Yhdysvallat - englanti - NLM (National Library of Medicine)

torrent pharmaceuticals limited - itraconazole (unii: 304nug5gf4) (itraconazole - unii:304nug5gf4) - itraconazole capsules are indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: - blastomycosis, pulmonary and extrapulmonary - histoplasmosis, including chronic cavitary pulmonary disease and disseminated, non-meningeal histoplasmosis, and - aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or who are refractory to amphotericin b therapy. specimens for fungal cultures and other relevant laboratory studies (wet mount, histopathology, serology) should be obtained before therapy to isolate and identify causative organisms. therapy may be instituted before the results of the cultures and other laboratory studies are known; however, once these results become available, antiinfective therapy should be adjusted accordingly. itraconazole capsules are also indicated for the treatment of the following fungal infections in non-immunocompromised patients: - onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (tinea unguium), and - onychomycosis of the fingernail due to dermatophytes (tinea unguium). prior to initiating treatment, appropriate nail specimens for laboratory testing (koh preparation, fungal culture, or nail biopsy) should be obtained to confirm the diagnosis of onychomycosis. (see clinical pharmacology: special populations, contraindications, warnings, and adverse reactions: post-marketing experience for more information.) blastomycosis: analyses were conducted on data from two open-label, non-concurrently controlled studies (n=73 combined) in patients with normal or abnormal immune status. the median dose was 200 mg/day. a response for most signs and symptoms was observed within the first 2 weeks, and all signs and symptoms cleared between 3 and 6 months. results of these two studies demonstrated substantial evidence of the effectiveness of itraconazole for the treatment of blastomycosis compared with the natural history of untreated cases. histoplasmosis: analyses were conducted on data from two open-label, non-concurrently controlled studies (n=34 combined) in patients with normal or abnormal immune status (not including hiv-infected patients). the median dose was 200 mg/day. a response for most signs and symptoms was observed within the first 2 weeks, and all signs and symptoms cleared between 3 and 12 months. results of these two studies demonstrated substantial evidence of the effectiveness of itraconazole for the treatment of histoplasmosis, compared with the natural history of untreated cases. histoplasmosis in hiv-infected patients: data from a small number of hiv-infected patients suggested that the response rate of histoplasmosis in hiv-infected patients is similar to that of non-hiv-infected patients. the clinical course of histoplasmosis in hiv-infected patients is more severe and usually requires maintenance therapy to prevent relapse. aspergillosis: analyses were conducted on data from an open-label, "single-patient-use" protocol designed to make itraconazole available in the u.s. for patients who either failed or were intolerant of amphotericin b therapy (n=190). the findings were corroborated by two smaller open-label studies (n=31 combined) in the same patient population. most adult patients were treated with a daily dose of 200 to 400 mg, with a median duration of 3 months. results of these studies demonstrated substantial evidence of effectiveness of itraconazole as a second-line therapy for the treatment of aspergillosis compared with the natural history of the disease in patients who either failed or were intolerant of amphotericin b therapy. onychomycosis of the toenail: analyses were conducted on data from three double-blind, placebo-controlled studies (n=214 total; 110 given itraconazole capsules) in which patients with onychomycosis of the toenails received 200 mg of itraconazole capsules once daily for 12 consecutive weeks. results of these studies demonstrated mycologic cure, defined as simultaneous occurrence of negative koh plus negative culture, in 54% of patients. thirty-five percent (35%) of patients were considered an overall success (mycologic cure plus clear or minimal nail involvement with significantly decreased signs) and 14% of patients demonstrated mycologic cure plus clinical cure (clearance of all signs, with or without residual nail deformity). the mean time to overall success was approximately 10 months. twenty-one percent (21%) of the overall success group had a relapse (worsening of the global score or conversion of koh or culture from negative to positive). onychomycosis of the fingernail: analyses were conducted on data from a double-blind, placebo-controlled study (n=73 total; 37 given itraconazole capsules) in which patients with onychomycosis of the fingernails received a 1-week course of 200 mg of itraconazole capsules b.i.d., followed by a 3-week period without itraconazole, which was followed by a second 1-week course of 200 mg of itraconazole capsules b.i.d. results demonstrated mycologic cure in 61% of patients. fifty-six percent (56%) of patients were considered an overall success and 47% of patients demonstrated mycologic cure plus clinical cure. the mean time to overall success was approximately 5 months. none of the patients who achieved overall success relapsed. itraconazole capsules should not be administered for the treatment of onychomycosis in patients with evidence of ventricular dysfunction such as congestive heart failure (chf) or a history of chf. (see boxed warning, warnings, precautions: drug interactions-calcium channel blockers, adverse reactions: post-marketing experience, and clinical pharmacology: special populations.) coadministration of a number of cyp3a4 substrates are contraindicated with itraconazole. some examples of drugs for which plasma concentrations increase are: methadone, disopyramide, dofetilide, dronedarone, quinidine, isavuconazole, ergot alkaloids (such as dihydroergotamine, ergometrine (ergonovine), ergotamine, methylergometrine (methylergonovine)), irinotecan, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisoldipine, ivabradine, ranolazine, eplerenone, cisapride, naloxegol, lomitapide, lovastatin, simvastatin, avanafil, ticagrelor, finerenone, voclosporin. in addition, coadministration with colchicine, fesoterodine and solifenacin is contraindicated in subjects with varying degrees of renal or hepatic impairment, and coadministration with eliglustat is contraindicated in subjects that are poor or intermediate metabolizers of cyp2d6 and in subjects taking strong or moderate cyp2d6 inhibitors. (see precautions: drug interactions section for specific examples.) this increase in drug concentrations caused by coadministration with itraconazole may increase or prolong both the pharmacologic effects and/or adverse reactions to these drugs. for example, increased plasma concentrations of some of these drugs can lead to qt prolongation and ventricular tachyarrhythmias including occurrences of torsade de pointes , a potentially fatal arrhythmia. some specific examples are listed in precautions: drug interactions. coadministration with venetoclax is contraindicated in patients with cll/sll during the dose initiation and ramp-up phase of venetoclax due to the potential for an increased risk of tumor lysis syndrome. itraconazole should not be administered for the treatment of onychomycosis to pregnant patients or to women contemplating pregnancy. itraconazole is contraindicated for patients who have shown hypersensitivity to itraconazole. there is limited information regarding cross-hypersensitivity between itraconazole and other azole antifungal agents. caution should be used when prescribing itraconazole to patients with hypersensitivity to other azoles.

