Onsolis (fentanyl buccal) for Cancer Pain: Side Effects & Dosage

What is Onsolis (fentanyl buccal), and how does it work?

Generic drug: fentanyl buccal

Brand name: Onsolis

Onsolis is:

• A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage breakthrough pain in adults (18 years of age and older) with cancer, who are already routinely taking other opioid pain medicines around-the-clock for cancer pain. Onsolis is started only after you have been taking other opioid pain medicines and your body has become used to them (you are opioid tolerant). Do not use Onsolis if you are not opioid tolerant
• A medicine that contains fentanyl in a small film (about the size of a dime or nickel) that sticks to the inside of your cheek.
• An opioid pain medicine that can put you at risk for overdose and death. Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse, and misuse that can lead to death.

What are the side effects of Onsolis?

The possible side effects of Onsolis may include:

• Constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain, weakness, anxiety, depression, rash, trouble sleeping, low red blood cell count, swelling of the arms, hands, legs and feet. Call your healthcare provider if you have any of these symptoms and they are severe.
• Decreased blood pressure. This can make you feel dizzy or lightheaded if you get up too fast from sitting or lying down.

Get emergency medical help if you have:

• trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue, or throat, extreme drowsiness, light-headedness when changing positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental changes such as confusion.
• These symptoms can be a sign that you have used too much
  Onsolis or the dose is too high for you. These symptoms may lead to serious problems or death if not treated right away. If you have any of these symptoms, do not use any more
  Onsolis until you have talked to your healthcare provider.

These are not all the possible side effects of
Onsolis. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov

WARNING

RISK OF RESPIRATORY DEPRESSION, MEDICATION ERRORS, ABUSE POTENTIAL

Respiratory Depression

Fatal respiratory depression has occurred in patients treated with immediate-release transmucosal fentanyl, including following use in opioid non-tolerant patients and improper dosing. The substitution of
Onsolis for any other fentanyl product may result in fatal overdose.

Due to the risk of respiratory depression,
Onsolis is contraindicated in the
management of acute or postoperative pain including headache/migraine and in
opioid non-tolerant patients. Onsolis must be kept out of reach of children.

The concomitant use of
Onsolis with CYP3A4 inhibitors may result in an increase
in fentanyl plasma concentrations, and may cause potentially fatal respiratory
depression.

Medication Errors

Substantial differences exist in the pharmacokinetic profile of
Onsolis compared to other fentanyl products that result in clinically important differences in the extent of absorption of fentanyl that could result in fatal overdose.

• When prescribing, do not convert patients on a mcg per mcg basis from any other fentanyl products toOnsolis.
• When dispensing, do not substitute an
  Onsolis prescription for other fentanyl products.

Abuse Potential

• Onsolis contains fentanyl, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics.
  Onsolis can be abused in a manner similar to other opioid agonists, legal or illicit.
• This should be considered when prescribing or dispensing Onsolis in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion.
• Because of the risk for misuse, abuse, addiction, and overdose, Onsolis is
  available only through a restricted program required by the Food and Drug
  Administration, called a Risk Evaluation and Mitigation Strategy (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. Further information is available at www.TIRFREMSAccess.com or by calling 1-866-822-1483.

What is the dosage for Onsolis?

Important Dosage And Administration Instructions

• Healthcare
  professionals who prescribe Onsolis on an outpatient basis must enroll in
  the TIRF REMS Access Program and comply with the requirements of the REMS to
  ensure safe use of Onsolis.
• Use the lowest effective dosage for the
  shortest duration consistent with individual patient treatment goals.
• It is important to minimize the number of strengths available to patients at any time to prevent confusion and possible overdose.
• Initiate the dosing regimen for each patient individually, taking into
  account the patient’s severity of pain, patient response, prior analgesic
  treatment experience, and risk factors for addiction, abuse, and misuse.
• Monitor patients closely for respiratory depression, especially within the
  first 24-72 hours of initiating therapy and following dosage increases with
  Onsolis and adjust the dosage accordingly.
• Instruct patients and
  caregivers to take steps to store Onsolis securely and to properly dispose
  of unused Onsolis as soon as no longer needed.
• Onsolis is not
  bioequivalent with other fentanyl products. Do not convert patients on a mcg
  per mcg basis from other fentanyl products. There are no conversion
  directions available for patients on any other fentanyl products. (Note:
  This includes oral, transdermal, or parenteral formulations of fentanyl.)
• Onsolis is NOT a generic version of any other oral transmucosal fentanyl
  product.

