Fentanyl is an active pharmaceutical ingredient in the Opioid Anesthetics group (N01AH). The information below is compiled per regulator from the product labels on record, with direct links to the original documents.
GBOfficial regulatory label· revised June 9, 2023[1]
Fentanyl is indicated for the treatment of breakthrough pain (BTP) in adults with cancer who are already receiving maintenance opioid therapy for chronic cancer pain. BTP is a transitory exacerbation of pain that occurs on a background of otherwise controlled persistent pain.
Patients receiving maintenance opioid therapy are those who are taking at least 60 mg of oral morphine daily, at least 25 micrograms of transdermal fentanyl per 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.
How to take
CACanada· Health Canada
24 products
Uses
CAOfficial regulatory label· revised March 22, 2025[2]
FENTORA (fentanyl buccal/sublingual effervescent tablets) is indicated only for the management of breakthrough pain in cancer patients 18 years of age and older who are already receiving and who are tolerant to continuous opioid therapy for their persistent baseline cancer pain.
Patients considered opioid tolerant are those who are taking at least 60 mg of oral morphine daily or an equianalgesic dose of another opioid daily for a week or longer (see 7 WARNINGS AND PRECAUTIONS). All patients starting treatment with FENTORA must begin with titration from the 100 mcg dose (see 4 DOSAGE AND ADMINISTRATION).
This product must not be used in opioid non-tolerant patients because life-threatening respiratory depression and death could occur at any dose in patients not on a chronic regimen of opioids. For this reason, FENTORA is contraindicated in the management of acute or post- operative pain, including headache/migraine, dental pain or use in the emergency room.
EUEuropean Union· EMA
3 products
Uses
EUOfficial regulatory label· revised January 19, 2026[3]
Effentora is indicated for the treatment of breakthrough pain (BTP) in adults with cancer who are already receiving maintenance opioid therapy for chronic cancer pain. BTP is a transitory exacerbation of pain that occurs on a background of otherwise controlled persistent pain.
Patients receiving maintenance opioid therapy are those who are taking at least 60 mg of oral morphine daily, at least 25 micrograms of transdermal fentanyl per 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.
How to take
USUnited States· FDA
1 product
Uses
USOfficial regulatory label· revised September 24, 2025[4]
1 INDICATIONS AND USAGE Fentanyl Citrate Injection is indicated 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. Fentanyl Citrate Injection is indicated 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 an opioid 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.
Drug interactions
Known interactions involving Fentanyl. Select one for details. This list is informational and not a complete interaction checker.
Showing 240 of 600. Type above to find a specific drug.
Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
[1]MHRA (UK) · PLGB514630058 · revised June 9, 2023
[2]Health Canada (DPD) · 02408007 · revised March 22, 2025
[3]European Medicines Agency · EMEA/H/C/000833 · revised January 19, 2026
[4]FDA DailyMed · 0c10e465-4117-48… · revised September 24, 2025 [PDF]
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
GBOfficial regulatory label· revised June 9, 2023[1]
4). Treatment should be initiated by and remain under the guidance of a physician experienced in the management of opioid therapy in cancer patients. Physicians should keep in mind the potential of abuse of fentanyl. Patients should be instructed not to use two different formulations of fentanyl concurrently for the treatment of breakthrough pain, and to dispose of any fentanyl product prescribed for BTP when switching to Fentanyl.
The number of tablet strengths available to the patients at any time should be minimised to prevent confusion and potential overdose. Fentanyl should be administered directly under the tongue at the deepest part. Fentanyl should not be swallowed, but allowed to completely dissolve in the sublingual cavity without chewing or sucking.
Patients should be advised not to eat or drink anything until the sublingual tablet is completely dissolved. After 30 minutes, if remnants from the Fentanyl tablet remain, they may be swallowed. In patients who have a dry mouth, water may be used to moisten the buccal mucosa before taking Fentanyl.
4 for warnings in children). Patients should be advised to keep Fentanyl in a locked storage space. Dose Titration Before patients are titrated with Fentanyl, it is expected that their background persistent pain will be controlled by use of opioid therapy and that they are typically experiencing no more than 4 episodes of breakthrough pain per day.
The object of dose titration is to identify an optimal maintenance dose for ongoing treatment of breakthrough pain episodes. This optimal dose should provide adequate analgesia with an acceptable level of adverse reactions. The optimal dose of Fentanyl will be determined by upward titration, on an individual patient basis.
Several doses are available for use during the dose titration phase. The initial dose of Fentanyl used should be 133 micrograms, titrating upwards as necessary through the range of available dosage strengths. Patients should be carefully monitored until an optimal dose is reached.
4). Switching from other fentanyl containing products to Fentanyl must not occur at a 1:1 ratio because of different absorption profiles. If patients are switched from another fentanyl containing product, a new dose titration with Fentanyl is required.
The following dose regimen is recommended for titration, although in all cases the physicianshould take into account the clinical need of the patient, age and concomitant illness. All patients must start therapy with a single 133 micrograms sublingual tablet.
If adequate analgesia is not obtained within 15-30 minutes of administration of a single tablet, a supplemental (second) 133 micrograms tablet may be administered. If treatment of a breakthrough pain episode requires more than one dosage unit, an increase in dose to the next higher available strength should be considered (Refer to figure below).
Dose escalation should continue in a stepwise manner until adequate analgesia is achieved. The dose strength for the supplemental (second) tablet should be increased from 133 to 267 micrograms at doses of 533 micrograms. This is illustrated in the schedule below.
No more than two (2) tablets should be administered for a single episode of breakthrough pain during this titration phase. FENTANYL TITRATION PROCESS Strength (micrograms) of first tablet per episode of breakthrough pain Strength (micrograms) of supplemental (second) tablet to be taken 15-30 minutes after first tablet, if required 133 133 267 133 400 133 533 267 800 - If adequate analgesia is achieved at the higher dose, but undesirable effects are considered unacceptable, an intermediate dose may be administered (using the 67 micrograms or 133 micrograms tablet).
Doses higher than 800 micrograms have not been evaluated in clinical studies. In order to minimise the risk of opioid–related adverse reactions and to identify the appropriate dose, it is imperative that patients be monitored closely by health professionals during the titration process.
