USA - engelsk - NLM (National Library of Medicine)

baxter healthcare corporation - ropivacaine hydrochloride (unii: v910p86109) (ropivacaine - unii:7io5lya57n) - ropivacaine hydrochloride is indicated for the production of local or regional anesthesia for surgery and for acute pain management. ropivacaine hydrochloride is contraindicated in patients with a known hypersensitivity to ropivacaine or to any local anesthetic agent of the amide type. risk summary there are no available human data on use of ropivacaine hydrochloride injection in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. local anesthetics may cause varying degrees of toxicity to the mother and fetus and adverse reactions include alterations of the central nervous system, peripheral vascular tone, and cardiac function (see clinical considerations) . no teratogenicity was observed at doses up to 0.3 times the maximum recommended human dose of 770 mg/24 hours for epidural use, and equal to the mrhd of 250 mg for nerve block use, based on body surface area (bsa) comparisons and a 60 kg human weight (see animal 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. labor or delivery local anesthetics, including ropivacaine, rapidly cross the placenta, and when used for epidural block can cause varying degrees of maternal, fetal, and neonatal toxicity [see clinical pharmacology (12)] . 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. maternal adverse reactions maternal hypotension has resulted from regional anesthesia. local anesthetics produce vasodilation by blocking sympathetic nerves. therefore, during treatment of systemic toxicity, maternal hypotension or fetal bradycardia following regional block, the parturient should be maintained in the left lateral decubitus position if possible, or manual displacement of the uterus off the great vessels be accomplished. elevating the patient's legs will also help prevent decreases in blood pressure. the fetal heart rate also should be monitored continuously, and electronic fetal monitoring is highly advisable. animal data no malformations were reported in embryo-fetal development toxicity studies conducted in pregnant new zealand white rabbits and sprague-dawley rats. during gestation days 6 to 18, rabbits received daily subcutaneous doses of ropivacaine at 1.3, 4.2, or 13 mg/kg/day (equivalent to 0.03, 0.10, and 0.33 times the maximum recommended human dose (mrhd) of 770 mg/24 hours, respectively, and 0.10, 0.32, and 1.0 times the mrhd of 250 mg for nerve block use, respectively based on body surface area (bsa) comparisons and a 60 kg human weight). rats received daily subcutaneous doses of 5.3, 11, and 26 mg/kg/day (equivalent to 0.07, 0.14, and 0.33 times the mrhd for epidural use, respectively, and 0.21, 0.43, and 1.0 times the mrhd for nerve block use, respectively, based on bsa comparisons) during gd 6 to 15. no treatment-related effects on late fetal development, parturition, litter size, lactation, neonatal viability, or growth of the offspring were reported in a prenatal and postnatal reproductive and development toxicity study; however functional endpoints were not evaluated. female rats were dosed daily subcutaneously from gd 15 to lactation day 20 at doses of 5.3, 11, and 26 mg/kg/day (equivalent to 0.07, 0.1, and 0.3 times the mrhd for epidural use, respectively, and 0.21, 0.43, and 1.0 times the mrhd for nerve block use, respectively), with maternal toxicity exhibited at the high dose. no adverse effects in physical developmental milestones or in behavioral tests were reported in a 2-generational reproduction study, in which rats received daily subcutaneous doses of 6.3, 12, and 23 mg/kg/day (equivalent to 0.08, 0.15, and 0.29 times the mrhd for epidural use, respectively, and 0.24, 0.45, and 0.88 times the mrhd for nerve block use, respectively, based on bsa comparisons) for 9 weeks before mating and during mating for males, and for 2 weeks before mating and during mating, pregnancy, and lactation, up to day 42 post coitus for females. significant pup loss was observed in the high dose group during the first 3 days postpartum, from a few hours up to 3 days after delivery compared to the control group, which was considered secondary to impaired maternal care due to maternal toxicity. no differences were observed in litter parameters, or fertility, mean gestation time, or number of live births were observed between the control (saline) and treatment groups [see carcinogenesis, mutagenesis, impairment of fertility (13.1)] . risk summary one publication reported that ropivacaine is present in human milk at low levels following administration of ropivacaine in women undergoing cesarean section. no adverse reactions were reported in the infants. there is no available information on the drug’s effects on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ropivacaine hydrochloride and any potential adverse effects on the breastfed child from ropivacaine hydrochloride or from the underlying maternal condition. the safety and efficacy of ropivacaine hydrochloride in pediatric patients have not been established. of the 2,978 subjects that were administered ropivacaine hydrochloride injection in 71 controlled and uncontrolled clinical studies, 803 patients (27%) were 65 years of age or older which includes 127 patients (4%) 75 years of age and over. ropivacaine hydrochloride injection was found to be safe and effective in the patients in these studies. clinical data in one published article indicate that differences in various pharmacodynamic measures were observed with increasing age. in one study, the upper level of analgesia increased with age, the maximum decrease of mean arterial pressure (map) declined with age during the first hour after epidural administration, and the intensity of motor blockade increased with age. this drug and its metabolites are known to be excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. elderly patients are more likely to have decreased hepatic, renal, or cardiac function, as well as concomitant disease. therefore, care should be taken in dose selection, starting at the low end of the dosage range, and it may be useful to monitor renal function [see clinical pharmacology (12.3)]. because amide-type local anesthetics such as ropivacaine are metabolized by the liver, these drugs, especially repeat doses, should be used cautiously in patients with hepatic disease. patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations [see warnings and precautions (5.11) ]. this drug and its metabolites are known to be excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. therefore, care should be taken in dose selection, starting at the low end of the dosage range, and it may be useful to monitor renal function [see clinical pharmacology (12.3)].

