Dosing & Uses
Dosage Forms & Strengths
intranasal: Schedule II
- 100mcg/100mcL spray (8 sprays/bottle)
- 300mcg/100mcL spray (8 sprays/bottle)
- 400mcg/100mcL spray (8 sprays/bottle)
Indicated only for breakthrough cancer pain in adults who are tolerant to opioid therapy for their underlying persistent cancer pain
Initial dose for all patients: 100 mcg in one nostril
If adequate analgesia is not achieved with the first 100 mcg dose, dose escalate in a step-wise manner over consecutive episodes of breakthrough pain until adequate analgesia with tolerable adverse effects is achieved
Individually titrate to an effective dose, from 100 mcg to 200 mcg to 400 mcg, and up to a maximum of 800 mcg; there are no clinical data to support using a combination of dose strengths to treat a breakthrough pain episode
Dose is a single spray into 1 nostril or single spray into each nostril (2 sprays)
Maximum dose is a single spray into 1 nostril or single spray into each nostril per episode; not to exceed 4 doses/24 hr
Wait at least 2 hr before repeating the dose for another episode of breakthrough pain
During any breakthrough pain episode, if adequate pain relief is not achieved within 30 minutes, the patient may use a rescue medication as directed by their healthcare provider
Available only through a restricted access program; for more information, see www.LazandaREMS.com or call 1-855-841-4234
- 100 mcg/dose: use 1 x 100 mcg spray
- 200 mcg/dose: use 2 x 100 mcg spray (1 spray in each nostril)
- 400 mcg/dose: use 1 x 400 mcg spray
- 800 mcg/dose: use 2 x 400 mcg spray (1 spray in each nostril)
- Patients should confirm the dose that works for them with a second episode of breakthrough pain and review with their physician to determine if that dose is appropriate, or whether a further adjustment is warranted
- If the response to the titrated fentanyl intranasal dose markedly changes, an adjustment of dose may be necessary
- Patients considered opioid tolerant are those taking a minimum of the following opioid doses or an equianalgesic dose of another opioid for 1 week or longer:
- morphine 60 mg/day PO
- fentanyl transdermal 25mcg/hr
- oxycodone 30 mg/day PO
- hydromorphone 8 mg/day PO
- oxymorphone 25 mg/day PO
Renal or Hepatic Impairment
Insufficient data exist for dosage modification with renal or hepatic impairment
Fentanyl primarily metabolized by CYP3A4 in liver and inactive metabolite excreted in urine
Caution if used with renal or hepatic impairment because of hepatic metabolism and renal excretion of fentanyl
Titrate to clinical effect for all patients, with special care taken in patients with severe renal or hepatic disease
<18 years: Safety and efficacy not established
Clinical trials included 148 (28%) patients who were aged 60 yr or older
No clinically meaningful difference was noted compared with younger patients
Elderly patients have been shown to be more sensitive to the effects of fentanyl when administered IV compared with younger individuals
Caution when individually titrating fentanyl intranasal in elderly individuals
Serious - Use Alternative
Significant - Monitor Closely
Adverse effects are for maintenance therapy unless otherwise specified
Dizziness (titration 4-14%)
Vomiting (titration 1-14%; maintenance 5-12%)
Nausea (titration 2-4%; maintenance 4-9%)
Black Box Warnings
Potential for abuse
- Fentanyl is an opioid agonist and a schedule II controlled substance (ie, has highest potential for abuse and risk of fatal overdose due to respiratory depression), with an abuse liability similar to other opioid analgesics
- Consider potential for abuse when prescribing/dispensing
- Serious adverse events, including deaths, in patients treated with other fentanyl dosage forms (eg, oral transmucosal, transdermal) have been reported
- Deaths occur as a result of improper patient selection (eg, use in opioid naïve patients) and/or improper dosing
- The substitution of fentanyl intranasal for any other fentanyl product may result in fatal overdose
Indicated only for breakthrough cancer pain
- Indicated only for breakthrough cancer pain in adults who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain
- Patients considered opioid tolerant are those taking at least morphine 60 mg/day PO, fentanyl transdermal 25mcg/hr, oxycodone 30 mg/day PO, hydromorphone 8 mg/day PO, oxymorphone 25 mg/day PO or an equianalgesic dose of another opioid for 1 week or longer
Contraindicated in patients not tolerant to opioids
- Contraindicated in management of acute or postoperative pain, including headache/migraine, dental pain, or use in the emergency room
- Life-threatening respiratory depression could occur at any dose in opioid non-tolerant patients
- When prescribing do not convert patients on a mcg per mcg basis from another fentanyl product to fentanyl intranasal
- All patients must begin with titration from 100 mcg/dose
- When dispensing, do not substitute fentanyl intranasal for any other fentanyl product; substantial differences exist in the pharmacokinetics that could result in clinically important differences in the rate and extent of absorption of fentanyl dosage forms and could result overdosage
- If breakthrough pain episode is not relieves, patients must wait at least 2 hr before taking another dose of fentanyl intranasal
- 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 schedule II opioids to treat cancer pain
Instructions to patients and caregivers
- Inform patients/caregivers that fentanyl intranasal contains a medicine in an amount that can be fatal in children, in individuals for whom it is not prescribed, and in those who are not opioid tolerant
- Fentanyl intranasal must be kept out the reach of children at all times
Available only via restricted access program
- Because of the risk for misuse, abuse, addiction, and overdose, fentanyl intranasal is available only through a restricted program required by the US Food and Drug Administration called the Lazanda REMS (Risk Evaluation and Mitigation Strategy) program
