Združene države Amerike - angleščina - NLM (National Library of Medicine)

genentech, inc. - emicizumab (unii: 7nl2e3f6k3) (emicizumab - unii:7nl2e3f6k3) - hemlibra is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients ages newborn and older with hemophilia a (congenital factor viii deficiency) with or without factor viii inhibitors. none. risk summary there are no available data on hemlibra use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. animal reproduction studies have not been conducted with emicizumab-kxwh. it is not known whether hemlibra can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. hemlibra should be used during pregnancy only if the potential benefit for the mother outweighs the risk to the fetus. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. the estimated 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 defect and miscarriage in clinically recognized pregnancies is 2 – 4% and 15 – 20%, respectively. risk summary there is no information regarding the presence of emicizumab-kxwh in human milk, the effects on the breastfed child, or the effects on milk production. human igg is known to be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for hemlibra and any potential adverse effects on the breastfed child from hemlibra or from the underlying maternal condition. contraception women of childbearing potential should use contraception while receiving hemlibra. the safety and efficacy of hemlibra have been established in pediatric patients. use of hemlibra in pediatric patients with hemophilia a is supported by two randomized trials (haven 1 and haven 3) and two single-arm trials (haven 2 and haven 4). all clinical trials included pediatric patients in the following age group: 47 adolescents (12 years up to less than 18 years). only haven 2 included pediatric patients in the following age groups: 55 children (2 years up to less than 12 years) and five infants (1 month up to less than 2 years). no differences in efficacy were observed between the different age groups [see clinical studies (14)] . the steady-state plasma trough concentrations of emicizumab-kxwh were comparable in adult and pediatric patients older than 6 months at equivalent weight-based doses. lower concentrations of emicizumab-kxwh were predicted in pediatric patients less than 6 months old [see clinical pharmacology (12.3)] . in general, the adverse reactions in hemlibra-treated pediatric patients were similar in type to those seen in adult patients with hemophilia a [see adverse reactions (6.1)] . clinical studies of hemlibra did not include a sufficient number of patients aged 65 and over to determine whether they respond differently from younger patients. other reported clinical experience has not identified differences in responses between the elderly and younger patients. be sure that you read, understand, and follow this instructions for use before injecting hemlibra. your healthcare provider should show you or your caregiver how to prepare, measure, and inject hemlibra properly before you use it for the first time. ask your healthcare provider if you have any questions. important information: - do not inject yourself or someone else unless you have been shown how to by your healthcare provider. - make sure the name hemlibra appears on the box and vial label. - before opening the vial, read the vial label to make sure you have the medicine strength(s) needed to give the dose prescribed by your healthcare provider. - your healthcare provider will determine your dose in milliliters (ml) that you will need to give based on your body weight. - hemlibra comes in multiple strengths. depending on your dose, you may need to use more than one vial to give your total prescribed dose. do not combine hemlibra vials of different concentrations in one injection to give the prescribed dose. - check the expiration date on the box and vial label. do not use if the expiration date has passed. - only use the vial one time. after you inject your dose, dispose of (throw away) any unused hemlibra left in the vial. do not save unused hemlibra in the vial for later use. - only use the syringes, transfer needles, and injection needles that your healthcare provider prescribes. - only use the syringes, transfer needles and injection needles one time. dispose of (throw away) any used syringes and needles in a sharps disposal container. - if your prescribed dose is more than 2 ml, you will need to give more than one injection of hemlibra. storing hemlibra: - store hemlibra in the refrigerator at 36°f to 46°f (2°c to 8°c). do not freeze. - store hemlibra in the original carton to protect the vials from light. - do not shake hemlibra. - take the vial out of the refrigerator 15 minutes before use and allow it to reach room temperature before preparing an injection. - before giving the injection, unopened vials of hemlibra may be stored out of the refrigerator and then returned to the refrigerator. hemlibra should not be stored out of the refrigerator: for more than a total of 7 days or at a temperature greater than 86°f (30°c). - for more than a total of 7 days or - at a temperature greater than 86°f (30°c). keep hemlibra and all medicines out of the reach of children. inspecting the hemlibra vial and your supplies: - collect all supplies listed below to prepare and give your injection. - check the expiration date on the box, on the vial label, and on the supplies listed below. do not use if the expiration date has passed. - inspect the supplies for damage. do not use if they appear damaged or if they have been dropped. - place the supplies on a clean, well-lit flat work surface. hemlibra is colorless to slightly yellow in color. do not use the vial if: - the medicine is cloudy, hazy, or colored. - the medicine contains particles. - the