Estados Unidos - inglês - NLM (National Library of Medicine)

apotex corp. - tramadol hydrochloride (unii: 9n7r477wck) (tramadol - unii:39j1lgj30j), acetaminophen (unii: 362o9itl9d) (acetaminophen - unii:362o9itl9d) - tramadol hydrochloride 37.5 mg - tramadol hydrochloride and acetaminophen tablets are indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.   limitations of use tramadol hydrochloride and acetaminophen tablets are indicated for short-term use of five days or less.   because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see warnings and precautions (5.1)] , reserve tramadol hydrochloride and acetaminophen tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics]: - have not been tolerated, or are not expected to be tolerated,  - have not provided adequate analgesia, or are not expected to provide adequate analgesia. tramadol hydrochloride and acetaminophen tablets are contraindicated for: - all children younger than 12 years of age [see warnings and precautions (5.4)]   - post-operative management in children younger than 18 years of age following tonsillectomy and/or adeno

Estados Unidos - inglês - NLM (National Library of Medicine)

apotex corp. - cefazolin sodium (unii: p380m0454z) (cefazolin - unii:ihs69l0y4t) - cefazolin 1 g - cefazolin for injection, usp is indicated in the treatment of the following serious infections due to susceptible organisms: respiratory tract infections: due to s. pneumoniae, klebsiella species , h. influenzae, s. aureus (penicillin-sensitive and penicillin-resistant), and group a beta-hemolytic streptococci . injectable benzathine penicillin is considered to be the drug of choice in treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. cefazolin for injection, usp is effective in the eradication of streptococci from the nasopharynx; however, data establishing the efficacy of cefazolin for injection, usp in the subsequent prevention of rheumatic fever are not available at present. urinary tract infections: due to e. coli, p. mirabilis, klebsiella species, and some strains of enterobacter and enterococci . skin and skin structure infections:  due to s. aureus (penicillin-sensitive and penicillin-resistant), group a beta-hemolytic streptococci, and other strains of streptococci. biliary tract infections: due to e. coli, various strains of streptococci, p. mirabilis,  klebsiella species, and s. aureus. bone and joint infections: due to s. aureus. genital infections: (i.e., prostatitis, epididymitis) due to e. coli, p. mirabilis, klebsiella species, and some strains of enterococci . septicemia:  due to s. pneumoniae, s. aureus (penicillin-sensitive and penicillin-resistant), p. mirabilis, e. coli, and  klebsiella species. endocarditis:  due to s. aureus (penicillin-sensitive and penicillin-resistant) and group a beta-hemolytic streptococci . perioperative prophylaxis: the prophylactic administration of cefazolin for injection, usp preoperatively, intraoperatively, and postoperatively may reduce the incidence of certain postoperative infections in patients undergoing surgical procedures which are classified as contaminated or potentially contaminated (e.g., vaginal hysterectomy, and cholecystectomy in high-risk patients such as those older than 70 years, with acute cholecystitis, obstructive jaundice, or common duct bile stones). the perioperative use of cefazolin for injection, usp may also be effective in surgical patients in whom infection at the operative site would present a serious risk (e.g., during open-heart surgery and prosthetic arthroplasty). the prophylactic administration of cefazolin for injection, usp should usually be discontinued within a 24-hour period after the surgical procedure.  in surgery where the occurrence of infection may be particularly devastating (e.g., open-heart surgery and prosthetic arthroplasty), the prophylactic administration of cefazolin for injection, usp may be continued for 3 to 5 days following the completion of surgery. if there are signs of infection, specimens for cultures should be obtained for the identification of the causative organism so that appropriate therapy may be instituted. (see dosage and administration.) to reduce the development of drug-resistant bacteria and maintain the effectiveness of cefazolin for injection, usp and other antibacterial drugs, cefazolin for injection, usp should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. cefazolin for injection, usp is contraindicated in patients with known allergy to the cephalosporin group of antibiotics.

