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

provepharm inc. - dihydroergotamine mesylate (unii: 81axn7r2qt) (dihydroergotamine - unii:436o5hm03c) - dihydroergotamine mesylate injection, usp is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes. there have been a few reports of serious adverse events associated with the coadministration of dihydroergotamine and potent cyp3a4 inhibitors, such as protease inhibitors and macrolide antibiotics, resulting in vasospasm that led to cerebral ischemia and/or ischemia of the extremities. the use of potent cyp3a4 inhibitors (i.e., ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, troleandomycin, ketoconazole, itraconazole) with dihydroergotamine is, therefore, contraindicated (see warnings, cyp3a4 inhibitors). dihydroergotamine mesylate injection, usp should not be given to patients with ischemic heart disease (e.g., angina pectoris, history of myocardial infarction, or documented silent ischemia) or to patients who have clinical symptoms or findings consistent with coronary artery vasospasm including prinzmetal's variant an

European Union - English - EMA (European Medicines Agency)

provepharm sas - methylthioninium chloride - methemoglobinemia - all other therapeutic products - acute symptomatic treatment of medicinal and chemical products- induced methaemoglobinaemia.methylthioninium chloride proveblue is indicated in adults, children and adolescents (aged 0 to 17 years old).

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

provepharm inc. - penicillin g benzathine (unii: rit82f58gk) (penicillin g - unii:q42t66vg0c) -

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

provepharm inc. - indigotindisulfonate sodium (unii: d3741u8k7l) (indigotindisulfonic acid - unii:x7oi7jf73p) - bludigo is indicated for use as a visualization aid in the cystoscopic assessment of the integrity of the ureters in adults following urological and gynecological open, robotic, or endoscopic surgical procedures. bludigo is contraindicated in patients with known hypersensitivity to indigotindisulfonate or any of its components [see warnings and precautions (5.2)]. risk summary available data from case reports, case series, observational studies and clinical experience with indigotindisulfonate sodium injection use in pregnant women over several decades have not identified a drug associated risk of adverse maternal and fetal adverse effects. indigotindisulfonate sodium injection use during the first trimester of pregnancy is rare; thus, the data are insufficient to evaluate for a drug associated risk of major birth defects and miscarriage. the majority of the published data were from intra-amniotic injections. animal reproduction studies using the intravenous route of administration have not been conducted.

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

provepharm inc. - phenylephrine hydrochloride (unii: 04ja59tnsj) (phenylephrine - unii:1ws297w6mv) - phenylephrine hydrochloride injection, 10 mg/ml is indicated for the treatment of clinically important hypotension resulting primarily from vasodilation in the setting of anesthesia. none risk summary data from randomized controlled trials and meta-analyses with phenylephrine hydrochloride injection use in pregnant women during cesarean section have not established a drug-associated risk of major birth defects and miscarriage. these studies have not identified an adverse effect on maternal outcomes or infant apgar scores [see data ]. there are no data on the use of phenylephrine during the first or second trimester. in animal reproduction and development studies in normotensive animals, evidence of fetal malformations was noted when phenylephrine was administered during organogenesis via a 1-hour infusion at 1.2 times the human daily dose (hdd) of 10 mg/60 kg/day. decreased pup weights were noted in offspring of pregnant rats treated with 2.9 times the hdd [see data ]. the estimated background risk of ma