cap covering the stopper is missing. - vial containing hemlibra - hemlibra instructions for use - alcohol wipes note: if you need to use more than one vial to inject your prescribed dose, you must use a new alcohol wipe for each vial. - gauze - cotton ball - syringe note: for injection amount up to 1 ml, use a 1 ml syringe. for injection amount between 1 ml and 2 ml, use a 2 ml or 3 ml syringe. - 18 gauge transfer needle with 5 micrometer filter. note: if you need to use more than one vial to inject your prescribed dose, you must use a new transfer needle for each vial. do not use the transfer needle to inject hemlibra. - injection needle with safety shield. you may use a 25, 26 or 27 gauge needle. do not use the injection needle to withdraw hemlibra from vial. - sharps disposal container - before use, allow the vial(s) to warm up to room temperature for about 15 minutes on a clean flat surface away from direct sunlight. - do not try to warm the vial by any other way. - wash your hands well with soap and water. - clean the chosen injection site area using an alcohol wipe. - let the skin dry for about 10 seconds. do not touch, fan, or blow on the cleaned area before your injection. - you can use your: thigh (front and middle). stomach area (abdomen), except for 2 inches around the navel (belly button). outer area of the upper arm (only if a caregiver is giving the injection). - thigh (front and middle). - stomach area (abdomen), except for 2 inches around the navel (belly button). - outer area of the upper arm (only if a caregiver is giving the injection). - you should use a different injection site each time you give an injection, at least 1 inch away from the area you used for your previous injection. - do not inject into areas that could be irritated by a belt or waistband. do not inject into moles, scars, bruises, or areas where the skin is tender, red, hard, or the skin is broken. preparing the syringe for injection: - hemlibra must not be stored in the syringe . - hemlibra in the syringe must be injected under the skin (subcutaneous injection) immediately. - dispose of (throw away) any used vial(s), needles, vial and injection needle caps, and used syringes in a sharps disposal container. important information after the injection: - do not rub the injection site after an injection. - if you see drops of blood at the injection site, you can press a sterile cotton ball or gauze over the injection site for at least 10 seconds, until bleeding has stopped. - if you have bruising (small area of bleeding under the skin), an ice pack can also be applied with gentle pressure to the site. if bleeding does not stop, please contact your healthcare provider. disposing of used hemlibra vial(s), needles, and syringes: - put your used needles and syringes in a fda-cleared sharps disposal container right away after use. do not dispose of (throw away) any loose needles and syringes in your household trash. - if you do not have a fda-cleared sharps disposal container, you may use a household container that is: made of heavy-duty plastic. can be closed with a tight-fitting, puncture resistant lid, without sharps being able to come out. upright and stable during use. leak-resistant. properly labeled to warn of hazardous waste inside the container. - made of heavy-duty plastic. - can be closed with a tight-fitting, puncture resistant lid, without sharps being able to come out. - upright and stable during use. - leak-resistant. - properly labeled to warn of hazardous waste inside the container. - when your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. there may be state or local laws about how you should throw away used needles and syringes. for more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the fda's website at: http://www.fda.gov/safesharpsdisposal. - do not dispose of (throw away) any used sharps disposal container in your household trash unless your community guidelines permit this. do not recycle your used sharps disposal container. important: always keep the sharps disposal container out of reach of children. 1. preparation - take the cap off the vial(s). - clean the top of the vial(s) stopper with an alcohol wipe. - dispose of (throw away) the vial cap(s) into the sharps disposal container. - push and twist the transfer needle with filter clockwise on to the syringe until it is fully attached. - slowly pull back on the plunger and draw air into the syringe that is the same amount for your prescribed dose. - hold the syringe by the barrel with the transfer needle pointing up. - carefully pull the transfer needle cap straight off and away from your body. do not throw the cap away. place the transfer needle cap down on a clean flat surface. you will need to recap the transfer needle after transferring the medicine. - do not touch the needle tip or place it on a surface after the needle cap has been removed. - keep the vial on the flat working surface and insert the transfer needle and syringe straight down into the center of the vial stopper. - keep the needle in the vial and turn the vial upside down. - with the needle pointing upwards, push on the plunger to inject the air from the syringe above the medicine. - keep your finger pressed down on the syringe plunger. - do not inject air into the medicine as this could create air bubbles or foam in the medicine. - slide the tip of the needle down so that it is within the medicine. - slowly pull back the plunger to prevent air bubbles/foam. fill the syringe with more than the amount of hemlibra needed for your prescribed dose. - be careful not to pull the plunger out of the syringe. - keep the needle in the vial and check the syringe for larger air bubbles. too large an air bubble can reduce the dose you receive. - remove the larger air bubbles by gently tapping the syringe barrel with your fingers until the air bubbles rise to the top of the syringe. move the tip of the needle above the medicine and slowly push the plunger up to push the air bubbles out of the syringe. - if the amount of hemlibra in the syringe is now at or below your prescribed dose, move the tip of the needle to within the medicine and slowly pull back the plunger until you have more than the amount of hemlibra needed for your prescribed dose. - be careful not to pull the plunger out of the syringe. - repeat the steps above until you have removed the larger air bubbles. do not use the transfer needle to inject hemlibra as this may cause harm such as pain and bleeding. 