Estados Unidos - inglês - NLM (National Library of Medicine)

apotex corp - mycophenolate sodium (unii: wx877sqi1g) (mycophenolic acid - unii:hu9dx48n0t) - mycophenolic acid 180 mg - mycophenolic acid are indicated for the prophylaxis of organ rejection in adult patients receiving a kidney transplant.  mycophenolic acid are indicated for the prophylaxis of organ rejection in pediatric patients 5 years of age and older who are at least 6 months post kidney transplant.  mycophenolic acid are to be used in combination with cyclosporine and corticosteroids. mycophenolic acid delayed-release tablets and mycophenolate mofetil (mmf) tablets and capsules should not be used interchangeably without physician supervision because the rate of absorption following the administration of these two products is not equivalent. mycophenolic acid delayed-release tablets are contraindicated in patients with a hypersensitivity to mycophenolate sodium, mycophenolic acid (mpa), mycophenolate mofetil, or to any of its excipients. reactions like rash, pruritus, hypotension, and chest pain have been observed in clinical trials and post marketing reports [see adverse reactions (6) ] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to mycophenolate during pregnancy and those becoming pregnant within 6 weeks of discontinuing mycophenolic acid treatment. to report a pregnancy or obtain information about the registry, visit www.mycophenolaterems.com or call 1-800-617-8191. risk summary following oral or intravenous (iv) administration, mmf is metabolized to mycophenolic acid (mpa), the active ingredient in mycophenolic acid delayed-release tablets and the active form of the drug. use of mmf during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of  multiple congenital malformations in multiple organ systems (see human data) . oral administration of mycophenolate to rats and rabbits during the period of organogenesis produced congenital malformations and pregnancy loss at doses less than the recommended clinical dose (0.05 and 1.1 times exposure at the recommended clinical doses in kidney transplant patients for rats and rabbits, respectively) (see animal data). risks and benefits of mycophenolic acid delayed-release tablets should be discussed with the patient. when appropriate, consider alternative immunosuppressants with less potential for embryo-fetal toxicity. the estimated background risk of pregnancy loss and congenital malformations in organ transplant populations is not clear. 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. data human data a spectrum of congenital malformations (including multiple malformations in individual newborns) has been reported in 23% to 27% of live births in mmf exposed pregnancies, based on published data from pregnancy registries. malformations that have been documented include external ear, eye, and other facial abnormalities, including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system. based on published data from pregnancy registries, the risk of first trimester pregnancy loss has been reported at 45% to 49% following mmf exposure. animal data   in animal reproductive toxicology studies, congenital malformations and pregnancy loss occurred when pregnant rats and rabbits received mycophenolate at dose multiples equivalent to and less than the recommended human dose. oral administration of mycophenolate sodium to pregnant rats from gestational day 7 to day 16 at a dose as low as 1 mg per kg resulted in malformations including anophthalmia, exencephaly, and umbilical hernia. the systemic exposure at this dose represents 0.05 times the clinical exposure at the human dose of 1,440 mg per day mycophenolic acid delayed-release tablets. oral administration of mycophenolate to pregnant rabbits from gestational day 7 to day 19 resulted in embryo-fetal lethality and malformations, including ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical hernia at doses equal to or greater than 80 mg per kg per day, in the absence of maternal toxicity. this corresponds to about 1.1 times the recommended clinical dose based on bsa. risk summary there are no data on the presence of mycophenolate in human milk, or the effects on milk production. there are limited data in the national transplantation pregnancy registry on the effects of mycophenolate on a breastfed child (see data) . studies in rats treated with mmf have shown mycophenolic acid to be present in milk. because available data are limited, it is not possible to exclude potential risks to a breastfeeding infant. