fentanyl transmucosal (Actiq, Fentora, Abstral, Onsolis, Subsys)

Dosing and uses of Actiq, Fentora (fentanyl transmucosal)

• Adult
• Pediatric

 

Adult dosage forms and strengths

troche/lozenge (Actiq): Schedule II

• 200mcg
• 400mcg
• 600mcg
• 800mcg
• 1200mcg
• 1600mcg

tablet, sublingual (Abstral): Schedule II

• 100mcg
• 200mcg
• 300mcg
• 400mcg
• 600mcg
• 800mcg

buccal tablet (Fentora): Schedule II

• 100mcg
• 200mcg
• 400mcg
• 600mcg
• 800mcg

soluble film (Onsolis): Schedule II

• 200mcg
• 400mcg
• 600mcg
• 800mcg
• 1200mcg

sublingual spray (Subsys): Schedule II

• 100mcg/spray
• 200mcg/spray
• 400mcg/spray
• 600mcg/spray
• 800mcg/spray

 

Breakthrough Cancer Pain

Only for patient already receiving and tolerant to opioid analgesics (ie, >60 mg morphine equivalent/day or 50 mcg transdermal fentanyl/hr)

 

Abstral

Initial dose: 100 mcg SL

Individually titrate to tolerable dose that provides adequeate analgeisa for breakthrough pain

Not to exceed 2 doses/breakthrough pain episode

Wait at least 2 hr before treating another episode of breakthrough pain

Limit consumption to 4 or fewer breakthrough pain episodes/24 hr

Administer on floor of mouth directly under tongue and allow to completely dissolve

Dose titration

• If adequate analgesia was not obtained with the first 100 mcg dose, continue dose escalation in a stepwise manner over consecutive breakthrough episodes until adequate analgesia with tolerable side effects achieved
• Increase the dose by 100 mcg multiples up to 400 mcg as needed If adequate analgesia is not obtained with a 400 mcg dose, the next titration step is 600 mcg
• If adequate analgesia is not obtained with a 600 mcg dose, the next titration step is 800 mcg
• During titration, patients can be instructed to use multiples of 100 mcg tablets and/or 200 mcg tablets for any single dose
• Instruct patients not to use more than 4 tablets at one time
• If adequate analgesia is not obtained 30 minutes after the use, may repeat the same dose
• Maintenance: Once an appropriate dose for pain management has been established, instruct patients to use only 1 tablet of the appropriate strength per dose

Dose conversion from Actiq

• The initial dose of Abstral is always 100 mcg with the only exception being patients already using Actiq
• For patients being converted from Actiq, instruct patient to stop use of Actiq and dispose of any remaining units
• Initial dose for Abstral when converting from patients taking Actiq:
• -Current Actiq dose = 200 mcg, initial Abstral dose = 100 mcg
• -Current Actiq dose = 400, 600, 800, or 1200 mcg, initial Abstral dose = 200 mcg
• -Current Actiq dose = 1600 mcg, initial Abstral dose = 400 mcg
• Titrating Abstral after converting from Actiq:
• -Converting from Actiq doses ≤400 mcg, initiate titration with 100 mcg Abstral and proceed using multiples of this strength
• -Converting from Actiq doses of 600, 800, or 1200 mcg, initiate titration with 200 mcg Abstral and proceed using multiples of this strength
• -Converting from Actiq doses of 1600 mcg, initiate titration with 400 mcg Abstral and proceed using multiples of this strength

 

Actiq

200 mcg dissolve in mouth over 15 min period, PRN; wait 15 min before taking next dose

Titrate up to 1600 mcg; limit consumption to <4 units/day

Gradual downward titration for discontinuation

Product substitution

• Substitution of Actiq for any other fentanyl product may result in fatal overdose
• Do not convert on a mcg per mcg basis to Actiq from other fentanyl products
• Do not substitute Actiq prescription for other fentanyl products; pharmacokinetic profile differs substantially and may result in fatal overdose

 

Fentora

Initial 100 mcg, may redose once after 30 min (place tab between upper cheek and gum till dissolves, any remnant after 30 min may be drunk with water); must wait at least 4 hours before treating another episode of breakthrough pain

Titrate PRn

Dose conversion from Actiq

• Initial 100 mcg if switching from 200-400 mcg Actiq
• Initial 200 mcg if switching from 600-800 mcg Actiq
• Initial 400 mcg if switching from 1200-1600 mcg Actiq