2. injection - remove the syringe and transfer needle from the vial. - using one hand, slide the transfer needle into the cap and scoop upwards to cover the needle. - once the needle is covered, push the transfer needle cap towards the syringe to fully attach it with one hand to prevent accidentally sticking yourself with the needle. - select and clean your injection site with an alcohol wipe. - let the skin dry for about 10 seconds. do not touch, fan, or blow on the cleaned area before your injection. - remove the transfer needle from the syringe by twisting counter-clockwise and gently pulling. - dispose of (throw away) the used transfer needle into a sharps disposal container. - push and twist the injection needle clockwise on to the syringe until it is fully attached. - move the safety shield away from the needle and towards the syringe barrel. - carefully pull the injection needle cap away from the syringe. - dispose of (throw away) the cap into a sharps disposal container. - do not touch the needle tip or allow it to touch any surface. - after the injection needle cap has been removed, hemlibra in the syringe must be injected right away. - slowly push the plunger to your prescribed dose. - ensure the top rim of the plunger is in line with the mark on the syringe for your prescribed dose. - pinch the selected injection site and fully insert the needle at a 45° to 90° angle with a quick, firm action. do not hold or push on the plunger while inserting the needle. - hold the position of the syringe and let go of the pinched injection site. - slowly inject all of hemlibra by gently pushing the plunger all the way down. - remove the needle and syringe from the injection site at the same angle as inserted. 3. disposal - move the safety shield forward 90°, away from the syringe barrel. - holding the syringe with one hand, press the safety shield down against a flat surface with a firm, quick motion until you hear a "click". - if you do not hear a click, look to see that the needle is fully covered by the safety shield. - keep your fingers behind the safety shield and away from the needle at all times. - do not remove the injection needle from the syringe. - put your used needles and syringes in a fda-cleared sharps disposal container right away after use. for further information, refer to the section "disposing of used hemlibra vial(s), needles, and syringes" above. - do not try to remove the used injection needle from the used syringe. - do not recap the injection needle with the cap. - important: always keep the sharps disposal container out of reach of children. - dispose of (throw away) any used vial(s), needles, vial and injection needle caps, and used syringes in a sharps disposal container. if you need to use more than one vial to get to your total prescribed dose, follow these steps after you have drawn up hemlibra from the first vial: - remove the syringe and transfer needle from the first vial. - using one hand , slide the transfer needle into the cap and scoop upwards to cover the needle. - once the needle is covered, push the transfer needle cap toward the syringe to fully attach it with one hand to prevent accidentally sticking yourself with the needle. - remove the transfer needle from the syringe by twisting counter- clockwise and gently pulling. - dispose of (throw away) the used transfer needle into a sharps disposal container. - push and twist a new transfer needle clockwise on to the syringe until it is fully attached. - slowly pull back the plunger and draw some air into the syringe. - hold the syringe by the barrel with the transfer needle cap pointing up. - carefully pull the transfer needle cap straight off and away from your body. do not throw the cap away. you will need to recap the transfer needle after drawing up the medicine. - do not touch the needle tip. - with the new vial on the flat working surface, insert the new transfer needle and syringe, straight down into the center of the vial stopper. - keep the transfer needle in the vial and turn the vial upside down. - with the needle pointing upwards, inject the air from the syringe above the medicine. - keep your finger pressed down on the syringe plunger. - do not inject air into the medicine as this could create air bubbles or foam in the medicine. - slide the tip of the needle down so that it is within the medicine. - slowly pull back the plunger to prevent air bubbles/foam. fill the syringe barrel with more than the amount of hemlibra needed for your prescribed dose. - be careful not to pull the plunger out of the syringe. do not use the transfer needle to inject hemlibra as this may cause harm such as pain and bleeding. for more information, go to www.hemlibra.com or call 1-866-hemlibra. hemlibra® [emicizumab-kxwh] manufactured by: genentech, inc . a member of the roche group 1 dna way south san francisco, ca 94080-4990 hemlibra® is a registered trademark of chugai pharmaceutical co., ltd., tokyo, japan ©2023 genentech, inc. all rights reserved. u.s. license no. 1048 this instructions for use has been approved by the u.s. food and drug administration. revised: 07/2023