USA - engelsk - NLM (National Library of Medicine)

baxter healthcare corporation - sodium chloride (unii: 451w47iq8x) (chloride ion - unii:q32zn48698, sodium cation - unii:lyr4m0nh37), sodium citrate, unspecified form (unii: 1q73q2julr) (anhydrous citric acid - unii:xf417d3psl, sodium cation - unii:lyr4m0nh37) - fact sheet for healthcare providers regiocit (sodium chloride and sodium citrate renal replacement and regional anticoagulant solution) for continuous renal replacement therapy for extracorporeal use only emergency use authorization for the united states the u.s. food and drug administration (fda) has issued an emergency use authorization (eua) to permit the emergency use of the unapproved product, regiocit: a replacement solution that contains citrate for regional citrate anticoagulation (rca) of the extracorporeal circuit. regiocit has been authorized for emergency use as a replacement solution in adult patients treated with continuous renal replacement therapy (crrt), and for whom rca is appropriate, during the covid-19 pandemic. regiocit is intended for use in a critical care setting. regiocit is intended to be used in continuous venovenous hemofiltration (cvvh) and continuous venovenous hemodiafiltration (cvvhdf) modalities. use of regiocit is limited to healthcare providers and/or institutions that baxter has qualified to administer regiocit for these emergency uses. regiocit has been authorized by fda for emergency use. regiocit is not fda-approved. regiocit is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of regiocit under section 564(b)(1) of the act, 21 u.s.c. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner. the scope of the eua is as follows: product description regiocit is a sterile, replacement solution intended for use in adult patients being treated with crrt and for whom rca is appropriate. regiocit, contains physiological concentrations of sodium (140 mmol/l), chloride (86 mmol/l), and a low concentration of citrate (18 mmol/l). • a separate systemic infusion of calcium must be administered during use of regiocit to prevent or treat hypocalcemia. blood calcium concentrations (ionized and total) must be monitored throughout crrt. • regiocit solution must be used in pre-dilution mode only, with appropriate extracorporeal renal replacement equipment intended for crrt, using an integrated pre-blood pump for rca and in combination with other replacement and/or dialysate solution to provide the recommended dose of crrt. • regiocit may only be administered by health care providers/institutions that have been qualified by baxter to administer the product. instructions for use renal replacement solution: not for direct intravenous infusion. the recommended effluent volume for patients receiving crrt for acute kidney injury (aki) is 20 to 25 ml/kg/h. this usually requires a higher prescription of effluent volume. the prescription of regiocit solution must consider the flow rates of the effluent and other therapeutic fluids, the patient’s fluid removal requirements, additional fluid inputs and outputs, and the desired acid-base and electrolyte balance. the mode of therapy, solute formulations, flow rates and length of therapy should be selected by the physician responsible for managing treatment depending on the clinical condition of the patient as well as the patient’s fluid, electrolyte, acid base and glucose balance. dialysate and replacement fluid formulations and flow rates are prescribed in accordance with the patient’s clinical needs. the use of a calcium-containing dialysate or replacement fluid is not recommended, since the calcium provided by these solutions may counteract the anticoagulant effect of citrate in the circuit. the rate at which regiocit solution is administered depends on the targeted citrate dose and the prescribed blood flow rate. the pre-filter infusion rate of regiocit solution is indexed to the blood flow rate to achieve a target blood citrate concentration of 3 mmol/l of blood (see table 1). flow rate for anticoagulation of the extracorporeal circuit should be titrated to achieve a post-filter concentration of ionized calcium in the range of 0.25 to 0.35 mmol/l. table 1: regiocit solution flow rates to achieve citrate dose of 3 mmol/l of blood prior to initiating therapy, the patient’s systemic ionized calcium concentration should be within the normal physiologic range (1.0 to 1.2 mmol/l) by adjustment of calcium supplementation. a separate infusion of calcium is always required during use of regiocit, due to loss in the effluent. calcium solution infusion is commenced at the rate of 4 mmol/h, when commencing therapy (see table 4). adjust or stop calcium infusion according to physician’s prescription when regiocit is stopped. citrate also acts as a buffer source (due to conversion to bicarbonate); the infusion rate of regiocit solution must be considered in relation to the rate at which buffer administration occurs from other sources (e.g., dialysate and/or replacement fluid). regiocit solution must be used together with a dialysis solution/replacement solution with appropriate bicarbonate concentration. monitoring of the post-filter blood ionized calcium (ica), systemic blood ica, and total blood calcium levels in conjunction with other laboratory and clinical parameters such as acid-base balance and serum electrolytes are essential to guide appropriate regiocit solution dosage based on the desired level of anticoagulation. levels should be taken at baseline, 1 hour after initiation (or adjustment), and every 6 hours (see table 2). rapidly decreasing systemic ionized calcium levels are an early indicator of citrate accumulation. measurement of total calcium and assessment of total-to-ionized calcium ratio is necessary. citrate accumulation causes systemic ionized calcium levels to drop and the ratio of total-to-ionized calcium increases (total-to-ionized calcium ratio > 2.5). in the presence of impaired citrate metabolism, a progressively higher calcium infusion rate is required to maintain the systemic ionized calcium concentration within the intended target. when a total-to-ionized-calcium ratio > 2.5 is recorded, any one of the following abnormalities reported concurrently increases the likelihood of citrate accumulation: in order to avoid metabolic alkalosis, acid-base balance and systemic ionized calcium can be measured using blood gas analysis. if metabolic alkalosis or citrate accumulation is suspected, decrease the citrate dose while tolerating a post-filter ionized calcium of < 0.5 mmol/l. this can be achieved by either decreasing the blood flow rate to decrease the overall citrate load, increasing the dialysate/replacement flow rate (when applicable) to increase the citrate removal, or decreasing the citrate flow to decrease the citrate dose. dialysate solutions contain bicarbonate below or above physiological range of 22 to 26 mmol/l, and increasing or decreasing the flow rates of the dialysate solutions can impact the acid-base status of the patient. plasma levels of sodium, magnesium, potassium, and glucose, and phosphate should be monitored regularly and should be supplemented as needed. table 2 provides a summary of the most important parameters to be monitored during rca therapy, as well as options for adjustment. table 2: monitoring and adjustment during rca therapy table 3 provides the regiocit solution flow rate adjustment based on a citrate dose adjustment of 0.5 mmol/l. table 3: regiocit solution flowrate adjustment based on a citrate dose adjustment of 0.5 mmol/l table 4 provides recommendations to maintain a systemic ionized calcium level between 1.0 mmol/l and 1.2 mmol/l. table 4: sliding scale of calcium infusion regiocit solution contains no calcium, and may lead to systemic ionized hypocalcemia due to loss of calcium bound to citrate in the effluent and/or in the case of systemic citrate accumulation. calcium reinfusion is required during use of regiocit and blood calcium