Usual Adult Dose for Chronic Pain

TRANSDERMAL PATCH:

• Due to the risk of respiratory depression, the transdermal patch is for use in opioid-tolerant patients only; opioid tolerant patients have been taking at least: morphine 60 mg daily, oral oxycodone 30 mg daily, oral hydromorphone 8 mg daily, or an equianalgesic dose of another opioid for 1 week or longer.
• Discontinue all other extended-release opioids when beginning therapy.

Initial doses: The initial dose should be individualized taking into account the patient's prior treatment experience. This dose may be calculated based on the dose conversion guidelines in the product package insert, local protocol, or another reliable reference; when calculating, be aware there is substantial inter-patient variability in the relative potency of different opioid drugs and products and therefore it is preferable to underestimate a 24-hour fentanyl requirement and provide rescue medication than to overestimate which could result in adverse reactions.
Dose titration:

• Initial: May increase dose after 3 days based on the daily dose of supplemental opioid analgesics required by the patient on the second or third day of the initial application.
• Further titration should occur after no less than two 3-day applications as it may take up to 6 days for fentanyl levels to reach equilibrium. Titration should be based on the daily dose of supplementary opioids required and the following ratio may be used: Increase transdermal fentanyl by 12 mcg//hr for use of supplemental oral morphine doses of 45 mg/24 hours.

Maintenance dose: Adjust dose to obtain an appropriate balance between pain management and opioid-related adverse reactions. During chronic therapy, periodically reassess the continued need for opioid analgesics.

Comments:

• Do not begin a patient on a fentanyl transdermal patch as their first opioid..
• A small number of patients may require a 48-hour dosing interval; an increase in dose should be evaluated before changing dosing intervals.
• For delivery rates in excess of 100 mcg/hour, multiple systems may be used.

Use: For the management of pain in opioid-tolerant patients, severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

Usual Adult Dose for Breakthrough Pain

TRANSMUCOSAL PRODUCTS

• For use in patients who are opioid-tolerant and taking around-the-clock opioids. Opioid tolerant patients have been taking at least: morphine 60 mg daily, oral oxycodone 30 mg daily, oral hydromorphone 8 mg daily, or an equianalgesic dose of another opioid for 1 week or longer.
• All transmucosal products must be individually titrated to an effective and tolerable dose. Once titrated, these products are used to treat up to 4 episodes of breakthrough pain a day; if a patient is experiencing more than 4 breakthrough episodes per day, the around-the-clock opioid dose should be re-evaluated. If the around-the-clock opioid dose is adjusted, re-adjustment of the transmucosal product may be necessary.
• Transmucosal fentanyl products are not bioequivalent; patients should not be interchanged on a mcg per mcg basis from 1 fentanyl product to any other fentanyl product

TRANSMUCOSAL LOZENGE (Actiq(R))
Initial dose: 200 mcg consumed over 15 minutes
Dose titration: If breakthrough pain is not relieved 15 minutes after completion of 1 unit (30 minutes after start), 1 additional unit of the same strength may be taken; Patients must wait at least 4 hours before re-treating. If breakthrough pain had not been relieved with 1 unit, the dose should be increased to the next highest strength with subsequent episodes of pain.
Maintenance dose: An effective dose is achieved when 1 unit is mostly sufficient to treat an episode of breakthrough pain; however, if there is inadequate analgesia a second dose of the same strength may be given 15 minutes after completion (30 minutes after start); no more than 2 doses should be used to treat any episode of breakthrough pain.
Maximum dose: 4 breakthrough episodes per day at intervals of at least 4 hours

Comments: The lozenge should be placed in mouth between cheek and lower gum and sucked; occasionally move from side to side using the handle; do not chew.

• If signs of excessive opioid effects appear before the unit is consumed, the unit should be removed immediately and subsequent doses should be decreased.

NASAL SPRAY (Lazanda(R))
Initial dose: 100 mcg sprayed in 1 nostril
Dose titration: If adequate analgesia is not achieved after 30 minutes, the dose should be escalated in a step-wise manner over consecutive episodes. Patients must wait at least 2 hours between doses. Patients should confirm the dose that works for them with a second episode of breakthrough pain.
Maintenance dose: Once an effective dose has been established, patients should use that dose for each subsequent breakthrough episode.
Maximum dose: 800 mcg per dose; 4 breakthrough episodes per day at intervals of at least 2 hours

SUBLINGUAL TABLETS (Abstral(R))
Initial dose: 100 mcg sublingually
Dose titration: If adequate analgesia is not obtained after 30 minutes, a second dose of the same strength may be taken. Patients must wait at least 2 hours before re-treating. Dose escalation should proceed in a stepwise manner (200 to 300 to 400 to 600 to 800 mcg) as needed. During titration, multiples of 100 mcg and/or 200 mcg tablets may be used for any single dose. Patients should not use more than 4 tablets at one time.
Maintenance dose: An effective dose is achieved when 1 dose is sufficient to treat most episodes of breakthrough pain; however, if there is inadequate analgesia a second dose of the same strength may be given after 30 minutes; no more than 2 doses should be used to treat any episode of breakthrough pain. Patients should limit treatment to 4 or fewer breakthrough episodes per day.
Maximum dose: 4 episodes per day; 800 mcg per dose at intervals of at least 2 hours

Comments: The sublingual tablet should be placed on the floor of the mouth and allowed to completely dissolve; do not eat or drink until the tablet is completely dissolved.

• The initial dose of the sublingual tablet is always 100 mcg except in patients receiving the transmucosal lozenge - see dose adjustment section for initial dosing recommendations for these patients.