Združene države Amerike - angleščina - NLM (National Library of Medicine)

genentech, inc. - mycophenolate mofetil (unii: 9242ecw6r0) (mycophenolic acid - unii:hu9dx48n0t) - mycophenolate mofetil 500 mg - cellcept [mycophenolate mofetil (mmf)] is indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney [see clinical studies (14.1)], heart [see clinical studies (14.2)] or liver transplants [see clinical studies (14.3)] , in combination with other immunosuppressants. allergic reactions to cellcept have been observed; therefore, cellcept is contraindicated in patients with a hypersensitivity to mycophenolate mofetil (mmf), mycophenolic acid (mpa) or any component of the drug product. cellcept intravenous is contraindicated in patients who are allergic to polysorbate 80 (tween). 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 cellcept treatment. to report a pregnancy or obtain information about the registry, visit www.mycophenolaterems.com or call 1-800-617-8191. risk summary use of mycophenolate mofetil (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 (0.01 to 0.05 times the recommended clinical doses in kidney and heart transplant patients) [see animal data]. consider alternative immunosuppressants with less potential for embryofetal toxicity. risks and benefits of cellcept should be discussed with the pregnant woman. 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, there were increased rates of fetal resorptions and malformations in the absence of maternal toxicity. oral administration of mmf to pregnant rats from gestational day 7 to day 16 produced increased embryofetal lethality and fetal malformations including anophthalmia, agnathia, and hydrocephaly at doses equivalent to 0.015 and 0.01 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for bsa. oral administration of mmf to pregnant rabbits from gestational day 7 to day 19 produced increased embryofetal lethality and fetal malformations included ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical hernia at dose equivalents as low as 0.05 and 0.03 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for 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 (mpa) 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 cellcept and any potential adverse effects on the breastfed infant from cellcept or from the underlying maternal condition. 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 34-40 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 patients who are considering pregnancy, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible. risks and benefits of cellcept should be discussed with the patient. pregnancy testing to prevent unplanned exposure during pregnancy, all females of reproductive potential should have a serum or urine pregnancy test with a sensitivity of at least 25 miu/ml immediately before starting cellcept. 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 embryofetal toxicity whenever possible. contraception female patients females of reproductive potential taking cellcept must receive contraceptive counseling and use acceptable contraception (see table 9 for acceptable contraception methods). patients must use acceptable birth control during the entire cellcept therapy, and for 6 weeks after stopping cellcept, unless the patient chooses abstinence. patients should be aware that cellcept reduces blood levels of the hormones from the oral contraceptive pill and could theoretically reduce its effectiveness [see drug interactions (7.2)]. - intrauterine devices (iuds) - tubal sterilization - patient's partner vasectomy - oral contraceptive pill - transdermal patch - vaginal ring - injection - implant - diaphragm with spermicide - cervical cap with spermicide - contraceptive sponge - male condom - female condom - diaphragm with spermicide - cervical cap with spermicide - contraceptive sponge - male condom - female condom male patients genotoxic effects have been observed in animal studies at exposures exceeding the human therapeutic exposures by approximately 1.25 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 cellcept and for at least 90 days after cessation of treatment [see use in special populations (8.1), nonclinical toxicology (13.1), patient counseling information (17.9)] . safety and effectiveness have been established in pediatric patients 3 months and older for the prophylaxis of organ rejection of allogenic kidney, heart or liver transplants. kidney transplant use of cellcept in this population is supported by evidence from adequate and well-controlled studies of cellcept in adults with additional data from one open-label, pharmacokinetic and safety study of cellcept in pediatric patients after receiving allogeneic kidney transplant (100 patients, 3 months to 18 years of age) [see dosage and administration (2.2), adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.1)] . heart transplant and liver transplant use of cellcept in pediatric heart transplant and liver transplant