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

provepharm inc. - tranexamic acid (unii: 6t84r30kc1) (tranexamic acid - unii:6t84r30kc1) - tranexamic acid injection is indicated in patients with hemophilia for short-term use (2 to 8 days) to reduce or prevent hemorrhage and reduce the need for replacement therapy during and following tooth extraction. tranexamic acid injection is contraindicated: - in patients with subarachnoid hemorrhage. anecdotal experience indicates that cerebral edema and cerebral infarction may be caused by tranexamic acid injection in such patients. - in patients with active intravascular clotting [see warnings and precautions (5.1)] . - in patients with hypersensitivity to tranexamic acid or any of the ingredients [ see warnings and precautions (5.4)] . risk summary available data from published studies, case series and case reports with tranexamic acid use in pregnant women in the second and third trimester and at the time of delivery have not clarified whether there is a drug-associated risk of miscarriage or adverse maternal or fetal outcomes. there are 2 (0.02%) infant cases with structural abnormalities that resulted in death when tranexamic acid was used during conception or the first trimester of pregnancy; however, due to other confounding factors the risk of major birth defects with use of tranexamic acid during pregnancy is not clear. tranexamic acid is known to pass the placenta and appears in cord blood at concentrations approximately equal to maternal concentration (see data) . reproduction studies performed in mice, rats, and rabbits have not revealed any adverse effects on the fetus due to tranexamic acid administered during organogenesis. doses examined were multiples of up to 3 times (mouse), 6 times (rat), and 3 times (rabbit) the maximum human dose based on body surface area in the mouse, rat, and rabbit, respectively (see data) . the estimated background risk for 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 the clinically recognized pregnancies is 2–4% and 15–20%, respectively. it is not known whether tranexamic acid use in pregnant women may cause a drug-associated risk of miscarriage or adverse maternal or fetal outcomes. for decisions regarding the use of tranexamic acid during pregnancy, the potential risk of tranexamic acid  administration on the fetus should always be considered along with the mother's clinical need for tranexamic acid ; an accurate risk-benefit evaluation should drive the treating physician's decision. data human data tranexamic acid passes through the placenta. the concentration in cord blood after an intravenous injection of 10 mg/kg to pregnant women is about 30 mg/l, as high as in the maternal blood. there were 13 clinical studies that described fetal and/or neonatal functional issues such as low apgar score, neonatal sepsis, cephalohematoma and 9 clinical studies that discussed alterations to growth including low birth weight and preterm birth at 22–36 weeks of gestation in fetuses and infants exposed to tranexamic acid in-utero. animal data in embryo-fetal development studies, tranexamic acid was administered to pregnant mice from gestation day (gd) 6 through gd 12 and rats from gd 9 through gd 14 at daily doses of 0.3 or 1.5 g/kg. there was no evidence of adverse developmental outcomes in mice and rats at multiple of 3 and 6 times the maximum recommended human dose based on body surface area in the mouse and rat, respectively. in rabbits, tranexamic acid was administered intravenously at doses of 50, 100, or 200 mg/kg/day or orally at doses of 100, 200, or 400 mg/kg/day from gd 6 through gd 18. there was no evidence of adverse developmental outcomes at dose multiples of 2 or 3 times, respectively, the maximum recommended human dose based on body surface area. intravenous doses of 200 mg/kg/day showed slightly retarded weight gain in pregnant rabbits. risk summary published literature reports the presence of tranexamic acid in human milk. there are no data on the effects of tranexamic acid on the breastfed child or the effects on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for tranexamic acid injection and any potential adverse effects on the breastfed child from tranexamic acid injection or from the underlying maternal condition. contraception concomitant use of tranexamic acid , which is an antifibrinolytic, with hormonal contraceptives may increase the risk for thromboembolic adverse reactions. advise patients to use an effective alternative (nonhormonal) contraceptive method [see warnings and precautions (5.1), drug interactions (7.1)] . there are limited data concerning the use of tranexamic acid injection in pediatric patients with hemophilia who are undergoing tooth extraction. the limited data suggest that there are no significant pharmacokinetic differences between adults and pediatric patients. clinical studies of tranexamic acid injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see dosage and administration (2.2), clinical pharmacology (12.3)] . reduce the dosage of tranexamic acid injection in patients with renal impairment, based on the patient's serum creatinine [see dosage and administration (2.2), clinical pharmacology (12.3)] .

