BELBUCA- buprenorphine hydrochloride film, soluble

Χώρα: Ηνωμένες Πολιτείες

Γλώσσα: Αγγλικά

Πηγή: NLM (National Library of Medicine)

Δραστική ουσία:

buprenorphine hydrochloride (UNII: 56W8MW3EN1) (buprenorphine - UNII:40D3SCR4GZ)

Διαθέσιμο από:

BioDelivery Sciences International Inc

INN (Διεθνής Όνομα):

BUPRENORPHINE HYDROCHLORIDE

Σύνθεση:

BUPRENORPHINE 75 ug

Οδός χορήγησης:

BUCCAL

Τρόπος διάθεσης:

PRESCRIPTION DRUG

Θεραπευτικές ενδείξεις:

BELBUCA is indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate. Limitations of Use - Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, and because of the greater risks of overdose and death with extended-release/long-acting opioid formulations [see Warnings and Precautions (5.1)] , reserve BELBUCA for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - BELBUCA is not indicated as an as-needed (prn) analgesic. BELBUCA is contraindicated in patients with: - Significant respiratory depression [see Warnings and Precautions (5.2)] - Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.7)] - Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.12)] - Hypersensitivity (e.g., anaphylaxis) to buprenorphine [see Warnings and Precautions (5.16), Adverse Reactions (6)] Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.4)] . There are no adequate and well-controlled studies of BELBUCA or buprenorphine in pregnant women. Limited published data on use of buprenorphine, the active ingredient in BELBUCA, in pregnancy, have not shown an increased risk of major malformations. Reproductive and developmental studies in rats and rabbits identified adverse events at approximately 2 times the maximum recommended human dose (MRHD) of 1.8 mg/day of BELBUCA. Embryofetal death was observed in both rats and rabbits administered buprenorphine during the period of organogenesis at doses approximately 54 and 2.2 times, respectively, the MRHD of 1.8 mg/day of buprenorphine. Pre-and postnatal development studies in rats demonstrated increased neonatal deaths at 2.7 times and above and dystocia at approximately 27 times the MRHD of 1.8 mg/day of buprenorphine. No clear teratogenic effects were seen when buprenorphine was administered during organogenesis with a range of doses 5 times or greater than the MRHD of 1.8 mg/day of buprenorphine. However, increases in skeletal abnormalities were noted in rats and rabbits administered buprenorphine daily during organogenesis at doses approximately 5.4 and 10.8 times the MRHD of 1.8 mg/day of buprenorphine, respectively. In a few studies, some events such as acephalus and omphalocele were also observed but these findings were not clearly treatment-related [see Data] . The background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy can occur regardless of the health of the mother or the use of medications. 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 Use of opioid analgesics for an extended period of time 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, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.4)] . 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. BELBUCA is not recommended for use in women immediately prior to labor, when shorter-acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics, including BELBUCA, 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. Data Animal Data The exposure margins listed below are based on body surface area comparisons (mg/m2 ) to MRHD of 1.8 mg buprenorphine via BELBUCA. Following oral administration to rats no teratogenic effects were observed at buprenorphine doses up to 250 mg/kg/day (estimated exposure approximately 1351 times the MRHD of 1.8 mg). Following oral administration to rabbits, no teratogenic effects were observed at buprenorphine doses up to 40 mg/kg/day (estimated exposure approximately 432 times the MRHD of 1.8 mg). No definitive drug-related teratogenic effects were observed in rats and rabbits at IM doses up to 30 mg/kg/day (estimated exposure approximately 161 times and 324 times, respectively, the MRHD of 1.8 mg). Acephalus was observed in one rabbit fetus from the low-dose group and omphalocele was observed in two rabbit fetuses from the same litter in the mid-dose group; no findings were observed in fetuses from the high-dose group. Following oral administration of buprenorphine to rats, dose-related post-implantation losses, evidenced by increases in the numbers of early resorptions with consequent reductions in the numbers of fetuses, were observed at doses of 10 mg/kg/day or greater (estimated exposure approximately 54 times the MRHD of 1.8 mg). In the rabbit, increased post-implantation losses occurred at an oral dose of 40 mg/kg/day. Following IM administration in the rat and the rabbit, post-implantation losses, as evidenced by decreases in live fetuses and increases in resorptions, occurred at 30 mg/kg/day. Buprenorphine was not teratogenic in rats or rabbits after IM or subcutaneous (SC) doses up to 5 mg/kg/day (estimated exposure was approximately 27 and 54 times, respectively, the MRHD of 1.8 mg), after IV doses up to 0.8 mg/kg/day (estimated exposure was approximately 4.3 and 8.7 times, respectively, the MRHD of 1.8 mg), or after oral doses up to 160 mg/kg/day in rats (estimated exposure was approximately 865 times the MRHD of 1.8 mg) and 25 mg/kg/day in rabbits (estimated exposure was approximately 270 times the MRHD of 1.8 mg). Significant increases in