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

glaxosmithkline llc - umeclidinium bromide (unii: 7an603v4jv) (umeclidinium - unii:ge2t1418sv) - umeclidinium 62.5 ug - incruse ellipta is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (copd). incruse ellipta is contraindicated in the following conditions: risk summary there are insufficient data on the use of umeclidinium in pregnant women to inform a drug‑associated risk. umeclidinium administered via inhalation or subcutaneously to pregnant rats and rabbits was not associated with adverse effect on embryofetal development at exposures approximately 50 and 200 times, respectively, the human exposure at the maximum recommended human daily inhaled dose (mrhdid). (see data.) the estimated risk of major birth defects and miscarriage for the indicated populations is unknown. 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: in separate embryofetal developmental studies, pregnant rats and rabbits received umeclidinium during the period of organogenesis at doses up to approximately 50 and 200 times the mrhdid, respectively (on an auc basis at maternal inhalation doses up to 278 mcg/kg/day in rats and at maternal subcutaneous doses up to 180 mcg/kg/day in rabbits). no evidence of teratogenic effects was observed in either species. in a perinatal and postnatal developmental study in rats, dams received umeclidinium during late gestation and lactation periods with no evidence of effects on offspring development at doses up to approximately 26 times the mrhdid (on an auc basis at maternal subcutaneous doses up to 60 mcg/kg/day). risk summary there is no information available on the presence of umeclidinium in human milk, the effects on the breastfed child, or the effects on milk production. umeclidinium was detected in the plasma of offspring of lactating rats treated with umeclidinium suggesting its presence in maternal milk. (see data.) the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for incruse ellipta and any potential adverse effects on the breastfed child from umeclidinium or from the underlying maternal condition. data subcutaneous administration of umeclidinium to lactating rats at greater than or equal to 60 mcg/kg/day resulted in a quantifiable level of umeclidinium in 2 of 54 pups, which may indicate transfer of umeclidinium in milk. the safety and effectiveness of incruse ellipta have not been established in pediatric patients. incruse ellipta is not indicated for use in pediatric patients. based on available data, no adjustment of the dosage of incruse ellipta in geriatric patients is necessary, but greater sensitivity in some older individuals cannot be ruled out. clinical trials of incruse ellipta included 810 subjects aged 65 years and older, and, of those, 183 subjects were aged 75 years and older. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects. patients with moderate hepatic impairment (child-pugh score of 7-9) showed no relevant increases in cmax or auc, nor did protein binding differ between subjects with moderate hepatic impairment and their healthy controls. studies in subjects with severe hepatic impairment have not been performed [see clinical pharmacology (12.3)] . patients with severe renal impairment (crcl <30 ml/min) showed no relevant increases in cmax or auc, nor did protein binding differ between subjects with severe renal impairment and their healthy controls. no dosage adjustment is required in patients with renal impairment [see clinical pharmacology (12.3)] . instructions for use incruse ellipta (in-cruise e-lip-ta) (umeclidinium inhalation powder) for oral inhalation use read this before you start: your incruse ellipta inhaler how to use your inhaler figure a figure b important notes: check the counter. see figure c. figure c prepare your dose: wait to open the cover until you are ready to take your dose. figure d step 1. open the cover of the inhaler. see figure d. figure e step 2. breathe out. see figure e. figure f step 3. inhale your medicine. see figure f. figure g figure h figure i step 4. breathe out slowly and gently. see figure i. figure j step 5. close the inhaler. see figure j. important note: when should you get a refill? figure k for more information about incruse ellipta or how to use your inhaler, call 1-888-825-5249. trademarks are owned by or licensed to the gsk group of companies. glaxosmithkline, durham, nc 27701 ©2023 gsk group of companies or its licensor. inc:3ifu this instructions for use has been approved by the u.s. food and drug administration               revised: december 2023