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for mycophenolic acid delayed-release tablets and any potential adverse effects on the breastfed infant from mycophenolic acid or from the underlying maternal condition. because available data are limited, it is not possible to exclude potential risks to a breastfeeding infant. data limited information is available from the national transplantation pregnancy registry. of seven infants reported by the national transplantation pregnancy registry to have been breastfed while the mother was taking mycophenolate, all were born at 34 to 40 weeks gestation and breastfed for up to 14 months. no adverse events were reported. females of reproductive potential must be made aware of the increased risk of first trimester pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention and planning.   pregnancy planning for female patients taking mycophenolic acid delayed-release tablets who are considering pregnancy, consider alternative immunosuppressants with less potential for embryo-fetal toxicity. risks and benefits of mycophenolic acid delayed-release tablets should be discussed with the patient.   pregnancy testing to prevent unplanned exposure during pregnancy, females of reproductive potential should have a serum or urine pregnancy test with a sensitivity of at least 25 miu/ml immediately before starting mycophenolic acid delayed-release tablets. another pregnancy test with the same sensitivity should be done 8 to 10 days later. repeat pregnancy tests should be performed during routine follow-up visits. results of all pregnancy tests should be discussed with the patient. in the event of a positive pregnancy test, consider alternative immunosuppressants with less potential for embryo-fetal toxicity whenever possible.   contraception female patients females of reproductive potential taking mycophenolic acid delayed-release tablets must receive contraceptive counseling and use acceptable contraception (see table 5 for acceptable contraception methods). patients must use acceptable birth control during entire mycophenolic acid delayed-release tablets therapy, and for 6 weeks after stopping mycophenolic acid delayed-release tablets, unless the patient chooses abstinence (she chooses to avoid heterosexual intercourse completely). patients should be aware that mycophenolic acid delayed-release tablets reduces blood levels of the hormones in the oral contraceptive pill and could theoretically reduce its effectiveness [see patient counseling information (17), drug interactions (7.8)]. table 5: acceptable contraception methods for females of reproductive potential pick from the following birth control options: or or male patients genotoxic effects have been observed in animal studies at exposures exceeding the human therapeutic exposures by approximately 2.5 times. thus, the risk of genotoxic effects on sperm cells cannot be excluded. based on this potential risk, sexually active male patients and/or their female partners are recommended to use effective contraception during treatment of the male patient and for at least 90 days after cessation of treatment. also, based on the potential risk of genotoxic effects, male patients should not donate sperm during treatment with mycophenolic acid delayed-release tablets and for at least 90 days after cessation of treatment [see use in specific populations (8.1), nonclinical toxicology (13.1), patient counseling information (17)]. the safety and effectiveness of mycophenolic acid delayed-release tablets have been established in pediatric kidney transplant patients 5 to 16 years of age who were initiated on mycophenolic acid delayed-release tablets at least 6 months post-transplant. use of mycophenolic acid delayed-release tablets in this age group is supported by evidence from adequate and well-controlled studies of mycophenolic acid delayed-release tablets in a similar population of adult kidney transplant patients with additional pharmacokinetic data in pediatric kidney transplant patients [see dosage and administration (2.2, 2.3 ) , clinical pharmacology (12.3) ] . pediatric doses for patients with bsa < 1.19 m2 cannot be accurately administered using currently available formulations of mycophenolic acid delayed-release tablets. the safety and effectiveness of mycophenolic acid delayed-release tablets in de novo pediatric kidney transplant patients and in pediatric kidney transplant patients below the age of 5 years have not been established. clinical studies of mycophenolic acid delayed-release tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. of the 372 patients treated with mycophenolic acid delayed-release tablets in the clinical trials, 6%(n = 21) were 65 years of age and older and 0.3% (n = 1) were 75 years of age and older. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Estados Unidos - inglês - NLM (National Library of Medicine)