concentrations (ionized and total) must be monitored. regiocit solution contains no magnesium. use of the regiocit solution may result in hypomagnesemia due to crrt effluent losses. magnesium levels must be monitored as infusion of magnesium may be necessary. regiocit solution contains no dextrose. administration of regiocit solution may lead to hypoglycemia. blood glucose levels must be monitored regularly. regiocit solution contains no potassium. the serum potassium concentration must be monitored before and during crrt. regiocit solution contains citrate, which contributes to the overall buffer load. metabolization of 1 mol of citrate generates 3 mol of bicarbonate. additional sodium bicarbonate (or buffer source) contained in the crrt fluids or in other fluids administered during therapy may increase the risk of metabolic alkalosis. metabolic alkalosis may occur if the net citrate administration rate exceeds that which is necessary to maintain acid–base balance. if metabolic alkalosis occurs, decrease the citrate dose, and/or increase the dialysate/replacement flow rate (when applicable) or change the composition of the crrt solution. metabolic acidosis may occur if metabolic clearance of citrate by the liver or skeletal muscle is impaired. if citrate accumulation develops and/or metabolic acidosis develops or worsens during therapy with regiocit solution, the infusion rate may need to be decreased or its administration stopped. metabolism of citrate (to bicarbonate) may be impaired in patients with hepatic impairment, resulting in accumulation of citrate. if regiocit solution is administered to patients with mild to moderate hepatic impairment, frequent monitoring of ph, electrolytes, total-to-ionized calcium ratio, and systemic ionized calcium is important to avoid electrolyte and/or acid–base imbalance. regiocit solution is hypoosmolar/hypotonic relative to standard crrt replacement fluids and should be used with caution in patients with traumatic brain injury, cerebral edema, or increased intracranial pressure. contraindications for the use of regiocit include: report adverse events or quality problems experienced with the use of this product. healthcare facilities and prescribing health care providers or their designee receiving regiocit will track all medication errors associated with the use of and all serious adverse events that are considered to be potentially attributable to regiocit use and must report these to fda using one of the following methods: call 1-800-fda-1088 for questions. submitted reports should state, “use of regiocit was under an eua” at the beginning of the question “describe event” for further analysis. contact baxter healthcare corporation at 1-866-888-2472 or global_pharmacovigilance_deerfield@baxter.com the united states fda has made regiocit available to treat patients in an icu during the covid-19 pandemic under an emergency access mechanism called an emergency use authorization (eua). the eua is supported by a secretary of health and human service (hhs) declaration that circumstances exist to justify the emergency use of drugs and biological products during the covid-19 pandemic. regiocit made available under an eua have not undergone the same type of review as an fda-approved product. fda may issue an eua when certain criteria are met, which includes that there are no adequate, approved, available alternatives. in addition, the fda decision is based on the totality of scientific evidence available showing that it is reasonable to believe that regiocit may be effective for use as a replacement solution in adult patients treated with continuous renal replacement therapy (crrt) and requiring regional citrate anticoagulation (rca) of the extracorporeal circuit in an icu setting during the coronavirus disease 2019 (covid-19) pandemic, and that the known and potential benefits of regiocit for such use outweigh the known and potential risks of regiocit. this eua for regiocit is in effect for the duration of the covid-19 declaration justifying emergency use of the products, unless terminated or revoked (after which the products may no longer be needed). the eua will end when the declaration is terminated or revoked or when there is a change in the approval status of the product such that an eua is no longer needed. this communication and product information is available on baxter healthcare’s website: to access covid-19 resources, product details, product use information, and the comprehensive prismaflex control unit operator’s manual and prismax control unit operator’s manual please visit the baxter healthcare acute therapies website at http://www.renalacute.com fda’s webpage also includes links to patient fact sheet and manufacturer’s instructions https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#covidtherapeutics. you are being given regiocit: a replacement solution for continuous renal replacement therapy (crrt) that also reduces the risk of filter clotting. this fact sheet contains information to help you understand the risks and benefits of taking the regiocit you have received or may receive. there is currently a shortage of u.s. food and drug administration (fda)-approved replacement solutions that may be used to provide crrt. regiocit is not an fda-approved medicine in the united states. regiocit is currently approved in europe and other countries. read this fact sheet for information about regiocit. talk to your health care provider if you have questions. it is your choice to receive regiocit or stop it at any time. what is covid-19? covid-19 is caused by a virus called a coronavirus. this type of coronavirus has not been seen before. this new virus was first found in people in december 2019. you can get covid-19 through contact with another person who has the virus. covid-19 illnesses have ranged from very mild (including some with no reported symptoms) to severe, including illness resulting in death. while information so far suggests that most covid-19 illness is mild, serious illness can happen and may cause some of your other medical conditions to become worse. older people and people of all ages with severe, long lasting (chronic) medical conditions like heart disease, lung disease and diabetes, for example seem to be at higher risk of being hospitalized for covid-19. what are the symptoms of covid-19? the symptoms of covid-19 are fever, cough, and shortness of breath, which may appear 2-14 days after exposure. serious illness, including breathing problems, can occur and may cause your other medical conditions to become worse. what is regiocit? regiocit is a replacement solution for crrt, which is a form of “dialysis” treatment, that also reduces the risk of filter clotting. replacement solutions are used during crrt to help correct acid-base abnormalities and electrolyte abnormalities, remove “uremic” and other toxins and facilitate the use of crrt to control fluid overload. what should i tell my healthcare provider before i receive regiocit? tell your healthcare provider about all of your medical conditions, including if you: who should not receive regiocit? do not take regiocit if you: what are the important possible side effects for regiocit? possible side effects of regiocit include: what other treatment choices are there? your healthcare provider may use a different replacement solution for crrt or a type of “dialysis” that does not require a replacement solution. how do i report side effects with regiocit? tell your healthcare provider right away if you have any side effects that bother you or do not go away. report side effects to fda medwatch at www.fda.gov/medwatch or call 1-800-fda-1088 or contact baxter healthcare corporation at 1-866-888-2472 or global_pharmacovigilance_deerfield@baxter.com. how can i learn more? what is an emergency use authorization (eua)? the united states fda has made regiocit available under an emergency access mechanism called an eua. the eua is supported by a secretary