European Union - English - EMA (European Medicines Agency)

pacira limited - cytarabine - meningeal neoplasms - antineoplastic agents, - intrathecal treatment of lymphomatous meningitis. in the majority of patients such treatment will be part of symptomatic palliation of the disease.

European Union - English - EMA (European Medicines Agency)

pacira limited - cytarabine - meningeal neoplasms - antineoplastic agents, - intrathecal treatment of lymphomatous meningitis. in the majority of patients such treatment will be part of symptomatic palliation of the disease.

European Union - English - EMA (European Medicines Agency)

pacira ireland limited - bupivacaine - acute pain - amides, anesthetics, local - exparel liposomal is indicated:in adults as a brachial plexus block or femoral nerve block for treatment of post-operative pain.in adults and children aged 6 years or older as a field block for treatment of somatic post-operative pain from small- to medium-sized surgical wounds.

United States - English - NLM (National Library of Medicine)

pacira pharmaceuticals, inc. - triamcinolone acetonide (unii: f446c597ka) (triamcinolone acetonide - unii:f446c597ka) - zilretta (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of osteoarthritis pain of the knee. limitation of use the efficacy and safety of repeat administration of zilretta have not been demonstrated. [see dosage and administration (2.1)] . zilretta is contraindicated in patients who are hypersensitive to triamcinolone acetonide, corticosteroids or any components of the product [see warnings and precautions (5.3) and how supplied/storage and handling (16)] . risk summary there are no data regarding the use of zilretta in pregnant women to inform a drug associated risk of adverse developmental outcomes. published studies on the association between corticosteroids and fetal outcomes have reported inconsistent findings and have important methodological limitations. the majority of published literature with corticosteroid exposure during pregnancy includes the oral, topical and inhaled dosage formulations; therefore, the applicability of these findings to a single intra-articular injection of triamcinolone acetonide is limited. in animal reproductive studies from the published literature, pregnant mice, rats, rabbits, or primates administered triamcinolone acetonide during the period of organogenesis at doses that produced exposures less than the maximum recommended human dose (mrhd) caused resorptions, decreased fetal body weight, craniofacial and/or other abnormalities such as omphalocele (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 risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. data animal data the exposure margins listed below are based on body surface area comparisons (mg/m2 ) to the highest daily triamcinolone acetonide exposure at the mrhd of 32 mg triamcinolone acetonide via zilretta. pregnant mice dosed with triamcinolone acetonide via intramuscular or subcutaneous injection at doses equivalent to 0.8 times the mrhd or higher during organogenesis caused cleft palate and a higher rate of resorption. in pregnant rats dosed with triamcinolone acetonide via intramuscular or subcutaneous injection at doses equivalent to 0.3 times the mrhd or higher during organogenesis caused developmental abnormality (cleft palate, omphalocele, late resorption, and growth retardation) and fetal mortality. no notable maternal toxicity was observed in rodents. pregnant rabbits dosed with triamcinolone acetonide via intramuscular injection for 4 days during organogenesis at doses equivalent to 0.15 times the mrhd or higher caused resorption and cleft palate. no notable maternal toxicity was observed. pregnant primates dosed with triamcinolone acetonide via intramuscular injection for 4 days during organogenesis at doses equivalent to 3 times the mrhd or higher caused severe craniofacial cns and skeletal/visceral malformation and higher prenatal death. no notable maternal toxicity was observed. no peri- and post-natal development studies of triamcinolone acetonide in animals have been conducted. risk summary there are no available data on the presence of triamcinolone acetonide in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. however, corticosteroids have been detected in human milk and may suppress milk production. it is not known whether intra-articular administration of zilretta could result in sufficient systemic absorption to produce detectable quantities in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for zilretta and any potential adverse effects on the breastfed infant from zilretta or from the underlying maternal condition. corticosteroids may result in menstrual pattern irregularities such as deviations in timing and duration of menses and an increased or decreased loss of blood. the safety and effectiveness of zilretta in pediatric patients have not been established. the adverse effects of corticosteroids in pediatric patients are similar to those in adults. carefully observe pediatric patients, including weight, height, linear growth, blood pressure, intraocular pressure, and clinical evaluation for the presence of infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis. weigh potential growth effects of treatment against clinical benefits obtained and the availability of treatment alternatives. of the total number of patients administered 32 mg zilretta in clinical studies (n=424), 143 patients were 65 years of age or older. no overall differences in safety or effectiveness were observed between elderly and younger subjects, and other reported clinical experience with triamcinolone acetonide has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. zilretta® (triamcinolone acetonide extended-release injectable suspension) for intra-articular injection only single-dose device do not reuse. important information - zilretta must be prepared using only the diluent supplied in the kit. - to ensure proper dosing, it is important that you follow the preparation and administration steps outlined in these instructions. - promptly inject zilretta after preparation to avoid settling of the suspension. - zilretta is supplied as a single-dose kit and administered as a suspension containing microspheres. - the zilretta powder vial contains an overfill to allow the appropriate dose to be withdrawn. zilretta is a suspension product and it is normal for some residue to be left behind on the vial walls after withdrawing the contents. - parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. - use proper aseptic technique throughout the dose preparation and administration