- Healthcare professionals who prescribe to outpatients, patients, pharmacies, and distributors must enroll in the program to prescribe, receive, dispense, and distribute respectively
- Additional information is available at www.LazandaREMS.com or by calling 1-855-841-4234
- Beginning March 2012, a single shared risk evaluation and mitigation strategy (REMS) for immediate-release transmucosal fentanyl products will be available that includes Lazanda
- This single program allows prescribers, patients, and pharmacists to enroll in a single access program instead of individual programs for each brand
NOT for use in management of pain in patients not tolerant to opioids because of life-threatening hypoventilation could occur at any dose in patients not already taking around-the-clock opioid therapy (see Black Box Warnings)
NOT for use of acute or postoperative pain, including headache/migraine, dental pain, or use in the emergency room (see Black Box Warnings)
Hypersensitivity or known intolerance
NOT equivalent to other fentanyl products used to treat breakthrough pain on a mcg per mcg vasis (see Black Box Warnings)
When prescribing, DO NOT convert fentanyl intranasal dose from other fentanyl products
When dispensing, DO NOT substitute fentanyl intranasal for any other fentanyl product prescription
Serious or fatal respiratory depression can occur even at recommended doses, particularly in elderly or debilitated patients (eg, COPD, head injury, increased ICP), opioid naïve patients, or when opioids are given in conjunction with other drugs that depress respiration
Additive CNS depression (eg, hypoventilation, hypotension, and profound sedation) may occur if coadministered with other opioids, sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, skeletal muscle relaxants, sedating antihistamines, and alcohol
Inform patients/caregivers that fentanyl intranasal must be kept out of reach from children at all times
Use by individuals for whom fentanyl intranasal is not prescribed or in those who are opioid naïve may result in death
Opioid analgesics impair the mental and /or physical ability required to perform potentially dangerous tasks (eg, driving a car, operating machinery)
Bradycardia observed with use of fentanyl IV, caution with use of fentanyl intranasal in patients with underlying bradycardic conditions
Not recommended for use within 14 days of MAO inhibitors because of severe and unpredictable potentiation by MAO inhibitors
Coadministration with CYP3A4 inhibitors (including grapefruit juice) may increase fentanyl plasma concentration and increase risk for fatal respiratory depression; monitor for signs of opioid toxicity
CYP3A4 inducers may result in decreased fentanyl plasma concentration and decrease efficacy; if CYP3A4 inducers are stopped or the dose reduced, a sudden increased fentanyl plasma concentration may occur
Fentanyl intranasal absorption is decreased when used in patients with allergic rhinitis treated with oxymetazoline
Pregnancy & Lactation
Pregnancy Category: C; chronic maternal treatment with fentanyl during pregnancy has been associated with transient respiratory depression, behavioral changes, or seizures in newborn infants’ characteristic of neonatal abstinence syndrome
Lactation: Excreted in human breast milk
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.
Mechanism of Action
Mu-opioid agonist with principal therapeutic action being analgesia
Other pharmacologic effects include respiratory depression by direct action on brain stem respiratory centers, miosis, reduced GI motility, histamine release, peripheral vasodilation
Inhibits ACTH, cortisol, and LH secretion, but stimulates prolactin, GH, and pancreatic secretion of insulin and glucagon; TSH may be inhibited or stimulated by opioids
Bioavailability: 20% higher than oral transmucosal fentanyl
Peak Plasma Time (mean): 15-21 minutes
Peak Plasma Concentration: 351.5-2844 pg/mL (dose dependent); use of intranasal oxymetazoline decreases Tmax by 32-40%
AUC: 2460.5-17,272 pg•hr/mL; slight decrease (10-17%) in patients with allergic rhinitis
Protein Bound: 80-85%; mainly to alpha-1-acid glycoprotein, also binds to albumin and lipoproteins to some extent
Vd: 4 L/kg
Metabolized by hepatic and intestinal mucosal CYP3A4
Metabolites: Norfentanyl (inactive metabolite)
Primarily (>90%) eliminated by biotransformation
Total body clearance: 42 L/hr (IV administration)
Excretion: feces (1%), urine (<7% unchanged, the rest as metabolites)
Prime the device before use by spraying into the pouch provided (4 sprays total to prime)
Insert nozzle of fentanyl intranasal bottle a short distance (about 0.5 inch or 1 cm) into the nose and point towards the bridge of the nose, tilting the bottle slightly
Press down firmly on the finger grips until they hear a ‘click’ and the number in the counting window advances by one
Advise patients that the fine mist spray is not always felt on the nasal mucosal membrane and to rely on the audible click and the advancement of the dose counter to confirm a spray has been administered
Discontinuation of therapy
- Patients no longer requiring opioid therapy, should discontinue fentanyl intranasal with a gradual downward titration of other opioids to minimize possible withdrawal effects
- Patients who continue to take chronic opioid therapy for persistent pain but no longer require treatment for breakthrough pain, fentanyl intranasal may be discontinued immediately
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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.
|1||This drug is available at the lowest co-pay. Most commonly, these are generic drugs.|
|2||This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.|
|3||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.|
|4||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.|
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