Israël - anglais - Ministry of Health

novartis israel ltd - nilotinib as monohydrate - capsules - nilotinib as monohydrate 200 mg - nilotinib - nilotinib - treatment of philadelphia chromosome positive chronic myeloid leukaemia (ph+ cml) in chronic or accelerated phase in patients resistant to or experiencing significant toxicity during treatment with imatinib.treatment of adult patients with newly diagnosed philadelphia chromosome positive chronic myelogenous leukemia in chronic phase.

Israël - anglais - Ministry of Health

novartis israel ltd - nilotinib as hydrochloride monohydrate - capsules - nilotinib as hydrochloride monohydrate 150 mg - nilotinib - nilotinib - treatment of adult patients with newly diagnosed philadelphia chromosome positive chronic myelogenous leukemia in chronic phase.

Union européenne - anglais - EMA (European Medicines Agency)

roche registration gmbh - saquinavir - hiv infections - antivirals for systemic use - invirase is indicated for the treatment of hiv-1-infected adult patients. invirase should only be given in combination with ritonavir and other antiretroviral medicinal products.

Union européenne - anglais - EMA (European Medicines Agency)

pfizer europe ma eeig - voriconazole - candidiasis; mycoses; aspergillosis - antimycotics for systemic use - voriconazole, is a broad spectrum, triazole antifungal agent and is indicated in adults and children aged 2 years and above as follows:treatment of invasive aspergillosis;treatment of in candidaemianon-neutropenic patients;treatment of fluconazole-resistant serious invasive candida infections (including c. krusei);treatment of serious fungal infections caused by scedosporium spp. and fusarium spp.vfend should be administered primarily to patients with progressive, possibly life-threatening infections.prophylaxis of invasive fungal infections in high risk allogeneic hematopoietic stem cell transplant (hsct) recipients.

États-Unis - anglais - NLM (National Library of Medicine)

corcept therapeutics incorporated - mifepristone (unii: 320t6rnw1f) (mifepristone - unii:320t6rnw1f) - mifepristone 300 mg - korlym (mifepristone) is a cortisol receptor blocker indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery. limitations of use: - korlym should not be used in the treatment of patients with type 2 diabetes unless it is secondary to cushing's syndrome. korlym is contraindicated in: - pregnancy [see dosage and administration (2.1), use in specific populations (8.1,8.3)] - patients taking drugs metabolized by cyp3a such as simvastatin, lovastatin, and cyp3a substrates with narrow therapeutic ranges, such as cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus, due to an increased risk of adverse events. [see drug interactions (7.1) and clinical pharmacology (12.3)] - patients receiving systemic corticosteroids for lifesaving purposes (e.g., immunosuppression after organ transplantation) because korlym antagonizes the effect of glucocorticoids. - women with a history of unexplained vaginal bleeding or with endometrial hyperplasia with atypia or endometrial carcinoma. - patients with known hypersensitivity to mifepristone or to any of the product components. risk summary korlym is contraindicated in pregnancy because the use of korlym results in pregnancy loss. there are no data that assess the risk of birth defects in women exposed to korlym during pregnancy. available data limited to exposure following a single dose of mifepristone during pregnancy showed a higher rate of major birth defects compared to the general population comparator (see data) . mifepristone administered to pregnant mice, rats, and rabbits during organogenesis caused pregnancy loss in all species at clinically relevant doses based on body surface area comparisons (see data) . the inhibition of both endogenous and exogenous progesterone by mifepristone at the progesterone receptor results in pregnancy loss. if korlym is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. [see contraindications (4)] the estimated risk of fetal loss is elevated in patients with active cushing's syndrome (24-30%), and the risk of major birth defects is unknown. in the u.s. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively. data human data there are no data on long term exposure to mifepristone in pregnancy. available data are limited to exposure to a single dose of mifepristone for pregnancy termination. in a prospective study in france of 46 pregnancies exposed to a single dose of mifepristone alone and 59 pregnancies exposed to a single dose of mifepristone and misoprostol, the overall major birth defect rate (4%) was greater than the general population background rate of 2 to 3% (2 birth defects in each group). there was no pattern of birth defects identified. animal data reproductive studies were performed in mice, rats and rabbits at doses of 0.25 to 4.0 mg/kg (less than human exposure at the maximum clinical dose, based on body surface area). because of the anti-progestational activity of mifepristone, fetal losses were much higher than in control animals. skull deformities were detected in rabbit studies at less than human exposure, although mifepristone did not cause any adverse developmental effects in rats or mice during organogenesis. these deformities were most likely due to the mechanical effects of uterine contractions resulting from antagonism of the progesterone receptor. risk summary mifepristone is present in human milk, however, there are no data on the amount of mifepristone in human milk, the effects on the breastfed infant, or the effects on milk production during long term use of mifepristone (see data) . the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for korlym and any potential adverse effects on the breastfed child from korlym or from the underlying maternal condition. clinical considerations to minimize exposure to a breastfed infant, women who discontinue or interrupt korlym treatment may consider pumping and discarding milk during treatment and for 18-21 days (5-6 half-lives) after the last dose, before breastfeeding. data available published data based on intake of a single dose of 600 mg of mifepristone in 10 breastfeeding women who were 6-12 months postpartum showed a small amount in breast milk (the estimated relative infant dose was 0.5%). the half-life of mifepristone is longer with repeat dosing compared to a single dose; therefore, there may be greater exposure with long term use. pregnancy testing due to its anti-progestational activity, korlym causes pregnancy loss. perform pregnancy testing before the initiation of treatment with korlym or if treatment is interrupted for more than 14 days in females of reproductive potential. contraception recommend non-hormonal contraception for the duration of treatment and for one month after stopping treatment . korlym interferes with the effectiveness of hormonal contraceptives. [see drug interactions (7.6)] safety and effectiveness of korlym in pediatric patients have not been established. clinical studies with korlym did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger people. the maximum dose should not exceed 600 mg per day in renally impaired patients. [see clinical pharmacology (12.3)] in patients with mild to moderate hepatic impairment, the maximum dose should not exceed 600 mg per day. the pharmacokinetics of mifepristone in patients with severe hepatic impairment has not been studied, and korlym should not be used in these patients. [see clinical pharmacology (12.3)]

