FENTANYL CITRATE lozenge

Χώρα: Ηνωμένες Πολιτείες

Γλώσσα: Αγγλικά

Πηγή: NLM (National Library of Medicine)

Δραστική ουσία:

FENTANYL CITRATE (UNII: MUN5LYG46H) (FENTANYL - UNII:UF599785JZ)

Διαθέσιμο από:

SpecGx LLC

INN (Διεθνής Όνομα):

FENTANYL CITRATE

Σύνθεση:

FENTANYL 200 ug

Οδός χορήγησης:

TRANSMUCOSAL

Τρόπος διάθεσης:

PRESCRIPTION DRUG

Θεραπευτικές ενδείξεις:

Oral transmucosal fentanyl citrate is indicated for the management of breakthrough pain in cancer patients 16 years of age and older 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, for one week or longer, around-the-clock medicine consisting of at least 60 mg of oral morphine per day, at least 25 mcg of transdermal fentanyl per hour, at least 30 mg of oral oxycodone per day, at least 8 mg of oral hydromorphone per day, at least 25 mg oral oxymorphone per day, at least 60 mg of oral hydrocodone per day, or an equianalgesic dose of another opioid. Patients must remain on around-the-clock opioids when taking oral transmucosal fentanyl citrate. Limitations of Use : - Not for use in opioid non-tolerant patients. Not for use in opioid non-tolerant patients. - Not for use in the management of acute or postoperative pain, including headache/migraine and dental pain [see Contraindications (4)] . Not for use in the management of acute or postoperative pain, including headache/migraine and dental pain [see Contraindications (4)] . - As a part of the TIRF REMS, oral transmucosal fentanyl citrate may be dispensed by outpatient pharmacies only to outpatients enrolled in the program [see Warnings and Precautions (5.7)] . For inpatient administration of oral transmucosal fentanyl citrate, patient and prescriber enrollment are not required. As a part of the TIRF REMS, oral transmucosal fentanyl citrate may be dispensed by outpatient pharmacies only to outpatients enrolled in the program [see Warnings and Precautions (5.7)] . For inpatient administration of oral transmucosal fentanyl citrate, patient and prescriber enrollment are not required. Oral transmucosal fentanyl citrate is contraindicated in: - Opioid non-tolerant patients: Life-threatening respiratory depression and death could occur at any dose in opioid non-tolerant patients [see Indications and Usage (1)]; Warnings and Precautions (5.1) [see Indications and Usage (1)] . - Significant respiratory depression [see Warnings and Precautions (5.1)] . Significant respiratory depression [see Warnings and Precautions (5.1)] . - Acute or postoperative pain including headache/migraine and dental pain, or acute pain in the emergency department. Acute or postoperative pain including headache/migraine and dental pain, or acute pain in the emergency department. - Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.9)] . Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.9)] . - Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.14)] . Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.14)] . - Known hypersensitivity to fentanyl or components of oral transmucosal fentanyl citrate (e.g., anaphylaxis, hypersensitivity) [see Adverse Reactions (6.2)] . Known hypersensitivity to fentanyl or components of oral transmucosal fentanyl citrate (e.g., anaphylaxis, hypersensitivity) [see Adverse Reactions (6.2)] . Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.8)] . Available data with oral transmucosal fentanyl citrate in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, fentanyl administration to pregnant rats during organogenesis was embryocidal at doses within the range of the human recommended dosing. When administered during gestation through lactation fentanyl administration to pregnant rats resulted in reduced pup survival at doses within the range of the human recommended dosing. No evidence of malformations were noted in animal studies completed to date [see Data] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset of neonatal withdrawal symptoms usually occurs in the first days after birth. The duration and severity of neonatal opioid withdrawal syndrome may vary. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.8)] . Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Oral transmucosal fentanyl citrate is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including oral transmucosal fentanyl citrate, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Data Human Data In women treated acutely with intravenous or epidural fentanyl during labor, symptoms of neonatal respiratory or neurological depression were no more frequent than would be expected in infants of untreated mothers. Transient neonatal muscular rigidity has been observed in infants whose mothers were treated with intravenous fentanyl. Animal Data Fentanyl (25, 50, or 100 mcg/kg) citrate was administered subcutaneously to pregnant rats during the period of organogenesis (Gestation Day, GD 6 to 17). Maternal toxicity and a decrease in fetal weights were observed at 100 mcg/kg but no teratogenicity was seen in the study (the no observed effect level of 50 mcg/kg is equivalent to 0.7 times the exposure of a single human dose of 1600 mcg per pain episode, based on an AUC comparison). Fentanyl (50, 100, or 250 mcg/kg) was also administered subcutaneously to pregnant rabbits during the period of organogenesis (GD 6 to 18). Maternal toxicity was noted at doses >100 mcg/kg. No teratogenicity was seen in the study (250 mcg/kg dose is equivalent to 3.5 times the exposure of a single human dose of 1600 mcg per pain episode, based on an AUC comparison). Fentanyl has been shown to embryocidal in pregnant rats at doses of 30 mcg/kg intravenously (0.2 times the 1600 mcg dose of oral transmucosal fentanyl citrate on a mg/m2 basis) from GD 6 to 18 and 160 mcg/kg subcutaneously (1 times the 1600 mcg dose of oral transmucosal fentanyl citrate based on a mg/m2 basis). No evidence of teratogenicity was reported. No evidence of malformations or adverse effects on the fetus was reported in a published