SUBLINGUAL SPRAY:
Initial dose: 100 mcg sprayed sublingually
Dose titration: If adequate analgesia is not obtained after 30 minutes, a second dose of the same strength may be used. Patients must wait at least 4 hours before re-treating. If breakthrough pain is not relieved with the 100 mcg dose, dose escalation should proceed in a stepwise manner (200 to 400 to 600 to 800 to 1200 to 1600 mcg) for subsequent episodes of pain.
Maintenance dose: An effective dose is achieved when 1 dose is sufficient to treat most episodes of breakthrough pain; however, if there is inadequate analgesia a second dose of the same strength may be given after 30 minutes; no more than 2 doses should be used to treat any episode of breakthrough pain. Patients should limit treatment to 4 or fewer breakthrough episodes per day.
Maximum dose: 4 episodes per day at intervals of at least 4 hours

Comments: Spray into mouth underneath the tongue.

• The initial dose of is always 100 mcg except in patients receiving the transmucosal lozenge - see dose adjustment section for initial dosing recommendations for these patients.

BUCCAL TABLETS (Fentora(R))
Initial dose: 100 mcg buccally
Dose titration: If adequate analgesia is not obtained after 30 minutes, a second dose of the same strength may be taken. Patients must wait at least 4 hours before re-treating. If breakthrough pain is not relieved with 100 mcg, the next dose should be two 100 mcg tablets (one on each side of the mouth in the buccal cavity). The patient may be further titrated in a stepwise manner. During titration, multiples of 100 mcg or 200 mcg tablets may be used for any single dose. Patients should not use more than 4 tablets at one time.
Maintenance dose: An effective dose is achieved when 1 dose is sufficient to treat most episodes of breakthrough pain; however, if there is inadequate analgesia a second dose of the same strength may be given after 30 minutes; no more than 2 doses should be used to treat any episode of breakthrough pain. Patients should limit treatment to 4 or fewer breakthrough episodes per day.
Maximum dose: 4 episodes per day; at intervals of at least 4 hours

Comments: Tablet should be placed in the buccal cavity (above the rear molar, between the upper cheek and gum); alternatively, may be placed under the tongue.

• The initial dose of is always 100 mcg except in patients receiving the transmucosal lozenge - see dose adjustment section for initial dosing recommendations for these patients.

Use: For the management of breakthrough pain in patients who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain.

Usual Adult Dose for Anesthesia

Premedication for Anesthesia:
50 to 100 mcg IM, 30 to 60 minutes prior to surgery.
Lozenge: 5 mcg/kg (400 mcg is the maximum dose).
Lower doses should be used for vulnerable patients.

General Anesthesia:
Total Low dose: 2 mcg/kg (minor procedures).
Maintenance low dose: Infrequently needed.
Total Moderate dose: 2 to 20 mcg/kg.
Maintenance moderate dose: 25 to 100 mcg IV/IM.
Total high dose: 20 to 50 mcg/kg (prolonged surgeries).
Maintenance high dose: 25 mcg to half of the initial dose.

Adjunct to Regional Anesthesia:
50 to 100 mcg IM or slow IV over 3 to 5 minutes as required.

Postoperative :
50 to 100 mcg IM. May repeat dose in 1 to 2 hours as needed.

Usual Pediatric Dose for Anesthesia

Doses should be titrated to appropriate effects; a wide range of doses is possible depending upon desired degree of analgesia/anesthesia, clinical environment, patient's status, and presence of opioid tolerance.

Neonates: Analgesia: International Evidence-Based Group for Neonatal Pain recommendations:
Intermittent doses: Slow IV push: 0.5 to 3 mcg/kg/dose

• Continuous IV infusion: 0.5 to 2 mcg/kg/hour
• Sedation/analgesia: Slow IV push: 1 to 4 mcg/kg/dose; may repeat every 2 to 4 hours
• Continuous sedation/analgesia: Initial IV bolus: 1 to 2 mcg/kg, then 0.5 to 1 mcg/kg/hour; titrate upward
• Mean required dose: Neonates with gestational age less than 34 weeks: 0.64 mcg/kg/hour; neonates with gestational age greater than or equal to 34 weeks: 0.75 mcg/kg/hour
• Continuous sedation/analgesia during extracorporeal membrane oxygenation (ECMO): Initial IV bolus: 5 to 10 mcg/kg slow IV push over 10 minutes, then 1 to 5 mcg/kg/hour; titrate upward; tolerance may develop; higher doses (up to 20 mcg/kg/hour) may be needed by day 6 of ECMO.

Younger infants:

• Sedation/analgesia: Slow IV push: 1 to 4 mcg/kg/dose; may repeat every 2 to 4 hours
• Continuous sedation/analgesia: Initial IV bolus: 1 to 2 mcg/kg, then 0.5 to 1 mcg/kg/hour; titrate upward
• Continuous sedation/analgesia during extracorporeal membrane oxygenation ECMO: Initial IV bolus: 5 to 10 mcg/kg slow IV push over 10 minutes, then 1 to 5 mcg/kg/hour; titrate upward; tolerance may develop; higher doses (up to 20 mcg/kg/hour) may be needed by day 6 of ECMO.

Older Infants and Children 1 to 12 years:

• Sedation for minor procedures/analgesia: IM or IV: 1 to 2 mcg/kg/dose; may repeat at 30 to 60 minute intervals. Note: Children 18 to 36 months of age may require 2 to 3 mcg/kg/dose.
• Intranasal: Children greater than or equal to 10 kg: 1.5 mcg/kg once (maximum: 100 mcg/dose); reported range: 1 to 2 mcg/kg; some studies allowed for additional incremental doses of 0.5 mcg/kg to be administered every 5 minutes, not to exceed a total dose of 3 mcg/kg depending on pain type and severity.
• Continuous sedation/analgesia: Initial IV bolus: 1 to 2 mcg/kg then 1 mcg/kg/hour; titrate upward; usual: 1 to 3 mcg/kg/hour; some require 5 mcg/kg/hour

Children greater than or equal to 5 years and less than 50 kg:
Patient-controlled analgesia (PCA): IV: Opioid-naive: Note: PCA has been used in children as young as 5 years of age; however, clinicians need to assess children 5 to 8 years of age to determine if they are able to use the PCA device correctly. All patients should receive an initial loading dose of an analgesic (to attain adequate control of pain) before starting PCA for maintenance. Adjust doses, lockouts, and limits based on required loading dose, age, state of health, and presence of opioid tolerance. Use lower end of dosing range for opioid-naive. Assess patient and pain control at regular intervals and adjust settings if needed.