Maintenance therapy Once an appropriate dose has been established, which may be more than one tablet, patients should be maintained on this dose and should limit consumption to a maximum of four Fentanyl doses per day. Dose re-adjustment If the response (analgesia or adverse reactions) to the titrated Fentanyl dose markedly changes, an adjustment of dose may be necessary to ensure that an optimal dose is maintained.
If more than four episodes of breakthrough pain are consistently experienced per day, then the dose of the long acting opioid used for persistent pain should be re-evaluated. If the long acting opioid or dose of long acting opioid is changed, the Fentanyl dose should be re- evaluated and re-titrated as necessary to ensure the patient is on an optimal dose.
It is imperative that any dose re-titration of any analgesic is monitored by a health professional. Discontinuation of therapy Fentanyl should be discontinued immediately if the patient no longer experiences breakthrough pain episodes.
The treatment for the persistent background pain should be kept as prescribed. If discontinuation of all opioid therapy is required, the patient must be closely followed by the doctor in order to manage the risk of abrupt withdrawal effects.
Use in elderly patients Dose titration needs to be approached with particular care and patients observed carefully for signs of fentanyl toxicity (see […]
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised June 9, 2023[1]
Typical opioid side effects are to be expected with Fentanyl. Frequently, these will cease or decrease in intensity with continued use of the product, as the patient is titrated to the most appropriate dose. However, the most serious adverse reactions are respiratory depression (potentially leading to apnoea or respiratory arrest), circulatory depression, hypotension and shock and all patients should be closely monitored for these.
Application site reactions, including gum bleeding, irritation, pain and ulcer have been reported in post-marketing use. Because the clinical trials of fentanyl were designed to evaluate safety and efficacy in treating breakthrough pain, all patients were also taking concomitant opioids, such as sustained-release morphine or transdermal fentanyl, for their persistent pain.
Thus it is not possible to definitively separate the effects of fentanyl alone. The following adverse reactions have been reported with Fentanyl and/or other fentanyl-containing compounds during clinical studies and post marketing experience.
6), Withdrawal CCRF21093 0009 syndrome*, pyrexia Investigations Weight decreased Injury, poisoning and procedural complications accidental injury (for example, falls) *opioid withdrawal symptoms, such as nausea, vomiting, diarrhoea, anxiety, chills, tremor andsweating have been observed with transmucosal fentanyl.
Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme.
uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
GBOfficial regulatory label· Warnings and precautions· revised June 9, 2023[1]
Accidental use in children Patients and their carers must be instructed that Fentanyl contains an active substance in an amount that can be fatal to a child. Death has been reported in children who have accidentally ingested Fentanyl.
Patients and their carers must be instructed to keep all units out of the sight and reach of children and to discard open and unopened units appropriately. An evaluation of each out-patient concerning possible accidental child exposures should be undertaken.
Maintenance opioid therapy The product must not be given to patients without maintenance opioid therapy as there is an increased risk of respiratory depression and death. It is important that the long acting opioid treatment used to treat the patient’s persistent pain has been stabilised before Fentanyl therapy begins and that the patient continues to be treated with the long acting opioid treatment whilst taking Fentanyl.
Drug dependence, tolerance and potential for abuse For all patients, prolonged use of this product may lead to drug dependence (addiction), even at therapeutic doses. , major depression). Additional support and monitoring may be necessary when prescribing for patients at risk of opioid misuse.
A comprehensive patient history should be taken to document concomitant medications, including over-the-counter medicines and medicines obtained on-line, and past and present medical and psychiatric conditions. Patients may find that treatment is less effective with chronic use and express a need to increase the dose to obtain the same level of pain control as initially experienced.
Patients may also supplement their treatment with additional pain relievers. These could be signs that the patient is developing tolerance. The risks of developing tolerance should be explained to the patient. Overuse or misuse may result in overdose and/or death.
It is important that patients only use medicines that are prescribed for them at the dose they have been prescribed and do not give this medicine to anyone else. Patients should be closely monitored for signs of misuse, abuse, or addiction.
The clinical need for analgesic treatment should be reviewed regularly. Tolerance, physical and psychological dependence may develop upon repeated administration of opioids such as fentanyl. However, iatrogenic addiction following therapeutic use of opioids is known to occur.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised June 9, 2023[1]
1. 1) as there is an increasedrisk of respiratory depression. 5). • Severe respiratory depression or severe obstructive lung conditions. • Treatment of acute pain other than breakthrough pain. • Patients being treated with medicinal products containing sodium oxybate.
• Contraindicated in opioid naive patients
This is not medical advice. Consult a qualified healthcare professional.
FENTORA is contraindicated in all post-operative pain, including post-operative cancer pain if the patient is not already opioid tolerant. The addition of the qualifier “non cancer” may be confusing as it could be interpreted to mean that FENTORA can be used for post- operative pain after surgery for cancer or post-operatively for cancer pain, both of which can occur in opioid non-tolerant patients.
The term “post-operative” already implies that the pain is due to surgery and not to cancer. FENTORA is intended to be used only in the care of opioid tolerant cancer patients and only by healthcare professionals who are knowledgeable of and skilled in the use of opioids to treat cancer pain.
3 Pediatrics). 4 Geriatrics). Patients over the age of 65 years tended to titrate to slightly lower doses than younger patients. Patients over the age of 65 years reported a slightly higher frequency for some adverse events specifically vomiting, constipation, and abdominal pain.
Therefore, caution should be exercised in individually titrating FENTORA in elderly patients to provide adequate efficacy while minimizing risk. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, concomitant disease or other drug therapy (see 10 CLINICAL PHARMACOLOGY, Special Populations and Conditions, Geriatrics).
How to take
CAOfficial regulatory label· revised March 22, 2025[2]
). This product must not be used in opioid non-tolerant patients because life-threatening respiratory depression and death could occur at any dose in patients not on a chronic regimen of opioids. For this reason, FENTORA is contraindicated in the management of acute or post- operative pain, including headache/migraine, dental pain or use in the emergency room.