procedure. - inspect all kit components to confirm they have not expired and the seals are intact. - for additional information, visit www.zilretta.com or call pacira pharmaceuticals, inc. at 1-844-353-9466. materials required (fig. 1) supplied - one 32 mg vial of zilretta microsphere powder - one 5 ml vial of sterile diluent - one sterile vial adapter not supplied - three sterile needles, 21-gauge, 1½" length - one sterile luer lock compatible syringe, 5 ml - sterile alcohol pads - paper towels or pad to cushion vial tapping (not shown in fig. 1) - medical-grade gloves (not shown in fig. 1) figure 1 1. vial preparation loosen powder. place two paper towels or a pad on a properly-cleaned hard surface. grip the top of the zilretta powder vial and tap firmly and repeatedly on the padded surface. tap the vial until excess powder is dislodged from the vial and stopper (fig. 2). before continuing, ensure that powder moves freely within the vial. figure 2 inspect zilretta powder vial. as shown in figure 3, the vial on the left, with the x, requires additional tapping because the powder is not properly dislodged. the vial on the right shows the powder properly dislodged and ready for the next step. figure 3 remove caps. remove the flip-off caps from the zilretta powder and diluent vials (fig. 4). figure 4 clean vials. clean the zilretta powder and diluent vial tops with an alcohol pad. use a separate alcohol pad for each vial. peel off vial adapter cover. peel off the paper cover from the vial adapter package (fig. 5). leave the adapter in the plastic holder. figure 5 attach vial adapter to zilretta powder vial. grip the plastic holder that contains the vial adapter. as shown in figure 6, place the zilretta powder vial on a flat surface. in a vertical orientation, gently push the adapter down onto the zilretta powder vial until the spike on the adapter penetrates the rubber stopper on the zilretta powder vial. the adapter will snap into place. figure 6 2. diluent preparation attach needle. attach a needle to the syringe and remove the needle guard. withdraw diluent. with a syringe and needle, withdraw 5 ml of diluent. replace the needle guard. 3. dose preparation remove holder. remove the plastic holder from the vial adapter (fig. 7). figure 7 remove needle. remove the needle from the syringe containing diluent. attach diluent syringe. attach the syringe onto the vial adapter by pushing down and turning clockwise until you feel resistance (fig. 8). figure 8 transfer diluent. slowly and completely push down the syringe plunger to transfer the diluent into the zilretta powder vial (fig. 9). note: equalize the pressure in the syringe by slowly pulling back the plunger to the 5 ml mark. ensure that no solution is drawn back into the syringe at this stage. figure 9 mix diluent and powder (fig.10). with the syringe still attached to the zilretta powder vial, hold the syringe and vial at a slight angle. tap the bottom edge of the vial firmly and repeatedly, in a circular motion, on the padded surface. swirl gently every five or six taps. tap for at least one minute until all powder is completely dispersed. note: avoid vigorous shaking of the vial to minimize foaming. note: at least one minute of tapping and gentle swirling is required to achieve uniform suspension. figure 10 inspect vial. inspect the zilretta powder vial to ensure no clumped powder is visible and a uniform suspension has been achieved. a properly mixed suspension will be milky white, contain no clumps, and move freely down the vial wall. as shown in figure 11, the vial on the left, with the x, requires more tapping and gentle swirling because the powder is not mixed properly with the diluent. the vial on the right shows the powder properly mixed and ready for the next step. figure 11 note: if needed, the zilretta suspension can be stored in the vial for up to 4 hours at ambient conditions. the syringe must remain on the vial adapter while the suspension remains in the vial. withdraw contents into syringe. swirl the vial gently for at least 10 seconds to ensure the powder is fully suspended. immediately depress the plunger fully and then invert the syringe so the vial is directly on top of the syringe (fig. 12). hold the syringe in a completely vertical position, per the illustration on the right, in figure 12. withdraw the full contents from the zilretta vial into the syringe. figure 12 note: zilretta is a suspension product and it is normal for some residue to be left behind on the vial walls after withdrawing the contents. remove syringe. remove the syringe from the vial adapter by turning counter-clockwise. remove air bubbles. attach a new needle to the syringe and remove the needle guard. inspect for bubbles with the syringe held in a completely vertical position (needle upward). if bubbles are observed, gently tap the syringe with your finger until the bubbles rise to the top. eliminate all bubbles by slowly depressing the plunger to displace the air from the syringe. replace the needle guard. attach new needle. remove and discard the needle. attach a new needle. 4. administration invert syringe. to ensure the powder is suspended, gently invert the syringe containing zilretta several times just prior to administration, as shown in figure 13. grip the syringe firmly and turn it so the syringe plunger is pointing straight down. then turn the syringe gently, 180 degrees, until the plunger is pointing straight up. invert the syringe several times to ensure a properly mixed suspension. figure 13 a properly mixed suspension will be uniformly milky white and contain no clumps. inspect syringe. as shown in figure 14, the syringe on the left, with the x, requires more inversions (turning) to properly mix the suspension. the syringe on the right shows the suspension properly mixed and ready for the next step. figure 14 administer zilretta. the usual technique for intra-articular injection should be followed. aspiration of synovial fluid may be performed based on clinical judgment prior to administration of zilretta. do not reuse excess zilretta. any excess suspension in the vial should be thrown away immediately after the injection. leftover zilretta in the vial must never be reused for another injection. note: the entire contents of the syringe must be injected to ensure the intended dose of zilretta is delivered. note: discard all used components in an appropriate medical waste container according to local regulations. note: zilretta is for intra-articular use only. zilretta is not intended for epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, or subcutaneous use. part number: 60-005-03 rev: 03/2022