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

ipsen biopharmaceuticals, inc. - mecasermin (unii: 7gr9i2683o) (mecasermin - unii:7gr9i2683o) - mecasermin 40 mg in 4 ml - severe primary igf-1 deficiency (primary igfd) increlex is indicated for the treatment of growth failure in pediatric patients 2 years of age and older with: - severe primary igf-1 deficiency or - growth hormone (gh) gene deletion who have developed neutralizing antibodies to gh. severe primary igf-1 deficiency (igfd) is defined by: - height standard deviation score ≤ –3.0 and - basal igf-1 standard deviation score ≤ –3.0 and - normal or elevated growth hormone (gh). limitations of use: increlex is not a substitute to gh for approved gh indications. increlex is not indicated for use in patients with secondary forms of igf-1 deficiency, such as gh deficiency, malnutrition, hypothyroidism, or chronic treatment with pharmacologic doses of anti-inflammatory corticosteroids. - known hypersensitivity increlex should not be used by patients who are allergic to mecasermin (rhigf-1) or any of the inactive ingredients in increlex, or who have experienced a severe hypersensitivity to increlex [see warnings and precautions (5.2) and adverse reactions (6.3)]. - closed epiphyses increlex should not be used for growth promotion in patients with closed epiphyses. - malignant neoplasia increlex is contraindicated in pediatric patients with malignant neoplasia or a history of malignancy [see warnings and precautions (5.7) and adverse reactions (6.3)]. risk summary there are no available data on increlex use in pregnant women. exposure to increlex during pregnancy is unlikely because the drug is not indicated for use after epiphyseal closure. in animal reproduction studies, there were no observed embryo-fetal development abnormalities with intravenous administration of increlex to pregnant rats and rabbits during fetal organogenesis given at exposures up to 11 and 3 times the maximum recommended human dose (mrhd) of 0.24 mg/kg/day based on body surface area (bsa), respectively (see data) . the estimated background risk of birth defects and miscarriage for the indicated population is unknown. 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 studies to assess embryo-fetal toxicity evaluated the effects of increlex during organogenesis in sprague dawley rats given 1, 4, and 16 mg/kg/day and in new zealand white rabbits given 0.125, 0.5, and 2 mg/kg/day, administered intravenously. there were no observed embryo-fetal developmental abnormalities in rats given up to 16 mg/kg/day (11 times the mrhd based on bsa comparison). in the rabbit study, the noael for fetal toxicity was 0.5 mg/kg/day (approximately equivalent to the mrhd based on bsa) due to an increase in fetal death at 2 mg/kg. increlex displayed no teratogenicity or maternal toxicity in rabbits given up to 2 mg/kg (3 times the mrhd based on bsa). risk summary there is no information available on the presence of mecasermin in human or animal milk, the effects of the drug on the breastfed infant, or the 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 increlex and any potential adverse effects on the breast-fed child from increlex or from the underlying maternal condition. toxicity (gasping syndrome) with benzyl alcohol serious adverse reactions including fatal reactions and the "gasping syndrome" occurred in premature neonates and infants in the intensive care unit who received drugs containing benzyl alcohol as a preservative. in these cases, benzyl alcohol dosages of 99 mg/kg/day to 234 mg/kg/day produced high levels of benzyl alcohol and its metabolites in the blood and urine (blood levels of benzyl alcohol were 0.61 mmol/l to 1.378 mmol/l). increlex contains 9 mg/ml benzyl alcohol as a preservative. additional adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. preterm, low-birth weight infants may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol. use of increlex in infants is not recommended [see warnings and precautions (5.8)] . safety and effectiveness in pediatric patients below the age of 2 years of age have not been established. the safety and effectiveness of increlex in patients aged 65 and over has not been established. instructions for use increlex® (eenk-ruh-lex) (mecasermin) injection for subcutaneous use read this instructions for use before you start using increlex and each time you get a refill. there may be new information. this information does not take the place of talking to your child's doctor about your child's medical condition or treatment. do not share your child's needles and syringes with another person. your child may give another person an infection or your child could get an infection from them. important : - inject increlex exactly as your child's doctor or nurse has shown you. - follow your doctor's instructions for the type of syringe and needle to use to prepare and inject your child's dose of increlex . - always use a new, unopened needle and syringe for each injection. - only use single-use, disposable needles and syringes. never reuse disposable needles and syringes. - throw away used needles and syringes in a puncture-resistant, disposable sharps container as soon as you finish giving the injection. see step 5 "how should i throw away (dispose of) used needles and syringes? " at the end of these instructions. supplies needed to give the injection: - 1 vial of increlex - 1 alcohol swab - 1 gauze or cotton ball - alcohol (to clean the skin at the injection site) - 1 sharps container for throwing away (disposing of) used needles and syringes. see step 5 "how should i throw away (dispose of) used needles and syringes? " at the end of these instructions. preparing the dose: - wash your hands before getting increlex ready for your child's injection. - check the liquid to make sure it is clear and colorless. do not use if it is cloudy or if you see particles. - check the expiration date printed on the label of the vial. do not use increlex if the expiration date has passed. - if you are using a new vial, remove the protective cap. do not remove the rubber top (see figure 1). figure 1: remove the protective cap - wipe the rubber top on the vial with an alcohol swab (see figure 2). figure 2: wipe rubber top with alcohol swab - before putting the needle into the vial, pull back on plunger to draw air into the syringe equal to the increlex dose. put the needle through the rubber top of the vial and push the plunger to inject air into the vial (see figure 3). figure 3: inject air into vial - leave the syringe in the vial and turn both upside down. hold the syringe and vial firmly (see figure 4). figure 4: prepare to withdraw liquid - make sure the tip of the needle is in the liquid (see figure 5). pull the plunger to withdraw the correct dose into the syringe (see figure 6). figure 5: tip in liquidfigure 6: withdraw correct dose - before you take the needle out of the vial, check the syringe for air bubbles. if bubbles are in the syringe, hold the vial and syringe with needle straight up and tap the side of the syringe until the bubbles float to the top. push the bubbles out with the plunger and draw liquid back in until you have the correct dose (see figure 7). figure 7: remove air bubbles and refill syringe - remove the needle from the vial. do not let the needle touch anything. you are now ready to inject (see figure 8). figure 8: ready to inject injecting the dose: inject increlex exactly as your child's doctor or nurse has shown you. do not give the increlex injection if your child is unable to eat within 20 minutes before or after the injection . - put used needles and syringes in an fda-cleared sharps disposal container right away after use. do not throw away (dispose of) loose needles and syringes in your household trash. - do not try to touch the needle. - if you do not have an fda-cleared sharps disposal container, you may use a household container that is: made of a heavy-duty plastic, can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, upright and stable during use, leak-resistant, and properly labeled to warn of hazardous waste inside the container. - made of a heavy-duty plastic, - can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, - upright and stable during use, - leak-resistant, and - properly labeled to warn of hazardous waste inside the container. - when your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. there may be state or local laws about how to throw away needles and syringes. for more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the fda's website at: http://www.fda.gov/safesharpsdisposal. - for the safety and health of you and others, needles and used syringes must never be re-used. - the used alcohol swabs, cotton balls, and gauze may be placed in your household trash. - do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. do not recycle your used sharps disposal container. - always keep the sharps disposal container out of the reach of children. how should i store increlex? - before opening : store new, unopened vials of increlex in the refrigerator between 36°f to 46°f (2°c to 8°c). - after opening : store opened vials of increlex in the refrigerator between 36°f to 46°f (2°c to 8°c) for 30 days after you start using the vial. throw away any unused increlex after 30 days. - do not freeze increlex. if a vial freezes, throw it away. - keep increlex out of direct light. - do not use increlex after the expiration date printed on the label. keep increlex and all medicines out of reach of children. this instructions for use has been approved by the u.s. food and drug administration. for additional information, call 855-463-5127. manufactured by: ipsen biopharmaceuticals, inc. cambridge, ma 02142 usa u.s. license no. 2194 www.ipsenus.com revised: october 2023

