Regno Unito - inglese - MHRA (Medicines & Healthcare Products Regulatory Agency)

indivior uk ltd - buprenorphine hydrochloride - sublingual tablet - 400microgram

Regno Unito - inglese - MHRA (Medicines & Healthcare Products Regulatory Agency)

indivior uk ltd - buprenorphine hydrochloride - sublingual tablet - 8mg

Regno Unito - inglese - MHRA (Medicines & Healthcare Products Regulatory Agency)

indivior uk ltd - buprenorphine hydrochloride - sublingual tablet - 2mg

Stati Uniti - inglese - NLM (National Library of Medicine)

indivior inc. - buprenorphine (unii: 40d3scr4gz) (buprenorphine - unii:40d3scr4gz) - buprenorphine 100 mg - sublocade is indicated for the treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a buprenorphine-containing product, followed by dose adjustment for a minimum of 7 days. sublocade should be used as part of a complete treatment plan that includes counseling and psychosocial support. sublocade should not be administered to patients who have been shown to be hypersensitive to buprenorphine or any component of the atrigel® delivery system [see warnings and precautions (5.11)] . risk summary the data on use of buprenorphine, the active ingredient in sublocade, in pregnancy, are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure. there are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations [see human data] . observational studies have reported congenital malformations among buprenorphine‐exposed pregnancies, but were also not designed appropriately to assess the risk of congenital malformations specifically due to buprenorphine exposure [see human data] . in animal reproduction studies with sublocade, sublocade administered subcutaneously to pregnant rats and rabbits during the period of organogenesis at a buprenorphine dose equivalent to 38 and 15 times, respectively, the maximum recommended human dose (mrhd) of 300 mg caused embryolethality, which appeared to be attributable primarily to the sublocade vehicle (atrigel® delivery system). in addition, reduced fetal body weights, increased visceral malformations and skeletal malformations were observed in rats and rabbits at buprenorphine doses equivalent to 38 and 15 times, respectively, the mrhd. these effects were also observed with the atrigel® delivery system alone, but the skeletal and visceral malformations in rat appear at least partially attributable to buprenorphine [see animal data] . based on animal data, advise pregnant women of the potential risk to a fetus. 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. sublocade should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. clinical considerations disease-associated maternal and embryo-fetal risk untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. in addition, untreated opioid addiction often results in continued or relapsing illicit opioid use. fetal/neonatal adverse reactions neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment with sublocade. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight. signs of neonatal withdrawal usually occur in the first days after birth. the duration and severity of neonatal opioid withdrawal syndrome may vary. observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.7)] . labor or delivery opioid-dependent women on buprenorphine maintenance therapy may require additional analgesia during labor. as with all opioids, use of buprenorphine prior to delivery may result in respiratory depression in the newborn. closely monitor neonates for signs of respiratory depression. an opioid antagonist such as naloxone should be available for reversal of opioid induced respiratory depression in the neonate. data human data studies have been conducted to evaluate neonatal outcomes in women exposed to buprenorphine during pregnancy. limited data on malformations from trials, observational studies, case series, and case reports on buprenorphine use in pregnancy do not indicate an increased risk of major malformations specifically due to buprenorphine. pregnancy in an opioid dependent woman poses challenges to treating physicians and potential hazards for the fetus including control of illicit drug, nicotine and alcohol use, infections, premature birth, abortion, low birth weight, toxaemia, third trimester bleeding, malpresentation, puerperal morbidity, fetal distress, meconium aspiration, narcotic withdrawal, postnatal growth deficiency, microcephaly, (neuro-) developmental disorders and increased neonatal mortality. a multicenter, double-blind, double-dummy, flexible-dose study in 175 pregnant women [maternal opioid treatment: human experimental research (mother)] was conducted to study outcomes in neonates born to mothers using methadone or buprenorphine, including the number of neonates requiring treatment for nows, the peak nows score, the total amount of morphine needed to treat nows, the length of hospital stay for neonates, and neonatal head circumference. the authors found that 18% of pregnant women in the methadone group