Note:
FENTORA is contraindicated in all post-operative pain, including post-operative cancer pain if the patient is not already opioid tolerant. The addition of the qualifier “non cancer” may be confusing as it could be interpreted to mean that FENTORA can be used for post- operative pain after surgery for cancer or post-operatively for cancer pain, both of which can occur in opioid non-tolerant patients.
The term “post-operative” already implies that the pain is due to surgery and not to cancer. FENTORA is intended to be used only in the care of opioid tolerant cancer patients and only by healthcare professionals who are knowledgeable of and skilled in the use of opioids to treat cancer pain.
3 Pediatrics). 4 Geriatrics). Patients over the age of 65 years tended to titrate to slightly lower doses than younger patients. Patients over the age of 65 years reported a slightly higher frequency for some adverse events specifically vomiting, constipation, and abdominal pain.
Therefore, caution should be exercised in individually titrating FENTORA in elderly patients to provide adequate efficacy while minimizing risk. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, concomitant disease or other drug therapy (see 10 CLINICAL PHARMACOLOGY, Special Populations and Conditions, Geriatrics).
2 CONTRAINDICATIONS • Opioid non-tolerant patients (use in acute or post-operative pain, including headache/migraine, dental pain or use in the emergency room). • Patients who are hypersensitive to the active substance, fentanyl citrate, or other opioid analgesics or to any ingredient in the formulation.
For a complete listing, see
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
CAOfficial regulatory label· Adverse reactions· revised March 22, 2025[2]
2 DOSAGE AND ADMINISTRATION, Adjustment or Reduction of Dosage). The administration of FENTORA should be guided by the response of the patient. Physical dependence, per se, is not ordinarily a concern when one is treating a patient with cancer and chronic pain, and fear of tolerance and physical dependence should not deter using doses that adequately relieve the pain.
FENTORA is an opioid with no approved use in the management of addictive disorders. Its proper usage in individuals with drug or alcohol dependence, either active or in remission, is for the management of breakthrough cancer pain requiring opioid analgesia.
Patients with a history of addiction to drugs or alcohol may be at higher risk of becoming addicted to FENTORA; extreme caution and awareness is warranted to mitigate the risk. Driving and Operating Machinery FENTORA may impair the mental and/or physical abilities needed for certain potentially hazardous activities such as driving a car or operating machinery.
Patients should be cautioned, accordingly. Patients should also be cautioned about the combined effects of fentanyl with other CNS depressants, including other opioids, phenothiazine, sedative/hypnotics, and alcohol or gabapentinioids (gabapentin or pregabalin).
Endocrine Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure.
If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal Product Monograph FENTORA fentanyl Page 20 of 69 Internal Use Only function to recover and continue corticosteroid treatment until adrenal function recovers.
Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.
Gastrointestinal FENTORA and other morphine-like opioids have been shown to decrease bowel motility. Fentanyl may obscure the diagnosis or clinical course of patients with acute abdominal conditions (see 2 CONTRAINDICATIONS).
Serotonin toxicity, also known as serotonin syndrome, is a potentially life-threatening condition and has been reported with opioids, including FENTORA, particularly during combined use with other serotonergic drugs. (See
CAOfficial regulatory label· Warnings and precautions· revised March 22, 2025[2]
). All patients starting treatment with FENTORA must begin with titration from the 100 mcg dose (see 4 DOSAGE AND ADMINISTRATION). This product must not be used in opioid non-tolerant patients because life-threatening respiratory depression and death could occur at any dose in patients not on a chronic regimen of opioids.
For this reason, FENTORA is contraindicated in the management of acute or post- operative pain, including headache/migraine, dental pain or use in the emergency room.
Note:
FENTORA is contraindicated in all post-operative pain, including post-operative cancer pain if the patient is not already opioid tolerant. The addition of the qualifier “non cancer” may be confusing as it could be interpreted to mean that FENTORA can be used for post- operative pain after surgery for cancer or post-operatively for cancer pain, both of which can occur in opioid non-tolerant patients.
The term “post-operative” already implies that the pain is due to surgery and not to cancer. FENTORA is intended to be used only in the care of opioid tolerant cancer patients and only by healthcare professionals who are knowledgeable of and skilled in the use of opioids to treat cancer pain.
3 Pediatrics). 4 Geriatrics). Patients over the age of 65 years tended to titrate to slightly lower doses than younger patients. Patients over the age of 65 years reported a slightly higher frequency for some adverse events specifically vomiting, constipation, and abdominal pain.
Therefore, caution should be exercised in individually titrating FENTORA in elderly patients to provide adequate efficacy while minimizing risk. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, concomitant disease or other drug therapy (see 10 CLINICAL PHARMACOLOGY, Special Populations and Conditions, Geriatrics).
2 CONTRAINDICATIONS • Opioid non-tolerant patients (use in acute or post-operative pain, including headache/migraine, dental pain or use in the emergency room). • Patients who are hypersensitive to the active substance, fentanyl citrate, or other opioid analgesics or to any ingredient in the formulation.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
CAOfficial regulatory label· Contraindications· revised March 22, 2025[2]
• Opioid non-tolerant patients (use in acute or post-operative pain, including headache/migraine, dental pain or use in the emergency room). • Patients who are hypersensitive to the active substance, fentanyl citrate, or other opioid analgesics or to any ingredient in the formulation.
For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. Anaphylaxis and hypersensitivity have been reported in association with the use of oral transmucosal fentanyl products. , ileus of any type). , acute appendicitis or pancreatitis).
• Patients with acute or severe bronchial asthma, chronic obstructive airway, or status asthmaticus. • Patients with acute respiratory depression, elevated carbon dioxide levels in the blood and cor pulmonale. • Patients with acute alcoholism, delirium tremens, and convulsive disorders.
• Patients with severe CNS depression, increased cerebrospinal or intracranial pressure, and head injury. • Patients taking monoamine oxidase (MAO) inhibitors (or within 14 days of such therapy). Product Monograph FENTORA fentanyl Page 6 of 69 Internal Use Only
This is not medical advice. Consult a qualified healthcare professional.