États-Unis - anglais - NLM (National Library of Medicine)

zydus lifesciences limited - voriconazole (unii: jfu09i87tr) (voriconazole - unii:jfu09i87tr) - voriconazole 50 mg - voriconazole tablets are indicated in adults and pediatric patients (2 years of age and older) 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, 14.5) and microbiology (12.4)].   voriconazole tablets are indicated in adults and pediatric patients (2 years of age and older) 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, 14.5) and microbiology (12.4)]. voriconazole tablets are indicated in adults and pediatric patients (2 years of age and older) for the treatment of esophageal candidiasis (ec) in adults and pediatric patients 2 years of age and older [see clinical studies (14.3, 14.5) and microbiology (12.4)]. voriconazole tablets are indicated for the treatment of serious fungal infections caused by scedosporium apiospermum (asexual form of pseudallescheria boydii ) and fusarium spp. including fusarium solani , in adults and pediatric patients 2 years of age and older intolerant of, or refractory to, other therapy [see clinical studies (14.4) 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. - voriconazole tablets are contraindicated in patients with known hypersensitivity to voriconazole or its excipients. there is no information regarding cross-sensitivity between voriconazole and other azole antifungal agents. caution should be used when prescribing voriconazole to patients with hypersensitivity to other azoles. - coadministration of pimozide , quinidine or ivabradine with voriconazole 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 with sirolimus is contraindicated because voriconazole significantly increases sirolimus concentrations [see drug interactions (7) and clinical pharmacology (12.3) ]. - coadministration of voriconazole 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 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 with rifabutin is contraindicated since voriconazole 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 with ergot alkaloids (ergotamine and dihydroergotamine) is contraindicated because voriconazole may increase the plasma concentration of ergot alkaloids, which may lead to ergotism [see drug interactions (7) ]. - coadministration of voriconazole with naloxegol is contraindicated because voriconazole may increase plasma concentrations of naloxegol which may precipitate opioid withdrawal symptoms [see drug interactions (7)] . - coadministration of voricoazole with tolvaptan is contraindicated because voriconazole may increase tolvaptan plasma concentrations and increase risk of adverse reactions [see drug interactions (7) ]. - coadministration of voriconazole 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 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 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 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 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 and any potential adverse effects on the breastfed child from voriconazole or from the underlying maternal condition. contraception advise females of reproductive potential to use effective contraception during treatment with voriconazole. 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 2 years of age and older based on evidence from adequate and well-controlled studies in adult and pediatric patients and additional pediatric pharmacokinetic and safety data. a total of 105 pediatric patients aged 2 to less than 12 [n=26] and aged 12 to less than 18 [n=79] from two, non-comparative phase 3 pediatric studies and 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 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 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)] . 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) ].