study in which pregnant rats were administered fentanyl continuously via subcutaneously implanted osmotic minipumps at doses of 10, 100, or 500 mcg/kg/day starting 2-weeks prior to breeding and throughout pregnancy. The high dose was approximately 3 times the human dose of 1600 mcg oral transmucosal fentanyl citrate per pain episode on a mg/m2 basis and produced mean steady-state plasma levels that are 3.4 times higher than the mean Cmax observed following administration of 1600 mcg dose of oral transmucosal fentanyl citrate in humans. In a postnatal development study, pregnant rats were treated from GD 6 through Lactation Day (LD) 20 with subcutaneous doses of fentanyl (25, 50, 100, and 400 mcg/kg). Maternal toxicity was noted at doses >100 mcg/kg. A reduction in pup growth and delayed attainment of developmental indices were observed at >100 mcg/kg. No difference in the number of live pups/litter was seen at birth, however, pup survival at LD 4 was reduced to 48% at 400 mcg/kg and by LD 21 pup survival was reduced to 30% and 26% at 100 and 400 mcg/kg, respectively. During lactation, fentanyl-related clinical signs (decreased activity, skin cold to touch, and moribund appearance) were noted in the F1 pups, most prominently in the 400 mcg/kg group. Pups from this group also had significantly reduced body weights throughout the lactation period. The dose of fentanyl administered to rats at which no developmental toxicity in the F1 generation was seen was 50 mcg/kg which is 0.6 times the exposure of a single human dose of 1600 mcg per pain episode, based on an AUC comparison. Risk Summary Fentanyl is present in breast milk. One published lactation study reports a relative infant dose of fentanyl of 0.024%. However, there is insufficient information to determine the effects of fentanyl on the breastfed infant and the effects of fentanyl on milk production. Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with oral transmucosal fentanyl citrate. Clinical Considerations Monitor infants exposed to oral transmucosal fentanyl citrate through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. Infertility Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Adverse Reactions (6.2), Clinical Pharmacology (12.2), Nonclinical Toxicology (13.1)] . Safety and effectiveness in pediatric patients below 16 years of age have not been established. In a clinical study, 15 opioid-tolerant pediatric patients with breakthrough pain, ranging in age from 5 to 15 years, were treated with oral transmucosal fentanyl citrate. The study was too small to allow conclusions on safety and efficacy in this patient population. Twelve of the fifteen opioid-tolerant children and adolescents aged 5 to 15 years in this study received oral transmucosal fentanyl citrate at doses ranging from 200 mcg to 600 mcg. The mean (CV%; range) dose-normalized (to 200 mcg) Cmax and AUC0-8 values were 0.87 ng/mL (51%; 0.42-1.30) and 4.54 ng•h/mL (42%; 2.37-6.0), respectively, for children ages 5 to <11 years old (N = 3) and 0.68 ng/mL (72%; 0.15-1.44) and 8.38 (192%; 0.84-50.78), respectively, for children ages ≥11 to <16 y (N = 9). Of the 257 patients in clinical studies of oral transmucosal fentanyl citrate in breakthrough cancer pain, 61 (24%) were 65 years of age and older, while 15 (6%) were 75 years of age and older. Those patients over the age of 65 years were titrated to a mean dose that was about 200 mcg less than the mean dose titrated to by younger patients. No difference was noted in the safety profile of the group over 65 years of age as compared to younger patients in oral transmucosal fentanyl citrate clinical trials. Elderly patients have been shown to be more sensitive to the effects of fentanyl when administered intravenously, compared with the younger population. Therefore, exercise caution when individually titrating oral transmucosal fentanyl citrate in elderly patients to provide adequate efficacy while minimizing risk. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of oral transmucosal fentanyl citrate slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.9)] . Fentanyl is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Insufficient information exists to make recommendations regarding the use of oral transmucosal fentanyl citrate in patients with impaired renal or hepatic function. Fentanyl is metabolized primarily via human cytochrome P450 3A4 isoenzyme system and mostly eliminated in urine. If the drug is used in these patients, it should be used with caution because of the hepatic metabolism and renal excretion of fentanyl. Both male and female opioid-tolerant cancer patients were studied for the treatment of breakthrough cancer pain. No clinically relevant sex differences were noted either in dosage requirement or in observed adverse reactions. Oral transmucosal fentanyl citrate contains fentanyl, a Schedule II controlled substance. Oral transmucosal fentanyl citrate contains fentanyl, a substance with a high potential for abuse similar to other opioids including hydrocodone, hydromorphone, methadone, morphine oxycodone, oxymorphone, and tapentadol. Oral transmucosal fentanyl citrate can be abused and is subject to misuse, addiction, and criminal diversion [see Warnings and Precautions (5.6)] . 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 healthcare 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. Healthcare 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. Oral transmucosal fentanyl citrate, 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 the Abuse of Oral Transmucosal Fentanyl Citrate Oral transmucosal fentanyl citrate is for oral transmucosal use only. Abuse of oral transmucosal fentanyl citrate poses a risk of overdose and death. The risk is increased with concurrent abuse of oral transmucosal fentanyl citrate with alcohol and other central nervous system depressants. 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 [see Use in Specific Populations (8.1)] .