patients is supported by adequate and well-controlled studies and pharmacokinetic data in adult heart transplant and liver transplant patients. additional supportive data include pharmacokinetic data in pediatric kidney transplant and pediatric liver transplant patients (8 liver transplant patients, 9 months to 5 years of age, in an open-label, pharmacokinetic and safety study) and published evidence of clinical efficacy and safety in pediatric heart transplant and pediatric liver transplant patients [see dosage and administration (2.3, 2.4), adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.1)] . clinical studies of cellcept did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between geriatric and younger patients. in general, dose selection for a geriatric patient should take into consideration the presence of decreased hepatic, renal or cardiac function and of concomitant drug therapies [see adverse reactions (6.1), drug interactions (7)]. patients with kidney transplant no dosage adjustments are needed in kidney transplant patients experiencing delayed graft function postoperatively but patients should be carefully monitored [see clinical pharmacology (12.3)]. in kidney transplant patients with severe chronic impairment of the graft (gfr <25 ml/min/1.73 m2 ), no dose adjustments are necessary; however, doses greater than 1 g administered twice a day should be avoided. patients with heart and liver transplant no data are available for heart or liver transplant patients with severe chronic renal impairment. cellcept may be used for heart or liver transplant patients with severe chronic renal impairment if the potential benefits outweigh the potential risks. patients with kidney transplant no dosage adjustments are recommended for kidney transplant patients with severe hepatic parenchymal disease. however, it is not known whether dosage adjustments are needed for hepatic disease with other etiologies [see clinical pharmacology (12.3)]. patients with heart transplant no data are available for heart transplant patients with severe hepatic parenchymal disease. read this instructions for use before you take or give cellcept for the first time and each time you get a refill. there may be new information. this information does not take the place of talking to your healthcare provider about your medical condition or treatment. important: - always use the oral dispenser provided with cellcept oral suspension to make sure you measure the right amount of medicine. if your cellcept oral suspension does not come with the oral dispenser, contact your pharmacist. - call your pharmacist if your oral dispenser is lost or damaged. - your pharmacist will write the expiration date on your cellcept oral suspension bottle label. do not use cellcept after the expiration date. - ask your doctor or pharmacist if you have any questions or are unsure about how to take or give the right amount of medicine. - the cellcept oral suspension should not be mixed with any type of liquids before taking or giving the dose. - do not let the cellcept oral suspension come in contact with the skin. if this happens, wash the skin well with soap and water. if the cellcept oral suspension gets in the eyes, rinse the eyes with plain water. - if you spill any cellcept oral suspension, wipe it up using paper towels wet with water. put the child-resistant bottle cap back on the bottle and wipe the outside of the bottle with wet paper towels. supplies needed to take or give a dose of cellcept oral suspension : to take or give a dose of cellcept oral suspension, you will need the bottle of medicine and the oral dispenser provided with the medicine (see figure 1 ). your pharmacist will insert the bottle adapter in the cellcept oral suspension bottle. do not remove the bottle adapter from the bottle. taking or giving a dose of cellcept oral suspension: - remove the plunger from the oral dispenser. - rinse the oral dispenser and plunger with water only and let them air dry on a paper towel. - when the oral dispenser and plunger are dry, put the plunger back in the oral dispenser for the next use. do not throw away the oral dispenser. store the oral dispenser in a clean, dry place. - do not boil the oral dispenser. do not use solvent-containing wipes to clean the oral dispenser. do not use cloths or wipes to dry the oral dispenser. how should i store cellcept oral suspension? - store the cellcept oral suspension at room temperature between 59°f to 86°f (15°c to 30°c), for up to 60 days. you can also store the cellcept oral suspension in the refrigerator between 36°f to 46°f (2°c to 8°c). ) - do not freeze. keep cellcept oral suspension and all medicines out of the reach of children. distributed by: genentech usa, inc. a member of the roche group 1 dna way south san francisco, ca 94080-4990 © 2022 genentech, inc. all rights reserved. this instructions for use has been approved by the u.s. food and drug administration. revised: august 2022