États-Unis - anglais - NLM (National Library of Medicine)

golden state medical supply, inc. - ketoconazole (unii: r9400w927i) (ketoconazole - unii:r9400w927i) - ketoconazole 200 mg - ketoconazole tablets are not indicated for treatment of onychomycosis, cutaneous dermatophyte infections, or candida infections. ketoconazole tablets should be used only when other effective antifungal therapy is not available or tolerated and the potential benefits are considered to outweigh the potential risks. ketoconazole tablets are indicated for the treatment of the following systemic fungal infections in patients who have failed or who are intolerant to other therapies: blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis. ketoconazole tablets should not be used for fungal meningitis because it penetrates poorly into the cerebrospinal fluid. coadministration of a number of cyp3a4 substrates such as dofetilide, quinidine, cisapride and pimozide is contraindicated with ketoconazole tablets. coadministration with ketoconazole can cause elevated plasma concentrations of these drugs and may increase or prolong both therapeutic and adverse effects to such an extent that a potentially serious adverse reaction may occur. for example, increased plasma concentrations of some of these drugs can lead to qt prolongation and sometimes resulting in life-threatening ventricular tachyarrhythmias including occurrences of torsades de pointes, a potentially fatal arrhythmia. (see precautions: drug interactions.) coadministration of ketoconazole tablets with lurasidone is contraindicated since it may result in an increase in lurasidone exposure and the potential for serious adverse reactions (see precautions: drug interactions). additionally, the following other drugs are contraindicated with ketoconazole tablets: methadone, disopyramide, dronedarone, ergot alkaloids such as dihydroergotamine, ergometrine, ergotamine, methylergometrine, irinotecan, lurasidone, oral midazolam, alprazolam, triazolam, felodipine, nisoldipine, ranolazine, tolvaptan, eplerenone, lovastatin, simvastatin and colchicine. (see precautions: drug interactions.) coadministration of ketoconazole tablets with oral midazolam, oral triazolam or alprazolam has resulted in elevated plasma concentrations of these drugs. this may potentiate and prolong hypnotic and sedative effects, especially with repeated dosing or chronic administration of these agents. concomitant administration of ketoconazole tablets with oral triazolam, oral midazolam or alprazolam is contraindicated. (see precautions: drug interactions.) coadministration of cyp3a4 metabolized hmg-coa reductase inhibitors such as simvastatin, and lovastatin is contraindicated with ketoconazole tablets. (see precautions: drug interactions.) concomitant administration of ergot alkaloids such as dihydroergotamine and ergotamine with ketoconazole tablets is contraindicated. (see precautions: drug interactions.) the use of ketoconazole tablets is contraindicated in patients with acute or chronic liver disease. ketoconazole tablets usp, 200 mg is contraindicated in patients who have shown hypersensitivity to the drug.

Royaume-Uni - anglais - MHRA (Medicines & Healthcare Products Regulatory Agency)

kyowa kirin international uk newco ltd - glyceryl trinitrate - rectal ointment - 4mg/1gram

Royaume-Uni - anglais - MHRA (Medicines & Healthcare Products Regulatory Agency)

de pharmaceuticals - itraconazole - oral capsule - 100mg

Royaume-Uni - anglais - MHRA (Medicines & Healthcare Products Regulatory Agency)

morningside healthcare ltd - clarithromycin - modified-release tablet - 500mg