of health and human service (hhs) declaration that circumstances exist to justify the emergency use of drugs and biological products during the covid-19 pandemic. regiocit has not undergone the same type of review as an fda-approved or cleared product. fda may issue an eua when certain criteria are met, which includes that there are no adequate, approved, available alternatives. in addition, the fda decision is based on the totality of scientific evidence available showing that it is reasonable to believe that the product may be effective in treatment of patients during the covid-19 pandemic. all of these criteria must be met to allow for the product to be used in the treatment of patients during the covid-19 pandemic, and that the known and potential benefits outweigh the known and potential risks for such use. the eua for regiocit is in effect for the duration of the covid-19 declaration justifying emergency use of these products, unless terminated or revoked (after which the products may no longer be used). regiocit has been authorized by fda for emergency use. regiocit is not fda-approved. regiocit is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of regiocit under section 564(b)(1) of the act, 21 u.s.c. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner. sodium chloride and sodium citrate solution for hemofiltration and regional citrate anticoagulation during continuous renal replacement therapy (crrt) sodium chloride 5.03 g/l, sodium citrate 5.29 g/l solution for extracorporeal use only. not for direct intravenous infusion en package insert............................................................................2 regiocit sodium chloride and sodium citrate solution for hemofiltration and regional citrate anticoagulation during continuous renal replacement therapy (crrt) sodium chloride 5.03 g/l, sodium citrate 5.29 g/l solution for extracorporeal use only, not for direct intravenous infusion regiocit (sodium chloride and sodium citrate) solution is indicated for use as replacement solution for regional citrate anticoagulation (rca) of the extracorporeal circuit in patients treated with continuous renal replacement therapy (crrt), particularly when systemic anticoagulation with heparin is contraindicated, e.g., in patients with increased bleeding risks. regiocit should be administered only under the supervision of a physician experienced in the use of crrt. pediatrics pediatrics (<18 years of age): no data are available to health canada; therefore, health canada has not authorized an indication for pediatric use. geriatrics geriatrics (> 65 years of age): evidence from clinical studies and experience suggests that use in the geriatric population is not associated with differences in safety or effectiveness. regiocit solution is contraindicated in: for extracorporeal use only. not for direct intravenous infusion. regiocit solution is used as a renal replacement solution. the product has an osmolarity of 244 mosm/l and a ph of approximately 7.4. dosing considerations dosing considerations of the drug: recommended dose and dosage adjustment the rate at which regiocit solution is administered depends on the targeted citrate dose and the prescribed blood flow rate (bfr). the prescription of the product must consider the flow rates of the effluent and other therapeutic fluids, the patient’s fluid removal requirements, additional fluid inputs and outputs, and the desired acid-base and electrolyte balance. regiocit solution should be prescribed and its administration (dose, infusion rate, and cumulative volume) established only by critical care or nephrology physicians experienced in administration of crrt. the pre-filter infusion rate of regiocit solution (based on its concentration) is indexed to the blood flow rate to achieve a target blood citrate concentration of 3 to 4 mmol/l in the blood. flow rate for anticoagulation of the extracorporeal circuit should be titrated to achieve a post-filter concentration of ionized calcium in the range 0.25 to 0.35 mmol/l. the patient’s systemic ionized calcium concentration should be maintained in the normal physiologic range by adjustment of calcium supplementation. administration monitoring of the post-filter blood ionized calcium (ica), systemic blood ica, and total blood calcium levels in conjunction with other laboratory and clinical parameters is essential to guide appropriate regiocit solution dosage based on the desired level of anticoagulation (see warnings and precautions). plasma levels of sodium, magnesium, potassium, and phosphate should also be monitored regularly and these electrolytes supplemented as needed. regiocit solution may be warmed to 37°c to enhance patient comfort. warming of the product prior to use should be done with dry heat only. solution should not be heated in water or in a microwave oven due to the potential for patient injury or discomfort. regiocit solution should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. do not administer unless the solution is clear and the seal is intact. electrolyte imbalance and acid–base balance abnormalities, e.g., hypocalcemia, metabolic alkalosis, etc. may occur in the event of an overdose. stop administration promptly (see warnings and precautions). in patients with impaired citrate metabolism, e.g., liver failure, circulatory shock etc, overdosage with regiocit solution may be manifested as citrate accumulation, metabolic acidosis, systemic total hypercalcemia and ionized hypocalcemia along with increased total calcium/ionized calcium ratio (see contraindications, and warnings and precautions). careful calcium supplementation can reverse the effects of an overdose. the risk can be minimized by close monitoring during treatment. table 1 – dosage forms, strengths, composition and packaging table 2 – electrolyte concentrations from the medicinal ingredients regiocit (sodium chloride and sodium citrate) solution is available in a 5 000 ml bag, with a luer connector valve and a spike connector. the bag is made of a multilayer film containing polyolefins and elastomers. this product is not made with natural rubber latex. there have been reports of system failure due to apparent operator error during administration of crrt with regiocit solution, leading to serious adverse events, including life-threatening hypocalcemia. plasma electrolyte and acid-base parameters should be closely monitored during crrt, and appropriate action taken if imbalances of electrolytes or acid-base balance are detected. instructions for use of regiocit and crrt must be strictly followed. cautionary statements are provided in warnings and precautions, endocrine and metabolism, hematologic, hepatic / biliary / pancreatic, and monitoring and laboratory tests, and in drug interactions to avoid the following when performing the crrt procedure: citrate accumulation special attention is required in patients with liver failure, including hepatic cirrhosis or acute hepatic failure, or in shock, since metabolism of citrate may be markedly reduced and patients may be thus exposed to citrate accumulation. in these circumstances, more frequent monitoring of citrate accumulation should be undertaken. with systemic citrate accumulation, metabolic acidosis and ionized hypocalcemia may ensue, and the ratio of total to ionized calcium in the blood rises. if total/ionized calcium ratio rises above 2.3, regiocit infusion should be reduced or stopped. crrt may then be continued without anticoagulation, or by using other means of anticoagulation. regiocit is contraindicated in patients with severe hepatic impairment or in circulatory shock with muscle hypoperfusion (see contraindications). excessive infusion of citrate can lead to acute hypocalcemia and metabolic alkalosis, with neurologic and cardiac complications. treatment consists of discontinuation of the citrate infusion and infusion of calcium. endocrine and metabolism hypocalcemia regiocit solution contains no calcium, and may