and 33% in the buprenorphine group discontinued treatment over the course of the pregnancy. they reported no significant difference in the incidence of nows, but in the prenatally buprenorphine-exposed condition, the duration of treatment for nows was shorter, duration of hospital stays were shorter and the amount of morphine required was significantly less; however, methodological concerns limit the conclusions that may be made. animal data in an embryofetal development study in rats, sublocade administered subcutaneously to pregnant animals before mating and again on gestation day (gd) 7 during the period of organogenesis resulted in increased post-implantation loss, which correlated with higher mean number of resorptions and decreased number of viable fetuses per litter, and decreased mean fetal body weights at 900 mg/kg (approximately 38 times the maximum recommended human dose [mrhd] of 300 mg of sublocade on an auc basis); however, similar effects were observed with an equivalent level of atrigel® delivery system alone, indicating they may be attributable to the vehicle. dose-related increases in incidences of skeletal malformations of the head and visceral malformations were observed with sublocade with significant changes at 900 mg/kg (approximately 38 times the mrhd on an auc basis). although similar effects were observed with equivalent levels of atrigel® delivery system, the incidence of skeletal malformations, primarily skull malformations, was higher in the sublocade groups suggesting that buprenorphine contributed to the increased incidence. based on these results, the noael for developmental toxicity was approximately 15 times the mrhd on an auc basis. in an embryofetal development study in rabbits, administration of a single subcutaneous injection of sublocade to pregnant animals on gd 7 during the period of organogenesis resulted an increased litter incidence of skeletal malformations at 155 mg/kg (approximately 7 times the mrhd on an auc basis), which appear to be buprenorphine-related adverse effects. there was also an increased litter incidence of external malformations, visceral, and skeletal malformations and variations at 390 mg/kg sublocade (approximately 15 times the mrhd on an auc basis); however, similar effects were observed with an equivalent level of the atrigel® delivery system, indicating they may be attributable to the vehicle. in addition, increased post-implantation loss, which correlated with increased mean number of resorptions and decreased mean number of viable fetuses, and decreased fetal body weights were observed at 390 mg/kg (approximately 15 times the mrhd on an auc basis); however, similar findings were also observed with an equivalent level of the atrigel® delivery system alone. based on these results, the noael for developmental toxicity for sublocade was 78 mg/kg (approximately 2 times the mrhd on an auc basis). in a pre- and postnatal development study in rats, sublocade was administered subcutaneously to pregnant animals once during implantation (on gd 7) and once during weaning (on lactation day 7). there were no adverse effects on offspring survival, sexual maturation, behavioral assessment, or reproductive performance at up to 300 mg/kg (approximately 15 times the mrhd on an auc basis). risk summary based on two studies in 13 lactating women maintained on buprenorphine treatment, buprenorphine and its metabolite norbuprenorphine are present in low levels in human milk and infant urine. available data have not shown adverse reactions in breastfed infants. caution should be exercised when sublocade is administered to a nursing woman. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for sublocade and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. clinical considerations advise breastfeeding women taking buprenorphine products to monitor the infant for increased drowsiness and breathing difficulties. data data were consistent from two studies (n=13) of breastfeeding infants whose mothers were maintained on sublingual doses of buprenorphine ranging from 2.4 to 24 mg/day, showing that the infants were exposed to less than 1% of the maternal daily dose. in a study of six lactating women who were taking a median sublingual buprenorphine dose of 0.29 mg/kg/day 5 to 8 days after delivery, breast milk provided a median infant dose of 0.42 mcg/kg/day of buprenorphine and 0.33 mcg/kg/day of norbuprenorphine, equal to 0.2% and 0.12%, respectively, of the maternal weight-adjusted dose (relative dose/kg (%) of norbuprenorphine was calculated from the assumption that buprenorphine and norbuprenorphine are equipotent). data from a study of seven lactating women who were taking a median sublingual buprenorphine dose of 7 mg/day an average of 1.12 months after delivery indicated that the mean milk concentrations (cavg ) of buprenorphine and norbuprenorphine were 3.65 mcg/l and 1.94 mcg/l respectively. based on the study data, and assuming milk consumption of 150 ml/kg/day, an exclusively