EUOfficial regulatory label· revised January 19, 2026[3]
Treatment should be initiated by and remain under the guidance of a physician experienced in the management of opioid therapy in cancer patients. Physicians should keep in mind the potential of abuse of fentanyl. Patients should be instructed not to use two different formulations of fentanyl concurrently for the treatment of breakthrough pain, and to dispose of any fentanyl product prescribed for BTP when switching to Effentora.
The number of tablet strengths available to the patients at any time should be minimised to prevent confusion and potential overdose. Posology Dose titration Effentora should be individually titrated to an “effective” dose that provides adequate analgesia and minimises adverse reactions.
In clinical studies, the effective dose of Effentora for BTP was not predictable from the daily maintenance dose of opioid. Patients should be carefully monitored until an effective dose is reached. Titration in patients not switching from other fentanyl containing products The initial dose of Effentora should be 100 micrograms, titrating upwards as necessary through the range of available tablets strengths (100, 200, 400, 600, 800 micrograms).
Titration in patients switching from other fentanyl containing products Due to different absorption profiles, switching must not be done at a 1:1 ratio. If switching from another oral fentanyl citrate product, independent dose titration with Effentora is required as bioavailability between products differs significantly.
However, in these patients, a starting dose higher than 100 micrograms may be considered. Method of titration During titration, if adequate analgesia is not obtained within 30 minutes after the start of administration of a single tablet, a second Effentora tablet of the same strength may be used.
If treatment of a BTP episode requires more than one tablet, an increase in dose to the next higher available strength should be considered to treat the next BTP episode. During titration, multiple tablets may be used: up to four 100 micrograms or up to four 200 micrograms tablets may be used to treat a single episode of BTP during dose titration according to the following schedule: 4 • If the initial 100 micrograms tablet is not efficacious, the patient can be instructed to treat the next episode of BTP with two 100 micrograms tablets.
It is recommended that one tablet should be placed in each side of the mouth. If this dose is considered to be the effective dose, treatment of successive episodes of BTP may be continued with a single 200 micrograms tablet of Effentora.
• If a single 200 micrograms tablet of Effentora (or two 100 micrograms tablets) is not considered to be efficacious the patient can be instructed to use two 200 micrograms tablets (or four 100 micrograms tablets) to treat the next episode of BTP.
It is recommended that two tablets should be placed in each side of the mouth. If this dose is considered to be the effective dose, treatment of successive episodes of BTP may be continued with a single 400 micrograms tablet of Effentora.
• For titration to 600 micrograms and 800 micrograms, tablets of 200 micrograms should be used. Doses above 800 micrograms were not evaluated in clinical studies. No more than two tablets should be used to treat any individual BTP episode, except when titrating using up to four tablets as described above.
Patients should wait at least 4 hours before treating another BTP episode with Effentora during titration. Maintenance therapy Once an effective dose has been established during titration, patients should continue to take this dose as a single tablet of that given strength.
Breakthrough pain episodes may vary in intensity and the required Effentora dose might increase over time due to progression of the underlying cancer disease. In these cases, a second tablet of the same strength may be used. If a second tablet of Effentora was required for several consecutive times, the usual maintenance dose is to be readjusted (see below).
Patients should wait at least 4 hours before treating another BTP episode with Effentora during maintenance therapy. Dose readjustment The maintenance dose of Effentora should be increased when a patient requires more than one tablet per BTP episode for several consecutive BTP episodes.
For dose-readjustment the same principles apply as outlined for dose titration (see above). Dose readjustment of the background opioid therapy may be required if patients consistently present with more than four BTP episodes per 24 hours.
4). Treatment duration and goals Before initiating treatment with Effentora, a treatment strategy including treatment duration and treatment goals, and a plan for end of the treatment, should be agreed together with the patient, in accordance with pain management guidelines.
During treatment, there should be frequent contact between the physician and the patient to evaluate the need for continued treatment, consider discontinuation and to adjust dosages if needed. 4). Effentora should not be used longer than necessary.
Discontinuation of therapy Effentora should be discontinued immediately if the patient no longer experiences breakthrough pain episodes. The treatment for the persistent background pain should be kept as prescribed. If discontinuation of all opioid therapy is required, the patient must be closely followed by the doctor in order to manage the risk of abrupt withdrawal effects.
4). Patients with xerostomia Patients experiencing xerostomia are advised to drink water to moisten […]
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
EUOfficial regulatory label· Adverse reactions· revised January 19, 2026[3]
Summary of the safety profile Typical opioid adverse reactions are to be expected with Effentora. Frequently, these will cease or decrease in intensity with continued use of the medicinal product, as the patient is titrated to the most appropriate dose.
However, the most serious adverse reactions are respiratory depression (potentially leading to apnoea or respiratory arrest), circulatory depression, hypotension and shock and all patients should be closely monitored for these. The clinical studies of Effentora were designed to evaluate safety and efficacy in treating BTP and all patients were also taking concomitant opioids, such as sustained-release morphine or transdermal fentanyl, for their persistent pain.
Therefore it is not possible to definitively separate the effects of Effentora alone. Tabulated list of adverse reactions The following adverse reactions have been reported with Effentora and/or other fentanyl-containing compounds during clinical studies and post marketing experience.
6) Drug tolerance Investigations Weight decreased Platelet count decreased Heart rate increased Haematocrit decreased Haemoglobin decreased Injury, poisoning and procedural complications Fall * See section Description of selected adverse reactions Description of selected adverse reactions Tolerance Tolerance can develop on repeated use.
Drug dependence Repeated use of Effentora can lead to drug dependence, even at therapeutic doses. 4). Opioid withdrawal symptoms such as nausea, vomiting, diarrhoea, anxiety, chills, tremor and sweating have been observed with transmucosal fentanyl.
9). 4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
EUOfficial regulatory label· Warnings and precautions· revised January 19, 2026[3]
Because of the risks, including fatal outcome, associated with accidental exposure, misuse, and abuse, patients and their carers must be advised to keep Effentora in a safe and secure place, not accessible by others. Accidental use in children Patients and their carers must be instructed that Effentora contains an active substance in an amount that can be fatal, especially to a child.
Therefore they must keep all tablets out of the sight and reach of children. Monitoring In order to minimise the risks of opioid-related undesirable effects and to identify the effective dose, it is imperative that patients be monitored closely by health professionals during the titration process.