apotex corp - trazodone hydrochloride (unii: 6e8zo8lrnm) (trazodone - unii:ybk48bxk30) - trazodone hydrochloride 50 mg - trazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (mdd) in adults. trazodone hydrochloride tablets are contraindicated in: - patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (maois), including maois such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome [see warnings and precautions (5.2), drug interactions (7.1)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for antidepressants at 1-844-405- 6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/ risk summary published prospective cohort studies, case series, and case reports over several decades with trazodone use in pregnant women have not identified any drug-associated

Estados Unidos - inglês - NLM (National Library of Medicine)

apotex corp. - cefazolin sodium (unii: p380m0454z) (cefazolin - unii:ihs69l0y4t) - cefazolin for injection, usp is indicated in the treatment of the following serious infections due to susceptible organisms: respiratory tract infections: due to s. pneumoniae, klebsiella species, h. influenzae, s. aureus (penicillin-sensitive and penicillin-resistant), and group a beta-hemolytic streptococci. injectable benzathine penicillin is considered to be the drug of choice in treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. cefazolin for injection, usp is effective in the eradication of streptococci from the nasopharynx; however, data establishing the efficacy of cefazolin for injection, usp in the subsequent prevention of rheumatic fever are not available at present. urinary tract infections: due to e. coli, p. mirabilis, klebsiella species, and some strains of enterobacter and enterococci. skin and skin structure infections:  due to s. aureus (penicillin-sensitive and penicillin-resistant), group a beta-hemolytic streptococci, and other strains of streptococci. biliary tract infections: due to e. coli, various strains of streptococci, p. mirabilis,  klebsiella species, and s. aureus. bone and joint infections: due to s. aureus. genital infections: (i.e., prostatitis, epididymitis) due to e. coli, p. mirabilis, klebsiella species, and some strains of enterococci. septicemia:  due to s. pneumoniae, s. aureus (penicillin-sensitive and penicillin-resistant), p. mirabilis, e. coli, and klebsiella species. endocarditis:  due to s. aureus (penicillin-sensitive and penicillin-resistant) and group a beta-hemolytic streptococci. perioperative prophylaxis: the prophylactic administration of cefazolin for injection, usp preoperatively, intraoperatively, and postoperatively may reduce the incidence of certain postoperative infections in patients undergoing surgical procedures which are classified as contaminated or potentially contaminated (e.g., vaginal hysterectomy, and cholecystectomy in high-risk patients such as those older than 70 years, with acute cholecystitis, obstructive jaundice, or common duct bile stones). the perioperative use of cefazolin for injection, usp may also be effective in surgical patients in whom infection at the operative site would present a serious risk (e.g., during open-heart surgery and prosthetic arthroplasty). the prophylactic administration of cefazolin for injection, usp should usually be discontinued within a 24-hour period after the surgical procedure.  in surgery where the occurrence of infection may be particularly devastating (e.g., open-heart surgery and prosthetic arthroplasty), the prophylactic administration of cefazolin for injection, usp may be continued for 3 to 5 days following the completion of surgery. if there are signs of infection, specimens for cultures should be obtained for the identification of the causative organism so that appropriate therapy may be instituted. (see dosage and administration.) to reduce the development of drug-resistant bacteria and maintain the effectiveness of cefazolin for injection, usp and other antibacterial drugs, cefazolin for injection, usp should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. cefazolin for injection, usp is contraindicated in patients with known allergy to the cephalosporin group of antibiotics.

Estados Unidos - inglês - NLM (National Library of Medicine)

apotex corp. - fluphenazine hydrochloride (unii: zou145w1xl) (fluphenazine - unii:s79426a41z) - fluphenazine hydrochloride tablets are indicated in the management of manifestations of psychotic  disorders. fluphenazine hydrochloride has not been shown effective in the management of behavioral complications in patients  with mental retardation. phenothiazines are contraindicated in patients with suspected or established subcortical brain damage, in patients receiving large doses of hypnotics, and in comatose or severely depressed states. the presence of blood dyscrasia or liver damage precludes the use of fluphenazine hydrochloride. fluphenazine hydrochloride is contraindicated in patients who have shown hypersensitivity to fluphenazine; cross-sensitivity to phenothiazine derivatives may occur.  

Estados Unidos - inglês - NLM (National Library of Medicine)