skeletal abnormalities (e.g., extra thoracic vertebra or thoraco-lumbar ribs) were noted in rats after SC administration of 1 mg/kg/day and up (estimated exposure was approximately 5.4 times the MRHD of 1.8 mg), but were not observed at oral doses up to 160 mg/kg/day. Increases in skeletal abnormalities in rabbits after IM administration of 5 mg/kg/day (estimated exposure was approximately 54 times the MRHD of 1.8 mg) or oral administration of 1 mg/kg/day or greater (estimated exposure was approximately 10.8 times the MRHD of 1.8 mg) were not statistically significant. In rabbits, buprenorphine produced statistically significant pre-implantation losses at oral doses of 1 mg/kg/day or greater and post-implantation losses that were statistically significant at IV doses of 0.2 mg/kg/day or greater (estimated exposure approximately 2.2 times the MRHD of 1.8 mg). Dystocia was noted in pregnant rats treated intramuscularly with buprenorphine during gestation and lactation at 5 mg/kg/day (approximately 27 times the MRHD of 1.8 mg). Fertility, pre-, and post-natal development studies with buprenorphine in rats indicated increases in neonatal mortality after oral doses of 0.8 mg/kg/day and up (approximately 4.3 times the MRHD of 1.8 mg), after IM doses of 0.5 mg/kg/day and up (approximately 2.7 times the MRHD of 1.8 mg), and after SC doses of 0.1 mg/kg/day and up (approximately 0.5 times the MRHD of 1.8 mg). An apparent lack of milk production during these studies likely contributed to the decreased pup viability and lactation indices. Delays in the occurrence of righting reflex and startle response were noted in rat pups at an oral dose of 80 mg/kg/day (approximately 432 times the MRHD of 1.8 mg). Risk Summary Based on two studies in 13 lactating women being treated for opioid dependence and their breastfed infants, buprenorphine and its metabolite norbuprenorphine are present in low levels in human milk and infant urine, and available data have not shown adverse reactions in breastfed infants [see Data] . There are no data on the effects of BELBUCA 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 BELBUCA. Clinical Considerations Monitor infants exposed to BELBUCA through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of buprenorphine is stopped or when breastfeeding is stopped. Data Based on limited data from a study of six lactating women being treated for opioid dependence who were taking a median oral dose of buprenorphine of 0.29 mg/kg/day 5-8 days after delivery, breast milk contained a median infant dose of 0.42 mcg/kg/day of buprenorphine and 0.33 mcg/kg/day of norbuprenorphine, which are equal to 0.2% and 0.12% of the maternal weight-adjusted dose. The median concentrations of buprenorphine and norbuprenorphine in infant urine were 1.0 nmol/L and 2.3 nmol/L, respectively. Based on limited data from a study of seven lactating women being treated for opioid dependence who were taking a median oral dose of buprenorphine of 7 mg/day an average of 1.12 months after delivery, the mean milk concentrations of buprenorphine and norbuprenorphine were 3.65 mcg/L and 1.94 mcg/L, respectively. Based on the limited data from this study, and assuming milk consumption of 150 mL/kg/day, an exclusively breastfed infant would receive an estimated mean of 0.55 mcg/kg/day of buprenorphine and 0.29 mcg/kg/day of norbuprenorphine, which are 0.38% and 0.18% of the maternal weight-adjusted dose. No adverse reactions were observed in the infants in these two studies. Infertility Use of opioids for an extended period of time 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)] . The safety and efficacy of BELBUCA have not been established in pediatric patients. Of the total number of patients that were treated with BELBUCA in controlled and open-label chronic pain trials (2,127), 340 patients were 65 years and older. Of those, 49 patients were aged 75 years and older. The incidences of selected BELBUCA-related adverse effects were higher in older subjects. No notable differences in pharmacokinetics were observed from population pharmacokinetic analysis in subjects aged 65 and older compared to younger subjects. Other reported clinical experience with buprenorphine has not identified differences in responses between the elderly and younger patients. Although specific dose adjustments on the basis of advanced age are not required for pharmacokinetic reasons, use caution in the elderly population to ensure safe use. 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 BELBUCA slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.7), Clinical Pharmacology (12.3)] . Buprenorphine 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 regularly evaluate renal function. BELBUCA has not been evaluated in patients with severe hepatic impairment. The effects of hepatic impairment on the pharmacokinetics of buprenorphine were evaluated in a pharmacokinetic study. Buprenorphine is extensively metabolized in the liver and buprenorphine plasma levels were found to be higher and the half-life was found to be longer in subjects with moderate and severe hepatic impairment, but not in subjects with mild hepatic impairment. Given that increased buprenorphine plasma levels are associated with a greater risk of toxicity and overdose, a dosage reduction in patients with severe hepatic impairment (i.e., Child-Pugh C) is recommended [see Dosage and Administration (2.6)] . Regularly evaluate patients with severe hepatic impairment for signs and symptoms of overdose. A dosage reduction in patients with moderate hepatic impairment (Child-Pugh B) is not needed; however, regularly evaluate these patients for signs and symptoms of toxicity or overdose. A dosage reduction in patients with mild hepatic impairment (Child-Pugh A) is not needed [see Dosage and Administration (2.6), Warnings and Precautions (5.19), Clinical Pharmacology (12.3)] . BELBUCA contains buprenorphine hydrochloride, a Schedule III controlled substance. BELBUCA contains buprenorphine, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see Warnings and Precautions (5.1)] . Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Misuse and abuse of BELBUCA increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. The risk is increased with concurrent abuse of BELBUCA with alcohol and/or other CNS depressants. Abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of addiction. All patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Patients at high risk of BELBUCA abuse include those with a history of prolonged use of any opioid, including products containing buprenorphine, those with a history of drug or alcohol abuse, or those who use BELBUCA in combination with other abused drugs. "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 people who abuse drugs and people with substance use disorder. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. BELBUCA, like other opioids, can be diverted for nonmedical 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 reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. Risks Specific to Abuse of BELBUCA Abuse of BELBUCA poses a risk of overdose and death. This risk is increased with concurrent use of BELBUCA with alcohol and/or other substances, including other opioids and benzodiazepines [see Warnings and Precautions (5.1, 5.3), Drug Interactions (7)] . BELBUCA is approved for buccal use only. Intentional compromise of the buccal film might result in the uncontrolled delivery of buprenorphine and pose a significant risk to the abuser that could result in overdose and death [see Warnings and Precautions (5.1)] . Abuse may occur by applying the buccal film in the absence of legitimate purpose, or by chewing, swallowing, snorting, or injecting buprenorphine extracted from the buccal film. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV. Both tolerance and physical dependence can develop during use of opioid therapy. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). Physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), 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 use. Do not abruptly discontinue BELBUCA in a patient physically dependent on opioids. Rapid tapering of BELBUCA in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. When discontinuing BELBUCA, gradually taper the dosage using a patient-specific plan that considers the following: the dose of BELBUCA the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for an extended period of time at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see Dosage and Administration (2.5), Warnings and Precautions (5.17)] . 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)] . BELBUCA (bel-BUE-kuh) (buprenorphine buccal film), CIII Before you use BELBUCA buccal film, it is important that you read the Medication Guide and these Patient Instructions for Use so that you use BELBUCA the right way. Ask your healthcare provider or pharmacist if you have any questions about the right way to use BELBUCA. Important: - BELBUCA buccal film is sealed in a foil package. Do not open the package until ready to use. After opening, use the entire BELBUCA buccal film right away. - Do not apply BELBUCA buccal film if the package seal is broken or the film is cut, damaged, or changed in any way. - BELBUCA buccal film is available in different strengths. Make sure you have the strength that has been prescribed for you. - Avoid placing BELBUCA buccal film to areas of the mouth with any open sores or lesions. Open the BELBUCA package: - Hold the foil package as shown below (see Figure A) . Fold along the dotted line at the top of the foil package. Figure A Figure A - Keep folded and tear down or cut with scissors at the notch in the direction of the scissors on the dotted line (see Figure B) . Tear all the way to the bottom. Be careful to avoid cutting and damaging the BELBUCA buccal film when using scissors. Figure B Figure B - Remove BELBUCA film from the foil package (see Figure C) . Figure C Figure C Use BELBUCA buccal film as follows: Figure D Figure E Figure F - Avoid eating food or drinking liquids until BELBUCA buccal film has dissolved. - Avoid touching or moving BELBUCA buccal film with your tongue or finger after it is in place. - Do not chew or swallow BELBUCA. - After BELBUCA is completely dissolved, rinse your mouth with water and swallow. Wait at least one hour before brushing your teeth. These Instructions for Use have been approved by the U.S. Food and Drug Administration. For more information call Collegium Pharmaceutical, Inc. at 855-331-5615. Manufactured for: Collegium Pharmaceutical, Inc., Stoughton, MA 02072 BELBUCA is a trademark of BioDelivery Sciences International, Inc., a wholly owned subsidiary of Collegium Pharmaceutical, Inc. ©2023 BioDelivery Sciences International, Inc. All rights reserved. BEL-001-MG-Dec2023