Malesia - englanti - NPRA (National Pharmaceutical Regulatory Agency, Bahagian Regulatori Farmasi Negara)

imeks pharma sdn. bhd. - caffeine; ergotamine tartrate -

Etelä-Afrikka - englanti - South African Health Products Regulatory Authority (SAHPRA)

adcock ingram limited - tablet - see ingredients - each tablet contains efavirenz 600,0 mg emtricitabine 200,0 mg tenofovir disoproxil fumarate 300,0 mg

Etelä-Afrikka - englanti - South African Health Products Regulatory Authority (SAHPRA)

adcock ingram limited - tablet - see ingredients - each tablet contains efavirenz 600,0 mg emtricitabine 200,0 mg tenofovir disoproxil fumarate 300,0 mg

Etelä-Afrikka - englanti - South African Health Products Regulatory Authority (SAHPRA)

adcock ingram limited - tablet - see ingredients - each tablet contains efavirenz 600,0 mg emtricitabine 200,0 mg tenofovir disoproxil fumarate 300,0 mg

Yhdysvallat - englanti - NLM (National Library of Medicine)

xellia pharmaceuticals usa llc - voriconazole (unii: jfu09i87tr) (voriconazole - unii:jfu09i87tr) - voriconazole for injection is indicated in adults and pediatric patients (aged 12 to 14 years weighing greater than or equal to 50 kg and those aged 15 years and older regardless of body weight) for the treatment of invasive aspergillosis (ia). in clinical trials, the majority of isolates recovered were aspergillus fumigatus . there was a small number of cases of culture-proven disease due to species of aspergillus other than a. fumigatus [see clinical studies (14.1) and microbiology (12.4)]. voriconazole for injection is indicated in adult and pediatric patients (aged 12 to 14 years weighing greater than or equal to 50 kg and those aged 15 years and older regardless of body weight) for the treatment of candidemia in non-neutropenic patients and the following candida infections: disseminated infections in skin and infections in abdomen, kidney, bladder wall, and wounds [see clinical studies (14.2) and microbiology (12.4)]. voriconazole for injection is indicated for the treatment of serious fungal infections caused by scedosporium apiospermum (asexual form of pseudallescheria boydii ) and fusarium spp . including fusarium solani , in adult and pediatric patients (aged 12 to 14 years weighing greater than or equal to 50 kg and those aged 15 years and older regardless of body weight) intolerant of, or refractory to, other therapy [see clinical studies (14.3) and microbiology (12.4)] . specimens for fungal culture and other relevant laboratory studies (including histopathology) should be obtained prior to therapy to isolate and identify causative organism(s). therapy may be instituted before the results of the cultures and other laboratory studies are known. however, once these results become available, antifungal therapy should be adjusted accordingly. additional pediatric use information is approved for pf prism c.v.'s vfend (voriconazole) for injection. however, due to pf prism c.v.'s marketing exclusivity rights, this drug product is not labeled with that information. - voriconazole for injection is contraindicated in patients with known hypersensitivity to voriconazole or its excipients. there is no information regarding cross-sensitivity between voriconazole for injection (voriconazole) and other azole antifungal agents. caution should be used when prescribing voriconazole for injection to patients with hypersensitivity to other azoles. - coadministration of pimozide, quinidine or ivabradine with voriconazole for injection is contraindicated because increased plasma concentrations of these drugs can lead to qt prolongation and rare occurrences of torsade de pointes [see drug interactions (7)] . - coadministration of voriconazole for injection with sirolimus is contraindicated because voriconazole for injection significantly increases sirolimus concentrations [see drug interactions (7) and clinical pharmacology (12.3)] . - coadministration of voriconazole for injection with rifampin, carbamazepine, long-acting barbiturates and st. john's wort is contraindicated because these drugs are likely to decrease plasma voriconazole concentrations significantly [see drug interactions (7) and clinical pharmacology (12.3)] . - coadministration of standard doses of voriconazole with efavirenz doses of 400 mg every 24 hours or higher is contraindicated, because efavirenz significantly decreases plasma voriconazole concentrations in healthy subjects at these doses. voriconazole also significantly increases efavirenz plasma concentrations [see drug interactions (7) and clinical pharmacology (12.3)] . - coadministration of voriconazole for injection with high-dose ritonavir (400 mg every 12 hours) is contraindicated because ritonavir (400 mg every 12 hours) significantly decreases plasma voriconazole concentrations. coadministration of voriconazole and low-dose ritonavir (100 mg every 12 hours) should be avoided, unless an assessment of the benefit/risk to the patient justifies the use of voriconazole [see drug interactions (7) and clinical pharmacology (12.3)] . - coadministration of voriconazole for injection with rifabutin is contraindicated since voriconazole for injection significantly increases rifabutin plasma concentrations and rifabutin also significantly decreases voriconazole plasma concentrations [see drug interactions (7) and clinical pharmacology (12.3)] . - coadministration of voriconazole for injection with ergot alkaloids (ergotamine and dihydroergotamine) is contraindicated because voriconazole for injection may increase the plasma concentration of ergot alkaloids, which may lead to ergotism [see drug interactions (7)] . - coadministration of voriconazole for injection with naloxegol is contraindicated because voriconazole for injection may increase plasma concentrations of naloxegol which may precipitate opioid withdrawal symptoms [see drug interactions (7)]. - coadministration of voriconazole for injection with tolvaptan is contraindicated because voriconazole for injection may increase tolvaptan plasma concentrations and increase risk of adverse reactions [see drug interactions (7)]. - coadministration of voriconazole for injection with venetoclax at initiation and during the ramp-up phase is contraindicated in patients with chronic lymphocytic leukemia (cll) or small lymphocytic lymphoma (sll) due to the potential for increased risk of tumor lysis syndrome [see drug interactions (7)]. - coadministration of voriconazole for injection with lurasidone is contraindicated since it may result in significant increases in lurasidone exposure and the potential for serious adverse reactions [see drug interactions (7)] . risk summary voriconazole can cause fetal harm when administered to a pregnant woman. there are no available data on the use of voriconazole for injection in pregnant women. in animal reproduction studies, oral voriconazole was associated with fetal malformations in rats and fetal toxicity in rabbits. cleft palates and hydronephrosis/hydroureter were observed in rat pups exposed to voriconazole during organogenesis at and above 10 mg/kg (0.3 times the rmd of 200 mg every 12 hours based on body surface area comparisons). in rabbits, embryomortality, reduced fetal weight and increased incidence of skeletal variations, cervical ribs and extrasternal ossification sites were observed in pups when pregnant rabbits were orally dosed at 100 mg/kg (6 times the rmd based on body surface area comparisons) during organogenesis. rats exposed to voriconazole from implantation to weaning experienced increased gestational length and dystocia, which were associated with increased perinatal pup mortality at the 10 mg/kg dose [see data] . if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, inform the patient of the potential hazard to the fetus [see warnings and precautions (5.9)] . the background risk of major birth defects and miscarriage for the indicated populations 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 voriconazole was administered orally to pregnant rats during organogenesis (gestation days 6-17) at 10, 30, and 60 mg/kg/day. voriconazole was associated with increased incidences of the malformations in hydroureter and hydronephrosis at 10 mg/kg/day or greater, approximately 0.3 times the recommended human dose (rmd) based on body surface area comparisons, and cleft palate at 60 mg/kg, approximately 2 times the rmd based on body surface area comparisons. reduced ossification of sacral and caudal vertebrae, skull, pubic, and hyoid bone, supernumerary ribs, anomalies of the sternebrae, and dilatation of the ureter/renal pelvis were also observed at doses of 10 mg/kg or greater. there was no evidence of maternal toxicity at any dose. voriconazole was administered orally to pregnant rabbits during the period of organogenesis (gestation days 7-19) at 10, 40, and 100 mg/kg/day. voriconazole was associated with increased post-implantation loss and decreased fetal body weight, in association with maternal toxicity (decreased body weight gain and food consumption) at 100 mg/kg/day (6 times the rmd based on body surface area comparisons). fetal skeletal variations (increases in the incidence of cervical rib and extra sternebral ossification sites) were observed at 100 mg/kg/day. in a peri- and postnatal toxicity study in rats, voriconazole was administered orally to female rats from implantation through the end of lactation at 1, 3, and 10 mg/kg/day. voriconazole prolonged the duration of gestation and labor and produced dystocia with related increases in maternal mortality and decreases in perinatal survival of f1 pups at 10 mg/kg/day, approximately 0.3 times the rmd. risk summary no data are available regarding the presence of voriconazole in human milk, the effects of voriconazole on the breastfed infant, or the effects on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for voriconazole for injection and any potential adverse effects on the breastfed child from voriconazole for injection or from the underlying maternal condition. contraception advise females of reproductive potential to use effective contraception during treatment with voriconazole for injection. the coadministration of voriconazole with the oral contraceptive, ortho-novum® (35 mcg ethinyl estradiol and 1 mg norethindrone), results in an interaction between these two drugs, but is unlikely to reduce the contraceptive effect. monitoring for adverse reactions associated with oral contraceptives and voriconazole is recommended [see drug interactions (7) and clinical pharmacology (12.3)] . the safety and effectiveness of voriconazole have been established in pediatric patients aged 12 to 14 years weighing greater than or equal to 50 kg and those aged 15 years and older regardless of body weight based on evidence from adequate and well-controlled studies in adult and pediatric patients and additional pediatric pharmacokinetic and safety data. a total of 51 pediatric patients aged 12 to less than 18 [n=51] from eight adult therapeutic trials provided safety information for voriconazole use in the pediatric population [see adverse reactions (6.1), clinical pharmacology (12.3), and clinical studies (14)] . safety and effectiveness in pediatric patients below the age of 2 years has not been established. therefore, voriconazole for injection is not recommended for pediatric patients less than 2 years of age. a higher frequency of liver enzyme elevations was observed in the pediatric patients [see dosage and administration (2.5), warnings and precautions (5.1), and adverse reactions (6.1)] . the frequency of phototoxicity reactions is higher in the pediatric population. squamous cell carcinoma has been reported in patients who experience photosensitivity reactions. stringent measures for photoprotection are warranted. sun avoidance and dermatologic follow-up are recommended in pediatric patients experiencing photoaging injuries, such as lentigines or ephelides, even after treatment discontinuation [see warnings and precautions (5.6)]. voriconazole for injection has not been studied in pediatric patients with hepatic or renal impairment [see dosage and administration (2.5, 2.6)] . hepatic function and serum creatinine levels should be closely monitored in pediatric patients [see dosage and administration (2.6) and warnings and precautions (5.1, 5.10)] . additional pediatric use information is approved for pf prism c.v.'s vfend (voriconazole) for injection. however, due to pf prism c.v.'s marketing exclusivity rights, this drug product is not labeled with that information. in multiple dose therapeutic trials of voriconazole, 9.2% of patients were ≥ 65 years of age and 1.8% of patients were ≥ 75 years of age. in a study in healthy subjects, the systemic exposure (auc) and peak plasma concentrations (cmax ) were increased in elderly males compared to young males. pharmacokinetic data obtained from 552 patients from 10 voriconazole therapeutic trials showed that voriconazole plasma concentrations in the elderly patients were approximately 80% to 90% higher than those in younger patients after either iv or oral administration. however, the overall safety profile of the elderly patients was similar to that of the young so no dosage adjustment is recommended [see clinical pharmacology (12.3)] .