Združene države Amerike - angleščina - NLM (National Library of Medicine)

genentech, inc. - rituximab (unii: 4f4x42syq6) (rituximab - unii:4f4x42syq6) - rituximab 10 mg in 1 ml - rituxan is indicated for the treatment of adult patients with: - relapsed or refractory, low-grade or follicular, cd20-positive, b-cell nhl as a single agent. - previously untreated follicular, cd20-positive, b-cell nhl in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy. - non-progressing (including stable disease), low-grade, cd20-positive, b-cell nhl as a single agent after first-line cyclophosphamide, vincristine, and prednisone (cvp) chemotherapy. - previously untreated diffuse large b-cell, cd20-positive nhl in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (chop) or other anthracycline-based chemotherapy regimens. rituxan is indicated for the treatment of pediatric patients aged 6 months and older with: - previously untreated, advanced stage, cd20-positive diffuse large b-cell lymphoma (dlbcl), burkitt lymphoma (bl), burkitt-like lymph

Združene države Amerike - angleščina - NLM (National Library of Medicine)

genentech, inc. - clonazepam (unii: 5pe9fde8gb) (clonazepam - unii:5pe9fde8gb) - clonazepam 0.5 mg - klonopin is useful alone or as an adjunct in the treatment of the lennox-gastaut syndrome (petit mal variant), akinetic, and myoclonic seizures. in patients with absence seizures (petit mal) who have failed to respond to succinimides, klonopin may be useful. some loss of effect may occur during the course of clonazepam treatment (see precautions: loss of effect). klonopin is indicated for the treatment of panic disorder, with or without agoraphobia, as defined in dsm-v. panic disorder is characterized by the occurrence of unexpected panic attacks and associated concern about having additional attacks, worry about the implications or consequences of the attacks, and/or a significant change in behavior related to the attacks. the efficacy of klonopin was established in two 6- to 9-week trials in panic disorder patients whose diagnoses corresponded to the dsm-iiir category of panic disorder (see clinical pharmacology: clinical trials). panic disorder (dsm-v) is characterized by recurrent unexpected panic attacks, i.e., a discrete period of intense fear or discomfort in which four (or more) of the following symptoms develop abruptly and reach a peak within 10 minutes: (1) palpitations, pounding heart or accelerated heart rate; (2) sweating; (3) trembling or shaking; (4) sensations of shortness of breath or smothering; (5) feeling of choking; (6) chest pain or discomfort; (7) nausea or abdominal distress; (8) feeling dizzy, unsteady, lightheaded or faint; (9) derealization (feelings of unreality) or depersonalization (being detached from oneself); (10) fear of losing control; (11) fear of dying; (12) paresthesias (numbness or tingling sensations); (13) chills or hot flushes. the effectiveness of klonopin in long-term use, that is, for more than 9 weeks, has not been systematically studied in controlled clinical trials. the physician who elects to use klonopin for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient (see dosage and administration). klonopin is contraindicated in patients with the following conditions: - history of sensitivity to benzodiazepines - clinical or biochemical evidence of significant liver disease - acute narrow angle glaucoma (it may be used in patients with open angle glaucoma who are receiving appropriate therapy). klonopin contains clonazepam, a schedule iv controlled substance. klonopin is a benzodiazepine and a cns depressant with a potential for abuse and addiction. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. abuse and misuse of benzodiazepines may lead to addiction. abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death. benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders (see warnings: abuse, misuse, and addiction). the following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo. the following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. death is more often associated with polysubstance use (especially benzodiazepines with other cns depressants such as opioids and alcohol). klonopin may produce physical dependence from continued therapy. physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use (see warnings: dependence and withdrawal reactions). to reduce the risk of withdrawal reactions, use a gradual taper to discontinue klonopin or reduce the dosage (see dosage and administration: discontinuation or dosage reduction of klonopin and warnings: dependence and withdrawal reactions). acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. more severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicidality. protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. protracted withdrawal symptoms may last weeks to more than 12 months. as a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used. tolerance to klonopin may develop from continued therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). tolerance to the therapeutic effect of klonopin may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines. following the short-term treatment of patients with panic disorder in studies 1 and 2 (see clinical pharmacology: clinical trials), patients were gradually withdrawn during a 7-week downward-titration (discontinuance) period. overall, the discontinuance period was associated with good tolerability and a very modest clinical deterioration, without evidence of a significant rebound phenomenon. however, there are not sufficient data from adequate and well-controlled long-term clonazepam studies in patients with panic disorder to accurately estimate the risks of withdrawal symptoms and dependence that may be associated with such use.

Združene države Amerike - angleščina - NLM (National Library of Medicine)