Initial Dosage

Initiate treatment with Onsolis for all patients with a single initial dose of 200 mcg film.

• Due to differences in the pharmacokinetic properties and individual variability, even patients switching from other fentanyl containing products to
  Onsolis must start with the 200 mcg dose.

Titration And Maintenance Of Therapy

• The objective of dose titration is to identify the individual patient’s effective and tolerable dose. The dose of
  Onsolis is not predicted from the daily maintenance dose of opioid used to manage the persistent cancer pain and
  MUST be determined by dose titration.
• From the initial dose, closely follow patients and change the dosage level until the patient reaches a dose that provides adequate analgesia.
• Individually titrate Onsolis to a dose that provides adequate analgesia with tolerable side effects. All patients MUST begin treatment using
  one 200 mcg Onsolis film.
•  If adequate pain relief is not achieved after one 200 mcg
  Onsolis film, titrate using multiples of the 200 mcg Onsolis film (for doses of 400, 600, or 800 mcg). Increase the dose by 200 mcg in each subsequent episode until the patient reaches a dose that provides adequate analgesia with tolerable side effects.
• Do not use more than four of the 200 mcg Onsolis films simultaneously. When multiple 200 mcg
  Onsolis films are used, they should not be placed on top of each other and may be placed on both sides of mouth.
• If adequate pain relief is not achieved after 800 mcg Onsolis (i.e.,
  four 200 mcg Onsolis films), and the patient has tolerated the 800 mcg dose, treat the next episode by using
  one 1200 mcg Onsolis film. Doses above 1200 mcg Onsolis should not be used.
• Once adequate pain relief is achieved with a dose between 200 mcg and 800 mcg
  Onsolis, the patient should use or safely dispose of all remaining 200 mcg
  Onsolis films [see Disposal Of Unused Onsolis below].
• Patients who require 1200 mcg Onsolis should dispose of all remaining unused 200 mcg
  Onsolis films [see Disposal Of Unused Onsolis below]. The patient should then get a prescription for
  Onsolis films of the dose determined by titration (i.e., 200, 400, 600, 800, or 1200 mcg) to treat subsequent episodes.
• Single doses should be separated by at least 2 hours. Onsolis should only be used once per breakthrough cancer pain episode, i.e.,
  Onsolis should not be redosed within an episode.
• During any episode of breakthrough cancer pain, if adequate pain relief
  is not achieved after Onsolis, the patient may use a rescue medication (after 30 minutes) as directed by their healthcare provider.

Dose Titration Illustration

Dosage Adjustment

• During maintenance treatment, if the prescribed dose no longer adequately manages the breakthrough cancer pain episode for several consecutive episodes, increase the dose of
  Onsolis as described in Dose Titration (2.3).
• Once a successful dose has been found, each episode is treated with a single film.
• Onsolis should be limited to four or fewer doses per day.
• Consider increasing the dose of the around-the-clock opioid medicine used for persistent cancer pain in patients experiencing more than four breakthrough cancer pain episodes daily.

Administration Of Onsolis

• Use the tongue to wet the inside of the cheek or rinse the mouth with water to wet the area for placement of
  Onsolis.
• Open the Onsolis package immediately prior to product use.
• Place the entire Onsolis film near the tip of a dry finger with the printed side facing up and hold in place.
• Place the printed side of the Onsolis film against the inside of the cheek.
• Press and hold the Onsolis film in place for 5 seconds. The Onsolis film should stay in place on its own after this period.
• Liquids may be consumed after 5 minutes.
• An Onsolis film, if chewed and swallowed, might result in lower peak
  concentrations and lower bioavailability than when used as directed.
• The Onsolis film should not be cut or torn prior to use.
• The Onsolis film will dissolve within 15 to 30 minutes after application. The film should not be manipulated with the tongue or finger(s) and eating food should be avoided until the film is dissolved.

Discontinuation Of Onsolis

• For patients no longer requiring opioid therapy, consider discontinuing
  Onsolis along with a gradual downward titration of other opioids to minimize possible withdrawal effects.
• In patients who continue to take their chronic opioid therapy for persistent pain but no longer require treatment for breakthrough pain,
  Onsolis therapy can usually be discontinued immediately [see Drug Abuse And Dependence
  section below].

Disposal Of Onsolis

• Patients and their household members must be advised to dispose of any buccal films remaining from a prescription as soon as they are no longer needed. Instructions are included in
  the product labeling.
• If additional assistance is required, call 1-800-469-0261.

What drugs interact with Onsolis?

Table 3 includes clinically significant drug interactions with Onsolis.