Yhdysvallat - englanti - NLM (National Library of Medicine)

truemed group llc - ergotamine tartrate (unii: mru5xh3b48) (ergotamine - unii:pr834q503t), caffeine (unii: 3g6a5w338e) (caffeine - unii:3g6a5w338e) -

Yhdysvallat - englanti - NLM (National Library of Medicine)

remedyrepack inc. - itraconazole (unii: 304nug5gf4) (itraconazole - unii:304nug5gf4) - itraconazole capsules are indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: - blastomycosis, pulmonary and extrapulmonary - histoplasmosis, including chronic cavitary pulmonary disease and disseminated, non-meningeal histoplasmosis, and - aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or who are refractory to amphotericin b therapy. specimens for fungal cultures and other relevant laboratory studies (wet mount, histopathology, serology) should be obtained before therapy to isolate and identify causative organisms. therapy may be instituted before the results of the cultures and other laboratory studies are known; however, once these results become available, antiinfective therapy should be adjusted accordingly. itraconazole capsules are also indicated for the treatment of the following fungal infections in non-immunocompromised patients: - onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (tinea unguium), and - onychomycosis of the fingernail due to dermatophytes (tinea unguium). prior to initiating treatment, appropriate nail specimens for laboratory testing (koh preparation, fungal culture, or nail biopsy) should be obtained to confirm the diagnosis of onychomycosis. (see clinical pharmacology: special populations, contraindications, warnings, and adverse reactions: post-marketing experience for more information.) blastomycosis: analyses were conducted on data from two open-label, non-concurrently controlled studies (n=73 combined) in patients with normal or abnormal immune status. the median dose was 200 mg/day. a response for most signs and symptoms was observed within the first 2 weeks, and all signs and symptoms cleared between 3 and 6 months. results of these two studies demonstrated substantial evidence of the effectiveness of itraconazole for the treatment of blastomycosis compared with the natural history of untreated cases. histoplasmosis: analyses were conducted on data from two open-label, non-concurrently controlled studies (n=34 combined) in patients with normal or abnormal immune status (not including hiv-infected patients). the median dose was 200 mg/day. a response for most signs and symptoms was observed within the first 2 weeks, and all signs and symptoms cleared between 3 and 12 months. results of these two studies demonstrated substantial evidence of the effectiveness of itraconazole for the treatment of histoplasmosis, compared with the natural history of untreated cases. histoplasmosis in hiv-infected patients: data from a small number of hiv-infected patients suggested that the response rate of histoplasmosis in hiv-infected patients is similar to that of non-hiv-infected patients. the clinical course of histoplasmosis in hiv-infected patients is more severe and usually requires maintenance therapy to prevent relapse. aspergillosis: analyses were conducted on data from an open-label, "single-patient-use" protocol designed to make itraconazole available in the u.s. for patients who either failed or were intolerant of amphotericin b therapy (n=190). the findings were corroborated by two smaller open-label studies (n=31 combined) in the same patient population. most adult patients were treated with a daily dose of 200 to 400 mg, with a median duration of 3 months. results of these studies demonstrated substantial evidence of effectiveness of itraconazole as a second-line therapy for the treatment of aspergillosis compared with the natural history of the disease in patients who either failed or were intolerant of amphotericin b therapy. onychomycosis of the toenail: analyses were conducted on data from three double-blind, placebo-controlled studies (n=214 total; 110 given itraconazole capsules) in which patients with onychomycosis of the toenails received 200 mg of itraconazole capsules once daily for 12 consecutive weeks. results of these studies demonstrated mycologic cure, defined as simultaneous occurrence of negative koh plus negative culture, in 54% of patients. thirty-five percent (35%) of patients were considered an overall success (mycologic cure plus clear or minimal nail involvement with significantly decreased signs) and 14% of patients demonstrated mycologic cure plus clinical cure (clearance of all signs, with or without residual nail deformity). the mean time to overall success was approximately 10 months. twenty-one percent (21%) of the overall success group had a relapse (worsening of the global score or conversion of koh or culture from negative to positive). onychomycosis of the fingernail: analyses were conducted on data from a double-blind, placebo-controlled study (n=73 total; 37 given itraconazole capsules) in which patients with onychomycosis of the fingernails received a 1-week course of 200 mg of itraconazole capsules b.i.d., followed by a 3-week period without itraconazole, which was followed by a second 1-week course of 200 mg of itraconazole capsules b.i.d. results demonstrated mycologic cure in 61% of patients. fifty-six percent (56%) of patients were considered an overall success and 47% of patients demonstrated mycologic cure plus clinical cure. the mean time to overall success was approximately 5 months. none of the patients who achieved overall success relapsed. itraconazole capsules should not be administered for the treatment of onychomycosis in patients with evidence of ventricular dysfunction such as congestive heart failure (chf) or a history of chf. (see boxed warning, warnings, precautions: drug interactions-calcium channel blockers, adverse reactions: post-marketing experience, and clinical pharmacology: special populations.) coadministration of a number of cyp3a4 substrates are contraindicated with itraconazole. plasma concentrations increase for the following drugs: methadone, disopyramide, dofetilide, dronedarone, quinidine, isavuconazole, ergot alkaloids (such as dihydroergotamine, ergometrine (ergonovine), ergotamine, methylergometrine (methylergonovine)), irinotecan, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisoldipine, ivabradine, ranolazine, eplerenone, cisapride, naloxegol, lomitapide, lovastatin, simvastatin, avanafil, ticagrelor, finerenone, voclosporin. in addition, coadministration with colchicine, fesoterodine and solifenacin is contraindicated in subjects with varying degrees of renal or hepatic impairment, and coadministration with eliglustat is contraindicated in subjects that are poor or intermediate metabolizers of cyp2d6 and in subjects taking strong or moderate cyp2d6 inhibitors. (see precautions: drug interactions section for specific examples.) this increase in drug concentrations caused by coadministration with itraconazole may increase or prolong both the pharmacologic effects and/or adverse reactions to these drugs. for example, increased plasma concentrations of some of these drugs can lead to qt prolongation and ventricular tachyarrhythmias including occurrences of torsade de pointes , a potentially fatal arrhythmia. specific examples are listed in precautions: drug interactions. coadministration with venetoclax is contraindicated in patients with cll/sll during the dose initiation and ramp-up phase venetoclax to the potential for an increased risk of tumor lysis syndrome. itraconazole should not be administered for the treatment of onychomycosis to pregnant patients or to women contemplating pregnancy. itraconazole is contraindicated for patients who have shown hypersensitivity to itraconazole. there is limited information regarding cross-hypersensitivity between itraconazole and other azole antifungal agents. caution should be used when prescribing itraconazoleto patients with hypersensitivity to other azoles.