breastfed infant would receive an estimated mean absolute infant dose (aid) of 0.55 mcg/kg/day of buprenorphine and 0.29 mcg/kg/day of norbuprenorphine, or a mean relative infant dose (rid) of 0.38% and 0.18%, respectively, of the maternal weight-adjusted dose. human data 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)] . animal data infertility male male fertility may be reduced based on animal data demonstrating adverse effects of sublocade on sperm parameters [see nonclinical toxicology (13.1)]. the safety and effectiveness of sublocade have not been established in pediatric patients. clinical studies of sublocade did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently than younger subjects. other reported clinical experience with buprenorphine has not identified differences in responses between geriatric and younger patients. due to possible decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in geriatric patients, the decision to prescribe sublocade should be made cautiously in individuals 65 years of age or older and these patients should be monitored for signs and symptoms of toxicity or overdose. the effect of hepatic impairment on the pharmacokinetics of sublocade has not been studied. the effect of hepatic impairment on the pharmacokinetics of sublingual buprenorphine has been evaluated in a pharmacokinetic study. while no clinically significant changes have been observed in subjects with mild hepatic impairment, the plasma levels have been shown to be higher and half-life values have been shown to be longer for buprenorphine in subjects with moderate and severe hepatic impairment. because of the long-acting nature of the product, adjustments to dosages of sublocade are not rapidly reflected in plasma buprenorphine levels. because buprenorphine levels cannot be rapidly adjusted, patients with pre-existing moderate to severe hepatic impairment are not candidates for treatment with sublocade. patients who develop moderate to severe hepatic impairment while being treated with sublocade should be monitored for signs and symptoms of toxicity or overdose caused by increased levels of buprenorphine. if signs and symptoms of toxicity or overdose occur within 2 weeks of sublocade administration, removal of the depot may be required [see dosage and administration (2.7), warnings and precautions (5.10), clinical pharmacology (12.3)] . clinical studies of sublocade did not include subjects with renal impairment. no differences in buprenorphine pharmacokinetics were observed between 9 dialysis-dependent and 6 normal patients following iv administration of 0.3 mg buprenorphine. sublocade contains buprenorphine, a schedule iii substance under the controlled substances act. sublocade contains buprenorphine, a schedule iii controlled substance that can be abused similar to other opioids. patients who continue to misuse, abuse, or divert buprenorphine products or other opioids should be provided with or referred for more intensive and structured treatment. abuse of buprenorphine poses a risk of overdose and death. this risk is increased with the abuse of buprenorphine and alcohol and other substances, especially benzodiazepines. sublocade is distributed through a restricted distribution system, which is intended to prevent the direct distribution to a patient. sublocade should only be dispensed directly to a healthcare provider for administration by a healthcare provider. it is supplied in prefilled syringes and is intended for administration only by subcutaneous injection by a healthcare provider. the entire contents of the prefilled syringe should be administered. after administration, a small amount (approximately 0.1 ml) of sublocade will remain in the needle and syringe and should be properly disposed of [see how supplied/storage and handling (16)] . sublocade is injected as a liquid, and the subsequent precipitation of the poly (dl-lactide-co-glycolide) polymer creates a solid depot which contains buprenorphine. after initial formation of the depot, buprenorphine is released via diffusion from, and the biodegradation of, the depot. clinical monitoring for evidence at the injection site of tampering or attempting to remove the depot should be ongoing throughout treatment. no accounts of subjects removing or attempting to remove the depot after administration of sublocade were reported in premarketing studies. buprenorphine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid type, characterized by moderate withdrawal signs and symptoms upon abrupt discontinuation. the withdrawal syndrome is typically milder than seen with full agonists and may be delayed in onset [see warnings and precautions (5.12)] . due to the long-acting nature of sublocade, withdrawal signs and symptoms may not be evident immediately following the discontinuation of treatment. neonatal opioid withdrawal syndrome (nows) is an expected and treatable outcome of prolonged use of opioids during pregnancy [see warnings and precautions (5.7)] .