genentech, inc. - vemurafenib (unii: 207smy3fqt) (vemurafenib - unii:207smy3fqt) - vemurafenib 240 mg - zelboraf® is indicated for the treatment of patients with unresectable or metastatic melanoma with braf v600e mutation as detected by an fda-approved test. limitation of use: zelboraf is not indicated for treatment of patients with wild-type braf melanoma [see warnings and precautions (5.2)] . zelboraf® is indicated for the treatment of patients with erdheim-chester disease (ecd) with braf v600 mutation. none. risk summary based on its mechanism of action, zelboraf can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . there are no available data on the use of zelboraf in pregnant women to determine the drug-associated risk; however, placental transfer of vemurafenib to a fetus has been reported. exposure to vemurafenib could not be achieved in animals at levels sufficient to fully address its potential toxicity in pregnant women. advise pregnant women of the potential harm to a fetus. the estimated background risks of major birth defects and miscarriage for the indicated population(s) are 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 vemurafenib showed no evidence of developmental toxicity in rat fetuses at doses up to 250 mg/kg/day (approximately 1.3 times the clinical exposure at 960 mg twice daily based on auc) or rabbit fetuses at doses up to 450 mg/kg/day (approximately 0.6 times the clinical exposure at 960 mg twice daily based on auc). fetal drug levels were 3–5% of maternal levels, indicating that vemurafenib has the potential to be transmitted from the mother to the developing fetus. there is no information available regarding the presence of vemurafenib in human milk, effects on the breastfed infant, or effects on milk production. because of the potential for serious adverse reactions in a breastfed infant, including malignancy, severe dermatologic reactions, qt prolongation, hepatotoxicity, photosensitivity, and ophthalmologic toxicity, [see warnings and precautions (5)] , advise women not to breastfeed during treatment with zelboraf and for 2 weeks after the final dose. contraception based on its mechanism of action, zelboraf can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . advise females of reproductive potential to use effective contraception during treatment with zelboraf and for 2 weeks after the final dose. the safety and effectiveness of zelboraf in pediatric patients have not been established. vemurafenib was studied in 6 adolescent patients 15 to 17 years of age with unresectable or metastatic melanoma with braf v600 mutation. a maximum tolerated dose was not reached with doses up to vemurafenib 960 mg twice daily. no new safety signals were observed. vemurafenib steady-state exposure in these 6 adolescent patients was generally similar to that in adults. clinical studies of zelboraf did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. no formal clinical study has been conducted to evaluate the effect of hepatic impairment on the pharmacokinetics of vemurafenib. no dose adjustment is recommended for patients with mild and moderate hepatic impairment based on a population pharmacokinetic analysis [see clinical pharmacology (12.3)]. the appropriate dose of zelboraf has not been established in patients with severe hepatic impairment. no formal clinical study has been conducted to evaluate the effect of renal impairment on the pharmacokinetics of vemurafenib. no dose adjustment is recommended for patients with mild and moderate renal impairment based on a population pharmacokinetic analysis [see clinical pharmacology (12.3)]. the appropriate dose of zelboraf has not been established in patients with severe renal impairment.

Združene države Amerike - angleščina - NLM (National Library of Medicine)

genentech, inc. - ocrelizumab (unii: a10sjl62jy) (ocrelizumab - unii:a10sjl62jy) - ocrelizumab 300 mg in 10 ml - ocrevus is indicated for the treatment of: - relapsing forms of multiple sclerosis (ms), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults - primary progressive ms, in adults ocrevus is contraindicated in patients with: - active hbv infection [see dosage and administration (2.1) and warnings and precautions (5.2)] - a history of life-threatening infusion reaction to ocrevus [see warnings and precautions (5.1)] pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy and fetal/neonatal/infant outcomes in women exposed to ocrevus during pregnancy. physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-833-872-4370 or visiting www.ocrevuspregnancyregistry.com. risk summary ocrevus is a humanized monoclonal antibody of an immunoglobulin g1 subtype and immunoglobulins are known to cross the placental barrier. there are no adequate data on the developmental risk associated with use of ocrevus in pregnant women. however, transient peripheral b-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-cd20 antibodies during pregnancy. b-cell levels in infants following maternal exposure to ocrevus have not been studied in clinical trials. the potential duration of b-cell depletion in such infants, and the impact of b-cell depletion on vaccine safety and effectiveness, is unknown [see warnings and precautions (5.2)] . following administration of ocrelizumab to pregnant monkeys at doses similar to or greater than those used clinically, increased perinatal mortality, depletion of b-cell populations, renal, bone marrow, and testicular toxicity were observed in the offspring in the absence of maternal toxicity [see data] . 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. the background risk of major birth defects and miscarriage for the indicated population is unknown. data animal data following intravenous administration of ocrevus to monkeys during organogenesis (loading doses of 15 or 75 mg/kg on gestation days 20, 21, and 22, followed by weekly doses of 20 or 100 mg/kg), depletion of b-lymphocytes in lymphoid tissue (spleen and lymph nodes) was observed in fetuses at both doses. intravenous administration of ocrevus (three daily loading doses of 15 or 75 mg/kg, followed by weekly doses of 20 or 100 mg/kg) to pregnant monkeys throughout the period of organogenesis and continuing through the neonatal period resulted in perinatal deaths (some associated with bacterial infections), renal toxicity (glomerulopathy and inflammation), lymphoid follicle formation in the bone marrow, and severe decreases in circulating b-lymphocytes in neonates. the cause of the neonatal deaths is uncertain; however, both affected neonates were found to have bacterial infections. reduced testicular weight was observed in neonates at the high dose. a no-effect dose for adverse developmental effects was not identified; the doses tested in monkey are 2 and 10 times the recommended human dose of 600 mg, on a mg/kg basis. risk summary there are no data on the presence of ocrelizumab in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. ocrelizumab was excreted in the milk of ocrelizumab-treated monkeys. human igg is excreted in human milk, and the potential for absorption of ocrelizumab to lead to b-cell depletion in the infant is unknown. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ocrevus and any potential adverse effects on the breastfed infant from ocrevus or from the underlying maternal condition. contraception women of childbearing potential should use effective contraception while receiving ocrevus and for 6 months after the last infusion of ocrevus [see clinical pharmacology (12.3)] . safety and effectiveness of ocrevus in pediatric patients have not been established. clinical studies of ocrevus did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Združene države Amerike - angleščina - NLM (National Library of Medicine)