apotex corp - fluvoxamine maleate (unii: 5lgn83g74v) (fluvoxamine - unii:o4l1xpo44w) - fluvoxamine maleate 25 mg - fluvoxamine maleate tablets are indicated for the treatment of obsessions and compulsions in patients with obsessive compulsive disorder (ocd), as defined in dsm-iii-r or dsm-iv. the obsessions or compulsions cause marked distress, are time-consuming, or significantly interfere with social or occupational functioning. obsessive compulsive disorder is characterized by recurrent and persistent ideas, thoughts, impulses or images (obsessions) that are ego-dystonic and/or repetitive, purposeful, and intentional behaviors (compulsions) that are recognized by the person as excessive or unreasonable. the efficacy of fluvoxamine maleate tablets was established in four trials in outpatients with ocd: two 10-week trials in adults, one 10-week trial in pediatric patients (ages 8 to 17), and one maintenance trial in adults [see clinical studies (14)]. coadministration coadministration of tizanidine, thioridazine, alosetron, or pimozide with fluvoxamine maleate tablets is contraindicated [see warnings and precautions (5.4, 5.5, 5.6, 5.7)]. serotonin syndrome and monoamine oxidase inhibitors (maois)   the use of maois intended to treat psychiatric disorders with fluvoxamine maleate tablets or within 14 days of stopping treatment with fluvoxamine maleate tablets is contraindicated because of an increased risk of serotonin syndrome. the use of fluvoxamine maleate tablets within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated [see dosage and administration (2.4), warnings and precautions (5.2)]. starting fluvoxamine maleate tablets in a patient who is being treated with maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see dosage and administration (2.5), warnings and precautions (5.2)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/.   risk summary based on data from published observational studies, exposure to ssris, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see warnings and precautions (5.10) and clinical considerations]. prolonged experience with fluvoxamine in pregnant women over decades, based on published observational studies, have not identified a clear drug-associated risk of major birth defects or miscarriage (see data). there are risks associated with untreated depression in pregnancy and risks of persistent pulmonary hypertension of the newborn (pphn) and poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (ssris), including fluvoxamine, during pregnancy (see clinical considerations).   when pregnant rats were treated orally with fluvoxamine throughout the period of organogenesis, increased embryofetal death and increased incidences of fetal eye abnormalities (folded retinas) was observed at doses ≥3 times the maximum recommended human dose (mrhd) of 300 mg/day given to adolescents on a mg/m2 basis. in addition, decreased fetal body weight was seen at a dose 6 times the mrhd given to adolescents on a mg/m2 basis. there were no adverse developmental effects in rabbits treated with fluvoxamine during the period of organogenesis up to a dose 2 times the mrhd given to adolescents on a mg/m2 basis. when fluvoxamine was administered orally to rats during pregnancy and lactation, increased pup mortality at birth was seen at a dose 2 times the mrhd given to adolescents on a mg/m2 basis. in addition, decreases in pup body weight and survival were observed at doses that are ≥0.13 times the mrhd given to adolescents (see data).   the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.   clinical considerations disease-associated maternal and/or embryo/fetal risk women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. this finding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum.   maternal adverse reactions use of fluvoxamine maleate tablets in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.10)] . fetal/neonatal adverse reactions neonates exposed to fluvoxamine maleate tablets and other ssris or snris late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. such complications can arise immediately upon delivery. reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. these features are consistent with either a direct toxic effect of ssris and snris or, possibly, a drug discontinuation syndrome. it should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see warnings and precautions (5.2)] .   data human data exposure during late pregnancy to ssris may have an increased risk for persistent pulmonary hypertension of the newborn (pphn). pphn occurs in 1 to 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality.   animal data when pregnant rats were given oral doses of fluvoxamine (60, 120, or 240 mg/kg) throughout the period of organogenesis, developmental toxicity in the form of increased embryofetal death and increased incidences of fetal eye abnormalities (folded retinas) was observed at doses of 120 mg/kg or greater (3 times the mrhd of 300 mg/day, given to adolescents on a mg/m2 basis). decreased fetal body weight was seen at the high dose of 240 mg/kg/day (6 times the mrhd given to adolescents on a mg/m2 basis). the no effect dose for developmental toxicity in this study was 60 mg/kg/day (1.6 times the mrhd given to adolescents on a mg/m2 basis).   in a study in which pregnant rabbits were administered doses of up to 40 mg/kg (approximately 2.1 times the mrhd given to adolescents on a mg/m2 basis) during the period of organogenesis, no adverse effects on embryofetal development were observed.   