Περίληψη προϊόντος:

Oral transmucosal fentanyl citrate is supplied in six dosage strengths. Each unit is individually wrapped in a child-resistant, protective blister package. These blister packages are packed 30 per shelf carton for use when patients have been titrated to the appropriate dose. Each dosage unit has a white to off-white color. Each individual solid drug matrix is marked with “FENTANYL” and the strength of the unit (“200 MCG”, “400 MCG”, “600 MCG”, “800 MCG”, “1200 MCG”, or “1600 MCG”). The dosage strength is also marked on the handle tag, the blister package and the carton. See blister package and carton for product information. Dosage Strength (fentanyl base) Carton/Blister Package Color NDC Number Imprint 200 mcg Gray NDC 0406-9202-30 FENTANYL, 200 MCG 400 mcg Blue NDC 0406-9204-30 FENTANYL, 400 MCG 600 mcg Orange NDC 0406-9206-30 FENTANYL, 600 MCG 800 mcg Purple NDC 0406-9208-30 FENTANYL, 800 MCG 1200 mcg Green NDC 0406-9212-30 FENTANYL, 1200 MCG 1600 mcg Burgundy NDC 0406-9216-30 FENTANYL, 1600 MCG Note: Colors are a secondary aid in product identification. Please be sure to confirm the printed dosage before dispensing. Store at 20° to 25°C (68° to 77°F) with excursions permitted between 15° and 30°C (59° to 86°F) until ready to use [see USP Controlled Room Temperature]. Protect oral transmucosal fentanyl citrate from freezing and moisture. Do not use if the blister package has been opened. Store oral transmucosal fentanyl citrate securely and dispose of properly [see Patient Counseling Information (17)] .