Maintenance opioid treatment It is important that the maintenance opioid treatment used to treat the patient’s persistent pain has been stabilised before Effentora therapy begins and that the patient continues to be treated with the maintenance opioid treatment whilst taking Effentora.
The product must not be given to patients without maintenance opioid therapy as there is an increased risk of respiratory depression and death. Respiratory depression As with all opioids, there is a risk of clinically significant respiratory depression associated with the use of fentanyl.
, use in patients without maintenance opioid therapy) and/or improper dosing have resulted in fatal outcome with Effentora as well as with other fentanyl products. 1. Chronic obstructive pulmonary disease Particular caution should be used when titrating Effentora in patients with non-severe chronic obstructive pulmonary disease or other medical conditions predisposing them to respiratory depression, as even normally therapeutic doses of Effentora may further decrease respiratory drive to the point of respiratory failure.
Sleep-related breathing disorders Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep- related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the total opioid dosage.
5). 7 Risks of concomitant administration with benzodiazepines or related drugs Concomitant use of opioids, including Effentora, with benzodiazepines or related drugs may result in profound sedation, respiratory depression, coma, and death.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
EUOfficial regulatory label· Contraindications· revised January 19, 2026[3]
1. • Patients without maintenance opioid therapy as there is an increased risk of respiratory depression. • Severe respiratory depression or severe obstructive lung conditions. • Treatment of acute pain other than breakthrough pain. • Patients being treated with medicinal products containing sodium oxybate.
This is not medical advice. Consult a qualified healthcare professional.
• 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.
How to take
USOfficial regulatory label· revised September 24, 2025[4]
2 DOSAGE AND ADMINISTRATION • Fentanyl Citrate Injection should be administered only by persons specifically trained in the use of intravenous anesthetics and management of the respiratory effects of potent opioids. 1 ). • Individualize dosing based on the factors such as age, body weight, physical status, underlying pathological condition, use of other drugs, type of anesthesia to be used, and the surgical procedure involved.
1 ) • Initiate treatment in adults with 50 mcg to 100 mcg. 2 ) • Initiate treatment in children 2 to 12 years of age, with a reduced dose as low as 2 mcg/kg to 3 mcg/kg. 1 Important Dosage and Administration Instructions Fentanyl Citrate Injection should be administered only by persons specifically trained in the use of intravenous anesthetics and management of the respiratory effects of potent opioids.
• Ensure that an opioid antagonist, resuscitative and intubation equipment, and oxygen are readily available. • Individualize dosage based on factors such as age, body weight, physical status, underlying pathological condition, use of other drugs, type of anesthesia to be used, and the surgical procedure involved.
• Monitor vital signs routinely. As with other potent opioids, the respiratory depressant effect of fentanyl may persist longer than the measured analgesic effect. The total dose of all opioid agonists administered should be considered by the practitioner before ordering opioid analgesics during recovery from anesthesia.
If Fentanyl Citrate Injection is administered with a CNS depressant, become familiar with the properties of each drug, particularly each product's duration of action. 3 )] . Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
2 Dosage Premedication in Adults 50 mcg to 100 mcg may be administered intramuscularly 30 to 60 minutes prior to surgery. Adjunct to General Anesthesia See Dosage Range Charts below.
Table 1:
Dosage Range Chart Total Dosage (expressed as fentanyl base) Low Dose —2 mcg/kg For use in minor, but painful, surgical procedures. May also provide some pain relief in the immediate postoperative period. Moderate Dose —2 mcg/kg to 20 mcg/kg For use in more major surgical procedures, in addition to adequate analgesia, may abolish some of the stress response.
Expect respiratory depression requiring artificial ventilation during anesthesia and careful observation of ventilation postoperatively is essential. High dose —20 mcg/kg to 50 mcg/kg For open heart surgery and certain more complicated neurosurgical and orthopedic procedures where surgery is more prolonged, and the stress response to surgery would be detrimental to the well-being of the patient.
In conjunction with nitrous oxide/oxygen has been shown to attenuate the stress response as defined by increased levels of circulating growth hormone, catecholamine, ADH and prolactin. Expect the need of postoperative ventilation and observation due to extended post-operative respiratory depression.
Maintenance Dose (expressed as fentanyl base) Low Dose —2 mcg/kg Additional dosages infrequently needed in these minor procedures. Moderate Dose —2 mcg/kg to 20 mcg/kg 25 mcg to 100 mcg Administer intravenously or intramuscularly as needed when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia.
High Dose —20 mcg/kg to 50 mcg/kg Maintenance dosage [ranging from 25 mcg to one half the initial loading dose] as needed based on vital signs indicative of stress and lightening of analgesia. Individualize the dosage especially if the anticipated remaining operative time is short.
Adjunct to Regional Anesthesia 50 mcg to 100 mcg may be administered intramuscularly or slowly intravenously, over one to two minutes, when additional analgesia is required. Postoperatively (recovery room) 50 mcg to 100 mcg 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 mcg/kg 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 mcg/kg to 100 mcg/kg may be administered with oxygen and a muscle relaxant.
In certain cases, doses up to 150 mcg/kg may be necessary to produce this anesthetic effect. It has been used for open heart surgery and certain other major surgical procedures in patients for whom protection of the myocardium from excess oxygen demand is particularly indicated, and for certain complicated neurological and orthopedic procedures.
3 Instructions for Use of Fentanyl Citrate Injection Prefilled Syringe INSTRUCTIONS FOR USE – MicroVault ® Figure 1: Outer Packaging (MicroVault ® ) and Prefilled Syringe NOTES: - Do not introduce any other fluid into the syringe at any time.
- Do not dilute for IV push. - Do not re-sterilize the syringe. - Do not use this product on a sterile field. - This product is for single dose only. 1. Once removed from the bundle, inspect the outer packaging by verifying: - Integrity of the tube and the cap.
- Tamper evident seal is intact (outer shrink wrap is not broken). Do not use if the outer packaging has been damaged. 2. Hold the outer packaging with both hands. To break the tamper evident seal, hold the tube and the cap close to the seal, and twist until broken.
