependence.

• It is potent enough to overcome the actions of partial opiate antagonists such as buprenorphine.
• Sufentanil was approved for use in the United States in 1984.
• Sufentanil is available as a solution for intravenous and epidural use in anesthesia generically and under the brand name Sufenta.
• It has similar adverse effects as fentanyl, but is not used for chronic pain management and should be used only by medical personnel trained in the use of intravenous anesthesia.

How does this medicine work?

• Fentanyl (fen’ tan il) is a synthetic phenylpiperidine which shares similar pain relieving activities with morphine, but is 50 to 100 times more potent.
• Like morphine, fentanyl is an agonist for the µ type opiate receptors which are found in the central nervous system but also on heart, lung, vascular and intestinal cells.
• Fentanyl has a rapid onset and short duration of action, making it particularly effective in anesthesia induction as well as maintenance.

What drug interactions can this medicine cause?

• Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.

Especially tell your doctor if you take:

• amiodarone (Nexterone, Pacerone)
• certain antibiotics such as clarithromycin (Biaxin, in PrevPac), erythromycin (Erythocin), telithromycin (Ketek), and troleandomycin (TAO) (not available in the US)
• certain antifungals such as fluconazole (Diflucan), itraconazole (Onmel, Sporanox), and ketoconazole (Nizoral); aprepitant (Emend)
• benzodiazepines such as alprazolam (Xanax), chlordiazepoxide (Librium), clonazepam (Klonopin), diazepam (Diastat, Valium), estazolam, flurazepam, lorazepam (Ativan), oxazepam, temazepam (Restoril), and triazolam (Halcion); cimetidine (Tagamet)
• diltiazem (Cardizem, Taztia, Tiazac, others)
• certain medications for human immunodeficiency virus (HIV) such as amprenavir (Agenerase), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), and saquinavir (Invirase)
• medications for mental illness and nausea
• muscle relaxants
• nefazodone
• sedatives
• sleeping pills
• tranquilizers
• verapamil (Calan, Covera, Verelan)
• antihistamines
• barbiturates such as phenobarbital
• buprenorphine (Buprenex, Subutex, in Suboxone)
• butorphanol (Stadol)
• carbamazepine (Carbatrol, Epitol, Tegretol)
• efavirenz (Sustiva, in Atripla)
• modafinil (Provigil)
• albuphine (Nubain)
• naloxone (Evzio, Narcan)
• nevirapine (Viramune)
• oral steroids such as dexamethasone, methylprednisolone (Medrol), and prednisone (Rayos)
• oxcarbazepine (Trileptal)
• pentazocine (Talwin)
• phenytoin (Dilantin, Phenytek)
• pioglitazone (Actos, in Actoplus Met, in Duetact)
• rifabutin (Mycobutin)
• rifampin (Rifadin, Rimactane, in Rifamate, in Rifater)
• St. John's wort.

Also tell your doctor or pharmacist if you are taking any of the following medications or if you have stopped taking them within the past two weeks:

• monoamine oxidase (MAO) inhibitors including isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate).

Is this medicine FDA approved?

• Fentanyl was approved for use in general anesthesia in the United States in 1968 and is still widely used in anesthesia practice.
• With the development of transdermal and buccal formulations of fentanyl, it was approved for use in pain management and has become the most widely used synthetic opioid in clinical practice.
• Current indications are as an adjunct to general anesthesia (intravenous, epidural or intrathecal) and for management of moderate-to-severe pain that is not responsive to nonopiate analgesics.
• Fentanyl is available in multiple formulations, including solutions for injection in multiple concentrations for anesthesia and acute pain management, and as transdermal patches, oral tablets and lozenges and nasal sprays for management of chronic pain.

How should this medicine be used?

Recommended dosage: Premedication in Adults:

• 50 to 100 mcg (0.05 to 0.1 mg) (1 to 2 mL) may be administered intramuscularly 30 to 60 minutes prior to surgery.

Adjunct to Regional Anesthesia:

• 50 to 100 mcg (0.05 to 0.1 mg) (1 to 2 mL) may be administered intramuscularly or slowly intravenously, over one to two minutes, when additional analgesia is required.

Postoperatively (recovery room):

• 50 to 100 mcg (0.05 to 0.1 mg) (1 to 2 mL) may be administered intramuscularly for the control of pain, tachypnea and emergence delirium.
• The dose may be repeated in one to two hours as needed.

For Induction and Maintenance in Children 2 to 12 Years of Age:

• A reduced dose as low as 2 to 3 mcg/kg is recommended.

As a General Anesthetic:

• As a technique to attenuate the responses to surgical stress without the use of additional anesthetic agents, doses of 50 to 100 mcg/kg (0.05 to 0.1 mg/kg) (1 to 2 mL/kg) may be administered with oxygen and a muscle relaxant.
• In certain cases, doses up to 150 mcg/kg (0.15 mg/kg) (3 mL/kg) may be necessary to produce this anesthetic effect.