Καθεστώς αδειοδότησης:

Abbreviated New Drug Application

Φύλλο οδηγιών χρήσης

FENTANYL CITRATE- FENTANYL CITRATE LOZENGE
SpecGx LLC
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Medication Guide
Oral Transmucosal Fentanyl Citrate (or
׳
ǝl ● tranz mu-kō
׳
s'l ● fĕn
׳
tǝ-nĭl ● sĭt
׳
rāt)
oral transmucosal lozenge, CII
IMPORTANT:
Do not use oral transmucosal fentanyl citrate unless you are regularly
using another opioid pain medicine
around-the-clock for at least one week or longer for your cancer pain
and your body is used to these
medicines (this means that you are opioid tolerant). You can ask your
healthcare provider if you are
opioid tolerant.
Keep oral transmucosal fentanyl citrate in a safe place away from
children.
Get emergency medical help right away if:
•
a child takes oral transmucosal fentanyl citrate. Oral transmucosal
fentanyl citrate can cause an
overdose and death in any child who uses it.
•
an adult who has not been prescribed oral transmucosal fentanyl
citrate uses it.
•
an adult who is not already taking opioids around-the-clock, uses oral
transmucosal fentanyl
citrate.
These are medical emergencies that can cause death. If possible,
remove oral transmucosal fentanyl
citrate from the mouth.
Oral transmucosal fentanyl citrate is:
•
A strong prescription pain medicine that contains an opioid (narcotic)
that is used to manage
breakthrough pain in adults (16 years of age and older) with cancer
who are already routinely
taking other opioid pain medicines around-the-clock for cancer pain.
Oral transmucosal fentanyl
citrate 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 oral
transmucosal fentanyl citrate if
you are not opioid tolerant.
•
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.
Important information about oral transmucosal fentanyl citrate:
•
Get emergency help or call 911 right away if you take too much oral
transmucosal fenta

Αρχείο Π.Χ.Π.

FENTANYL CITRATE- FENTANYL CITRATE LOZENGE
SPECGX LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE ORAL
TRANSMUCOSAL
FENTANYL CITRATE SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR ORAL
TRANSMUCOSAL FENTANYL CITRATE.
ORAL TRANSMUCOSAL FENTANYL CITRATE, ORAL TRANSMUCOSAL LOZENGE, CII
INITIAL U.S. APPROVAL: 1968
WARNING: LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL
INGESTION;
RISKS FROM CYTOCHROME P450 3A4 INTERACTION; RISKS FROM CONCOMITANT USE
WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; RISK OF MEDICATION
ERRORS;
ADDICTION, ABUSE, AND MISUSE; REMS; AND NEONATAL OPIOID WITHDRAWAL
SYNDROME
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
SERIOUS, LIFE-THREATENING, AND/OR FATAL RESPIRATORY DEPRESSION HAS
OCCURRED. MONITOR
CLOSELY, ESPECIALLY UPON INITIATION OR FOLLOWING A DOSE INCREASE. DUE
TO THE RISK OF
FATAL RESPIRATORY DEPRESSION, ORAL TRANSMUCOSAL FENTANYL CITRATE IS
CONTRAINDICATED IN
OPIOID NON-TOLERANT PATIENTS (1) AND IN MANAGEMENT OF ACUTE OR
POSTOPERATIVE PAIN,
INCLUDING HEADACHE/MIGRAINES. (5.1)
ACCIDENTAL INGESTION OF ORAL TRANSMUCOSAL FENTANYL CITRATE, ESPECIALLY
BY CHILDREN,
CAN RESULT IN A FATAL OVERDOSE OF FENTANYL. KEEP OUT OF REACH OF
CHILDREN. ENSURE
PROPER STORAGE AND DISPOSAL. (2.8, 5.2)
CONCOMITANT USE WITH CYP3A4 INHIBITORS (OR DISCONTINUATION OF CYP3A4
INDUCERS) CAN
RESULT IN A FATAL OVERDOSE OF FENTANYL. (5.3, 7, 12.3)
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 PRESCRIBING FOR USE
IN 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 AND SEDATION. (5.4, 7)
WHEN PRESCRIBING, DO NOT CONVERT PATIENTS ON A MCG PER MCG BASIS FROM
ANY OTHER
FENTANYL PRODUCT TO ORAL TRANSMUCOSAL FENTANYL CITRA