lead to systemic ionized hypocalcemia, due to loss of calcium bound to citrate in the effluent and/or in the case of systemic citrate accumulation (see dosage and administration, administration). electrolyte and acid–base balance regiocit solution contains citrate, which can influence the patient’s electrolyte and acid–base balance. plasma electrolyte and acid–base parameters should be closely monitored during crrt. closely monitor sodium, magnesium, potassium, phosphate, and calcium. infusion of electrolytes may be needed to supplement any loss. hypercalcemia medicinal products containing calcium used for maintenance of calcium homeostasis in crrt patients can increase the risk of hypercalcemia, and can result in a reduced anticoagulation effect. care should be taken to avoid excessive titration in administering calcium as this can lead to hypercalcemia. frequent monitoring of ph, electrolytes, total-to-ionized calcium ratio, and systemic ionized calcium is important to avoid electrolyte and/or acid-base imbalance. hypomagnesemia regiocit solution contains no magnesium. use of the regiocit solution may result in hypomagnesemia due to crrt effluent losses (see dosage and administration, administration). hypoglycemia regiocit solution contains no dextrose. administration of regiocit solution may lead to hypoglycemia. blood glucose levels should be monitored regularly. hypokalemia regiocit solution contains no potassium. the serum potassium concentration must be monitored before and during crrt. metabolic alkalosis regiocit solution contains citrate, which contributes to the overall buffer load. additional sodium bicarbonate (or buffer source) contained in the crrt fluids or in other fluids administered during therapy may increase the risk of metabolic alkalosis. metabolic alkalosis may occur if the net citrate administration rate exceeds that which is necessary to maintain acid–base balance. if metabolic alkalosis occurs, decrease the citrate dose, and/or increase the dialysate flow rate or change the composition of the crrt solution. blood calcium levels, ph and bicarbonate should be monitored regularly in patients with metabolic alkalosis since this condition may potentiate hypocalcemia. metabolic acidosis metabolic acidosis may occur if metabolic clearance of citrate by the liver or skeletal muscle is impaired (see contraindications). if citrate accumulation develops and/or metabolic acidosis develops or worsens during therapy with regiocit, the infusion rate may need to be decreased or its administration stopped. hypo-osmolarity/hypotonicity regiocit solution is hypo-osmolar/hypotonic relative to standard crrt replacement fluids and should be used with caution in patients with traumatic brain injury, cerebral edema, or increased intracranial pressure. instructions for use of regiocit must be strictly followed. incorrect use of the access ports or other restrictions to fluid flow may lead to incorrect patient weight loss and may result in machine alarms being set off. continuing treatment without resolving the originating cause may lead to patient injury or death. careful ongoing assessment is required of all solutions infused during regiocit administration, whether related to crrt dialysis fluids or to other solutions infused systemically. regiocit has a physiological sodium level of 140 mmol/l. however, sodium losses occurring during crrt must be balanced as part of overall fluid and electrolyte management to avoid a drop in blood sodium level leading to systemic hyponatremia. hematologic hemodynamic status and fluid balance the patient’s hematocrit, hemodynamic status and fluid balance should be monitored throughout the procedure. hepatic/biliary/pancreatic use in patients with mild to moderate hepatic impairment systemic metabolism of citrate to bicarbonate may be impaired in patients with hepatic impairment, resulting in accumulation of citrate. if regiocit solution is administered to patients with mild to moderate hepatic impairment, frequent monitoring of ph, electrolytes, total-to-ionized calcium ratio, and systemic ionized calcium is important to avoid electrolyte and/or acid–base imbalance (see contraindications). monitoring and laboratory tests plasma electrolyte and acid–base parameters should be closely monitored during crrt. closely monitor sodium, magnesium, potassium, phosphate, calcium, blood glucose levels, hematocrit, hemodynamic status and fluid balance, ph, bicarbonate, total-to-ionized calcium ratio, and systemic ionized calcium. infusion of electrolytes may be needed to supplement any loss. special populations pregnant women there are no adequate data from the use of regiocit solution in pregnant women. physicians should carefully consider the potential risks and benefits for each specific patient before administering regiocit solution. breast-feeding there are no adequate data from the use of regiocit solution in lactating women. physicians should carefully consider the potential risks and benefits for each specific patient before administering regiocit solution. it is unknown if the drug is excreted in human milk. because many drugs are excreted in human milk, caution should be exercised. pediatrics pediatrics (< 18 years of age): no data are available to health canada; therefore, health canada has not authorized an indication for pediatric use. geriatrics geriatrics (> 65 years of age): evidence from clinical studies and experience suggests that use in the geriatric population is not associated with differences in safety or effectiveness. adverse reactions adverse reaction overview the following adverse reactions represent those adverse reactions that are thought to have an association with the use of regiocit solution or that may occur in conjunction with performing the crrt procedure: adverse reactions reported with other crrt products include: clinical trial adverse reactions because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. in an open-label randomised study, 54 patients were administered rca with an equimolar solution of citrate, sodium and chloride, as contained in regiocit solution, and 49 received systemic anticoagulation with unfractionated heparin (ufh) while undergoing crrt using continuous venovenous hemodiafiltration. adverse events related to metabolic disorders occurred in 26% of patients in the rca-treated group, compared to 28% of patients in the ufh-treated group. these adverse events were generally transient and reversible. metabolic alkalosis was seen in 6% of patients treated with rca, compared to none treated with ufh, and metabolic acidosis was reported in 6% and 2% of patients in the rca and ufh groups, respectively. six patients treated with rca experienced severe hypocalcemia, compared to one patient treated with ufh. in a second hemodiafiltration trial which evaluated 19 patients randomised to an equimolar solution of citrate, sodium and chloride, as contained in regiocit solution, and 11 patients randomised to ufh anticoagulation, hypocalcemia requiring intervention was reported in 3 patients treated with rca, with 2 of these patients requiring treatment interruption of rca. post-market adverse reactions to date, adverse events reported in the post-marketing setting for regiocit appear to be consistent with those listed above in adverse reaction overview. overview the blood concentration of filterable/dialyzable drugs may be reduced during treatment due to their removal by the extracorporeal filter. corresponding corrective therapy should be instituted if necessary to establish the desired blood concentrations for drugs removed during treatment. patient monitoring at an appropriate frequency is required. when prescribing regiocit, the physician needs to consider the use of other anticoagulants along with other buffer-containing and electrolyte solutions (including crrt replacement fluid and dialysate). drug-drug interactions the drugs listed in this table are based on either drug interaction case