Table 3 Clinically Significant Drug Interactions with Onsolis

Inhibitors of CYP3A4Clinical Impact:The concomitant use of
Onsolis and CYP3A4 inhibitors can increase the plasma
concentration of fentanyl, resulting in increased or prolonged opioid
effects, particularly when an inhibitor is added after a stable dose of
Onsolis is achieved.After stopping a CYP3A4 inhibitor, as
the effects of the inhibitor decline, the fentanyl plasma concentration
will decrease, resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to fentanyl.Intervention:If concomitant use is necessary, consider dosage reduction of
Onsolis until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals.If a CYP3A4 inhibitor is discontinued, consider increasing the
Onsolis dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.ExamplesMacrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir)CYP3A4 InducersClinical Impact:The concomitant use of
Onsolis with CYP3A4 inducers can decrease the plasma
concentration of fentanyl, resulting in decreased efficacy or onset of a
withdrawal syndrome in patients who have developed physical dependence to
fentanyl.After stopping a CYP3A4 inducer, as the effects
of the inducer decline, the fentanyl plasma concentration will increase, which could increase or prolong both the therapeutic effects and adverse reactions and may cause serious respiratory depression.Intervention:
If concomitant use is necessary, consider increasing the Onsolis dosage
until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider
Onsolis dosage reduction and monitor for signs of respiratory depression.ExamplesRifampin, carbamazepine, phenytoinBenzodiazepines and other Central Nervous System (CNS) DepressantsClinical Impact:Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, increases the risk of respiratory depression, profound sedation, coma, and death.Intervention:Reserve concomitant prescribing of these drugs for use in patients for whom
alternative treatment options are inadequate. Limit dosages and durations to
the minimum required. Monitor patients for signs of respiratory depression
and sedation.Examples:Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol.Serotonergic DrugsClinical Impact:
The concomitant use of opioids with other drugs that affect the serotonergic
neurotransmitter system has resulted in serotonin syndrome.Intervention:If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue
Onsolis if serotonin syndrome is suspected.Examples:Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).Monoamine Oxidase Inhibitors (MAOIs)Clinical Impact:MAOI interactions with opioids may manifest as serotonin syndrome or opioid
toxicity (e.g., respiratory depression, coma).Intervention:The use of
Onsolis is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.Examples:phenelzine, tranylcypromine, linezolidMixed Agonist/Antagonist and Partial Agonist Opioid AnalgesicsClinical Impact:May reduce the analgesic effect of
Onsolis and/or precipitate withdrawal symptoms.Intervention:Avoid concomitant use.Examples:butorphanol, nalbuphine, pentazocine, buprenorphineMuscle RelaxantsClinical Impact:Fentanyl may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.Intervention:Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of
Onsolis and/or the muscle relaxant as necessary.DiureticsClinical Impact:Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.Intervention:Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.Anticholinergic DrugsClinical Impact:The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.Intervention:Monitor patients for signs of urinary retention or reduced gastric motility when
Onsolis is used concomitantly with anticholinergic drugs.

Does Onsolis cause addiction or withdrawal symptoms?

Drug Abuse And Dependence

Controlled Substance

• Onsolis contains fentanyl, a Schedule II controlled substance.

Abuse

• Onsolis contains fentanyl, a substance with a high potential for abuse similar
  to other opioids including hydrocodone, hydromorphone, methadone, morphine,
  oxycodone, oxymorphone, and tapentadol.
• Onsolis can be abused and is subject to
  misuse, addiction, and criminal diversion.
• All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use.
• Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects.
• Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.
• “Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating health care provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.
• Abuse and addiction are separate and distinct from physical dependence and tolerance. Health care providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.
• Onsolis, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.
• Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of Onsolis

• Onsolis is for buccal route use only. Abuse of Onsolis poses a risk of overdose and death. The risk is increased with concurrent abuse of
  Onsolis with alcohol and other central nervous system depressants. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

Dependence

• Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.
• Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug.
• Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine).
• Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.
• Infants born to mothers physically dependent on opioids will also be physically
  dependent and may exhibit respiratory difficulties and withdrawal signs.

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Is Onsolis safe to use while pregnant or breastfeeding?

• Prolonged use of Onsolis during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated.
• Onsolis may cause fetal harm and to inform the healthcare provider of a known or suspected pregnancy.
• Nursing mothers should monitor infants for increased sleepiness (more than usual), breathing difficulties, or limpness.
  Seek immediate medical care if you notice these signs.

• Chronic use of opioids may cause reduced fertility. It is not known whether these effects on fertility are reversible.