genentech, inc. - rituximab (unii: 4f4x42syq6) (rituximab - unii:4f4x42syq6), hyaluronidase (human recombinant) (unii: 743quy4vd8) (hyaluronidase (human recombinant) - unii:743quy4vd8) - rituximab 120 mg in 1 ml - rituxan hycela is indicated for the treatment of adult patients with: - relapsed or refractory, follicular lymphoma as a single agent. - previously untreated follicular lymphoma in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy. - non-progressing (including stable disease), follicular lymphoma as a single agent after first-line cyclophosphamide, vincristine, and prednisone (cvp) chemotherapy. rituxan hycela is indicated for the treatment of adult patients with previously untreated diffuse large b-cell lymphoma in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (chop) or other anthracycline-based chemotherapy regimens. rituxan hycela is indicated, in combination with fludarabine and cyclophosphamide (fc), for the treatment of adult patients with previously untreated and previously treated cll. - initiate treatment with rituxan hycela only after patients

Združene države Amerike - angleščina - NLM (National Library of Medicine)

genentech, inc. - vismodegib (unii: 25x868m3ds) (vismodegib - unii:25x868m3ds) - vismodegib 150 mg - erivedge is indicated for the treatment of adults with metastatic basal cell carcinoma, or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery and who are not candidates for radiation. none. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to erivedge during pregnancy. report pregnancies to genentech at 1-888-835-2555. risk summary based on its mechanism of action and findings from animal reproduction studies, erivedge can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . in animal reproduction studies, oral administration of vismodegib during organogenesis at doses below the 150 mg clinical dose resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats (see data) . there are no human data on the use of erivedge in pregnant women. advise pregnant women of the potential risk to a fetus. in the u.s. general population, the estim

Združene države Amerike - angleščina - NLM (National Library of Medicine)

genentech, inc. - saquinavir mesylate (unii: uhb9z3841a) (saquinavir - unii:l3je09kz2f) - saquinavir 200 mg - invirase in combination with ritonavir and other antiretroviral agents is indicated for the treatment of hiv-1 infection in adults (over the age of 16 years). the following points should be considered when initiating therapy with invirase/ritonavir: invirase/ritonavir is contraindicated in patients with congenital long qt syndrome, those with refractory hypokalemia or hypomagnesemia, and in combination with drugs that both increase saquinavir plasma concentrations and prolong the qt interval [see warnings and precautions (5.4) and clinical pharmacology (12.2)] . invirase/ritonavir is contraindicated in patients with complete atrioventricular (av) block without implanted pacemakers, or patients who are at high risk of complete av block [see warnings and precautions (5.3)] . invirase/ritonavir is contraindicated in patients with clinically significant hypersensitivity (e.g., anaphylactic reaction, stevens-johnson syndrome) to saquinavir, saquinavir mesylate, or any of its ingredients. invirase/ ritonavir is con

Združene države Amerike - angleščina - NLM (National Library of Medicine)

genentech, inc. - ibandronate sodium (unii: j12u072ql0) (ibandronic acid - unii:umd7g2653w) - ibandronic acid 3 mg in 3 ml - boniva injection is indicated for the treatment of osteoporosis in postmenopausal women. in postmenopausal women with osteoporosis, boniva increases bone mineral density (bmd) and reduces the incidence of vertebral fractures [see clinical studies (14)] . the safety and effectiveness of boniva for the treatment of osteoporosis are based on clinical data of one year duration. the optimal duration of use has not been determined. all patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis. patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. patients who discontinue therapy should have their risk for fracture re-evaluated periodically. boniva is contraindicated in patients with the following conditions: - hypocalcemia [see warnings and precautions (5.1)] - known hypersensitivity to boniva injection or to any of its excipients. cases of anaphylaxis, including fatal events, have been