Usual concentration: Determined by weight; some clinicians use the following:

• Children less than 12 kg: 10 mcg/mL
• Children 12 to 30 kg: 25 mcg/mL
• Children greater than 30 kg: 50 mcg/mL
• Demand dose: Usual initial: 0.5 to 1 mcg/kg/dose; usual range: 0.5 to 1 mcg/kg/dose
• Lockout: Usual initial: 5 doses/hour
• Lockout interval: Range: 6 to 8 minutes
• Usual basal rate: 0 to 0.5 mcg/kg/hour

Children greater than 12 years to adult:

• Sedation for minor procedures/analgesia: IV: 0.5 to 1 mcg/kg/dose; may repeat after 30 to 60 minutes; or 25 to 50 mcg, repeat full dose in 5 minutes if needed, may repeat 4 to 5 times with 25 mcg at 5 minute intervals if needed. Note: Higher doses are used for major procedures.

Continuous sedation/analgesia:

• Less than 50 kg: Initial IV bolus: 1 to 2 mcg/kg; continuous infusion rate: 1 to 2 mcg/kg/hour
• Greater than 50 kg: Initial IV bolus: 1 to 2 mcg/kg or 25 to 100 mcg/dose; continuous infusion rate: 1 to 2 mcg/kg/hour or 25 to 200 mcg/hour

Patient-controlled analgesia (PCA): IV: Children greater than 50 kg, Adolescents greater than 50 kg, and Adults: Note: All patients should receive an initial loading dose of an analgesic (to attain adequate control of pain) before starting PCA for maintenance. Adjust doses, lockouts, and limits based on required loading dose, age, state of health, and presence of opioid tolerance. Use lower end of dosing range for opioid-naive. Assess patient and pain control at regular intervals and adjust settings if needed:

• Usual concentration: 50 mcg/mL
• Demand dose: Usual initial: 20 mcg; usual range: 10 to 50 mcg
• Lockout interval: Usual initial: 6 minutes; usual range: 5 to 8 minutes
• Usual basal rate: less than or equal to 50 mcg/hour

Preoperative sedation, adjunct to regional anesthesia, postoperative pain: IM, IV: 25 to 100 mcg/dose

Adjunct to general anesthesia: Slow IV:

• Low dose: 0.5 to 2 mcg/kg/dose depending on the indication
• Moderate dose: Initial: 2 to 20 mcg/kg/dose; Maintenance (bolus or infusion): 1 to 2 mcg/kg/hour. Discontinuing fentanyl infusion 30 to 60 minutes prior to the end of surgery will usually allow adequate ventilation upon emergence from anesthesia. For "fast-tracking" and early extubation following major surgery, total fentanyl doses are limited to 10 to 15 mcg/kg.
• High dose: 20 to 50 mcg/kg/dose; Note: High dose fentanyl as an adjunct to general anesthesia is rarely used, but is still described in the manufacturer label.

General anesthesia without additional anesthetic agents: IV: 50 to 100 mcg/kg with oxygen and skeletal muscle relaxant

Usual Pediatric Dose for Pain

Doses should be titrated to appropriate effects; a wide range of doses is possible depending upon desired degree of analgesia/anesthesia, clinical environment, patient's status, and presence of opioid tolerance.

Neonates: Analgesia: International Evidence-Based Group for Neonatal Pain recommendations:
Intermittent doses: Slow IV push: 0.5 to 3 mcg/kg/dose

• Continuous IV infusion: 0.5 to 2 mcg/kg/hour
• Sedation/analgesia: Slow IV push: 1 to 4 mcg/kg/dose; may repeat every 2 to 4 hours
• Continuous sedation/analgesia: Initial IV bolus: 1 to 2 mcg/kg, then 0.5 to 1 mcg/kg/hour; titrate upward
• Mean required dose: Neonates with gestational age less than 34 weeks: 0.64 mcg/kg/hour; neonates with gestational age greater than or equal to 34 weeks: 0.75 mcg/kg/hour
• Continuous sedation/analgesia during extracorporeal membrane oxygenation (ECMO): Initial IV bolus: 5 to 10 mcg/kg slow IV push over 10 minutes, then 1 to 5 mcg/kg/hour; titrate upward; tolerance may develop; higher doses (up to 20 mcg/kg/hour) may be needed by day 6 of ECMO.

Younger infants:

• Sedation/analgesia: Slow IV push: 1 to 4 mcg/kg/dose; may repeat every 2 to 4 hours
• Continuous sedation/analgesia: Initial IV bolus: 1 to 2 mcg/kg, then 0.5 to 1 mcg/kg/hour; titrate upward
• Continuous sedation/analgesia during extracorporeal membrane oxygenation ECMO: Initial IV bolus: 5 to 10 mcg/kg slow IV push over 10 minutes, then 1 to 5 mcg/kg/hour; titrate upward; tolerance may develop; higher doses (up to 20 mcg/kg/hour) may be needed by day 6 of ECMO.