United States - English - NLM (National Library of Medicine)

pacira pharmaceuticals, inc. - bupivacaine (unii: y8335394ro) (bupivacaine - unii:y8335394ro) - bupivacaine 13.3 mg in 1 ml - exparel is indicated to produce postsurgical: - local analgesia via infiltration in patients aged 6 years and older - regional analgesia via an interscalene brachial plexus nerve block in adults - regional analgesia via a sciatic nerve block in the popliteal fossa in adults - regional analgesia via an adductor canal block in adults limitations of use the safety and effectiveness of exparel have not been established to produce postsurgical regional analgesia via other nerve blocks besides an interscalene brachial plexus nerve block, a sciatic nerve block in the popliteal fossa, or an adductor canal block. exparel is contraindicated in obstetrical paracervical block anesthesia [see use in specific populations (8.1)]. while exparel has not been tested with this technique, the use of bupivacaine hcl with this technique has resulted in fetal bradycardia and death. risk summary there are no studies conducted with exparel in pregnant women. in animal reproduction studies, embryo-fetal deaths were observed with subcutaneous administration of bupivacaine to rabbits during organogenesis at a dose equivalent to 1.6 times the maximum recommended human dose (mrhd) of 266 mg. subcutaneous administration of bupivacaine to rats from implantation through weaning produced decreased pup survival at a dose equivalent to 1.5 times the mrhd [see data] . based on animal data, advise pregnant women of the potential risks to a fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. however, the background risk in the u.s. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies. clinical considerations labor or delivery bupivacaine is contraindicated for obstetrical paracervical block anesthesia. while exparel has not been studied with this technique, the use of bupivacaine for obstetrical paracervical block anesthesia has resulted in fetal bradycardia and death. bupivacaine can rapidly cross the placenta, and when used for epidural, caudal, or pudendal block anesthesia, can cause varying degrees of maternal, fetal, and neonatal toxicity [see clinical pharmacology (12.3)] . the incidence and degree of toxicity depend upon the procedure performed, the type, and amount of drug used, and the technique of drug administration. adverse reactions in the parturient, fetus, and neonate involve alterations of the central nervous system, peripheral vascular tone, and cardiac function. data animal data bupivacaine hydrochloride was administered subcutaneously to rats and rabbits during the period of organogenesis (implantation to closure of the hard plate). rat doses were 4.4, 13.3, and 40 mg/kg/day (equivalent to 0.2, 0.5 and 1.5 times the mrhd, respectively, based on the bsa comparisons and a 60 kg human weight) and rabbit doses were 1.3, 5.8, and 22.2 mg/kg/day (equivalent to 0.1, 0.4 and 1.6 times the mrhd, respectively, based on the bsa comparisons and a 60 kg human weight). no embryo-fetal effects were observed in rats at the doses tested with the high dose causing increased maternal lethality. an increase in embryo-fetal deaths was observed in rabbits at the high dose in the absence of maternal toxicity. decreased pup survival was noted at 1.5 times the mrhd in a rat pre- and post-natal development study when pregnant animals were administered subcutaneous doses of 4.4, 13.3, and 40 mg/kg/day bupivacaine hydrochloride (equivalent to 0.2, 0.5 and 1.5 times the mrhd, respectively, based on the bsa comparisons and a 60 kg human weight) from implantation through weaning (during pregnancy and lactation). risk summary limited published literature reports that bupivacaine and its metabolite, pipecoloxylidide, are present in human milk at low levels. there is no available information on effects of the drug in the breastfed infant or effects of the drug on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for exparel and any