Administration:

• Fentanyl comes as a lozenge on a handle (Actiq), a sublingual tablet (Abstral), a film (Onsolis), and a buccal tablet (Fentora) to dissolve in the mouth. Fentanyl is used as needed to treat breakthrough pain but not more often than four times a day.
• Your doctor will probably start you on a low dose of fentanyl and gradually increase your dose until you find the dose that will relieve your breakthrough pain.
• If you still have pain 30 minutes after using fentanyl films (Onsolis), your doctor may tell you to use another pain medication to relieve that pain, and may increase your dose of fentanyl films (Onsolis) to treat your next episode of pain .
• Talk to your doctor about how well the medication is working and whether you are experiencing any side effects so that your doctor can decide whether your dose should be adjusted.
• Do not use fentanyl more than four times a day.
• Swallow the buccal tablet whole; do not split, chew, or crush.
• Also do not chew or bite the lozenge on a handle; only suck on this medication as directed.
• Do not stop using fentanyl without talking to your doctor.
• Your doctor may decrease your dose gradually.
• If you suddenly stop using fentanyl, you may experience unpleasant withdrawal symptoms.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As a lozenge on a handle (Actiq), a sublingual (underneath the tongue) tablet (Abstral), a film (Onsolis), and a buccal (between the gum and cheek) tablet (Fentora) to dissolve in the mouth.

This medicine is available in fallowing brand namesː

• Abstral; Actiq; Fentora; Onsolis

What side effects can this medication cause?

The most common side effects of this medicine include:

• respiratory depression, apnea, rigidity, and bradycardia; if these remain untreated, respiratory arrest, circulatory depression or cardiac arrest could occur.

• Other adverse reactions that have been reported are hypertension, hypotension, dizziness, blurred vision, nausea, emesis, diaphoresis, pruritus, urticaria, laryngospasm and anaphylaxis.

When a tranquilizer is used with Fentanyl Citrate Injection, the following adverse reactions can occur:

• chills and/or shivering, restlessness, and postoperative hallucinatory episodes (sometimes associated with transient periods of mental depression); extrapyramidal symptoms (dystonia, akathisia, and oculogyric crisis) have been observed up to 24 hours postoperatively.

• Cases of cardiac dysrhythmias, cardiac arrest, and death have been reported following the use of fentanyl citrate with a neuroleptic agent.

Fentanyl can cause serious side effects, including:

• Addiction, Abuse, and Misuse
• Life-Threatening Respiratory Depression
• Interactions with Benzodiazepines or Other CNS Depressants
• Severe Cardiovascular Depression
• Serotonin Syndrome
• Gastrointestinal Adverse Reactions
• Seizures
• Adrenal insufficiency
• Anaphylaxis
• Androgen deficiency

What special precautions should I follow?

• Fentanyl Citrate Injection contains fentanyl, a Schedule II controlled substance. As an opioid, Fentanyl Citrate Injection exposes users to the risks of addiction, abuse, and misuse.
• Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. To reduce the risk of respiratory depression, proper dosing and titration of Fentanyl Citrate Injection are essential. As with other potent opioids, the respiratory depressant effect of Fentanyl Citrate Injection may persist longer than the measured analgesic effect.
• Fentanyl Citrate Injection may cause muscle rigidity, particularly involving the muscles of respiration. Manage with neuromuscular blocking agent.
• Fentanyl Citrate Injection may cause severe bradycardia, severe hypotension including orthostatic hypotension, and syncope. Monitor these patients for signs of hypotension after initiating or titrating the dosage of Fentanyl Citrate Injection.
• Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of fentanyl with serotonergic drugs. Potentially life-threatening condition could result from concomitant serotonergic drug administration. Discontinue Fentanyl Citrate Injection if serotonin syndrome is suspected.
• Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid.
• Fentanyl Citrate Injection may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of increasing intracranial pressure.
• Fentanyl may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms.
• Fentanyl may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during Fentanyl Citrate Injection therapy.
• Fentanyl Citrate Injection may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery after Fentanyl Citrate Injection administration.
• Many neuroleptic agents have been associated with QT prolongation, torsades de pointes, and cardiac arrest. ECG monitoring is indicated when a neuroleptic agent is used in conjunction with Fentanyl Citrate Injection as an anesthetic premedication, for the induction of anesthesia, or as an adjunct in the maintenance of general or regional anesthesia. When Fentanyl Citrate Injection is used with a neuroleptic and an EEG is used for postoperative monitoring, the EEG pattern may return to normal slowly.
• If you will be using the lozenges (Actiq), talk to your dentist about the best way to care for your teeth during your treatment. The lozenges contain sugar and may cause tooth decay and other dental problems.
• Fentanyl may cause constipation. Talk to your doctor about changing your diet and using other medications to treat or prevent constipation.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death.
• Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations

Management of overdosage:

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.
• In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques.
• The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose.
• In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome.
• If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be initiated with care and by titration with smaller than usual doses of the antagonist.

Can this medicine be used in pregnancy?

• Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome.
• Available data with Fentanyl Citrate Injection in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage.

Can this medicine be used in children?

• The safety and efficacy of Fentanyl Citrate Injection in children under two years of age have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• FENTANYL CITRATE

Inactive ingredient:

• Sodium Hydroxide

Who manufactures and distributes this medicine?

Manufactured by:

• Akorn
• Lake Forest, IL

What should I know about storage and disposal of this medication?

• Store at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).
• Protect from light.

• Dailymed label info on Fentanyl
• FDA Fentanyl

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