Older Infants and Children 1 to 12 years:

• Sedation for minor procedures/analgesia: IM or IV: 1 to 2 mcg/kg/dose; may repeat at 30 to 60 minute intervals. Note: Children 18 to 36 months of age may require 2 to 3 mcg/kg/dose.
• Intranasal: Children greater than or equal to 10 kg: 1.5 mcg/kg once (maximum: 100 mcg/dose); reported range: 1 to 2 mcg/kg; some studies allowed for additional incremental doses of 0.5 mcg/kg to be administered every 5 minutes, not to exceed a total dose of 3 mcg/kg depending on pain type and severity.
• Continuous sedation/analgesia: Initial IV bolus: 1 to 2 mcg/kg then 1 mcg/kg/hour; titrate upward; usual: 1 to 3 mcg/kg/hour; some require 5 mcg/kg/hour

Children greater than or equal to 5 years and less than 50 kg:
Patient-controlled analgesia (PCA): IV: Opioid-naive: Note: PCA has been used in children as young as 5 years of age; however, clinicians need to assess children 5 to 8 years of age to determine if they are able to use the PCA device correctly. All patients should receive an initial loading dose of an analgesic (to attain adequate control of pain) before starting PCA for maintenance. Adjust doses, lockouts, and limits based on required loading dose, age, state of health, and presence of opioid tolerance. Use lower end of dosing range for opioid-naive. Assess patient and pain control at regular intervals and adjust settings if needed.

Usual concentration: Determined by weight; some clinicians use the following:

• Children less than 12 kg: 10 mcg/mL
• Children 12 to 30 kg: 25 mcg/mL
• Children greater than 30 kg: 50 mcg/mL
• Demand dose: Usual initial: 0.5 to 1 mcg/kg/dose; usual range: 0.5 to 1 mcg/kg/dose
• Lockout: Usual initial: 5 doses/hour
• Lockout interval: Range: 6 to 8 minutes
• Usual basal rate: 0 to 0.5 mcg/kg/hour

Children greater than 12 years to adult:

• Sedation for minor procedures/analgesia: IV: 0.5 to 1 mcg/kg/dose; may repeat after 30 to 60 minutes; or 25 to 50 mcg, repeat full dose in 5 minutes if needed, may repeat 4 to 5 times with 25 mcg at 5 minute intervals if needed. Note: Higher doses are used for major procedures.

Continuous sedation/analgesia:

• Less than 50 kg: Initial IV bolus: 1 to 2 mcg/kg; continuous infusion rate: 1 to 2 mcg/kg/hour
• Greater than 50 kg: Initial IV bolus: 1 to 2 mcg/kg or 25 to 100 mcg/dose; continuous infusion rate: 1 to 2 mcg/kg/hour or 25 to 200 mcg/hour

Patient-controlled analgesia (PCA): IV: Children greater than 50 kg, Adolescents greater than 50 kg, and Adults: Note: All patients should receive an initial loading dose of an analgesic (to attain adequate control of pain) before starting PCA for maintenance. Adjust doses, lockouts, and limits based on required loading dose, age, state of health, and presence of opioid tolerance. Use lower end of dosing range for opioid-naive. Assess patient and pain control at regular intervals and adjust settings if needed:

• Usual concentration: 50 mcg/mL
• Demand dose: Usual initial: 20 mcg; usual range: 10 to 50 mcg
• Lockout interval: Usual initial: 6 minutes; usual range: 5 to 8 minutes
• Usual basal rate: less than or equal to 50 mcg/hour

Preoperative sedation, adjunct to regional anesthesia, postoperative pain: IM, IV: 25 to 100 mcg/dose

Adjunct to general anesthesia: Slow IV:

• Low dose: 0.5 to 2 mcg/kg/dose depending on the indication
• Moderate dose: Initial: 2 to 20 mcg/kg/dose; Maintenance (bolus or infusion): 1 to 2 mcg/kg/hour. Discontinuing fentanyl infusion 30 to 60 minutes prior to the end of surgery will usually allow adequate ventilation upon emergence from anesthesia. For "fast-tracking" and early extubation following major surgery, total fentanyl doses are limited to 10 to 15 mcg/kg.
• High dose: 20 to 50 mcg/kg/dose; Note: High dose fentanyl as an adjunct to general anesthesia is rarely used, but is still described in the manufacturer label.

General anesthesia without additional anesthetic agents: IV: 50 to 100 mcg/kg with oxygen and skeletal muscle relaxant

Usual Pediatric Dose for Sedation

Doses should be titrated to appropriate effects; a wide range of doses is possible depending upon desired degree of analgesia/anesthesia, clinical environment, patient's status, and presence of opioid tolerance.

Neonates: Analgesia: International Evidence-Based Group for Neonatal Pain recommendations:
Intermittent doses: Slow IV push: 0.5 to 3 mcg/kg/dose

• Continuous IV infusion: 0.5 to 2 mcg/kg/hour
• Sedation/analgesia: Slow IV push: 1 to 4 mcg/kg/dose; may repeat every 2 to 4 hours
• Continuous sedation/analgesia: Initial IV bolus: 1 to 2 mcg/kg, then 0.5 to 1 mcg/kg/hour; titrate upward
• Mean required dose: Neonates with gestational age less than 34 weeks: 0.64 mcg/kg/hour; neonates with gestational age greater than or equal to 34 weeks: 0.75 mcg/kg/hour
• Continuous sedation/analgesia during extracorporeal membrane oxygenation (ECMO): Initial IV bolus: 5 to 10 mcg/kg slow IV push over 10 minutes, then 1 to 5 mcg/kg/hour; titrate upward; tolerance may develop; higher doses (up to 20 mcg/kg/hour) may be needed by day 6 of ECMO.

Younger infants:

• Sedation/analgesia: Slow IV push: 1 to 4 mcg/kg/dose; may repeat every 2 to 4 hours
• Continuous sedation/analgesia: Initial IV bolus: 1 to 2 mcg/kg, then 0.5 to 1 mcg/kg/hour; titrate upward
• Continuous sedation/analgesia during extracorporeal membrane oxygenation ECMO: Initial IV bolus: 5 to 10 mcg/kg slow IV push over 10 minutes, then 1 to 5 mcg/kg/hour; titrate upward; tolerance may develop; higher doses (up to 20 mcg/kg/hour) may be needed by day 6 of ECMO.