studies or clinical trials, or potential interactions due to the expected magnitude and seriousness of the interaction (i.e., those identified as contraindicated). table 3 - established or potential drug-drug interactions mechanism of action citrate provides regional anticoagulation of blood in the continuous renal replacement therapy (crrt) extracorporeal circuit by binding calcium and rendering calcium unavailable to the clotting cascade. several steps of the clotting cascade are dependent on calcium and the absence of calcium prevents clotting in the circuit. during crrt, pre-dilution infusion of citrate into the access line of the extracorporeal circuit provides only regional extracorporeal anticoagulation (and thus avoids systemic anticoagulation of the patient) for two reasons. first, once blood from the extracorporeal circuit is returned to the patient, it mixes with the central venous blood which contains calcium. the second way in which a systemic anticoagulant effect is avoided is by infusion of calcium in the post-filter (return) bloodline of the extracorporeal circuit. this procedure not only helps neutralize citrate’s anticoagulant effect in the patient’s blood, but also prevents any depletion of the patient’s calcium stores which may result from the loss of calcium (bound to citrate) in the crrt effluent fluid. pharmacodynamics citrate provides anticoagulation by its ability to form complexes with ionized calcium, making it unavailable to the clotting cascade. in regiocit, sodium concentration has been set to 140 mmol/l as critically ill patients may develop severe hyponatremia. chloride is set to the level required to balance cations as the solution is hydrogen carbonate free. sodium and chloride are normal constituents of the human body and are considered to be pharmacologically inactive. citrate is a normal metabolite in the human body that acts as a first intermediate substance in the krebs cycle. regiocit does not contain potassium or glucose. two studies provide information on the dose/response relationship between citrate concentration and anticoagulation. in one study, ex-vivo anticoagulation with anticoagulant citrate dextrose formula a (acd-a) in blood collected from six healthy volunteers was studied. the study concluded that the clinically relevant effects of citrate anticoagulation rely solely on the disturbed formation of the calcium-dependent coagulation factors complexes. in this study, the anticoagulation effects of citrate were monitored either by methods that quantify clot formation (i.e., activated clotting time) or by direct assessment of ionized calcium levels. the correlation between concentrations of ionized calcium and clotting times revealed almost no anticoagulant effect when ionized calcium levels were up to or above 0.50 mmol/l, while clotting times showed a steep increase when calcium levels were decreased below 0.50 mmol/l. with respect to maximum effect, 5.65 mmol/l citrate induced clotting times of infinity in all samples. pharmacokinetics citrate is a normal metabolite in the human body and an intermediate substance in the krebs cycle. this physiological pathway is capable of processing high amounts of citric acid as long as it occurs at low concentrations. the krebs cycle takes place in the mitochondria, and all cells that contain these cellular organelles can metabolize citrate. tissues rich in mitochondria such as liver, skeletal muscles, and kidney therefore have a higher capacity for citrate generation and elimination. absorption: absorption of sodium and chloride is determined by the patient’s clinical condition, metabolic status, and residual renal function. distribution: extracellular citrate can be transported from the blood across the plasma membrane by a group of proteins i.e. the plasma membrane citrate transporters (pmcts) into the cells and then metabolized in various organs and tissues. metabolism: citrate is an intermediate in the central metabolic pathway called krebs cycle as mentioned above. citrate is rapidly metabolized mainly in the liver, but can also be metabolized by other organs/tissues. elimination: any excess of circulating citrate is normally excreted via the kidneys. special populations and conditions hepatic insufficiency: when treating decompensated cirrhosis patients, one should also consider: store at 4 °c to 30 °c. do not freeze or expose to excessive heat. aseptic technique should be used throughout the handling and administration to the patient. remove the overwrap from the bag immediately before use. use only if the overwrap is not damaged, all seals are intact, and the solution is clear. press bag firmly to test for any leakage. if leakage is discovered, discard the solution immediately since sterility can no longer be assured. follow the instructions below when connecting the solution bags for correct use of the access ports. regiocit sodium chloride and sodium citrate solution read this carefully before you start taking regiocit solution and each time you get a refill. this leaflet is a summary and will not tell you everything about this drug. talk to your healthcare professional about your medical condition and treatment and ask if there is any new information about regiocit solution. what is regiocit solution used for? how does regiocit solution work? this medicine is to be administered into the blood circuit outside of your body when you have crrt. this medicine is to be used in hospitals and administered by medical professionals only. what are the ingredients in regiocit solution? medicinal ingredients: sodium chloride and sodium citrate non-medicinal ingredients: hydrochloric acid, water regiocit solution comes in the following dosage forms: solution with 5.03 g/l of sodium chloride and 5.29 g/l of sodium citrate do not use regiocit solution if: to help avoid side effects and ensure proper use, talk to your healthcare professional before you take regiocit solution. talk about any health conditions or problems you may have, including if you: • have diabetes • have been treated for chronic kidney disease • have a history of liver disease tell your healthcare professional about all the medicines you take, including any drugs, vitamins, minerals, natural supplements or alternative medicines. the following may interact with regiocit solution: • medicinal products that contain calcium, sodium bicarbonate, or any form of vitamin d. how to take regiocit solution: your healthcare professional will prescribe and administer the product. overdose: if you think you have taken too much regiocit solution, contact your healthcare professional, hospital emergency department or regional poison control centre immediately, even if there are no symptoms. what are possible side effects from using regiocit solution? these are not all the possible side effects you may feel when taking regiocit solution. if you experience any side effects, contact your healthcare professional. the following side effects have been associated with other crrt products: the possible side effects can be resulted from your crrt procedure: if you have a troublesome symptom or side effect that is not listed here or becomes bad enough to interfere with your daily activities, talk to your healthcare professional. reporting side effects you can report any suspected side effects associated with the use of health products to health canada by: note: contact your health professional if you need information about how to manage your side effects. the canada vigilance program does not provide medical advice. storage: store at 4 °c to 30 °c. do not freeze or expose to excessive heat. keep out of reach and sight of children. if you want more information about regiocit solution: the content of this leaflet was prepared by baxter corporation, mississauga, ontario l5n 0c2, canada. last revised: august 13, 2020 barcode 0 719002 429008 baxter and regiocit are trademarks of baxter international inc. or its subsidiaries. baxter logo