Israel - English - Ministry of Health

lundbeck israel ltd. - nalmefene as hydrochloride dihydrate - film coated tablets - nalmefene as hydrochloride dihydrate 18.06 mg - nalmefene - selincro is indicated for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high drinking risk level (drl), without physical withdrawal symptoms and who do not require immediate detoxification.selincro should only be prescribed in conjunction with continuous psychosocial support focused on treatment adherence and reducing alcohol consumption.selincro should be initiated only in patients who continue to have a high drl two weeks after initial assessment.

Israel - English - Ministry of Health

lundbeck israel ltd. - nalmefene as hydrochloride dihydrate - film coated tablets - nalmefene as hydrochloride dihydrate 18.06 mg - nalmefene - selincro is indicated for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high drinking risk level (drl), without physical withdrawal symptoms and who do not require immediate detoxification.selincro should only be prescribed in conjunction with continuous psychosocial support focused on treatment adherence and reducing alcohol consumption.selincro should be initiated only in patients who continue to have a high drl two weeks after initial assessment.

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

sanofi-aventis healthcare pty ltd t/a sanofi consumer healthcare - sodium ascorbate, quantity: 112.5 mg (equivalent: ascorbic acid, qty 100 mg); ascorbic acid, quantity: 150 mg; zinc gluconate, quantity: 45 mg (equivalent: zinc, qty 6.5 mg) - tablet, chewable - excipient ingredients: hypromellose; magnesium stearate; maize starch; glucose monohydrate; microcrystalline cellulose; sucralose; silicon dioxide; maltodextrin; ascorbic acid; purified water; acacia; soya oil; dunaliella salina; citric acid; sucrose; mixed (low-alpha type) tocopherols concentrate; flavour - maintain/support collagen formation ; maintain/support healthy immune system function ; decrease/reduce/relieve common cold duration ; decrease/reduce/relieve the severity of common cold symptoms ; maintain/support skin health ; maintain/support wound healing