Stati Uniti - inglese - NLM (National Library of Medicine)

indivior inc. - buprenorphine hydrochloride (unii: 56w8mw3en1) (buprenorphine - unii:40d3scr4gz), naloxone hydrochloride (unii: f850569pqr) (naloxone - unii:36b82amq7n) - buprenorphine and naloxone sublingual film is indicated for treatment of opioid dependence. buprenorphine and naloxone sublingual film should be used as part of a complete treatment plan that includes counseling and psychosocial support. buprenorphine and naloxone sublingual film is contraindicated in patients with a history of hypersensitivity to buprenorphine or naloxone as serious adverse reactions, including anaphylactic shock, have been reported [see warnings and precautions (5.9)] . risk summary the data on use of buprenorphine, one of the active ingredients in buprenorphine and naloxone sublingual film, in pregnancy, are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure. there are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations [see data]. observational studies have reported on congenital malformations among bu

Malta - inglese - Medicines Authority

indivior europe limited 27 windsor place, dublin 2, ireland - buprenorphine - sublingual tablet - buprenorphine 2 mg - other nervous system drugs

Malta - inglese - Medicines Authority

indivior europe limited 27 windsor place, dublin 2, ireland - buprenorphine - sublingual tablet - buprenorphine 8 mg - other nervous system drugs

Nuova Zelanda - inglese - Medsafe (Medicines Safety Authority)

pharmacy retailing (nz) ltd t/a healthcare logistics - buprenorphine hydrochloride 12.96mg equivalent to 12 mg buprenorphine; naloxone hydrochloride dihydrate 3.66mg equivalent to 3 mg naloxone;   - wafer - active: buprenorphine hydrochloride 12.96mg equivalent to 12 mg buprenorphine naloxone hydrochloride dihydrate 3.66mg equivalent to 3 mg naloxone   excipient: acesulfame potassium citric acid hypromellose e-15 maltitol natural lime flavour (3000180) opacode white ns-78-18007 polyethylene oxide sodium citrate sunset yellow fcf - treatment of opioid dependence, within a framework of medical, social and psychological treatment.

Nuova Zelanda - inglese - Medsafe (Medicines Safety Authority)

pharmacy retailing (nz) ltd t/a healthcare logistics - buprenorphine hydrochloride 2.16mg equivalent to 2 mg buprenorphine; naloxone hydrochloride dihydrate 0.61mg equivalent to 0.5 mg naloxone;   - wafer - active: buprenorphine hydrochloride 2.16mg equivalent to 2 mg buprenorphine naloxone hydrochloride dihydrate 0.61mg equivalent to 0.5 mg naloxone   excipient: acesulfame potassium citric acid hypromellose e-5 maltitol natural lime flavour (3000180) opacode white ns-78-18007 oxidised polyethylene sodium citrate sunset yellow fcf - treatment of opioid dependence, within a framework of medical, social and psychological treatment.

Nuova Zelanda - inglese - Medsafe (Medicines Safety Authority)

pharmacy retailing (nz) ltd t/a healthcare logistics - buprenorphine hydrochloride 4.32mg equivalent to 4 mg buprenorphine; naloxone hydrochloride dihydrate 1.22mg equivalent to 1 mg naloxone;   - wafer - active: buprenorphine hydrochloride 4.32mg equivalent to 4 mg buprenorphine naloxone hydrochloride dihydrate 1.22mg equivalent to 1 mg naloxone   excipient: acesulfame potassium citric acid hypromellose e-5 maltitol natural lime flavour (3000180) opacode white ns-78-18007 oxidised polyethylene sodium citrate sunset yellow fcf - treatment of opioid dependence, within a framework of medical, social and psychological treatment.