Περίληψη προϊόντος:

BELBUCA (buprenorphine buccal film) films are supplied in cartons containing 60 individual child-resistant foil packages as follows: Store at 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C and 30°C (59°F and 86°F). Store BELBUCA securely and dispose of properly.

Καθεστώς αδειοδότησης:

New Drug Application

Φύλλο οδηγιών χρήσης

BioDelivery Sciences International Inc
----------
This Medication Guide has been approved by the U.S. Food and Drug
Administration. Revised
12/2023
Medication Guide
BELBUCA® (bel-BUE-kuh)
(buprenorphine buccal film), CIII
BELBUCA is:
•
A strong prescription pain medicine that contains an opioid (narcotic)
that is used to manage
severe and persistent pain that requires an extended treatment period
with a daily opioid pain
medicine when other pain medicines do not treat your pain well enough
or you cannot tolerate
them.
•
A long-acting 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.
•
Not to be taken on an "as needed" basis.
Important information about BELBUCA:
•
Get emergency help or call 911 right away if you take too much BELBUCA
(overdose). When
you first start taking BELBUCA, when your dose is changed, or if you
take too much (overdose),
serious or life-threatening breathing problems that can lead to death
may occur. Talk to your
healthcare provider about naloxone, a medicine for the emergency
treatment of an opioid
overdose.
•
Taking BELBUCA with other opioid medicines, benzodiazepines, alcohol,
or other central
nervous system depressants (including street drugs) can cause severe
drowsiness, decreased
awareness, breathing problems, coma, and death.
•
Never give anyone else your BELBUCA. They could die from taking it.
Selling or giving away
BELBUCA is against the law.
•
Store BELBUCA securely, out of sight and reach of children, and in a
location not accessible by
others, including visitors to the home.
Do not use BELBUCA if you have:
•
severe asthma, trouble breathing, or other lung problems.
•
a bowel blockage or have narrowing of the stomach or intestines.
Before taking BELBUCA, tell your healthcare provider if you have a
history of:
•
head injury, seizures
•
liver, kidney, thyroid problems
•
problems urinating
•
tooth problems,

Αρχείο Π.Χ.Π.

BELBUCA- BUPRENORPHINE HYDROCHLORIDE FILM, SOLUBLE
BIODELIVERY SCIENCES INTERNATIONAL INC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
BELBUCA SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR BELBUCA.
BELBUCA (BUPRENORPHINE BUCCAL FILM), CIII
INITIAL U.S. APPROVAL: 1981
WARNING: SERIOUS LIFE-THREATENING RISKS FROM USE OF BELBUCA
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
BELBUCA EXPOSES USERS TO RISKS OF ADDICTION, ABUSE, AND MISUSE, WHICH
CAN LEAD TO
OVERDOSE AND DEATH. ASSESS PATIENT'S RISK BEFORE PRESCRIBING AND
REASSESS REGULARLY
FOR THESE BEHAVIORS AND CONDITIONS. (5.1)
SERIOUS, LIFE-THREATENING, OR FATAL RESPIRATORY DEPRESSION MAY OCCUR,
ESPECIALLY
DURING INITIATION OR FOLLOWING A DOSAGE INCREASE. TO REDUCE THE RISK
OF RESPIRATORY
DEPRESSION, PROPER DOSING AND TITRATION OF BELBUCA ARE ESSENTIAL.
INSTRUCT PATIENTS
ON PROPER ADMINISTRATION OF BELBUCA TO REDUCE THE RISK. (2.1, 2.8,
5.2)
ACCIDENTAL EXPOSURE TO BELBUCA, ESPECIALLY IN CHILDREN, CAN RESULT IN
FATAL OVERDOSE
OF BUPRENORPHINE. (5.2)
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. (5.3, 7)
IF OPIOID USE IS REQUIRED FOR AN EXTENDED PERIOD OF TIME IN A PREGNANT
WOMAN,
ADVISE THE PATIENT OF THE RISK OF NEONATAL OPIOID WITHDRAWAL SYNDROME,
WHICH MAY
BE LIFE-THREATENING IF NOT RECOGNIZED AND TREATED. ENSURE THAT
MANAGEMENT BY
NEONATOLOGY EXPERTS WILL BE AVAILABLE AT DELIVERY. (5.4)
HEALTHCARE PROVIDERS ARE STRONGLY ENCOURAGED TO COMPLETE A
REMS-COMPLIANT
EDUCATION PROGRAM AND TO COUNSEL PATIENTS AND CAREGIVERS ON SERIOUS
RISKS, SAFE
USE, AND THE IMPORTANCE OF READING THE MEDICATION GUIDE WITH EACH
PRESCRIPTION.
(5.5)
RECENT MAJOR CHANGES
Boxed Warning
12/2023
Indications and Usage (1)
12/2023
Dosage and Admin