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

remedyrepack inc. - meloxicam (unii: vg2qf83cgl) (meloxicam - unii:vg2qf83cgl) - meloxicam is indicated for relief of the signs and symptoms of osteoarthritis [ see clinical studies (14.1)]. meloxicam is indicated for relief of the signs and symptoms of rheumatoid arthritis [ see clinical studies (14.1) ]. meloxicam is indicated for relief of the signs and symptoms of pauciarticular or polyarticular course juvenile rheumatoid arthritis in patients who weighs ≥ 60 kg [ see dosage and administration ( 2.4) and clinical studies (14.2)]. meloxicam is contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to meloxicam or any components of the drug product [ see warnings and precautions ( 5.7, 5.9) ] - history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other nsaids. severe, sometimes fatal, anaphylactic reactions to nsaids have been reported in such patients [ see warnings and precautions ( 5.7, 5.8) ] - in the setting of coronary artery bypass graft (cabg) surgery [ see warnings and precautions ( 5.1) ] risk summary use of nsaids, including meloxicam, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. because of these risks, limit dose and duration of meloxicam use between about 20 and 30 weeks of gestation, and avoid meloxicam use at about 30 weeks of gestation and later in pregnancy ( see   clinical considerations, data ). premature closure of fetal ductus arteriosus use of nsaids, including meloxicam, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment use of nsaids at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. data from observational studies regarding potential embryofetal risks of nsaid use in women in the first or second trimesters of pregnancy are inconclusive. in animal reproduction studies, embryofetal death was observed in rats and rabbits treated during the period of organogenesis with meloxicam at oral doses equivalent to 0.65- and 6.5-times the maximum recommended human dose (mrhd) of meloxicam. increased incidence of septal heart defects were observed in rabbits treated throughout embryogenesis with meloxicam at an oral dose equivalent to 78-times the mrhd. in pre- and post-natal reproduction studies, there was an increased incidence of dystocia, delayed parturition, and decreased offspring survival at 0.08-times mrhd of meloxicam. no teratogenic effects were observed in rats and rabbits treated with meloxicam during organogenesis at an oral dose equivalent to 2.6 and 26-times the mrhd [see data] . based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. in animal studies, administration of prostaglandin synthesis inhibitors such as meloxicam, resulted in increased pre- and post-implantation loss. prostaglandins also have been shown to have an important role in fetal kidney development. in published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. the estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations fetal/neonatal adverse reactions premature closure of fetal ductus arteriosus: avoid use of nsaids in women at about 30 weeks gestation and later in pregnancy, because nsaids, including meloxicam, can cause premature closure of the fetal ductus arteriosus ( see data ). oligohydramnios/neonatal renal impairment: if an nsaid is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. if meloxicam treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. if oligohydramnios occurs, discontinue meloxicam and follow up according to clinical practice ( see data ). labor or delivery there are no studies on the effects of meloxicam during labor or delivery. in animal studies, nsaids, including meloxicam, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. data human data premature closure of fetal ductus arteriosus: published literature reports that the use of nsaids at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment: published studies and postmarketing reports describe maternal nsaid use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. these adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after nsaid initiation. in many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. there have been a limited number of case reports of maternal nsaid use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. these limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal nsaid use. because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to nsaids through maternal use is uncertain. animal data meloxicam was not teratogenic when administered to pregnant rats during fetal organogenesis at oral doses up to 4 mg/kg/day (2.6-fold greater than the mrhd of 15 mg of meloxicam based on bsa comparison). administration of meloxicam to pregnant rabbits throughout embryogenesis produced an increased incidence of septal defects of the heart at an oral dose of 60 mg/kg/day (78-fold greater than the mrhd based on bsa comparison). the no effect level was 20 mg/kg/day (26-fold greater than the mrhd based on bsa conversion). in rats and rabbits, embryolethality occurred at oral meloxicam doses of 1 mg/kg/day and 5 mg/kg/day, respectively (0.65- and 6.5-fold greater, respectively, than the mrhd based on bsa comparison) when administered throughout organogenesis. oral administration of meloxicam to pregnant rats during late gestation through lactation increased the incidence of dystocia, delayed parturition, and decreased offspring survival at meloxicam doses of 0.125 mg/kg/day or greater (0.08-times mrhd based on bsa comparison). risk summary there are no human data available on whether meloxicam is present in human milk, or on the effects on breastfed infants, or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for meloxicam and any potential adverse effects on the breastfed infant from the meloxicam or from the underlying maternal condition. data animal data meloxicam was present in the milk of lactating rats at concentrations higher than those in plasma. infertility females based on the mechanism of action, the use of prostaglandin-mediated nsaids, including meloxicam, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. small studies in women treated with nsaids have also shown a reversible delay in ovulation. consider withdrawal of nsaids, including meloxicam, in women who have difficulties conceiving or who are undergoing investigation of infertility. the safety and effectiveness of meloxicam in pediatric jra patients from 2 to 17 years of age has been evaluated in three clinical trials [ see dosage and administration ( 2.3), adverse reactions ( 6.1) and clinical studies ( 14.2) ]. elderly patients, compared to younger patients, are at greater risk for nsaid-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. if the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [ see warnings and precautions ( 5.1, 5.2, 5.3, 5.6, 5.14) ]. no dose adjustment is necessary in patients with mild to moderate hepatic impairment. patients with severe hepatic impairment have not been adequately studied. since meloxicam is significantly metabolized in the liver and hepatotoxicity may occur, use meloxicam with caution in patients with hepatic impairment [ see warnings and precautions ( 5.3) and clinical pharmacology ( 12.3) ]. no dose adjustment is necessary in patients with mild to moderate renal impairment. patients with severe renal impairment have not been studied. the use of meloxicam in subjects with severe renal impairment is not recommended. in patients on hemodialysis, meloxicam should not exceed 7.5 mg per day. meloxicam is not dialyzable [ see dosage and administration ( 2.1) and clinical pharmacology ( 12.3) ].