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

provepharm inc. - piperacillin sodium (unii: m98t69q7hp) (piperacillin anhydrous - unii:9i628532gx), tazobactam sodium (unii: uxa545abtt) (tazobactam - unii:se10g96m8w) - piperacillin and tazobactam for injection is indicated in adults and pediatric patients (2 months of age and older) for the treatment of appendicitis (complicated by rupture or abscess) and peritonitis caused by beta-lactamase producing isolates of escherichia coli or the following members of the bacteroides fragilis group: b. fragilis , b. ovatus , b. thetaiotaomicron , or b. vulgatus . piperacillin and tazobactam for injection is indicated in adults and pediatric patients (2 months of age and older) for the treatment of nosocomial pneumonia (moderate to severe) caused by beta lactamase producing isolates of staphylococcus aureus and by piperacillin/tazobactam-susceptible acinetobacter baumannii , haemophilus influenzae , klebsiella pneumoniae , and pseudomonas aeruginosa (nosocomial pneumonia caused by p. aeruginosa should be treated in combination with an aminoglycoside) [see dosage and administration (2)] . piperacillin and tazobactam for injection is indicated in adults for the treatment of uncomplicated and complicated skin and skin structure infections, including cellulitis, cutaneous abscesses and ischemic/diabetic foot infections caused by beta-lactamase producing isolates of staphylococcus aureus . piperacillin and tazobactam for injection is indicated in adults for the treatment of postpartum endometritis or pelvic inflammatory disease caused by beta-lactamase producing isolates of escherichia coli . piperacillin and tazobactam for injection is indicated in adults for the treatment of community-acquired pneumonia (moderate severity only) caused by beta-lactamase producing isolates of haemophilus influenzae . to reduce the development of drug-resistant bacteria and maintain the effectiveness of piperacillin and tazobactam for injection and other antibacterial drugs, piperacillin and tazobactam for injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by 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. piperacillin and tazobactam for injection is contraindicated in patients with a history of allergic reactions to any of the penicillins, cephalosporins, or beta-lactamase inhibitors. risk summary piperacillin and tazobactam cross the placenta in humans. however, there are insufficient data with piperacillin and/or tazobactam in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. no fetal structural abnormalities were observed in rats or mice when piperacillin/tazobactam was administered intravenously during organogenesis at doses 1 to 2 times and 2 to 3 times the human dose of piperacillin and tazobactam, respectively, based on body-surface area (mg/m2 ). however, fetotoxicity in the presence of maternal toxicity was observed in developmental toxicity and peri/postnatal studies conducted in rats (intraperitoneal administration prior to mating and throughout gestation or from gestation day 17 through lactation day 21) at doses less than the maximum recommended human daily dose based on body-surface area (mg/m2 ) [see data ]. the background risk of major 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 in embryo-fetal development studies in mice and rats, pregnant animals received intravenous doses of piperacillin/tazobactam up to 3000/750 mg/kg/day during the period of organogenesis. there was no evidence of teratogenicity up to the highest dose evaluated, which is 1 to 2 times and 2 to 3 times the human dose of piperacillin and tazobactam, in mice and rats respectively, based on body-surface area (mg/m2 ). fetal body weights were reduced in rats at maternally toxic doses at or above 500/62.5 mg/kg/day, minimally representing 0.4 times the human dose of both piperacillin and tazobactam based on body-surface area (mg/m2 ). a fertility and general reproduction study in rats using intraperitoneal administration of tazobactam or the combination piperacillin/tazobactam prior to mating and through the end of gestation, reported a decrease in litter size in the presence of maternal toxicity at 640 mg/kg/day tazobactam (4 times the human dose of tazobactam based on body-surface area), and decreased