Maintenance dosing

• Once titrated to an effective dose, patients should generally use only 1 tablet of the appropriate strength per breakthrough pain episode
• On occasion when the breakthrough pain episode is not relieved after 30 minutes, patients may take ONLY ONE additional dose using the same strength for that episode
• Must wait at least 4 hours before treating another episode of breakthrough pain
• Once an effective dose is determined using the titration scheme outlined above, an alternate route to buccal administration is sublingual

 

Onsolis

Initial dose: 200-mcg film placed buccally with breakthrough pain episode

If pain relief not achieved, titrate using multiples of the 200-mcg film (ie, increase dose by 200 mcg in each subsequent episode until adequate pain relief); not to exceed 4 of the 200-mcg films per breakthrough pain episode; do not place films on top of one another, but may place on both sides of mouth

Once pain relief achieved: Treat subsequent breakthrough pain using the determined dose within range of 200-800 mcg

If pain relief not achieved with 800 mcg

• Treat next episode using 1 film containing 1200 mcg; not to exceed 1200 mcg per pain episode
• Separate each dose by at least 2 h, use only once per breakthrough pain episode (do not redose), and limit to 4 or fewer doses daily; if experiencing >4 breakthrough pain episodes per day, consider increasing dose of around-the-clock opioid medication for persistent pain
• Rescue pain medication may be used as directed after 30 min following Onsolis if adequate pain relief not achieved

Administration

• Use tongue to wet inside of cheek or rinse mouth with water to wet area before film placement
• Place pink side of film against inside of cheek and hold in place for 5 seconds
• Avoid consuming liquids for 5 min after film placement
• Do not eat until film dissolves

 

Subsys

Initial dose is alwasy 100 mcg SL

Individually titrate after initial dose to provide adequate analgesia and minimize side effects

When prescribing, do not switch patients on a mcg per mcg basis from any other oral transmucosal fentanyl product (not equivalent on mcg per mcg with other fentanyl products)

Dose titration

• From the 100 mcg initial dose, closely follow patients and change the dosage level until the patient reaches a dose that provides adequate analgesia using a single dosage per breakthrough cancer pain episode with tolerable side effects; patients should record their use of Subsys over several episodes of breakthrough cancer pain and review their experience with their physicians to determine if a dosage adjustment is warranted
• For each breakthrough pain episode treated, if pain is not relieved after 30 minutes, patients may take only 1 additional dose of the same strength for that episode; thus patients should take a maximum of 2 doses of Subsys for any breakthrough pain episode
• Patients must wait at least 4 hours before treating another episode of breakthrough pain
• If there is a need to titrate to a 200 mcg dose, prescribe 200 mcg Subsys units
• Subsequent titration steps are 400 mcg, 600 mcg, 800 mcg, 1200 mcg and 1600 mcg (see prescribing information)
• To reduce the risk of overdose during titration, patients should have only one strength of Subsys available at any time

 

Other information

Not equivalent on a mcg-per-mcg basis to any other oral transmucosal fentanyl product

Individually titrate to dose providing adequate analgesia with tolerable adverse effects

Only available via special access program; single shared risk evaluation and mitigation strategy (REMS) for immediate-release transmucosal fentanyl products will begin in March 2012

This single REMS allows prescribers, patients, and pharmacists to enroll in a single access program

 

Pediatric dosage forms and strengths

Actiq: <16 years: not recommended

Abstral; Fentora; Onslis; Subsys: <18 years: not recommended

 

Actiq, Fentora (fentanyl transmucosal) adverse (side) effects

>10%

Asthenia

Confusion

Constipation

Dry mouth

Nausea

Somnolence

Sweating

Vomiting

 

1-10%

Abdominal pain

Anorexia

Anxiety

Apnea

Depression

Diarrhea

Dizziness

Dyspepsia

Dyspnea

Euphoria

Fatigue

Hallucinations

Headache

Hemoptysis

Hypoventilation

Influenza-like symptoms

Nervousness

Pharyngitis

Pruritus

Urinary retention

Upper respiratory tract infection

 