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

remedyrepack inc. - meloxicam (unii: vg2qf83cgl) (meloxicam - unii:vg2qf83cgl) - meloxicam is indicated for relief of the signs and symptoms of osteoarthritis [ see clinical studies (14.1)]. meloxicam is indicated for relief of the signs and symptoms of rheumatoid arthritis [ see clinical studies (14.1) ]. meloxicam is indicated for relief of the signs and symptoms of pauciarticular or polyarticular course juvenile rheumatoid arthritis in patients who weighs ≥ 60 kg [ see dosage and administration ( 2.4) and clinical studies (14.2)]. meloxicam is contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to meloxicam or any components of the drug product [ see warnings and precautions ( 5.7, 5.9) ] - history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other nsaids. severe, sometimes fatal, anaphylactic reactions to nsaids have been reported in such patients [ see warnings and precautions ( 5.7, 5.8) ] - in the setting of coronary artery bypass graft (cabg) surgery [ see warnings and precautions ( 5.1) ] risk summary use of nsaids, including meloxicam, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. because of these risks, limit dose and duration of meloxicam use between about 20 and 30 weeks of gestation, and avoid meloxicam use at about 30 weeks of gestation and later in pregnancy ( see   clinical considerations, data ). premature closure of fetal ductus arteriosus use of nsaids, including meloxicam, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment use of nsaids at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. data from observational studies regarding potential embryofetal risks of nsaid use in women in the first or second trimesters of pregnancy are inconclusive. in animal reproduction studies, embryofetal death was observed in rats and rabbits treated during the period of organogenesis with meloxicam at oral doses equivalent to 0.65- and 6.5-times the maximum recommended human dose (mrhd) of meloxicam. increased incidence of septal heart defects were observed in rabbits treated throughout embryogenesis with meloxicam at an oral dose equivalent to 78-times the mrhd. in pre- and post-natal reproduction studies, there was an increased incidence of dystocia, delayed parturition, and decreased offspring survival at 0.08-times mrhd of meloxicam. no teratogenic effects were observed in rats and rabbits treated with meloxicam during organogenesis at an oral dose equivalent to 2.6 and 26-times the mrhd [see data] . based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. in animal studies, administration of prostaglandin synthesis inhibitors such as meloxicam, resulted in increased pre- and post-implantation loss. prostaglandins also have been shown to have an important role in fetal kidney development. in published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. the estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations fetal/neonatal adverse reactions premature closure of fetal ductus arteriosus: avoid use of nsaids in women at about 30 weeks gestation and later in pregnancy, because nsaids, including meloxicam, can cause premature closure of the fetal ductus arteriosus ( see data ). oligohydramnios/neonatal renal impairment: if an nsaid is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. if meloxicam treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. if oligohydramnios occurs, discontinue meloxicam and follow up according to clinical practice ( see data ). labor or delivery there are no studies on the effects of meloxicam during labor or delivery. in animal studies, nsaids, including meloxicam, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. data human data premature closure of fetal ductus arteriosus: published literature reports that the use of nsaids at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment: published studies and postmarketing reports describe maternal nsaid use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. these adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after nsaid initiation. in many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. there have been a limited number of case reports of maternal nsaid use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. these limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal nsaid use. because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to nsaids through maternal use is uncertain. animal data meloxicam was not teratogenic when administered to pregnant rats during fetal organogenesis at oral doses up to 4 mg/kg/day (2.6-fold greater than the mrhd of 15 mg of meloxicam based on bsa comparison). administration of meloxicam to pregnant rabbits throughout embryogenesis produced an increased incidence of septal defects of the heart at an oral dose of 60 mg/kg/day (78-fold greater than the mrhd based on bsa comparison). the no effect level was 20 mg/kg/day (26-fold greater than the mrhd based on bsa conversion). in rats and rabbits, embryolethality occurred at oral meloxicam doses of 1 mg/kg/day and 5 mg/kg/day, respectively (0.65- and 6.5-fold greater, respectively, than the mrhd based on bsa comparison) when administered throughout organogenesis. oral administration of meloxicam to pregnant rats during late gestation through lactation increased the incidence of dystocia, delayed parturition, and decreased offspring survival at meloxicam doses of 0.125 mg/kg/day or greater (0.08-times mrhd based on bsa comparison). risk summary there are no human data available on whether meloxicam is present in human milk, or on the effects on breastfed infants, or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for meloxicam and any potential adverse effects on the breastfed infant from the meloxicam or from the underlying maternal condition. data animal data meloxicam was present in the milk of lactating rats at concentrations higher than those in plasma. infertility females based on the mechanism of action, the use of prostaglandin-mediated nsaids, including meloxicam, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. small studies in women treated with nsaids have also shown a reversible delay in ovulation. consider withdrawal of nsaids, including meloxicam, in women who have difficulties conceiving or who are undergoing investigation of infertility. the safety and effectiveness of meloxicam in pediatric jra patients from 2 to 17 years of age has been evaluated in three clinical trials [ see dosage and administration ( 2.3), adverse reactions ( 6.1) and clinical studies ( 14.2) ]. elderly patients, compared to younger patients, are at greater risk for nsaid-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. if the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [ see warnings and precautions ( 5.1, 5.2, 5.3, 5.6, 5.14) ]. no dose adjustment is necessary in patients with mild to moderate hepatic impairment. patients with severe hepatic impairment have not been adequately studied. since meloxicam is significantly metabolized in the liver and hepatotoxicity may occur, use meloxicam with caution in patients with hepatic impairment [ see warnings and precautions ( 5.3) and clinical pharmacology ( 12.3) ]. no dose adjustment is necessary in patients with mild to moderate renal impairment. patients with severe renal impairment have not been studied. the use of meloxicam in subjects with severe renal impairment is not recommended. in patients on hemodialysis, meloxicam should not exceed 7.5 mg per day. meloxicam is not dialyzable [ see dosage and administration ( 2.1) and clinical pharmacology ( 12.3) ].