in other reproduction studies in which female rats were dosed orally during pregnancy and lactation (5, 20, 80, or 160 mg/kg), increased pup mortality at birth was seen at doses of 80 mg/kg/day (2 times the mrhd given to adolescents on a mg/m2 basis) or greater and decreases in pup body weight and survival were observed at all doses (low effect dose approximately 0.13 times the mrhd given to adolescents on a mg/m2 basis). data from published literature report the presence of fluvoxamine is in human milk (see data). no adverse effects on the breastfed infant have been reported in most cases of maternal use of fluvoxamine during breastfeeding. however, there are reports of diarrhea, vomiting, decreased sleep, and agitation (see clinical considerations). there are no data on the effect of fluvoxamine on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for fluvoxamine and any potential adverse effects on the breastfed child from fluvoxamine or from the underlying maternal condition.   clinical considerations monitor infants exposed to fluvoxamine through breast milk for diarrhea, vomiting, decreased sleep, and agitation.   data milk drug concentrations ≤ 425 ng/ml were observed following maternal dosing of fluvoxamine 25 mg/day to 300 mg/day in published case reports and case series. infertility animal findings suggest fertility may be impaired while taking fluvoxamine [see nonclinical toxicology (13.1)]. the efficacy of fluvoxamine maleate for the treatment of obsessive compulsive disorder was demonstrated in a 10-week multicenter placebo controlled study with 120 outpatients ages 8 to 17. in addition, 99 of these outpatients continued open-label fluvoxamine maleate treatment for up to another one to three years, equivalent to 94 patient years. the adverse event profile observed in that study was generally similar to that observed in adult studies with fluvoxamine [ see adverse reactions (6.3), dosage and administration (2.2)]. decreased appetite and weight loss have been observed in association with the use of fluvoxamine as well as other ssris. consequently, regular monitoring of weight and growth is recommended if treatment of a child with an ssri is to be continued long term.   the risks, if any, that may be associated with fluvoxamine’s extended use in children and adolescents with ocd have not been systematically assessed. the prescriber should be mindful that the evidence relied upon to conclude that fluvoxamine is safe for use in children and adolescents derives from relatively short term clinical studies and from extrapolation of experience gained with adult patients. in particular, there are no studies that directly evaluate the effects of long term fluvoxamine use on the growth, cognitive behavioral development, and maturation of children and adolescents. although there is no affirmative finding to suggest that fluvoxamine possesses a capacity to adversely affect growth, development or maturation, the absence of such findings is not compelling evidence of the absence of the potential of fluvoxamine to have adverse effects in chronic use [see warnings and precautions (5.1)].   safety and effectiveness in the pediatric population other than pediatric patients with ocd have not been established [see boxed warning; warnings and precautions (5.1)] . anyone considering the use of fluvoxamine maleate tablets in a child or adolescent must balance the potential risks with the clinical need. approximately 230 patients participating in controlled premarketing studies with fluvoxamine maleate tablets were 65 years of age or over. no overall differences in safety were observed between these patients and younger patients. other reported clinical experience has not identified differences in response between the elderly and younger patients. however, ssris and snris, including fluvoxamine maleate tablets, have been associated with several cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event [see warnings and precautions (5.13)] . furthermore, the clearance of fluvoxamine is decreased by about 50% in elderly compared to younger patients [see clinical pharmacology (12.3)], and greater sensitivity of some older individuals also cannot be ruled out. consequently, a lower starting dose should be considered in elderly patients and fluvoxamine maleate tablets should be slowly titrated during initiation of therapy. fluvoxamine maleate tablets are not a controlled substance. the potential for abuse, tolerance and physical dependence with fluvoxamine maleate has been studied in a nonhuman primate model. no evidence of dependency phenomena was found. the discontinuation effects of fluvoxamine maleate tablets were not systematically evaluated in controlled clinical trials. fluvoxamine maleate tablets were not systematically studied in clinical trials for potential for abuse, but there was no indication of drug-seeking behavior in clinical trials. it should be noted, however, that patients at risk for drug dependency were systematically excluded from investigational studies of fluvoxamine maleate. generally, it is not possible to predict on the basis of preclinical or premarketing clinical experience the extent to which a cns active drug will be misused, diverted, and/or abused once marketed. consequently, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of fluvoxamine maleate misuse or abuse (i.e., development of tolerance, incrementation of dose, drug-seeking behavior).