Australien - engelsk - Department of Health (Therapeutic Goods Administration)

hill-rom pty ltd - 15325 - patient positioning device, vacuum stabilized, partial body - patient support and fixation accessories are medical accessories for operating tables which are intended to support, fixate and hold the patient on the operating table.

USA - engelsk - NLM (National Library of Medicine)

baxter healthcare corporation - daptomycin (unii: nwq5n31vkk) (daptomycin - unii:nwq5n31vkk) - dapzura rt is indicated for the treatment of adult and pediatric patients (1 to 17 years of age) with complicated skin and skin structure infections (csssi) caused by susceptible isolates of the following gram-positive bacteria: staphylococcus aureus (including methicillin-resistant isolates), streptococcus pyogenes, streptococcus agalactiae, streptococcus dysgalactiae subsp. equisimilis, and enterococcus faecalis (vancomycin-susceptible isolates only). dapzura rt is indicated for the treatment of adult patients with staphylococcus aureus bloodstream infections (bacteremia), including adult patients with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates. dapzura rt is indicated for the treatment of pediatric patients (1 to 17 years of age) with staphylococcus aureus bloodstream infections (bacteremia). dapzura rt is not indicated for the treatment of pneumonia. dapzura rt is not indicated for the treatment of left-sided infective endocarditis due to s. aureus . the clinical trial of daptomycin for injection in adult patients with s. aureus bloodstream infections included limited data from patients with left-sided infective endocarditis; outcomes in these patients were poor [see clinical studies (14.2)]. daptomycin for injection has not been studied in patients with prosthetic valve endocarditis. dapzura rt is not recommended in pediatric patients younger than 1 year of age due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) observed in neonatal dogs [see warnings and precautions (5.7) and nonclinical toxicology (13.2)] . appropriate specimens for microbiological examination should be obtained in order to isolate and identify the causative pathogens and to determine their susceptibility to daptomycin. to reduce the development of drug-resistant bacteria and maintain the effectiveness of dapzura rt and other antibacterial drugs, dapzura rt should be used only to prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information is available, it should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. empiric therapy may be initiated while awaiting test results. dapzura rt is contraindicated in: • patients with known hypersensitivity to daptomycin [see warnings and precautions (5.1)]. risk summary limited published data on use of daptomycin for injection in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies performed in rats and rabbits daptomycin was administered intravenously during organogenesis at doses 2 and 4–times, respectively, the recommended 6 mg/kg human dose (on a body surface area basis). no evidence of adverse developmental outcomes was observed. the 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 2-4% and 15-20%, respectively. data animal data in pregnant rats, daptomycin was administered intravenously at doses of 5, 20, or 75 mg/kg/day during the gestation days 6 to 18. maternal body weight gain was decreased at 75 mg/kg/day. no embryo/fetal effects were noted at the highest dose of 75 mg/kg/day, a dose approximately 2-fold higher than in humans at the recommended maximum dose of 6 mg/kg (based on body surface area). in pregnant rabbits, daptomycin was administered intravenously at doses of 5, 20, or 75 mg/kg/day during the gestation days 6 to 15. maternal body weight gain and food consumption were decreased at 75 mg/kg/day. no embryo/fetal effects were noted at the highest dose of 75 mg/kg/day, a dose approximately 4-fold higher than in humans at the maximum recommended dose of 6 mg/kg (based on body surface area). in a combined fertility and pre/postnatal development study, daptomycin was administered intravenously to female rats at doses of 2, 25, 75 mg/kg/day from 14-days pre-mating through lactation/postpartum day 20). no effects on pre/postnatal development were observed up to the highest dose of 75 mg/kg/day, a dose approximately 2-fold higher than the maximum recommended human dose of 6 mg/kg (based on body surface area)1 . risk summary limited published data report that daptomycin is present in human milk at infant doses of 0.1% of the maternal dose [see data] 2,3,4 . there is no information on the effects of daptomycin on the breastfed infant or the effects of daptomycin on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for daptomycin for injection and any potential adverse effects on the breastfed infant from daptomycin for injection or from the underlying maternal condition. the safety and effectiveness of daptomycin for injection in the treatment of csssi and s. aureus bloodstream infections (bacteremia) have been established in the age groups 1 to 17 years of age. use of daptomycin for injection in these age groups is supported by evidence from adequate and well-controlled studies in adults, with additional data from pharmacokinetic studies in pediatric patients, and from safety, efficacy and pk studies in pediatric patients with csssi and s. aureus bloodstream infections [see adverse reactions (6.1), clinical pharmacology (12.3), and clinical studies (14.1 , 14.2 )] . safety and effectiveness in pediatric patients below the age of one year have not been established. avoid use of dapzura rt in pediatric patients younger than one year of age due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) observed in neonatal dogs [see warnings and precautions (5.7) and nonclinical toxicology (13.2)]. dapzura rt is not indicated in pediatric patients with renal impairment because dosage has not been established in these patients. dapzura rt has not been studied in pediatric patients with other bacterial infections. dapzura rt is contraindicated in adult and pediatric patients with hfi. because a diagnosis of hfi may not yet be established in pediatric patients, obtain a careful history of hfi symptoms with sorbitol/fructose/sucrose exposure prior to administration of dapzura rt [see warnings and precautions (5.11) ] . of the 534 adult patients treated with daptomycin for injection in phase 3 controlled clinical trials of complicated skin and skin structure infections (csssi), 27% were 65 years of age or older and 12% were 75 years of age or older. of the 120 adult patients treated with daptomycin for injection in the phase 3 controlled clinical trial of s. aureus bacteremia/endocarditis, 25% were 65 years of age or older and 16% were 75 years of age or older. in phase 3 adult clinical trials of csssi and s. aureus bacteremia/endocarditis, clinical success rates were lower in patients ≥65 years of age than in patients <65 years of age. in addition, treatment-emergent adverse events were more common in patients ≥65 years of age than in patients <65 years of age. the exposure of daptomycin was higher in healthy elderly subjects than in healthy young adult subjects. however, no adjustment of dapzura rt dosage is warranted for elderly patients with creatinine clearance (clcr ) ≥30 ml/min [see dosage and administration (2.6) and clinical pharmacology (12.3)]. daptomycin is eliminated primarily by the kidneys; therefore, a modification of dapzura rt dosage interval is recommended for adult patients with clcr <30 ml/min, including patients receiving hemodialysis or continuous ambulatory peritoneal dialysis (capd). in adult patients with renal impairment, both renal function and creatine phosphokinase (cpk) should be monitored more frequently than once weekly [see dosage and administration (2.6), warnings and precautions (5.2, 5.10 ), and clinical pharmacology (12.3)]. the dosage regimen for dapzura rt in pediatric patients with renal impairment has not been established.