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

remedyrepack inc. - meloxicam (unii: vg2qf83cgl) (meloxicam - unii:vg2qf83cgl) - meloxicam tablets are indicated for relief of the signs and symptoms of osteoarthritis [see clinical studies   ( 14.1) ]. meloxicam tablets are indicated for relief of the signs and symptoms of rheumatoid arthritis [see clinical studies   ( 14.1) ]. meloxicam tablets are indicated for relief of the signs and symptoms of pauciarticular or polyarticular course juvenile rheumatoid arthritis in patients who weigh ≥60 kg [ see dosage and administration ( 2.4) and clinical studies ( 14.2) ]. meloxicam is contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to meloxicam or any components of the drug product [ see warnings and precautions ( 5.7, 5.9) ] - history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other nsaids. severe, sometimes fatal, anaphylactic reactions to nsaids have been reported in such patients [ see warnings and precautions ( 5.7, 5.8) ] - in the setting of coronary artery bypass graft (cabg) surgery [ see warnings and precautions ( 5.1) ] risk summary   use of nsaids, including meloxicam, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. because of these risks, limit dose and duration of meloxicam use between about 20 and 30 weeks of gestation, and avoid meloxicam use at about 30 weeks of gestation and later in pregnancy (see clinical considerations, data). premature closure of fetal ductus arteriosus use of nsaids, including meloxicam, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment use of nsaids at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. data from observational studies regarding potential embryofetal risks of nsaid use in women in the first or second trimesters of pregnancy are inconclusive. in animal reproduction studies, embryofetal death was observed in rats and rabbits treated during the period of organogenesis with meloxicam at oral doses equivalent to 0.65- and 6.5-times the maximum recommended human dose (mrhd) of meloxicam. increased incidence of septal heart defects were observed in rabbits treated throughout embryogenesis with meloxicam at an oral dose equivalent to 78-times the mrhd. in pre- and post-natal reproduction studies, there was an increased incidence of dystocia, delayed parturition, and decreased offspring survival at 0.08-times mrhd of meloxicam. no teratogenic effects were observed in rats and rabbits treated with meloxicam during organogenesis at an oral dose equivalent to 2.6 and 26-times the mrhd [see data] . based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. in animal studies, administration of prostaglandin synthesis inhibitors, such as meloxicam, resulted in increased pre- and post-implantation loss. prostaglandins also have been shown to have an important role in fetal kidney development. in published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. the estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations fetal/neonatal adverse reactions premature closure of fetal ductus arteriosus: avoid use of nsaids in women at about 30 weeks gestation and later in pregnancy, because nsaids, including meloxicam, can cause premature closure of the fetal ductus arteriosus (see data). oligohydramnios/neonatal renal impairment: if an nsaid is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. if meloxicam treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. if oligohydramnios occurs, discontinue meloxicam and follow up according to clinical practice (see data). labor or delivery there are no studies on the effects of meloxicam during labor or delivery. in animal studies, nsaids, including meloxicam, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth.   data human data premature closure of fetal ductus arteriosus: published literature reports that the use of nsaids at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment: published studies and postmarketing reports describe maternal nsaid use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. these adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after nsaid initiation. in many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. there have been a limited number of case reports of maternal nsaid use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. these limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal nsaid use. because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to nsaids through maternal use is uncertain. animal data meloxicam was not teratogenic when administered to pregnant rats during fetal organogenesis at oral doses up to 4 mg/kg/day (2.6-fold greater than the mrhd of 15 mg of meloxicam based on bsa comparison). administration of meloxicam to pregnant rabbits throughout embryogenesis produced an increased incidence of septal defects of the heart at an oral dose of 60 mg/kg/day (78-fold greater than the mrhd based on bsa comparison). the no effect level was 20 mg/kg/day (26-fold greater than the mrhd based on bsa conversion). in rats and rabbits, embryolethality occurred at oral meloxicam doses of 1 mg/kg/day and 5 mg/kg/day, respectively (0.65and 6.5-fold greater, respectively, than the mrhd based on bsa comparison) when administered throughout organogenesis. oral administration of meloxicam to pregnant rats during late gestation through lactation increased the incidence of dystocia, delayed parturition, and decreased offspring survival at meloxicam doses of 0.125 mg/kg/day or greater (0.08-times mrhd based on bsa comparison). risk summary there are no human data available on whether meloxicam is present in human milk, or on the effects on breastfed infants, or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for meloxicam and any potential adverse effects on the breastfed infant from the meloxicam or from the underlying maternal condition. data animal data meloxicam was present in the milk of lactating rats at concentrations higher than those in plasma. infertility females based on the mechanism of action, the use of prostaglandin-mediated nsaids, including meloxicam, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. small studies in women treated with nsaids have also shown a reversible delay in ovulation. consider withdrawal of nsaids, including meloxicam, in women who have difficulties conceiving or who are undergoing investigation of infertility. the safety and effectiveness of meloxicam in pediatric jra patients from 2 to 17 years of age has been evaluated in three clinical trials [see dosage and administration ( 2.3), adverse reactions ( 6.1) and clinical studies ( 14.2)]. elderly patients, compared to younger patients, are at greater risk for nsaid associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. if the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [ see warnings and precautions ( 5.1, 5.2, 5.3, 5.6, 5.14) ]. no dose adjustment is necessary in patients with mild to moderate hepatic impairment. patients with severe hepatic impairment have not been adequately studied. since meloxicam is significantly metabolized in the liver and hepatotoxicity may occur, use meloxicam with caution in patients with hepatic impairment [ see warnings and precautions ( 5.3) and clinical pharmacology ( 12.3) ]. no dose adjustment is necessary in patients with mild to moderate renal impairment. patients with severe renal impairment have not been studied. the use of meloxicam in subjects with severe renal impairment is not recommended. in patients on hemodialysis, meloxicam should not exceed 7.5 mg per day. meloxicam is not dialyzable [ see dosage and administration ( 2.1) and clinical pharmacology ( 12.3) ].