Estados Unidos - inglês - NLM (National Library of Medicine)

apotex corp - paroxetine hydrochloride (unii: x2els050d8) (paroxetine - unii:41vrh5220h) - paroxetine 12.5 mg - paroxetine hcl cr is indicated in adults for the treatment of: - major depressive disorder (mdd) - panic disorder (pd) - social anxiety disorder (sad) - premenstrual dysphoric disorder (pmdd) paroxetine hcl cr is contraindicated in patients: - taking, or within 14 days of stopping, maois (including the maois linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see warnings and precautions (5.2), drug interactions (7)]. - paroxetine hcl cr should not be used in patients receiving medications that can prolong qt interval and are also metabolized by cyp450 2d6,such as thioridazine or pimozide [see drug interactions (7),warnings and precautions (5.3)]. - with known hypersensitivity (e.g., anaphylaxis, angioedema, stevens-johnson syndrome) to paroxetine or to any of the inactive ingredients in paroxetine hcl cr [see adverse reactions (6.1, 6.2)]. pregnancy exposure registry   there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidep

Estados Unidos - inglês - NLM (National Library of Medicine)

apotex corp. - modafinil (unii: r3uk8x3u3d) (modafinil - unii:r3uk8x3u3d) - modafinil 100 mg - modafinil tablets are indicated to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (osa), or shift work disorder (swd). limitations of use in osa, modafinil tablets are indicated to treat excessive sleepiness and not as treatment for the underlying obstruction. if continuous positive airway pressure (cpap) is the treatment of choice for a patient, a maximal effort to treat with cpap for an adequate period of time should be made prior to initiating and during treatment with modafinil tablets for excessive sleepiness. modafinil tablets are contraindicated in patients with known hypersensitivity to modafinil or armodafinil or its inactive ingredients [see warnings and precautions (5.1, 5.2, 5.3)] . pregnancy category c there are no adequate and well-controlled studies of modafinil in pregnant women. intrauterine growth restriction and spontaneous abortion have been reported in association with modafinil (a mixture of r- and s-modafinil) and armodafinil (the r-enantiomer of modafinil). although the pharmacology of modafinil is not identical to that of the sympathomimetic amines, it does share some pharmacologic properties with this class. certain of these drugs have been associated with intrauterine growth restriction and spontaneous abortions. whether the cases reported with modafinil are drug-related is unknown. in studies of modafinil and armodafinil conducted in rats (modafinil, armodafinil) and rabbits (modafinil), developmental toxicity was observed at clinically relevant plasma exposures. modafinil tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. modafinil (50, 100, or 200 mg/kg/day) administered orally to pregnant rats throughout organogenesis caused, in the absence of maternal toxicity, an increase in resorptions and an increased incidence of visceral and skeletal variations in the offspring at the highest dose tested. the higher no-effect dose for embryofetal developmental toxicity in rats (100 mg/kg/day) was associated with a plasma modafinil auc less than that in humans at the recommended human dose (rhd) of modafinil tablets (200 mg/day). however, in a subsequent study of up to 480 mg/kg/day of modafinil, no adverse effects on embryofetal development were observed. oral administration of armodafinil (60, 200, or 600 mg/kg/day) to pregnant rats throughout organogenesis resulted in increased incidences of fetal visceral and skeletal variations and decreased fetal body weight at the highest dose tested. the highest no-effect dose for embryofetal developmental toxicity in rats (200 mg/kg/day) was associated with a plasma armodafinil auc less than that in humans at the rhd of modafinil tablets. modafinil administered orally to pregnant rabbits throughout organogenesis at doses of up to 100 mg/kg/day had no effect on embryofetal development; however, the doses used were too low to adequately assess the effects of modafinil on embryofetal development. in a subsequent developmental toxicity study evaluating doses of 45, 90, and 180 mg/kg/day in pregnant rabbits, the incidences of fetal structural alterations and embryofetal death were increased at the highest dose. the highest no-effect dose for developmental toxicity (100 mg/kg/day) was associated with a plasma modafinil auc similar to that in humans at the rhd of modafinil tablets. modafinil administration to rats throughout gestation and lactation at oral doses of up to 200 mg/kg/day resulted in decreased viability in the offspring at doses greater than 20 mg/kg/day, a dose resulting in a plasma modafinil auc less than that in humans at the rhd of modafinil tablets. no effects on postnatal developmental and neurobehavioral parameters were observed in surviving offspring. it is not known whether modafinil or its metabolites are excreted in human milk. because many drugs are excreted in human milk, caution should be exercised when modafinil