USA - engelsk - NLM (National Library of Medicine)

baxter healthcare corporation - clindamycin phosphate (unii: eh6d7113i8) (clindamycin - unii:3u02el437c) - clindamycin injection usp in 5% dextrose products are indicated in the treatment of serious infections caused by susceptible anaerobic bacteria. clindamycin injection usp in 5% dextrose products are also indicated in the treatment of serious infections due to susceptible strains of streptococci, pneumococci, and staphylococci. its use should be reserved for penicillin-allergic patients or other patients for whom, in the judgment of the physician, a penicillin is inappropriate. because of the risk of antibiotic-associated pseudomembranous colitis, as described in the boxed warning , before selecting clindamycin the physician should consider the nature of the infection and the suitability of less toxic alternatives (e.g., erythromycin). bacteriologic studies should be performed to determine the causative organisms and their susceptibility to clindamycin. indicated surgical procedures should be performed in conjunction with antibiotic therapy. clindamycin injection usp in 5% dextrose is indicated in the treatment of serious infections caused by susceptible strains of the designated organisms in the conditions listed below: lower respiratory tract infections including pneumonia, empyema, and lung abscess caused by anaerobes, streptococcus pneumoniae , other streptococci (except e. faecalis ), and staphylococcus aureus . skin and skin structure infections caused by streptococcus pyogenes , staphylococcus aureus , and anaerobes. gynecological infections including endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulitis, and postsurgical vaginal cuff infection caused by susceptible anaerobes. intra-abdominal infections including peritonitis and intra-abdominal abscess caused by susceptible anaerobic organisms. septicemia caused by staphylococcus aureus , streptococci (except enterococcus faecalis ), and susceptible anaerobes. bone and joint infections including acute hematogenous osteomyelitis caused by staphylococcus aureus and as adjunctive therapy in the surgical treatment of chronic bone and joint infections due to susceptible organisms. to reduce the development of drug-resistant bacteria and maintain the effectiveness of clindamycin injection usp in 5% dextrose and other antibacterial drugs, clindamycin injection usp in 5% dextrose should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. this drug is contraindicated in individuals with a history of hypersensitivity to preparations containing clindamycin or lincomycin.

Malaysia - engelsk - NPRA (National Pharmaceutical Regulatory Agency, Bahagian Regulatori Farmasi Negara)

novartis corporation (malaysia) sdn. bhd. - secukinumab -

Australien - engelsk - Department of Health (Therapeutic Goods Administration)

janssen-cilag pty ltd - guselkumab, quantity: 100 mg - injection, solution - excipient ingredients: water for injections; histidine; sucrose; polysorbate 80; histidine hydrochloride monohydrate - plaque psoriasis,tremfya is indicated for the treatment of adult patients (18 years or older) with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.,psoriatic arthritis,tremfya is indicated for the treatment of adult patients with active psoriatic arthritis, who have had an inadequate response to, or are intolerant to prior dmard therapy.

Malta - engelsk - Medicines Authority

pharmacare srl via marghera, 29 20149, milan, italy - soft capsule - colecalciferol 10000 iu - vitamins

Malta - engelsk - Medicines Authority

pharmacare srl via marghera, 29 20149, milan, italy - soft capsule - colecalciferol 25000 iu - vitamins

Australien - engelsk - Department of Health (Therapeutic Goods Administration)

natus medical pty ltd - 43267 - patient positioning sensor - patient positioning sensor