litter size and an increase in fetuses with ossification delays and variations of ribs, concurrent with maternal toxicity at ≥640/160 mg/kg/day piperacillin/tazobactam (0.5 times and 1 times the human dose of piperacillin and tazobactam, respectively, based on body-surface area). peri/postnatal development in rats was impaired with reduced pup weights, increased stillbirths, and increased pup mortality concurrent with maternal toxicity after intraperitoneal administration of tazobactam alone at doses ≥320 mg/kg/day (2 times the human dose based on body surface area) or of the combination piperacillin/tazobactam at doses ≥640/160 mg/kg/day (0.5 times and 1 times the human dose of piperacillin and tazobactam, respectively, based on body-surface area) from gestation day 17 through lactation day 21. risk summary piperacillin is excreted in human milk; tazobactam concentrations in human milk have not been studied. no information is available on the effects of piperacillin and tazobactam on the breastfed child or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for piperacillin and tazobactam for injection and any potential adverse effects on the breastfed child from piperacillin and tazobactam for injection or from the underlying maternal condition. the safety and effectiveness of piperacillin and tazobactam for injection for intra-abdominal infections, and nosocomial pneumonia have been established in pediatric patients 2 months of age and older. use of piperacillin and tazobactam for injection in pediatric patients 2 months of age and older with intra-abdominal infections including appendicitis and/or peritonitis is supported by evidence from well-controlled studies and pharmacokinetic studies in adults and in pediatric patients. this includes a prospective, randomized, comparative, open-label clinical trial with 542 pediatric patients 2 to 12 years of age with intra-abdominal infections (including appendicitis and/or peritonitis), in which 273 pediatric patients received piperacillin/tazobactam [ see adverse reactions (6.1) and clinical pharmacology (12.3)] . use of piperacillin and tazobactam for injection in pediatric patients 2 months of age and older with nosocomial pneumonia is supported by evidence from well-controlled studies in adults with nosocomial pneumonia, a simulation study performed with a population pharmacokinetic model, and a retrospective, cohort study of pediatric patients with nosocomial pneumonia in which 140 pediatric patients were treated with piperacillin and tazobactam for injection and 267 patients treated with comparators (which included ticarcillin-clavulanate, carbapenems, ceftazidime, cefepime, or ciprofloxacin) [ see adverse reactions (6.1) and clinical pharmacology (12.3) ] . the safety and effectiveness of piperacillin and tazobactam for injection have not been established in pediatric patients less than 2 months of age [ see clinical pharmacology (12) and dosage and administration (2) ] . dosage of piperacillin and tazobactam for injection in pediatric patients with renal impairment has not been determined. patients over 65 years are not at an increased risk of developing adverse effects solely because of age. however, dosage should be adjusted in the presence of renal impairment [ see dosage and administration (2) ] . in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. piperacillin and tazobactam for injection contains 65 mg (2.84 meq) of sodium per gram of piperacillin in the combination product. at the usual recommended doses, patients would receive between 780 and 1040 mg/day (34.1 and 45.5 meq) of sodium. the geriatric population may respond with a blunted natriuresis to salt loading. this may be clinically important with regard to such diseases as congestive heart failure. this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. in patients with creatinine clearance ≤ 40 ml/min and dialysis patients (hemodialysis and capd), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of renal function impairment [ see dosage and administration (2) ] . dosage adjustment of piperacillin and tazobactam for injection is not warranted in patients with hepatic cirrhosis [ see clinical pharmacology (12.3) ] . as with other semisynthetic penicillins, piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.