Older Infants and Children 1 to 12 years:

• Sedation for minor procedures/analgesia: IM or IV: 1 to 2 mcg/kg/dose; may repeat at 30 to 60 minute intervals. Note: Children 18 to 36 months of age may require 2 to 3 mcg/kg/dose.
• Intranasal: Children greater than or equal to 10 kg: 1.5 mcg/kg once (maximum: 100 mcg/dose); reported range: 1 to 2 mcg/kg; some studies allowed for additional incremental doses of 0.5 mcg/kg to be administered every 5 minutes, not to exceed a total dose of 3 mcg/kg depending on pain type and severity.
• Continuous sedation/analgesia: Initial IV bolus: 1 to 2 mcg/kg then 1 mcg/kg/hour; titrate upward; usual: 1 to 3 mcg/kg/hour; some require 5 mcg/kg/hour

Children greater than or equal to 5 years and less than 50 kg:
Patient-controlled analgesia (PCA): IV: Opioid-naive: Note: PCA has been used in children as young as 5 years of age; however, clinicians need to assess children 5 to 8 years of age to determine if they are able to use the PCA device correctly. All patients should receive an initial loading dose of an analgesic (to attain adequate control of pain) before starting PCA for maintenance. Adjust doses, lockouts, and limits based on required loading dose, age, state of health, and presence of opioid tolerance. Use lower end of dosing range for opioid-naive. Assess patient and pain control at regular intervals and adjust settings if needed.

Usual concentration: Determined by weight; some clinicians use the following:

• Children less than 12 kg: 10 mcg/mL
• Children 12 to 30 kg: 25 mcg/mL
• Children greater than 30 kg: 50 mcg/mL
• Demand dose: Usual initial: 0.5 to 1 mcg/kg/dose; usual range: 0.5 to 1 mcg/kg/dose
• Lockout: Usual initial: 5 doses/hour
• Lockout interval: Range: 6 to 8 minutes
• Usual basal rate: 0 to 0.5 mcg/kg/hour

Children greater than 12 years to adult:

• Sedation for minor procedures/analgesia: IV: 0.5 to 1 mcg/kg/dose; may repeat after 30 to 60 minutes; or 25 to 50 mcg, repeat full dose in 5 minutes if needed, may repeat 4 to 5 times with 25 mcg at 5 minute intervals if needed. Note: Higher doses are used for major procedures.

Continuous sedation/analgesia:

• Less than 50 kg: Initial IV bolus: 1 to 2 mcg/kg; continuous infusion rate: 1 to 2 mcg/kg/hour
• Greater than 50 kg: Initial IV bolus: 1 to 2 mcg/kg or 25 to 100 mcg/dose; continuous infusion rate: 1 to 2 mcg/kg/hour or 25 to 200 mcg/hour

Patient-controlled analgesia (PCA): IV: Children greater than 50 kg, Adolescents greater than 50 kg, and Adults: Note: All patients should receive an initial loading dose of an analgesic (to attain adequate control of pain) before starting PCA for maintenance. Adjust doses, lockouts, and limits based on required loading dose, age, state of health, and presence of opioid tolerance. Use lower end of dosing range for opioid-naive. Assess patient and pain control at regular intervals and adjust settings if needed:

• Usual concentration: 50 mcg/mL
• Demand dose: Usual initial: 20 mcg; usual range: 10 to 50 mcg
• Lockout interval: Usual initial: 6 minutes; usual range: 5 to 8 minutes
• Usual basal rate: less than or equal to 50 mcg/hour

Preoperative sedation, adjunct to regional anesthesia, postoperative pain: IM, IV: 25 to 100 mcg/dose

Adjunct to general anesthesia: Slow IV:

• Low dose: 0.5 to 2 mcg/kg/dose depending on the indication
• Moderate dose: Initial: 2 to 20 mcg/kg/dose; Maintenance (bolus or infusion): 1 to 2 mcg/kg/hour. Discontinuing fentanyl infusion 30 to 60 minutes prior to the end of surgery will usually allow adequate ventilation upon emergence from anesthesia. For "fast-tracking" and early extubation following major surgery, total fentanyl doses are limited to 10 to 15 mcg/kg.
• High dose: 20 to 50 mcg/kg/dose; Note: High dose fentanyl as an adjunct to general anesthesia is rarely used, but is still described in the manufacturer label.

General anesthesia without additional anesthetic agents: IV: 50 to 100 mcg/kg with oxygen and skeletal muscle relaxant

Usual Pediatric Dose for Breakthrough Pain

TRANSMUCOSAL LOZENGE (Actiq[R])
Age 16 years or older:

• For use in patients who are opioid-tolerant and taking around-the-clock opioids. Opioid tolerant patients have been taking at least: morphine 60 mg daily, oral oxycodone 30 mg daily, oral hydromorphone 8 mg daily, or an equianalgesic dose of another opioid for 1 week or longer.
• Must be individually titrated to an effective and tolerable dose. Once titrated, treat up to 4 episodes of breakthrough pain a day; if a patient is experiencing more than 4 breakthrough episodes per day, the around-the-clock opioid dose should be re-evaluated. If the around-the-clock opioid dose is adjusted, re-adjustment of the transmucosal product may be necessary.
• Transmucosal fentanyl products are not bioequivalent; patients should not be interchanged on a mcg per mcg basis from 1 fentanyl product to any other fentanyl product

Initial dose: 200 mcg consumed over 15 minutes
Dose titration: If breakthrough pain is not relieved 15 minutes after completion of 1 unit (30 minutes after start), 1 additional unit of the same strength may be taken; Patients must wait at least 4 hours before re-treating. If breakthrough pain had not been relieved with 1 unit, the dose should be increased to the next highest strength with subsequent episodes of pain.
Maintenance dose: An effective dose is achieved when 1 unit is mostly sufficient to treat an episode of breakthrough pain; however, if there is inadequate analgesia a second dose of the same strength may be given 15 minutes after completion (30 minutes after start); no more than 2 doses should be used to treat any episode of breakthrough pain.
Maximum dose: 4 breakthrough episodes per day at intervals of at least 4 hours

Comments: The lozenge should be placed in mouth between cheek and lower gum and sucked; occasionally move from side to side using the handle; do not chew.