(See Figure 2) Figure 2 3. Remove the cap of the outer packaging by pulling it straight away from the tube to avoid dislodging the plunger rod of the syringe. (See Figure 3) Figure 3 4. Remove the syringe from the tube. 5. Visually inspect the syringe.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. 6. Twist off the syringe tip cap. Do not remove the plastic wrap label around the luer lock collar.
(See Figure 4) Figure 4 7. Expel air bubble(s). Adjust the dose (if applicable). 8. Administer the dose ensuring that pressure is maintained on the plunger rod during the entire administration. 9. Discard the used syringe into an appropriate receptacle.
For more information concerning this drug, please call Fresenius Kabi USA, LLC at 1-800-551-7176.
INSTRUCTIONS FOR USE – Blister Pack Figure 1:
Outer Packaging and Prefilled Syringe NOTES: - Do not introduce any other fluid into the syringe at any time. - Do not dilute for IV push. - Do not re-sterilize the syringe. - Do not use this product on a sterile field. - This product is for single dose only.
1. Inspect the outer packaging (blister pack) to confirm the integrity of the packaging. Do not use if the blister pack or the prefilled syringe has been damaged. 2. Remove the syringe from the outer packaging. (See Figure 2) Figure 2 3.
Visually inspect the syringe. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. 4. Twist off the syringe tip cap. Do not remove the label around the luer lock collar.
(See Figure 3) Figure 3 5. Expel air bubble (s). Adjust the dose (if applicable). 6. Administer the dose ensuring that pressure is maintained on the plunger rod during the entire administration. 7. Discard the used syringe into an appropriate receptacle.
For more information concerning this drug, please call Fresenius Kabi USA, LLC at 1-800-551-7176. jpg
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised September 24, 2025[4]
12 )] The following adverse reactions associated with the use of fentanyl were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
As with other opioid agonists, the most common serious adverse reactions reported to occur with fentanyl are 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, laryngospasm, diaphoresis, serotonin syndrome, adrenal insufficiency, and anaphylaxis. It has been reported that secondary rebound respiratory depression may occasionally occur postoperatively.
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.
When they occur, extrapyramidal symptoms can usually be controlled with anti-parkinson agents. Postoperative drowsiness is also frequently reported following the use of neuroleptics with fentanyl citrate. Cases of cardiac dysrhythmias, cardiac arrest, and death have been reported following the use of fentanyl citrate with a neuroleptic agent.
Most common serious adverse reactions were respiratory depression, apnea, rigidity, and bradycardia. gov/medwatch.
Serotonin syndrome :
Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.
Adrenal insufficiency :
Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. 2 )] . 7 )] .
Hypoglycemia:
Causes of hypoglycemia have been reported in patients taking opioids. , diabetes).
USOfficial regulatory label· Warnings and precautions· revised September 24, 2025[4]
5 WARNINGS AND PRECAUTIONS • Risks of Skeletal Muscle Rigidity and Skeletal Muscle Movement : Manage with neuromuscular blocking agent. See full prescribing information for more detail on managing these risks. 5 ) • Severe Cardiovascular Depression : Monitor during dosage initiation and titration.
6 ) • Opioid-Induced Hyperalgesia and Allodynia : Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation.
7 ) • Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. Discontinue Fentanyl Citrate Injection if serotonin syndrome is suspected. 8 ) • Adrenal Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid.
9 ) • Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, or Head Injury : Monitor for sedation and respiratory depression. 1 Addiction, Abuse, and Misuse 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 [see Drug Abuse and Dependence ( 9 )] . Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use.
Consider these risks when handling Fentanyl Citrate Injection. Strategies to reduce these risks include proper product storage and control practices for a C-II drug. Contact local state professional licensing board or state-controlled substances authority for information on how to prevent and detect abuse or diversion of this product.
2 Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death.
Adequate facilities should be available for postoperative monitoring and ventilation of patients administered anesthetic doses of Fentanyl Citrate Injection. It is essential that these facilities be fully equipped to handle all degrees of respiratory depression.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised September 24, 2025[4]
This is not medical advice. Consult a qualified healthcare professional.
Fentanyl can be abused in a manner similar to other opioids and all patients treated with opioids require monitoring for signs of abuse and addiction. Patients at increased risk of opioid abuse may still be appropriately treated with opioids; however, these patients will require additional monitoring for signs of misuse, abuse or addiction.
Repeated use of fentanyl-containing product may lead to Opioid Use Disorder (OUD). Abuse or intentional misuse of fentanyl-containing product may result in overdose and/or death. , major depression, anxiety and personality disorders).
, too early requests for refills). This includes the review of concomitant opioids and psycho-active drugs (like benzodiazepines). For patients with signs and symptoms of OUD, consultation with an addiction specialist should be considered.
Drug withdrawal syndrome Prior to starting treatment with any opioids, a discussion should be held with patients to put in place a withdrawal strategy for ending treatment with fentanyl. Drug withdrawal syndrome may occur upon abrupt cessation of therapy or dose reduction.
When a patient no longer requires therapy, it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take weeks to months. The opioid drug withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations.
Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.
If women take this drug during pregnancy, there is a risk that their newborn infants will experience neonatal withdrawal syndrome. Hyperalgesia Hyperalgesia may be diagnosed if the patient on long-term opioid therapy presents with increased pain.
This might be qualitatively and anatomically distinct from pain related to disease progression or to breakthrough pain resulting from development of opioid tolerance. Pain associated with hyperalgesia tends to be more diffuse than the pre-existing pain and less defined in quality.
Symptoms of hyperalgesia may resolve with a reduction of opioid dose. Endocrine effects Opioids may influence the hypothalamic-pituitary-adrenal or gonadal axes. Some changes that can be seen include an increase in serum prolactin and decrease in plasma cortisol and testosterone.
Clinical signs and symptoms may manifest from these hormonal changes. Cases of adrenal insufficiency have been reported with opioid use including fentanyl, more often following greater than one month of use. 8). Respiratory depression As with all opioids, there is a risk of clinically significant respiratory depression associated with the use of fentanyl, patients should be monitored accordingly.