potential adverse effects on the breastfed infant from exparel or from the underlying maternal condition. the safety and effectiveness of exparel to produce postsurgical local analgesia via infiltration have been established in pediatric patients aged 6 years and older. use of exparel for this indication is supported by evidence from adequate and well-controlled studies in adults, and pharmacokinetic (pk) and safety data in pediatric patients aged 6 years and older from studies peds-1 and peds-2 [see adverse reactions (6.1), clinical pharmacology (12.3)]. - study peds-1 was a multicenter, randomized, open-label, two-part study (nct03682302) to evaluate the pk and safety of exparel for local infiltration in pediatric patients aged 6 to less than 17 years who were undergoing spine or cardiac surgery (postsurgically, patients were administered opioid rescue medication according to the study site's standard of care). group 1: 61 patients aged 12 to less than 17 years, undergoing spine surgeries, were randomized 1:1 to receive either exparel 4 mg/kg (maximum 266 mg) or bupivacaine hcl 2 mg/kg (maximum 175 mg). group 2: 34 patients aged 6 to less than 12 years, undergoing either spine or cardiac surgeries, received open-label exparel 4 mg/kg (maximum up to 266 mg). - group 1: 61 patients aged 12 to less than 17 years, undergoing spine surgeries, were randomized 1:1 to receive either exparel 4 mg/kg (maximum 266 mg) or bupivacaine hcl 2 mg/kg (maximum 175 mg). - group 2: 34 patients aged 6 to less than 12 years, undergoing either spine or cardiac surgeries, received open-label exparel 4 mg/kg (maximum up to 266 mg). - study peds-2 was a phase 1, open-label study that evaluated the pk and safety of 4 mg/kg (maximum 266 mg) of exparel (administered intraoperatively prior to wound closure) in 15 pediatric patients aged 12 to less than 17 who were undergoing spinal surgery. the safety and effectiveness of exparel have not been established to produce postsurgical: - local analgesia via infiltration in pediatric patients aged less than 6 years old. - regional analgesia via an interscalene brachial plexus nerve block, sciatic nerve block in the popliteal fossa, or adductor canal block in pediatric patients. of the total number of patients in the exparel local infiltration clinical studies (n=823), 171 patients were greater than or equal to 65 years of age and 47 patients were greater than or equal to 75 years of age. of the total number of patients in the exparel nerve block clinical studies (n= 1046), 312 patients were greater than or equal to 65 years of age and 70 patients were greater than or equal to 75 years of age. no overall differences in safety or effectiveness of exparel have been observed between patients 65 years of age and older and younger adult patients. in clinical studies, differences in various pharmacokinetic parameters have been observed between patients 65 years of age and older and younger adult patients. bupivacaine is known to be substantially excreted by the kidney, and the risk of adverse reactions to bupivacaine may be greater in patients with renal impairment than in patients with normal renal function. because patients 65 years of age and older are more likely to have renal impairment, increase monitoring for exparel-associated adverse reactions [see adverse reactions (6)]. amide-type local anesthetics, such as bupivacaine, are metabolized by the liver. patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations, and potentially local anesthetic systemic toxicity [see clinical pharmacology (12.3)]. therefore, consider increased monitoring for local anesthetic systemic toxicity in patients with moderate to severe hepatic disease. bupivacaine is known to be substantially excreted by the kidney, and the risk of adverse reactions to exparel may be greater in patients with renal impairment than in patients with normal renal function. therefore, in patients with renal impairment, increase monitoring for exparel-associated adverse reactions [see adverse reactions (6)].