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

remedyrepack inc. - meloxicam (unii: vg2qf83cgl) (meloxicam - unii:vg2qf83cgl) - meloxicam is indicated for relief of the signs and symptoms of osteoarthritis [ see clinical studies (14.1)]. meloxicam is indicated for relief of the signs and symptoms of rheumatoid arthritis [ see clinical studies (14.1) ]. meloxicam is indicated for relief of the signs and symptoms of pauciarticular or polyarticular course juvenile rheumatoid arthritis in patients who weighs ≥ 60 kg [ see dosage and administration ( 2.4) and clinical studies (14.2)]. meloxicam is contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to meloxicam or any components of the drug product [ see warnings and precautions ( 5.7, 5.9) ] - history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other nsaids. severe, sometimes fatal, anaphylactic reactions to nsaids have been reported in such patients [ see warnings and precautions ( 5.7, 5.8) ] - in the setting of coronary artery bypass graft (cabg) surgery [ see warnings and precautions ( 5.1) ] risk summary use of nsaids, including meloxicam, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. because of these risks, limit dose and duration of meloxicam use between about 20 and 30 weeks of gestation, and avoid meloxicam use at about 30 weeks of gestation and later in pregnancy ( see   clinical considerations, data ). premature closure of fetal ductus arteriosus use of nsaids, including meloxicam, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment use of nsaids at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. data from observational studies regarding potential embryofetal risks of nsaid use in women in the first or second trimesters of pregnancy are inconclusive. in animal reproduction studies, embryofetal death was observed in rats and rabbits treated during the period of organogenesis with meloxicam at oral doses equivalent to 0.65- and 6.5-times the maximum recommended human dose (mrhd) of meloxicam. increased incidence of septal heart defects were observed in rabbits treated throughout embryogenesis with meloxicam at an oral dose equivalent to 78-times the mrhd. in pre- and post-natal reproduction studies, there was an increased incidence of dystocia, delayed parturition, and decreased offspring survival at 0.08-times mrhd of meloxicam. no teratogenic effects were observed in rats and rabbits treated with meloxicam during organogenesis at an oral dose equivalent to 2.6 and 26-times the mrhd [see data] . based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. in animal studies, administration of prostaglandin synthesis inhibitors such as meloxicam, resulted in increased pre- and post-implantation loss. prostaglandins also have been shown to have an important role in fetal kidney development. in published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. the estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations fetal/neonatal adverse reactions premature closure of fetal ductus arteriosus: avoid use of nsaids in women at about 30 weeks gestation and later in pregnancy, because nsaids, including meloxicam, can cause premature closure of the fetal ductus arteriosus ( see data ). oligohydramnios/neonatal renal impairment: if an nsaid is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. if meloxicam treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. if oligohydramnios occurs, discontinue meloxicam and follow up according to clinical practice ( see data ). labor or delivery there are no studies on the effects of meloxicam during labor or delivery. in animal studies, nsaids, including meloxicam, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. data human data premature closure of fetal ductus arteriosus: published literature reports that the use of nsaids at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment: published studies and postmarketing reports describe maternal nsaid use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. these adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after nsaid initiation. in many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. there have been a limited number of case reports of maternal nsaid use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. these limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal nsaid use. because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to nsaids through maternal use is uncertain. animal data meloxicam was not teratogenic when administered to pregnant rats during fetal organogenesis at oral doses up to 4 mg/kg/day (2.6-fold greater than the mrhd of 15 mg of meloxicam based on bsa comparison). administration of meloxicam to pregnant rabbits throughout embryogenesis produced an increased incidence of septal defects of the heart at an oral dose of 60 mg/kg/day (78-fold greater than the mrhd based on bsa comparison). the no effect level was 20 mg/kg/day (26-fold greater than the mrhd based on bsa conversion). in rats and rabbits, embryolethality occurred at oral meloxicam doses of 1 mg/kg/day and 5 mg/kg/day, respectively (0.65- and 6.5-fold greater, respectively, than the mrhd based on bsa comparison) when administered throughout organogenesis. oral administration of meloxicam to pregnant rats during late gestation through lactation increased the incidence of dystocia, delayed parturition, and decreased offspring survival at meloxicam doses of 0.125 mg/kg/day or greater (0.08-times mrhd based on bsa comparison). risk summary there are no human data available on whether meloxicam is present in human milk, or on the effects on breastfed infants, or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for meloxicam and any potential adverse effects on the breastfed infant from the meloxicam or from the underlying maternal condition. data animal data meloxicam was present in the milk of lactating rats at concentrations higher than those in plasma. infertility females based on the mechanism of action, the use of prostaglandin-mediated nsaids, including meloxicam, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. small studies in women treated with nsaids have also shown a reversible delay in ovulation. consider withdrawal of nsaids, including meloxicam, in women who have difficulties conceiving or who are undergoing investigation of infertility. the safety and effectiveness of meloxicam in pediatric jra patients from 2 to 17 years of age has been evaluated in three clinical trials [ see dosage and administration ( 2.3), adverse reactions ( 6.1) and clinical studies ( 14.2) ]. elderly patients, compared to younger patients, are at greater risk for nsaid-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. if the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [ see warnings and precautions ( 5.1, 5.2, 5.3, 5.6, 5.14) ]. no dose adjustment is necessary in patients with mild to moderate hepatic impairment. patients with severe hepatic impairment have not been adequately studied. since meloxicam is significantly metabolized in the liver and hepatotoxicity may occur, use meloxicam with caution in patients with hepatic impairment [ see warnings and precautions ( 5.3) and clinical pharmacology ( 12.3) ]. no dose adjustment is necessary in patients with mild to moderate renal impairment. patients with severe renal impairment have not been studied. the use of meloxicam in subjects with severe renal impairment is not recommended. in patients on hemodialysis, meloxicam should not exceed 7.5 mg per day. meloxicam is not dialyzable [ see dosage and administration ( 2.1) and clinical pharmacology ( 12.3) ].