tablets are administered to a nursing woman. safety and effectiveness in pediatric patients have not been established. modafinil tablets are not approved in this population for any indication. serious skin rashes, including erythema multiforme major (emm) and stevens-johnson syndrome (sjs) have been associated with modafinil use in pediatric patients [see warnings and precautions (5.1)] . in a controlled 6-week study, 165 pediatric patients (aged 5 to 17 years) with narcolepsy were treated with modafinil (n=123), or placebo (n=42). there were no statistically significant differences favoring modafinil over placebo in prolonging sleep latency as measured by mslt, or in perceptions of sleepiness as determined by the clinical global impression-clinician scale (cgi-c). in the controlled and open-label clinical studies, treatment emergent adverse reactions of the psychiatric and nervous system included tourette’s syndrome, insomnia, hostility, increased cataplexy, increased hypnagogic hallucinations, and suicidal ideation. transient leukopenia, which resolved without medical intervention, was also observed. in the controlled clinical study, 3 of 38 girls, ages 12 or older, treated with modafinil experienced dysmenorrhea compared to 0 of 10 girls who received placebo. there were three 7 to 9 week, double-blind, placebo-controlled, parallel group studies in children and adolescents (aged 6 to 17 years) with attention-deficit hyperactivity disorder (adhd). two of the studies were flexible-dose studies (up to 425 mg/day), and the third was a fixed-dose study (340 mg/day for patients <30 kg and 425 mg/day for patients ≥30 kg). although these studies showed statistically significant differences favoring modafinil over placebo in reducing adhd symptoms as measured by the adhd-rs (school version), there were 3 cases of serious rash including one case of possible sjs among 933 patients exposed to modafinil in this program. modafinil is not approved for use in treating adhd. in clinical trials, experience in a limited number of modafinil-treated patients who were greater than 65 years of age showed an incidence of adverse reactions similar to other age groups. in elderly patients, elimination of modafinil and its metabolites may be reduced as a consequence of aging. therefore, consideration should be given to the use of lower doses and close monitoring in this population [see dosage and administration (2.4) and clinical pharmacology (12.3)] . in patients with severe hepatic impairment, the dose of modafinil tablets should be reduced to one-half of that recommended for patients with normal hepatic function [see dosage and administration (2.3) and clinical pharmacology (12.3)] . modafinil tablets contain modafinil, a schedule iv controlled substance. in humans, modafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking, and feelings typical of other cns stimulants. in in vitro binding studies, modafinil binds to the dopamine reuptake site and causes an increase in extracellular dopamine, but no increase in dopamine release. modafinil is reinforcing, as evidenced by its self-administration in monkeys previously trained to self-administer cocaine. in some studies, modafinil was also partially discriminated as stimulant-like. physicians should follow patients closely, especially those with a history of drug and/or stimulant (e.g., methylphenidate, amphetamine, or cocaine) abuse. patients should be observed for signs of misuse or abuse (e.g., incrementation of doses or drug-seeking behavior). the abuse potential of modafinil (200, 400, and 800 mg) was assessed relative to methylphenidate (45 and 90 mg) in an inpatient study in individuals experienced with drugs of abuse. results from this clinical study demonstrated that modafinil produced psychoactive and euphoric effects and feelings consistent with other scheduled cns stimulants (methylphenidate). in one placebo-controlled clinical trial, the effects of modafinil withdrawal were monitored following 9 weeks of modafinil use. there were no reported withdrawal symptoms with modafinil during 14 days of observation, although sleepiness returned in narcoleptic patients.

Estados Unidos - inglês - NLM (National Library of Medicine)

apotex corp. - aripiprazole (unii: 82vfr53i78) (aripiprazole - unii:82vfr53i78) - aripiprazole 1 mg in 1 ml - aripiprazole oral solution is indicated for the treatment of: - schizophrenia [see clinical studies (14.1)]   - acute treatment of manic and mixed episodes associated with bipolar i disorder [see clinical studies (14.2)]  - adjunctive treatment of major depressive disorder [see  clinical studies (14.3)]  - irritability associated with autistic disorder [see clinical studies (14.4)]  - treatment of tourette’s disorder [see clinical studies (14.5)] aripiprazole oral solution is contraindicated in patients with a history of a hypersensitivity reaction to aripiprazole. reactions have ranged from pruritus/urticaria to anaphylaxis [see adverse reactions (6.2)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including aripiprazole, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or visit http://wom