Frequency not defined

Abnormal coordination, thinking, gait, dreams

Amnesia

Agitation

Application site reaction

Back pain

Bronchitis

Fever

Flatulence

Hiccups

Accidental injury

Micturition disorder

Mucosal inflammation

Paranoid reaction

Paresthesia

Rash

Rhinitis, sinusitis

Speech disorder

Syncope

Tremor

Bradycardia

QT-interval prolongation

Severe cardiac arrhythmias

Cardiac arrest

ST segment elevation

Ventricular tachycardia

MI

Angina pectoris

Respiratory/circulatory depression

Respiratory arrest

Shock

Visual disturbances

Mental clouding

Sedation

Coma

Dysphoria

Weakness

Faintness

Seizures

Urinary retention

Oliguria

Sweating

Flushing

Warmness of face/neck/upper thorax

Urticaria

 

Warnings

Black box warnings

Reports of serious adverse events, including deaths, in patients treated with Fentora have been reported. Deaths occurred as a result of improper patient selection (eg, use in patients not opioid tolerant) and/or improper dosing. The substitution of Fentora (buccal table formulation) for any other fentanyl product may result in fatal overdose.

Buccal tablets contain an opioid agonist and a Schedule II controlled substance with an abuse liability potential similar to other opioid analgesics. This should be considered when prescribing or dispensing fentanyl buccal tablets in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.

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

Special care must be used when dosing this drug in buccal form. If the breakthrough pain episode is not relieved after 30 minutes, patients may take only one additional dose using the same strength and must wait at least 4 hours before taking another dose.

Because life-threatening respiratory depression could occur at any dose in patients not opioid tolerant, fentanyl buccal tablets are contraindicated in the management of acute or postoperative pain, including headache/migraine. Deaths have occurred in patients not opioid tolerant. Patients and their caregivers must be instructed that fentanyl buccal tablets contain a medicine in an amount that can be fatal to a child.

Patients and their caregivers must be instructed to keep all tablets out of the reach of children (See Information for Patients and Caregivers for disposal instructions).

When prescribing, do not convert patients on a microgram per microgram basis from Actiq (transmucosal) to Fentora (buccal tablet). Carefully consult the Initial Dosing Recommendations table.

When dispensing, do not substitute a Fentora (buccal tablet) prescription for other products. The substitution of Fentora for any other fentanyl products may result in fatal overdose because of differences that exist in the pharmacokinetic profile of buccal tablet.

Fentanyl buccal tablets are intended for use only in the care of opioid-tolerant cancer patients and only by healthcare professional who are knowledgeable of and skilled in the use of Schedule II opioids to treat cancer pain.

The concomitant use of this drug with strong and moderate cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations and may cause potentially fatal respiratory depression.

 

Contraindications

Hypersensitivity/opioid non-tolerant

Acute or postoperative pain

Diarrhea from toxicity (until toxins cleared), paralytic ileus, respiratory depression, acute/severe bronchial asthma

Within 2 wk of MAO inhibitors

 

Cautions

Acute pancreatitis, Addison's disease, BPH, cardiac arrhythmias, CNS depression, drug abuse/dependence, emotional lability, gallbladder disease, GI disorder, pseudomembranous colitis, GI surgery, head injury, hypothyroidism/untreated myxedema, intracranial HTN, brain tumor, toxic psychosis, urethral stricture, urinary tract surgery, seizures, acute alcoholism, delirium tremens, shock, cor pulmonale, chronic pulmonary disease, emphysema, hypercapnia, kyphoscoliosis, severe obesity, renal/hepatic impairment, elderly/debilitated patients

To dispose, flush drug matrix down toilet

Actiq: prescribe 6 units of each new dose during titration period

Mucositis (>Grade I)

Fentora: do not break tab in mouth or swallow

Onsolis: after buccal placement, do not drink for at least 5 min, do not eat until film dissolves (15-30 min)

Use with CYP3A4 inhibitors or other CNS depressants may cause potentially fatal respiratory depression, hypotension, and profound sedation (dosage adjustments warranted)

 

Pregnancy and lactation

Pregnancy category: C

Lactation: excreted in breast milk; not recommended because of the possibility of sedation and respiratory depression in the infant

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Actiq, Fentora (fentanyl transmucosal)

Mechanism of action

Narcotic agonist-analgesic of opiate receptors; inhibits ascending pain pathways, which causes alteration in response to pain; produces analgesia, respiratory depression, and sedation

 

Pharmacokinetics

Bioavailability: Onsolis 71%

Duration: 1-2 hr

Peak Plasma Time: 0.5-4 hr

Metabolism: CYP3A4 (Predominantly)

Metabolite: norfentanyl (inactive)

Half-Life: 1.5-6 hr

Excretion: urine, feces