Yhdysvallat - englanti - NLM (National Library of Medicine)

endo usa, inc. - posaconazole (unii: 6tk1g07bhz) (posaconazole - unii:6tk1g07bhz) - posaconazole injection is indicated for the treatment of invasive aspergillosis in adults and pediatric patients 13 years of age and older. posaconazole is indicated for the prophylaxis of invasive aspergillus and candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (hsct) recipients with graft-versus-host disease (gvhd) or those with hematologic malignancies with prolonged neutropenia from chemotherapy [see clinical studies (14.1)] as follows: - posaconazole injection : adults and pediatric patients 2 years of age and older posaconazole is contraindicated in persons with known hypersensitivity to posaconazole or other azole antifungal agents. posaconazole is contraindicated with sirolimus. concomitant administration of posaconazole with sirolimus increases the sirolimus blood concentrations by approximately 9-fold and can result in sirolimus toxicity [see drug interactions (7.1) and clinical pharmacology (12.3)] . posaconazole is contraindicated with cyp3a4 substrates that prolong the qt interval. concomitant administration of posaconazole with the cyp3a4 substrates, pimozide and quinidine may result in increased plasma concentrations of these drugs, leading to qtc prolongation and cases of torsades de pointes [see warnings and precautions (5.2) and drug interactions (7.2)] . coadministration with the hmg-coa reductase inhibitors that are primarily metabolized through cyp3a4 (e.g., atorvastatin, lovastatin, and simvastatin) is contraindicated since increased plasma concentration of these drugs can lead to rhabdomyolysis [see drug interactions (7.3) and clinical pharmacology (12.3)] . posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism [see drug interactions (7.4)] . coadministration of posaconazole with venetoclax at initiation and during the ramp-up phase is contraindicated in patients with chronic lymphocytic leukemia (cll) or small lymphocytic lymphoma (sll) due to the potential for increased risk of tumor lysis syndrome [see warnings and precautions (5.10) and drug interactions (7.16)]. risk summary based on findings from animal data, posaconazole may cause fetal harm when administered to pregnant women. available data for use of posaconazole in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal reproduction studies, skeletal malformations (cranial malformations and missing ribs) and maternal toxicity (reduced food consumption and reduced body weight gain) were observed when posaconazole was dosed orally to pregnant rats during organogenesis at doses ≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of posaconazole in healthy volunteers. in pregnant rabbits dosed orally during organogenesis, increased resorptions, reduced litter size, and reduced body weight gain of females were seen at doses 5 times the exposure achieved with the 400 mg twice daily oral suspension regimen. doses of ≥ 3 times the clinical exposure caused an increase in resorptions in these rabbits (see data) . based on animal data, advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data posaconazole resulted in maternal toxicity (reduced food consumption and reduced body weight gain) and skeletal malformations (cranial malformations and missing ribs) when given orally to pregnant rats during organogenesis (gestational days 6 through 15) at doses ≥27 mg/kg (≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of drug in healthy volunteers). the no-effect dose for malformations and maternal toxicity in rats was 9 mg/kg, which is 0.7 times the exposure achieved with the 400 mg twice daily oral suspension regimen. no malformations were seen in rabbits dosed during organogenesis (gestational days 7 through 19) at doses up to 80 mg/kg (5 times the exposure achieved with the 400 mg twice daily oral suspension regimen). in the rabbit, the no-effect dose was 20 mg/kg, while high doses of 40 mg/kg and 80 mg/kg (3 or 5 times the clinical exposure) caused an increase in resorptions. in rabbits dosed at 80 mg/kg, a reduction in body weight gain of females and a reduction in litter size were seen. risk summary there are no data on the presence of posaconazole in human milk, the effects on the breastfed infant, or the effects on milk production. posaconazole is excreted in the milk of lactating rats. when a drug is present in animal