• If signs of excessive opioid effects appear before the unit is consumed, the unit should be removed immediately and subsequent doses should be decreased.

Use: For the management of breakthrough pain in adolescents 16 years or older who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain.

Usual Pediatric Dose for Chronic Pain

Do not initiate the transdermal patch as the first opioid; do not initiate in opioid nontolerant patients

• Discontinue or taper all other extended-release opioids when initiating therapy
• Individualize dose taking into account severity of pain, response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse

2 years or older: 1 patch applied transdermally every 72 hours

• Dose may be calculated using dose conversion guidelines in the product package insert, local protocol, or another reliable reference; when calculating, be aware there is substantial inter-patient variability in the relative potency of different opioid drugs and products and therefore it is preferable to underestimate a 24-hour fentanyl requirement and provide rescue medication than to overestimate and overdose the patient with the first dose.

DOSE TITRATION: May increase dose after 3 days based on the daily dose of supplemental opioid analgesics required by the patient on the second or third day of the initial application.

• Further titration should occur after no less than two 3-day applications as it may take up to 6 days for fentanyl levels to reach equilibrium; titration should be based on the daily dose of supplementary opioids required and the following ratio may be used:
• Increase transdermal fentanyl by 12 mcg/hr for use of supplemental oral morphine doses of 45 mg/24 hours.

MAINTENANCE dose: Adjust dose to obtain an appropriate balance between pain management and opioid-related adverse reactions. During chronic therapy, periodically reassess the continued need for opioid analgesics.

Comments:

• Due to risks of addiction and abuse, and misuse of opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release/long acting formulations, reserve use for those whom alternative treatment options are ineffective, not tolerated, or would otherwise be inadequate to provide sufficient pain management.
• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals; dosing intervals less than every 72 hours were not studied in children and adolescents and are not recommended.
• Monitor closely for respiratory depression, especially in the first 24 to 72 hours of intimating therapy and with any increase in dose.
• Opioid tolerant patients have been taking at least: morphine 60 mg/day, oral oxycodone 30 mg/day, hydromorphone 8 mg/day orally, oxymorphone 25 mg/day orally, hydrocodone 60 mg/day or an equianalgesic dose of another opioid for 1 week or longer.

Use: For the management of pain in opioid-tolerant patients, severe enough to require daily, around the clock, long term opioid treatment and for which alternative treatment options are inadequate.

Renal Dose Adjustments

Transdermal patches:
Mild to moderate renal impairment: Start with one half of the usual dosage
Severe renal impairment: Avoid use

No specific dose adjustment guidelines for other dose forms have been suggested; however, caution is advised along with observation and dose reduction if indicated.

Liver Dose Adjustments

Transdermal patches:
Mild to moderate hepatic impairment: Start with one half of the usual dosage
Severe hepatic impairment: Avoid use

No specific dose adjustment guidelines for other dose forms have been suggested; however, caution is advised along with observation and dose reduction if indicated.

Dose Adjustments

• Different dose forms of this drug are not bioequivalent. Patients should not be converted on a mcg per mcg basis from other dose forms. Product labeling or local protocol should be consulted when switching patients from one dose form to another.
• Elderly patients may be more sensitive to the effects of fentanyl than younger patients. Close monitoring and a reduced dosage should be considered in elderly and debilitated patients.
• When discontinuing fentanyl transdermal system and not converting to another opioid, use a gradual downward titration, such as halving the dose every 6 days, in order to reduce the possibility of withdrawal symptoms.
• Consult the most current therapeutic guidelines and/or the manufacturer product information for dosing recommendations.

CYP450 3A4 Inhibitors and Inducers: Increased fentanyl plasma concentrations may result from concomitant use with CYP450 3A4 inhibitors or discontinuation of concomitantly used CYP450 3A4 inducers; monitor patients concomitantly receiving any CYP450 3A4 inducers or inhibitors and make dose adjustments as appropriate.

Concomitant use with other CNS depressants, including other opioids, sedative or hypnotics, general anesthetics, phenothiazines, tranquilizers, skeletal muscle relaxants, sedating antihistamines, and alcoholic beverages may produce increased depressant effects; monitor patients receiving concomitant CNS depressants and consider adjusting fentanyl dose.

Initial Dose Recommendations for Patients on Transmucosal Lozenges (Actiq(R)):

• For patients with a current fentanyl transmucosal lozenge dose of 200 mcg, initiate fentanyl sublingual tablets (Abstral(R)) at 100 mcg; for a current transmucosal lozenge dose of 400 mcg, 600 mcg, 800 mcg, or 1200 mcg, initiate sublingual tablets at 200 mcg; for a current transmucosal lozenge dose of 1600 mcg, initiate sublingual tablets at 400 mcg; proceed with titration outlined in the dosing section.
• For patients with a current fentanyl transmucosal lozenge of 200 mcg or 400 mcg, initiate fentanyl buccal dose (Fentoral(R)) at 100 mcg; for a current transmucosal lozenge dose of 600 mcg or 800 mcg, initiate buccal tablet at 200 mcg; for a current transmucosal lozenge dose of 1200 mcg or 1600 mcg, initiate buccal dose at 400 mcg (2x200 mcg) ; proceed with titration outlined in the dosing section.
• For patients with a current fentanyl transmucosal lozenge of 200 mcg or 400 mcg, initiate fentanyl sublingual spray (Subsys(R)) at 100 mcg; for a current transmucosal lozenge dose of 600 mcg or 800 mcg, initiate sublingual spray at 200 mcg; for a current transmucosal lozenge dose of 1200 mcg or 1600 mcg, initiate sublingual spray at 400 mcg; proceed with titration outlined in the dosing section.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for:

• All opioids intended for outpatient use. The new FDA Opioid Analgesic REMS is a designed to assist in communicating the serious risks of opioid pain medications to patients and health care professionals. It includes a medication guide and elements to assure safe use. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm.
• Transmucosal Immediate-Release Fentanyl (TIRF) Products (sublingual tablets, oral lozenges, buccal tablets, nasal spray, and sublingual spray); it includes a medication guide, elements to assure safe use, and an implementation system.