Particular caution should be used when […]
For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. Anaphylaxis and hypersensitivity have been reported in association with the use of oral transmucosal fentanyl products. , ileus of any type). , acute appendicitis or pancreatitis).
• Patients with acute or severe bronchial asthma, chronic obstructive airway, or status asthmaticus. • Patients with acute respiratory depression, elevated carbon dioxide levels in the blood and cor pulmonale. • Patients with acute alcoholism, delirium tremens, and convulsive disorders.
• Patients with severe CNS depression, increased cerebrospinal or intracranial pressure, and head injury. • Patients taking monoamine oxidase (MAO) inhibitors (or within 14 days of such therapy). Product Monograph FENTORA fentanyl Page 6 of 69 Internal Use Only 3 SERIOUS WARNINGS AND PRECAUTIONS Serious Warnings and Precautions Proper Patient Selection • FENTORA (fentanyl buccal/sublingual effervescent tablets) is intended to be used only in the care of opioid tolerant patients with cancer and only by healthcare professionals who are knowledgeable of, and skilled in, the use of opioids to treat cancer pain.
• FENTORA is an opioid analgesic indicated only for the management of breakthrough pain in cancer patients 18 years of age and older who are already receiving and who are tolerant to continuous opioid therapy for their persistent baseline cancer pain.
Patients considered opioid-tolerant are those who have taken at least 60 mg of oral morphine daily, at least 25 mcg/hr of transdermal fentanyl, at least 30 mg of oral oxycodone daily, at least 8 mg of oral hydromorphone daily, at least 25 mg oral oxymorphone daily, or an equianalgesic dose of another opioid daily for a week or longer.
• FENTORA is contraindicated for use in opioid non-tolerant patients including those using opioids intermittently, on an as needed basis (see 2 CONTRAINDICATIONS). 4 DRUG INTERACTIONS, Drug-Drug Interactions). Addiction, Abuse, and Misuse • FENTORA poses risks of opioid addiction, abuse, and misuse, which can lead to overdose and death.
Each patient's risk should be assessed prior to prescribing FENTORA, and all patients should be monitored regularly for the development of these behaviours or conditions (see 7 WARNINGS AND PRECAUTIONS). FENTORA should be stored securely to avoid theft or misuse.
Product Monograph FENTORA fentanyl Page 7 of 69 Internal Use Only Life-threatening Respiratory Depression: OVERDOSE • Fatal respiratory depression has occurred in patients treated with FENTORA, including following use in opioid non-tolerant patients and improper dosing.
The substitution of FENTORA for any other fentanyl product may result in fatal overdose. • Infants exposed in-utero or through breast milk are at risk of life-threatening respiratory depression upon […]
Because of these risks, concomitant prescribing of opioids and benzodiazepines or related drugs should be made only in patients for whom alternative treatment options are inadequate. If a decision is made to prescribe Effentora concomitantly with benzodiazepines or related drugs, the lowest effective dosages and minimum durations of concomitant use should be chosen.
5). Increased intracranial pressure, impaired consciousness Effentora should only be administered with extreme caution in patients who may be particularly susceptible to the intracranial effects of CO2 retention, such as those with evidence of increased intracranial pressure or impaired consciousness.
Opioids may obscure the clinical course of a patient with a head injury and should be used only if clinically warranted. Bradyarrhythmias Fentanyl may produce bradycardia. Fentanyl should be used with caution in patients with previous or pre-existing bradyarrythmias.
Hepatic or renal impairment In addition, Effentora should be administered with caution to patients with hepatic or renal impairment. The influence of hepatic and renal impairment on the pharmacokinetics of the medicinal product has not been evaluated, however, when administered intravenously the clearance of fentanyl has been shown to be altered in hepatic and renal impairment due to alterations in metabolic clearance and plasma proteins.
After administration of Effentora, impaired hepatic and renal function may both increase the bioavailability of swallowed fentanyl and decrease its systemic clearance, which could lead to increased and prolonged opioid effects. Therefore, special care should be taken during the titration process in patients with moderate or severe hepatic or renal impairment.
Careful consideration should be given to patients with hypovolaemia and hypotension. Serotonin Syndrome Caution is advised when Effentora is co-administered with drugs that affect the serotoninergic neurotransmitter systems. The development of a potentially life-threatening serotonin syndrome may occur with the concomitant use of serotonergic drugs such as Selective Serotonin Re-uptake Inhibitors (SSRIs) and Serotonin Norepinephrine Re-uptake Inhibitors (SNRIs), and with drugs which impair metabolism of serotonin (including Monoamine Oxidase Inhibitors [MAOIs]).
This may occur within the recommended dose. , nausea, vomiting, diarrhoea). If serotonin syndrome is suspected, treatment with Effentora should be discontinued. Tolerance and opioid use disorder (abuse and dependence) Tolerance, physical dependence and psychological dependence may develop upon repeated administration of opioids.
Fentanyl can be abused in a manner similar to other opioids and all patients treated with opioids require monitoring for signs of abuse and addiction. Patients at increased risk of opioid abuse may still be appropriately treated with opioids; however, these patients will require additional monitoring for signs of misuse, abuse, or addiction.
Repeated use of Effentora may […]
Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status [see Overdosage ( 10 )] . Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
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.
The total dose of all opioid agonists administered should be considered by the practitioner before ordering opioid analgesics during recovery from anesthesia. Certain forms of conduction anesthesia, such as spinal anesthesia and some peridural anesthetics can alter respiration by blocking intercostal nerves.
2 )] Fentanyl Citrate Injection can also alter respiration. Therefore, when Fentanyl Citrate Injection is used to supplement these forms of anesthesia, the anesthetist should be familiar with the physiological alterations involved and be prepared to manage them in the patients selected for these forms of anesthesia.
Patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of Fentanyl Citrate Injection.
Elderly, cachectic, or debilitated patients may have altered pharmacokinetics or altered clearance compared to younger, healthier patients resulting in greater risk for respiratory depression. Monitor such patients closely including vital signs, particularly when initiating and titrating Fentanyl Citrate Injection and when Fentanyl Citrate Injection is given concomitantly with other drugs that depress respiration.
1 )] . Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. 1 )]. 3 Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants When benzodiazepines or other CNS depressants are used with Fentanyl Citrate Injection, pulmonary arterial pressure may be decreased.