milk, it is likely that the drug will be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for posaconazole and any potential adverse effects on the breastfed child from posaconazole or from the underlying maternal condition. the safety and effectiveness of posaconazole injection for the prophylaxis of invasive aspergillus  and candida  infections have been established in pediatric patients aged 2 and older who are at high risk of developing these infections due to being severely immunocompromised, such as hsct recipients with gvhd or those with hematologic malignancies with prolonged neutropenia from chemotherapy. the safety and effectiveness of posaconazole injection for the treatment of invasive aspergillosis have been established in pediatric patients aged 13 years and older. use of posaconazole in these age groups is supported by evidence from adequate and well-controlled studies of posaconazole in adult and pediatric patients and additional pharmacokinetic and safety data in pediatric patients 2 years of age and older [see adverse reactions (6.1), clinical pharmacology (12.3) and clinical studies (14)]. the safety and effectiveness of posaconazole have not been established in pediatric patients younger than 2 years of age. no overall differences in the safety of posaconazole injection was observed between geriatric patients and younger adult patients in the clinical trials; therefore, no dosage adjustment is recommended for any formulation of posaconazole in geriatric patients. no clinically meaningful differences in the pharmacokinetics of posaconazole were observed in geriatric patients compared to younger adult patients during clinical trials [see clinical pharmacology (12.3)]. of the 279 patients treated with posaconazole injection in the posaconazole injection study, 52 (19%) were greater than 65 years of age. no overall differences in the pharmacokinetics and safety were observed between elderly and young subjects during clinical trials, but greater sensitivity of some older individuals cannot be ruled out. posaconazole injection should be avoided in patients with moderate or severe renal impairment (egfr <50 ml/min), unless an assessment of the benefit/risk to the patient justifies the use of posaconazole injection. in patients with moderate or severe renal impairment (egfr <50 ml/min), receiving the posaconazole injection, accumulation of the intravenous vehicle, sbecd, is expected to occur. serum creatinine levels should be closely monitored in these patients, and, if increases occur, consideration should be given to changing to oral posaconazole therapy [see dosage and administration (2.9) and warnings and precautions (5.5)] . after a single oral dose of noxafil oral suspension 400 mg, the mean auc was 43%, 27%, and 21% higher in subjects with mild (child-pugh class a, n=6), moderate (child-pugh class b, n=6), or severe (child-pugh class c, n=6) hepatic impairment, respectively, compared to subjects with normal hepatic function (n=18). compared to subjects with normal hepatic function, the mean cmax was 1% higher, 40% higher, and 34% lower in subjects with mild, moderate, or severe hepatic impairment, respectively. the mean apparent oral clearance (cl/f) was reduced by 18%, 36%, and 28% in subjects with mild, moderate, or severe hepatic impairment, respectively, compared to subjects with normal hepatic function. the elimination half-life (t½) was 27 hours, 39 hours, 27 hours, and 43 hours in subjects with normal hepatic function and mild, moderate, or severe hepatic impairment, respectively. it is recommended that no dose adjustment of  posaconazole injection is needed in patients with mild to severe hepatic impairment (child-pugh class a, b, or c) [see dosage and administration (2)  and warnings and precautions (5.4)] .  however, a specific study has not been conducted with posaconazole injection. the pharmacokinetics of posaconazole are comparable in males and females.  no adjustment in the dosage of posaconazole is necessary based on gender. the pharmacokinetic profile of posaconazole is not significantly affected by race.  no adjustment in the dosage of posaconazole is necessary based on race. pharmacokinetic modeling suggests that patients weighing greater than 120 kg may have lower posaconazole plasma drug exposure.  it is, therefore, suggested to closely monitor for breakthrough fungal infections [see clinical pharmacology (12.3)] .