United States - English - NLM (National Library of Medicine)

pacira pharmaceuticals inc. - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - injection, lipid complex - 10 mg in 1 ml - depodur is an extended-release liposome injection of morphine sulfate intended for single-dose administration by the epidural route, at the lumbar level, for the treatment of pain following major surgery. depodur is administered prior to surgery or after clamping the umbilical cord during cesarean section. depodur is not intended for intrathecal, intravenous, or intramuscular administration. administration of depodur into the thoracic epidural space or higher has not been evaluated and therefore is not recommended. depodur is contraindicated in patients with known hypersensitivity to morphine, morphine salts, or any components of the product. depodur, as with all opiates, is contraindicated in patients with respiratory depression, acute or severe bronchial asthma, and upper airway obstruction. any contraindications for an epidural injection preclude the administration of depodur. depodur, as with all opiates, is contraindicated in any patient who has or is suspected of having paralytic ileus. depodur should n

United Kingdom - English - MHRA (Medicines & Healthcare Products Regulatory Agency)

napp pharmaceuticals ltd - cytarabine liposomal pegylated - suspension for injection - 10mg/1ml

Australia - English - Department of Health (Therapeutic Goods Administration)

orphan australia pty ltd - morphine sulfate -

Australia - English - Department of Health (Therapeutic Goods Administration)

aspen pharmacare australia pty ltd - morphine sulfate pentahydrate, quantity: 10 mg/ml - injection, suspension - excipient ingredients: dioleoylphosphatidylcholine; dipalmitoylphosphatidylglycerol; cholesterol; triolein; tricaprylin; sodium chloride; dilute hydrochloric acid; water for injections - for the relief of post-operative pain following major orthopaedic, abdominal, or pelvic surgery via the lumbar epidural route at a maximum recommended dose of 10 mg. appropriate monitoring must be maintained for at least 48 hours - see precautions.

United States - English - NLM (National Library of Medicine)

sigma-tau pharmaceuticals, inc. - cytarabine (unii: 04079a1rdz) (cytarabine - unii:04079a1rdz) - cytarabine 50 mg in 5 ml