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

remedyrepack inc. - meloxicam (unii: vg2qf83cgl) (meloxicam - unii:vg2qf83cgl) - meloxicam is indicated for relief of the signs and symptoms of osteoarthritis [ see clinical studies (14.1)]. meloxicam is indicated for relief of the signs and symptoms of rheumatoid arthritis [ see clinical studies (14.1) ]. meloxicam is indicated for relief of the signs and symptoms of pauciarticular or polyarticular course juvenile rheumatoid arthritis in patients who weighs ≥ 60 kg [ see dosage and administration ( 2.4) and clinical studies (14.2)]. meloxicam is contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to meloxicam or any components of the drug product [ see warnings and precautions ( 5.7, 5.9) ] - history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other nsaids. severe, sometimes fatal, anaphylactic reactions to nsaids have been reported in such patients [ see warnings and precautions ( 5.7, 5.8) ] - in the setting of coronary artery bypass graft (cabg) surgery [ see warnings and precautions ( 5.1) ] risk summary use of nsaids, including meloxicam, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. because of these risks, limit dose and duration of meloxicam use between about 20 and 30 weeks of gestation, and avoid meloxicam use at about 30 weeks of gestation and later in pregnancy ( see   clinical considerations, data ). premature closure of fetal ductus arteriosus use of nsaids, including meloxicam, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment use of nsaids at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. data from observational studies regarding potential embryofetal risks of nsaid use in women in the first or second trimesters of pregnancy are inconclusive. in animal reproduction studies, embryofetal death was observed in rats and rabbits treated during the period of organogenesis with meloxicam at oral doses equivalent to 0.65- and 6.5-times the maximum recommended human dose (mrhd) of meloxicam. increased incidence of septal heart defects were observed in rabbits treated throughout embryogenesis with meloxicam at an oral dose equivalent to 78-times the mrhd. in pre- and post-natal reproduction studies, there was an increased incidence of dystocia, delayed parturition, and decreased offspring survival at 0.08-times mrhd of meloxicam. no teratogenic effects were observed in rats and rabbits treated with meloxicam during organogenesis at an oral dose equivalent to 2.6 and 26-times the mrhd [see data] . based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. in animal studies, administration of prostaglandin synthesis inhibitors such as meloxicam, resulted in increased pre- and post-implantation loss. prostaglandins also have been shown to have an important role in fetal kidney development. in published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. the estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations fetal/neonatal adverse reactions premature closure of fetal ductus arteriosus: avoid use of nsaids in women at about 30 weeks gestation and later in pregnancy, because nsaids, including meloxicam, can cause premature closure of the fetal ductus arteriosus ( see data ). oligohydramnios/neonatal renal impairment: if an nsaid is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. if meloxicam treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. if oligohydramnios occurs, discontinue meloxicam and follow up according to clinical practice ( see data ). labor or delivery there are no studies on the effects of meloxicam during labor or delivery. in animal studies, nsaids, including meloxicam, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. data human data premature closure of fetal ductus arteriosus: published literature reports that the use of nsaids at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment: published studies and postmarketing reports describe maternal nsaid use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. these adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after nsaid initiation. in many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. there have been a limited number of case reports of maternal nsaid use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. these limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal nsaid use. because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to nsaids through maternal use is uncertain. animal data meloxicam was not teratogenic when administered to pregnant rats during fetal organogenesis at oral doses up to 4 mg/kg/day (2.6-fold greater than the mrhd of 15 mg of meloxicam based on bsa comparison). administration of meloxicam to pregnant rabbits throughout embryogenesis produced an increased incidence of septal defects of the heart at an oral dose of 60 mg/kg/day (78-fold greater than the mrhd based on bsa comparison). the no effect level was 20 mg/kg/day (26-fold greater than the mrhd based on bsa conversion). in rats and rabbits, embryolethality occurred at oral meloxicam doses of 1 mg/kg/day and 5 mg/kg/day, respectively (0.65- and 6.5-fold greater, respectively, than the mrhd based on bsa comparison) when administered throughout organogenesis. oral administration of meloxicam to pregnant rats during late gestation through lactation increased the incidence of dystocia, delayed parturition, and decreased offspring survival at meloxicam doses of 0.125 mg/kg/day or greater (0.08-times mrhd based on bsa comparison). risk summary there are no human data available on whether meloxicam is present in human milk, or on the effects on breastfed infants, or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for meloxicam and any potential adverse effects on the breastfed infant from the meloxicam or from the underlying maternal condition. data animal data meloxicam was present in the milk of lactating rats at concentrations higher than those in plasma. infertility females based on the mechanism of action, the use of prostaglandin-mediated nsaids, including meloxicam, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. small studies in women treated with nsaids have also shown a reversible delay in ovulation. consider withdrawal of nsaids, including meloxicam, in women who have difficulties conceiving or who are undergoing investigation of infertility. the safety and effectiveness of meloxicam in pediatric jra patients from 2 to 17 years of age has been evaluated in three clinical trials [ see dosage and administration ( 2.3), adverse reactions ( 6.1) and clinical studies ( 14.2) ]. elderly patients, compared to younger patients, are at greater risk for nsaid-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. if the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [ see warnings and precautions ( 5.1, 5.2, 5.3, 5.6, 5.14) ]. no dose adjustment is necessary in patients with mild to moderate hepatic impairment. patients with severe hepatic impairment have not been adequately studied. since meloxicam is significantly metabolized in the liver and hepatotoxicity may occur, use meloxicam with caution in patients with hepatic impairment [ see warnings and precautions ( 5.3) and clinical pharmacology ( 12.3) ]. no dose adjustment is necessary in patients with mild to moderate renal impairment. patients with severe renal impairment have not been studied. the use of meloxicam in subjects with severe renal impairment is not recommended. in patients on hemodialysis, meloxicam should not exceed 7.5 mg per day. meloxicam is not dialyzable [ see dosage and administration ( 2.1) and clinical pharmacology ( 12.3) ].