Yhdysvallat - englanti - NLM (National Library of Medicine)

gland pharma limited - posaconazole (unii: 6tk1g07bhz) (posaconazole - unii:6tk1g07bhz) - posaconazole injection is indicated for the treatment of invasive aspergillosis in adults and pediatric patients 13 years of age and older. posaconazole injection is indicated for the prophylaxis of invasive aspergillus and candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (hsct) recipients with graft-versus-host disease (gvhd) or those with hematologic malignancies with prolonged neutropenia from chemotherapy [see clinical studies (14.1)] as follows: - posaconazole injection: adults and pediatric patients 2 years of age and older posaconazole is contraindicated in persons with known hypersensitivity to posaconazole or other azole antifungal agents. posaconazole is contraindicated with sirolimus. concomitant administration of posaconazole with sirolimus increases the sirolimus blood concentrations by approximately 9-fold and can result in sirolimus toxicity [see drug interactions (7.1) and clinical pharmacology (12.3) ]. posaconazole is contraindicated with cyp3a4 substrates that prolong the qt interval. concomitant administration of posaconazole with the cyp3a4 substrates, pimozide and quinidine may result in increased plasma concentrations of these drugs, leading to qtc prolongation and cases of torsades de pointes [see warnings and precautions (5.2) and drug interactions (7.2) ]. coadministration with the hmg-coa reductase inhibitors that are primarily metabolized through cyp3a4 (e.g., atorvastatin, lovastatin, and simvastatin) is contraindicated since increased plasma concentration of these drugs can lead to rhabdomyolysis [see drug interactions (7.3) and clinical pharmacology (12.3) ]. posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism [see drug interactions (7.4) ]. coadministration of posaconazole with venetoclax at initiation and during the ramp-up phase is contraindicated in patients with chronic lymphocytic leukemia (cll) or small lymphocytic lymphoma (sll) due to the potential for increased risk of tumor lysis syndrome [see warnings and precautions (5.10) and drug interactions (7.16) ]. risk summary based on findings from animal data, posaconazole may cause fetal harm when administered to pregnant women. available data for use of posaconazole in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal reproduction studies, skeletal malformations (cranial malformations and missing ribs) and maternal toxicity (reduced food consumption and reduced body weight gain) were observed when posaconazole was dosed orally to pregnant rats during organogenesis at doses ≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of posaconazole in healthy volunteers. in pregnant rabbits dosed orally during organogenesis, increased resorptions, reduced litter size, and reduced body weight gain of females were seen at doses 5 times the exposure achieved with the 400 mg twice daily oral suspension regimen. doses of ≥ 3 times the clinical exposure caused an increase in resorptions in these rabbits (see data ). based on animal data, advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data posaconazole resulted in maternal toxicity (reduced food consumption and reduced body weight gain) and skeletal malformations (cranial malformations and missing ribs) when given orally to pregnant rats during organogenesis (gestational days 6 through 15) at doses ≥27 mg/kg (≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of drug in healthy volunteers). the no-effect dose for malformations and maternal toxicity in rats was 9 mg/kg, which is 0.7 times the exposure achieved with the 400 mg twice daily oral suspension regimen. no malformations were seen in rabbits dosed during organogenesis (gestational days 7 through 19) at doses up to 80 mg/kg (5 times the exposure achieved with the 400 mg twice daily oral suspension regimen). in the rabbit, the no-effect dose was 20 mg/kg, while high doses of 40 mg/kg and 80 mg/kg (3 or 5 times the clinical exposure) caused an increase in resorptions. in rabbits dosed at 80 mg/kg, a reduction in body weight gain of females and a reduction in litter size were seen. risk summary there are no data on the presence of posaconazole in human milk, the effects on the breastfed infant, or the effects on milk production. posaconazole is excreted in the milk of lactating rats. when a drug is present in animal milk, it is likely that the drug will be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for posaconazole and any potential adverse effects on the breastfed child from posaconazole or from the underlying maternal condition. the