For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm.

US BOXED WARNINGS:

• ADDICTION, ABUSE, and MISUSE: The drug exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing and monitor regularly for the development of these behaviors or conditions.

RISK EVALUATION AND MITIGATION STRATEGY (REMS): To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to complete a REMS-compliant education program; counsel patients and/or their caregivers, with every prescription on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and consider other tools to improve patient, household, and community safety.

• LIFE-THREATENING RESPIRATORY DEPRESSION: Serious, life-threatening, or fatal respiratory depression may occur, even when used as recommended. Monitor for respiratory depression, especially during initiation and following dose increases. Because of the risk of respiratory depression, this drug is contraindicated for use as an as-needed analgesic, in non-opioid tolerant patients, in acute pain, and in postoperative pain.
• ACCIDENTAL EXPOSURE: Deaths due to fatal overdose of this drug have occurred due to accidental exposure. Strict adherence to the recommended handling and disposal instructions is of the utmost importance to prevent accidental exposure.
• NEONATAL OPIOID WITHDRAWAL SYNDROME: Prolonged use of this drug during pregnancy may result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated; treatment requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
• CYP450 3A4 INTERACTION: Concomitant use with CYP450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. Additionally, discontinuation of a concomitantly used CYP450 3A4 inducer may result in an increase in fentanyl plasma concentrations. Monitor all patients concomitantly receiving any CYP450 3A4 inhibitor or inducer.
• RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant use for patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required, and follow patients for signs and symptoms of respiratory depression.

Additional Warnings for Transdermal Systems:

• RISK OF INCREASED FENTANYL ABSORPTION WITH APPLICATION OF EXTERNAL HEAT: Exposure of the application site and surrounding area to direct external heat sources, such as heating pads or electric blankets, heat or tanning lamps, sunbathing, hot baths, saunas, hot tubs, and heated water beds may increase drug absorption and has resulted in fatal overdose and death. Warn patients to avoid exposing the application site and surrounding area to direct external heat sources.

Additional Warnings for Transmucosal Immediate-Release Fentanyl (TIRF) Products (sublingual and buccal tablets, transmucosal lozenges, nasal and sublingual spray):

• MEDICATION ERRORS: Substantial differences in the pharmacokinetic profile of fentanyl products exist that may result in clinically important differences in the extent of absorption and possible fatal overdose. When prescribing, do not convert patients on a mcg per mcg basis; when dispensing, do not substitute one TIRF for any other fentanyl products.
• REMS: TIRFs are available only through a REMS. Under the Transmucosal Immediate Release Fentanyl (TIRF) REMS Access program, outpatients, healthcare professionals who prescribe to outpatients, pharmacies, and distributors must enroll in the program.

Iontophoretic transdermal system: This drug has been voluntarily withdrawn from the market by the manufacturer; all unused product should have been returned by 9/1/17.

• Buccal tablets, Nasal spray, and Sublingual tablets and spray: Safety and efficacy have not been established in patients younger than 18 years.
• Oral transmucosal lozenge: Safety and efficacy have not been established in patients younger than 16 years.
• Parenteral and Transdermal systems: Safety and efficacy have not been established in patients younger than 2 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule II

Dialysis

Data not available

Other Comments

Administration Advice:
Parenteral administration:

• May be administered by slow IV infusion (over 1 to 2 minutes) or IM injection.

Transdermal patch:

• Patches should be worn continuously for 72 hours.
• Patches should be applied to non-irritated, and non-irradiated skin on the torso or upper arms.
• A non-hairy application site is preferred; however, hair may be clipped (not shaven) prior to application.
• The application site may be cleaned with water and should be dry prior to application; soaps, oils, lotions, or other agents that may irritate or alter the characteristics of the skin should not be used.
• The patch should be applied immediately after removal from the sealed package; press firmly in place for 30 seconds.
• Application sites should be rotated.
• If there is a problem with adhesion, the edges may be taped with first aid tape; if the problem persists, overlay the patch with a transparent adhesive film dressing.
• If the patch falls off before 72 hours, dispose of it by folding in half and flushing down the toilet; apply a new patch to a different skin site.
• Anyone handling the patch should wash their hands immediately with soap and water.

Transmucosal lozenge:

• Once titrated to an effective dose, patients should generally consume 1 unit for each episode of breakthrough pain; occasionally, an additional unit of the same strength may be taken if analgesia is inadequate after 15 minutes (30 minutes from start of dosing); at least 4 hours must elapse before treating a new episode; a maximum of 2 doses may be used for each episode of breakthrough pain.
• Open the blister package with scissors immediately prior to use; place lozenge in the mouth against the cheek and lower gum.
• Move lozenge around using the applicator provided over a 15 minute period, longer or shorter consumption may affect efficacy; the lozenge should be sucked and not chewed.
• If any of the drug matrix remains on the handle, place the handle under hot running water until it is dissolved and then dispose of out of the reach of children.

Sublingual tablets:

• Once titrated to an effective dose, patients should generally take 1 dose for each episode of breakthrough pain; occasionally, an additional dose of the same strength may be taken 30 minutes later if analgesia is inadequate; at least 2 hours must elapse before treating a new episode; a maximum of 2 doses may be used for each episode of breakthrough pain.
• Immediately after removal from blister, place tablet underneath the deepest part of the tongue; allow tablet to complete dissolve in the sublingual space without chewing or sucking.
• Patients should not eat and drink until after the tablet has completely dissolved.
• In patients who have a dry mouth, water may be used to moisten the mouth prior to administration.