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

provepharm inc. - piperacillin sodium (unii: m98t69q7hp) (piperacillin anhydrous - unii:9i628532gx), tazobactam sodium (unii: uxa545abtt) (tazobactam - unii:se10g96m8w) - piperacillin and tazobactam for injection is indicated in adults and pediatric patients (2 months of age and older) for the treatment of appendicitis (complicated by rupture or abscess) and peritonitis caused by beta-lactamase producing isolates of escherichia coli or the following members of the bacteroides fragilis group: b. fragilis, b. ovatus, b. thetaiotaomicron , or b. vulgatus. piperacillin and tazobactam for injection is indicated in adults and pediatric patients (2 months of age and older) for the treatment of nosocomial pneumonia (moderate to severe) caused by beta lactamase producing isolates of staphylococcus aureus and by piperacillin/tazobactam-susceptible acinetobacter baumannii , haemophilus influenzae , klebsiella pneumoniae , and pseudomonas aeruginosa (nosocomial pneumonia caused by p. aeruginosa should be treated in combination with an aminoglycoside) [ see dosage and administration (2) ] . piperacillin and tazobactam for injection is indicated in adults for the treatment of uncomplicated and complicated skin and skin structure infections, including cellulitis, cutaneous abscesses and ischemic/diabetic foot infections caused by beta-lactamase producing isolates of staphylococcus aureus . piperacillin and tazobactam for injection is indicated in adults for the treatment of postpartum endometritis or pelvic inflammatory disease caused by beta-lactamase producing isolates of escherichia coli . piperacillin and tazobactam for injection is indicated in adults for the treatment of community-acquired pneumonia (moderate severity only) caused by beta-lactamase producing isolates of haemophilus influenzae . to reduce the development of drug-resistant bacteria and maintain the effectiveness of piperacillin and tazobactam for injection and other antibacterial drugs, piperacillin and tazobactam for injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by 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. piperacillin and tazobactam for injection is contraindicated in patients with a history of allergic reactions to any of the penicillins, cephalosporins, or beta-lactamase inhibitors. risk summary piperacillin and tazobactam cross the placenta in humans. however, there are insufficient data with piperacillin and/or tazobactam in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. no fetal structural abnormalities were observed in rats or mice when piperacillin/tazobactam was administered intravenously during organogenesis at doses 1 to 2 times and 2 to 3 times the human dose of piperacillin and tazobactam, respectively, based on body-surface area (mg/m2 ). however, fetotoxicity in the presence of maternal toxicity was observed in developmental toxicity and peri/postnatal studies conducted in rats (intraperitoneal administration prior to mating and throughout gestation or from gestation day 17 through lactation day 21) at doses less than the maximum recommended human daily dose based on body-surface area (mg/m2 ) [see data] . the background risk of major 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 in embryo-fetal development studies in mice and rats, pregnant animals received intravenous doses of piperacillin/tazobactam up to 3000/750 mg/kg/day during the period of organogenesis. there was no evidence of teratogenicity up to the highest dose evaluated, which is 1 to 2 times and 2 to 3 times the human dose of piperacillin and tazobactam, in mice and rats respectively, based on body-surface area (mg/m2 ). fetal body weights were reduced in rats at maternally toxic doses at or above 500/62.5 mg/kg/day, minimally representing 0.4 times the human dose of both piperacillin and tazobactam based on body-surface area (mg/m2 ). a fertility and general reproduction study in rats using intraperitoneal administration of tazobactam or the combination piperacillin/tazobactam prior to mating and through the end of gestation, reported a decrease in litter size in the presence of maternal toxicity at 640 mg/kg/day tazobactam (4 times the human dose of tazobactam based on body-surface area), and decreased litter size and an increase in fetuses with ossification delays and variations of ribs, concurrent with maternal toxicity at ≥640/160 mg/kg/day piperacillin/tazobactam (0.5 times and 1 times the human dose of piperacillin and tazobactam, respectively, based on body-surface area). peri/postnatal development in rats was impaired with reduced pup weights, increased stillbirths, and increased pup mortality concurrent with maternal toxicity after intraperitoneal administration of tazobactam alone at doses ≥320 mg/kg/day (2 times the human dose based on body surface area) or of the combination piperacillin/tazobactam at doses ≥640/160 mg/kg/day (0.5 times and 1 times the human dose of piperacillin and tazobactam, respectively, based on body-surface area) from gestation day 17 through lactation day 21. risk summary piperacillin is excreted in human milk; tazobactam concentrations in human milk have not been studied. no information is available on the effects of piperacillin and tazobactam on the breastfed child or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for piperacillin and tazobactam for injection and any potential adverse effects on the breastfed child from piperacillin and tazobactam for injection or from the underlying maternal condition. the safety and effectiveness of piperacillin and tazobactam for injection for intra-abdominal infections, and nosocomial pneumonia have been established in pediatric patients 2 months of age and older. use of piperacillin and tazobactam for injection in pediatric patients 2 months of age and older with intra-abdominal infections including appendicitis and/or peritonitis is supported by evidence from well-controlled studies and pharmacokinetic studies in adults and in pediatric patients. this includes a prospective, randomized, comparative, open-label clinical trial with 542 pediatric patients 2 to 12 years of age with intra-abdominal infections (including appendicitis and/or peritonitis), in which 273 pediatric patients received piperacillin/tazobactam [ see adverse reactions (6.1) and  clinical pharmacology (12.3) ] . use of piperacillin and tazobactam for injection in pediatric patients 2 months of age and older with nosocomial pneumonia is supported by evidence from well-controlled studies in adults with nosocomial pneumonia, a simulation study performed with a population pharmacokinetic model, and a retrospective, cohort study of pediatric patients with nosocomial pneumonia in which 140 pediatric patients were treated with piperacillin and tazobactam for injection and 267 patients treated with comparators (which included ticarcillin-clavulanate, carbapenems, ceftazidime, cefepime, or ciprofloxacin) [see adverse reactions (6.1) and clinical pharmacology (12.3)] . the safety and effectiveness of piperacillin and tazobactam for injection have not been established in pediatric patients less than 2 months of age [see clinical pharmacology (12) and dosage and administration (2)] . dosage of piperacillin and tazobactam for injection in pediatric patients with renal impairment has not been determined. patients over 65 years are not at an increased risk of developing adverse effects solely because of age. however, dosage should be adjusted in the presence of renal impairment [see dosage and administration (2)] . in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. piperacillin and tazobactam for injection contains 65 mg (2.84 meq) of sodium per gram of piperacillin in the combination product. at the usual recommended doses, patients would receive between 780 and 1040 mg/day (34.1 and 45.5 meq) of sodium. the geriatric population may respond with a blunted natriuresis to salt loading. this may be clinically important with regard to such diseases as congestive heart failure. this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. in patients with creatinine clearance ≤ 40 ml/min and dialysis patients (hemodialysis and capd), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of renal function impairment [see dosage and administration (2)] . dosage adjustment of piperacillin and tazobactam for injection is not warranted in patients with hepatic cirrhosis [see clinical pharmacology (12.3)] . as with other semisynthetic penicillins, piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.