safety and effectiveness of posaconazole injection for the prophylaxis of invasive aspergillus and candida infections have been established in pediatric patients aged 2 and older who are at high risk of developing these infections due to being severely immunocompromised, such as hsct recipients with gvhd or those with hematologic malignancies with prolonged neutropenia from chemotherapy. the safety and effectiveness of posaconazole injection for the treatment of invasive aspergillosis have been established in pediatric patients aged 13 years and older. use of posaconazole in these age groups is supported by evidence from adequate and well-controlled studies of posaconazole in adult and pediatric patients and additional pharmacokinetic and safety data in pediatric patients 2 years of age and older [see adverse reactions (6.1), clinical pharmacology (12.3) and clinical studies (14) ]. the safety and effectiveness of posaconazole have not been established in pediatric patients younger than 2 years of age. no overall differences in the safety of posaconazole injection was observed between geriatric patients and younger adult patients in the clinical trials; therefore, no dosage adjustment is recommended for any formulation of posaconazole in geriatric patients. no clinically meaningful differences in the pharmacokinetics of posaconazole were observed in geriatric patients compared to younger adult patients during clinical trials [see clinical pharmacology (12.3) ]. of the 279 patients treated with posaconazole injection in the posaconazole injection study, 52 (19%) were greater than 65 years of age. of the 230 patients treated with noxafil® (posaconazole) delayed-release tablets , 38 (17%) were greater than 65 years of age. of the 605 patients randomized to noxafil® (posaconazole) oral suspension in noxafil oral suspension study 1 and study 2, 63 (10%) were ≥65 years of age. of the 288 patients randomized to posaconazole injection/  noxafil® (posaconazole) delayed-release tablets in the aspergillosis treatment study, 85 (29%) were ≥65 years of age. no overall differences in the pharmacokinetics and safety were observed between elderly and young subjects during clinical trials, but greater sensitivity of some older individuals cannot be ruled out. posaconazole injection should be avoided in patients with moderate or severe renal impairment (egfr <50 ml/min), unless an assessment of the benefit/risk to the patient justifies the use of posaconazole injection. in patients with moderate or severe renal impairment (egfr <50 ml/min), receiving the posaconazole injection, accumulation of the intravenous vehicle, sbecd, is expected to occur. serum creatinine levels should be closely monitored in these patients, and, if increases occur, consideration should be given to changing to oral posaconazole therapy [see dosage and administration (2.9) and warnings and precautions (5.5) ]. after a single oral dose of noxafil® oral suspension 400 mg, the mean auc was 43%, 27%, and 21% higher in subjects with mild (child-pugh class a, n=6), moderate (child-pugh class b, n=6), or severe (child-pugh class c, n=6) hepatic impairment, respectively, compared to subjects with normal hepatic function (n=18). compared to subjects with normal hepatic function, the mean cmax was 1% higher, 40 % higher, and 34% lower in subjects with mild, moderate, or severe hepatic impairment, respectively. the mean apparent oral clearance (cl/f) was reduced by 18%, 36%, and 28% in subjects with mild, moderate, or severe hepatic impairment, respectively, compared to subjects with normal hepatic function. the elimination half-life (t½) was 27 hours, 39 hours, 27 hours, and 43 hours in subjects with normal hepatic function and mild, moderate, or severe hepatic impairment, respectively. it is recommended that no dose adjustment of posaconazole injection is needed in patients with mild to severe hepatic impairment (child-pugh class a, b, or c) [see dosage and administration (2) and warnings and precautions (5.4) ]. however, a specific study has not been conducted with posaconazole injection. the pharmacokinetics of posaconazole are comparable in males and females. no adjustment in the dosage of posaconazole injection is necessary based on gender. the pharmacokinetic profile of posaconazole is not significantly affected by race. no adjustment in the dosage of posaconazole injection is necessary based on race. pharmacokinetic modeling suggests that patients weighing greater than 120 kg may have lower posaconazole plasma drug exposure. it is, therefore, suggested to closely monitor for breakthrough fungal infections [see clinical pharmacology (12.3)].