Sublingual spray:

• Once titrated to an effective dose, patients should generally take 1 dose for each episode of breakthrough pain; 1 additional dose of the same strength may be taken 30 minutes later if analgesia is inadequate; at least 4 hours must elapse before treating a new episode; a maximum of 2 doses may be used for each episode of breakthrough pain.
• Open the blister pack with scissors immediately prior to use; carefully spray dose into mouth under the tongue.

Nasal spray:

• No more than 1 dose should be taken for each episode of breakthrough pain and at least 2 hours must elapse before treating a new episode.
• To prime the bottle for initial use, firmly press down 4 times on the finger grips; with each press, a click should be heard, after 4 clicks a green bar should appear in the counting window and the bottle is ready.
• Re-priming will be necessary if the bottle is not used for more than 5 days; to re-prime, spray 1 time into the pouch.
• To administer, patients should sit or stand in an upright position, insert the tip a short distance into nose and point the tip toward the bridge of nose, this will tilt the bottle slightly.
• Close off the other nostril with 1 finger; firmly press down on the finger grips until a click is heard, and breathe in gently through nose and out through mouth 1 time after spraying; do not sniff after spraying.
• It is normal not to feel the spray go into the nose, after the click, the number in the counting window should increase by 1 and this indicates that a spray has been given.
• If more than 1 spray is needed, repeat process alternating nostrils; the maximum number of sprays that may be used to be treat an episode of breakthrough pain is 4 (2 sprays in each nostril, alternating, e.g., right, left, right, left).
• Patient should remain upright, preferably sitting for 1 minute after using spray.
• Avoid blowing nose for at least 30 minutes after each spray.

Buccal tablets:

• Once titrated to an effective dose, patients should generally take 1 dose for each episode of breakthrough pain; 1 additional dose of the same strength may be taken 30 minutes later if analgesia is inadequate; at least 4 hours must elapse before treating a new episode; a maximum of 2 doses may be used for each episode of breakthrough pain.
• Peel back blister and remove tablet, do not push tablet through blister as this may damage the tablet.
• Immediately after removing tablet from blister, place tablet in buccal cavity (above a rear molar between upper cheek and gum).
• Leave in buccal cavity for 14 to 25 minutes or until the tablet has dissolved; if after 30 minutes remnants of the tablet remain, these may be swallowed with some water.
• Food should not be consumed while tablet is in buccal cavity.
• The tablet should not be split, sucked, chewed, or swallowed whole; patients should alternate sides of the mouth when administering subsequent doses.
• Alternatively, the buccal tablet may be placed under the tongue (sublingually).

Storage requirements: KEEP OUT OF THE REACH OF CHILDREN

• Store at 20 to 25C (68F to 77F); excursions permitted between 15C and 30C (59F to 86F).
• Parenteral products: Protect from light
• Transdermal Patches: Store in original pouches
• Sublingual tablets: Store in original blister unit
• Transmucosal Lozenges: Store in original blister package; protect from freezing and moisture; may obtain a Child Safety Kit from manufacturer
• Nasal Spray: Store at up to 25C; do not freeze; return bottle to child-resistant container after each use; put pouch in cardboard carton and store securely; protect from light
• Buccal tablets: Store in original blister package; protect from freezing and moisture
• Sublingual Spray: Store in original blister package; may obtain a Child Safety Kit from manufacturer.

Preparation and Disposal:

• The individual manufacturer product information should be consulted for complete information on preparation and disposal.

IV compatibility:

• Fentanyl solution for injection is incompatible with thiopental sodium and methohexital sodium

General:

• This drug should be prescribed by healthcare professional who are knowledgeable in the use of potent opioids.
• Except for the parenteral product, patients should be opioid tolerant prior to initiating therapy; patients receiving transmucosal products for breakthrough pain should be receiving around-the-clock opioid pain medication.
• Switching between fentanyl products should not occur at 1:1 ratio as fentanyl products are not bioequivalent.
• For patients receiving other opioid analgesics and switching to this drug, it is safer to underestimate a patient's 24-hour oral requirement and provide rescue medication than overestimate and manage an adverse reaction; there is substantial inter-patient variation in the relative potency of different opioid drugs that conversion tables are not able to capture.
• During chronic therapy, periodically reassess the continued need for opioid analgesics.

Monitoring:

• Monitor regularly for the development of addiction, abuse, and misuse.
• Respiratory: Monitor closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and following dose increases.
• Cardiovascular: Monitor at risk patients for signs of hypotension on initiation and with each dose titration; monitor patients with bradyarrhythmias for changes in heart rate, particularly upon drug initiation.
• Gastrointestinal: Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.
• Nervous System: Monitor for signs of sedation and respiratory depression in patients who may be susceptible; monitor patients with a history of seizures for worsened seizure control.
• Renal/Hepatic impairment: Monitor for fentanyl toxicity
• Transdermal Patch: Monitor febrile patients closely for fentanyl toxicity

Patient advice:

• Patients should be instructed to read the US FDA-approved Medication Guide each time this drug is dispensed; they should understand the safe use, serious risks, and proper storage and disposal of this drug.
• This drug should be stored safely out of the sight and reach of children; accidental use by a child is a medical emergency and can result in death.
• Taking this drug, even when taken as recommended can result in addiction, abuse, and misuse; instruct patients not to share their drug with others and protect their drug from theft or misuse.
• Patients should understand the risks of life-threatening respiratory depression, and be informed as to when this risk is greatest.
• This drug may cause drowsiness, dizziness, impaired thinking and/or motor skills; patients should be aware of these dangers and avoid driving or other potentially dangerous tasks while taking this drug.
• Women of child bearing potential should understand that prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome and that prompt recognition and treatment will be necessary.

Frequently asked questions

• Which painkiller should you use?
• Which drugs cause opioid-induced constipation?
• What are the symptoms of a fentanyl overdose?
• Why is fentanyl so dangerous?
• Fentanyl test strips: where to get & how to use?
• How long does Fentanyl stay in your system?
• Carfentanil vs Fentanyl: Which is more dangerous?
• How does fentanyl compare to heroin or other opiates?