This fact should be considered by those who conduct diagnostic and surgical procedures where interpretation of pulmonary arterial pressure measurements might determine final management of the patient. When high dose or anesthetic dosages of Fentanyl Citrate Injection are employed, even relatively small dosages of diazepam may cause cardiovascular depression.
When Fentanyl Citrate Injection is used with CNS depressants, hypotension can occur. If it occurs, consider the possibility of hypovolemia and manage with appropriate parenteral fluid therapy. When operative conditions permit, consider repositioning the patient to improve venous return to the heart.
Exercise care in moving and repositioning of patients because of the possibility of orthostatic hypotension. If volume expansion with fluids plus other countermeasures do not correct hypotension, consider administration of pressor agents other than epinephrine.
Epinephrine may paradoxically decrease blood pressure in patients treated with a neuroleptic that blocks alpha adrenergic activity. , nonbenzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids).
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see Drug Interactions ( 7 )].
If the decision is made to manage postoperative pain with Fentanyl Citrate Injection concomitantly with a benzodiazepine or other CNS depressant, start dosing with the lowest effective dosage and titrate based on clinical response.
Monitor patients closely for signs and symptoms of respiratory depression, sedation, and hypotension. Fluids or other measures to counter hypotension should be available [see Drug Interactions ( 7 )]. 2 )] , particularly when an inhibitor is added after a stable dose of Fentanyl Citrate Injection is achieved .
Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in Fentanyl Citrate Injection-treated patients may increase fentanyl plasma concentrations and prolong opioid adverse reactions. 1 ), Drug Interactions ( 7 )].
Concomitant use of Fentanyl Citrate Injection with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor, could result in lower than expected fentanyl plasma concentrations, decreased efficacy, or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to fentanyl.
1 ), Drug Interactions ( 7 )] . 5 Risks of Muscle Rigidity and Skeletal Muscle Movement Fentanyl Citrate Injection may cause muscle rigidity, particularly involving the muscles of respiration. The incidence and severity of muscle rigidity is dose related.
These effects are related to the dose and speed of injection. Skeletal muscle rigidity also has been reported to occur or recur infrequently in the extended postoperative period usually following high dose administration. In addition, skeletal muscle movements of various groups in the extremities, neck, and external eye have been reported during induction of anesthesia with Fentanyl Citrate Injection; these reported movements have, on rare occasions, been strong enough to pose patient management problems.
These effects are related to the dose and speed of injection and its incidence can be reduced by: 1) administration of up to 1/4 of the full paralyzing dose of a non-depolarizing neuromuscular blocking agent just prior to administration of Fentanyl Citrate Injection; 2) administration of a full paralyzing dose of a neuromuscular blocking agent following loss of eyelash reflex when Fentanyl Citrate Injection is used in anesthetic doses titrated by slow intravenous infusion; or, 3) simultaneous administration of Fentanyl Citrate Injection and a full paralyzing dose of a neuromuscular blocking agent when Fentanyl Citrate Injection is used in rapidly administered anesthetic dosages.
The neuromuscular blocking agent used should be compatible with the patient's cardiovascular status. 6 Severe Cardiovascular Depression Fentanyl Citrate Injection may cause severe bradycardia, severe hypotension including orthostatic hypotension, and syncope.
, phenothiazines or general anesthetics) [see Drug Interactions ( 7 )]. In patients with circulatory shock, Fentanyl Citrate Injection may cause vasodilation that can further reduce cardiac output and blood pressure. Monitor these patients for signs of hypotension after initiating or titrating the dosage of Fentanyl Citrate Injection.
7 Opioid-Induced Hyperalgesia and Allodynia Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. 3 )]. Symptoms of OIH include (but may not be limited to) increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily non-painful stimuli (allodynia).
These symptoms may suggest OIH only if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior. Cases of OIH have been reported, both with short-term and longer-term use of opioid analgesics.
Though the mechanism of OIH is not fully understood, multiple biochemical pathways have been implicated. Medical literature suggests a strong biological plausibility between opioid analgesics and OIH and allodynia. If a patient is suspected to be experiencing OIH, carefully consider appropriately decreasing the dose of the current opioid analgesic or opioid rotation (safely switching the patient to a different opioid moiety) [see Dosage and Administration ( 2 )].
8 Serotonin Syndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of fentanyl with serotonergic drugs. , cyclobenzaprine, metaxalone), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) [see Drug Interactions ( 7 )] .
This may occur within the recommended dosage range. , nausea, vomiting, diarrhea) and can be fatal. The onset of symptoms generally occurs within several hours to a few days of concomitant use but may occur later than that. Discontinue Fentanyl Citrate Injection if serotonin syndrome is suspected.
9 Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure.
If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers.
Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.
, those with evidence of increased intracranial pressure or brain tumors), Fentanyl Citrate Injection may reduce respiratory drive, and the resultant CO 2 retention can further increase intracranial pressure. Monitor such patients for signs of increasing intracranial pressure.
] Opioids may also obscure the clinical course in a patient with a head injury. 11 Risks of Use in Patients with Gastrointestinal Conditions 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. 12 Increased Risk of Seizures in Patients with Seizure Disorders Fentanyl may increase the frequency of seizures in patients with seizure disorders and may increase the risk of seizures occurring in other clinical setting associated with seizures.
Monitor patients with a history of seizure disorders for worsened seizure control during Fentanyl Citrate Injection therapy. 13 Risks of Driving and Operating Machinery Fentanyl Citrate Injection may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery after Fentanyl Citrate Injection administration.
Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of Fentanyl Citrate Injection and know how they will react to the medication. 14 Risks due to Interaction with Neuroleptic Agents Many neuroleptic agents have been associated with QT prolongation, torsades de pointes, and cardiac arrest.
, diuretics) that may cause electrolyte imbalance. Elevated blood pressure, with and without pre-existing hypertension, has been reported following administration of Fentanyl Citrate Injection combined with a neuroleptic. This might be due to unexplained alterations in sympathetic activity following large doses; however, it is also frequently attributed to anesthetic and surgical stimulation during light anesthesia.
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.