Spojené štáty - angličtina - NLM (National Library of Medicine)

lake erie medical dba quality care products llc - topiramate (unii: 0h73wjj391) (topiramate - unii:0h73wjj391) - topiramate 50 mg - topiramate tablets, usp and topiramate capsules (sprinkle) are indicated as initial monotherapy in patients 10 years of age and older with partial onset or primary generalized tonic-clonic seizures. effectiveness was demonstrated in a controlled trial in patients with epilepsy who had no more than 2 seizures in the 3 months prior to enrollment. safety and effectiveness in patients who were converted to monotherapy from a previous regimen of other anticonvulsant drugs have not been established in controlled trials [see clinical studies (14.1) ]. topiramate tablets, usp and topiramate capsules (sprinkle) are indicated as adjunctive therapy for adults and pediatric patients ages 2 to 16 years with partial onset seizures or primary generalized tonic-clonic seizures, and in patients 2 years of age and older with seizures associated with lennox-gastaut syndrome [see clinical studies (14.2)] none.  pregnancy category d.[see warnings and precautions (5.6)] topiramate can cause fetal harm when administered to a pregn

Spojené štáty - angličtina - NLM (National Library of Medicine)

apotheca inc. - topiramate (unii: 0h73wjj391) (topiramate - unii:0h73wjj391) - topiramate 25 mg - topiramate tablets, usp are indicated as initial monotherapy in patients 2 years of age and older with partial onset or primary generalized tonic-clonic seizures. safety and effectiveness in patients who were converted to monotherapy from a previous regimen of other anticonvulsant drugs have not been established in controlled trials [see clinical studies ( 14.1)] . topiramate tablets, usp are indicated as adjunctive therapy for adults and pediatric patients ages 2 to 16 years with partial onset seizures or primary generalized tonic-clonic seizures, and in patients 2 years of age and older with seizures associated with lennox-gastaut syndrome [see clinical studies ( 14.2)] . additional pediatric use information for patients ages 12 to 17 years is approved for janssen pharmaceuticals, inc.’s topamax (topiramate) tablets and sprinkle capsules. however, due to janssen pharmaceuticals, inc.’s marketing exclusivity rights,

Spojené štáty - angličtina - NLM (National Library of Medicine)

proficient rx lp - topiramate (unii: 0h73wjj391) (topiramate - unii:0h73wjj391) - topiramate 100 mg - topiramate tablets, usp are indicated as initial monotherapy in patients 2 years of age and older with partial onset or primary generalized tonic-clonic seizures. safety and effectiveness in patients who were converted to monotherapy from a previous regimen of other anticonvulsant drugs have not been established in controlled trials [see clinical studies (14.1)] . topiramate tablets, usp are indicated as adjunctive therapy for adults and pediatric patients ages 2 to 16 years with partial onset seizures or primary generalized tonic-clonic seizures, and in patients 2 years of age and older with seizures associated with lennox-gastaut syndrome [see clinical studies (14.2)] . additional pediatric use information for patients ages 12 to 17 years is approved for janssen pharmaceuticals, inc.’s topamax (topiramate) tablets and sprinkle capsules. however, due to janssen pharmaceuticals, inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. none. pregnancy category d. [

Spojené štáty - angličtina - NLM (National Library of Medicine)

apotheca inc. - topiramate (unii: 0h73wjj391) (topiramate - unii:0h73wjj391) - topiramate 100 mg - topiramate tablets, usp are indicated as initial monotherapy in patients 2 years of age and older with partial onset or primary generalized tonic-clonic seizures. safety and effectiveness in patients who were converted to monotherapy from a previous regimen of other anticonvulsant drugs have not been established in controlled trials [see clinical studies ( 14.1)] . topiramate tablets, usp are indicated as adjunctive therapy for adults and pediatric patients ages 2 to 16 years with partial onset seizures or primary generalized tonic-clonic seizures, and in patients 2 years of age and older with seizures associated with lennox-gastaut syndrome [see clinical studies ( 14.2)] . additional pediatric use information for patients ages 12 to 17 years is approved for janssen pharmaceuticals, inc.’s topamax (topiramate) tablets and sprinkle capsules. however, due to janssen pharmaceuticals, inc.’s marketing exclusivity rights,

Spojené štáty - angličtina - NLM (National Library of Medicine)

nucare pharmaceuticals, inc. - topiramate (unii: 0h73wjj391) (topiramate - unii:0h73wjj391) - topiramate 25 mg - topiramate tablets, usp are indicated as initial monotherapy in patients 2 years of age and older with partial onset or primary generalized tonic-clonic seizures. safety and effectiveness in patients who were converted to monotherapy from a previous regimen of other anticonvulsant drugs have not been established in controlled trials [see clinical studies ( 14.1)] . topiramate tablets, usp are indicated as adjunctive therapy for adults and pediatric patients ages 2 to 16 years with partial onset seizures or primary generalized tonic-clonic seizures, and in patients 2 years of age and older with seizures associated with lennox-gastaut syndrome [see clinical studies ( 14.2)] . additional pediatric use information for patients ages 12 to 17 years is approved for janssen pharmaceuticals, inc.’s topamax (topiramate) tablets and sprinkle capsules. however, due to janssen pharmaceuticals, inc.’s marketing exclusivity rights,

Spojené štáty - angličtina - NLM (National Library of Medicine)

apotheca inc. - topiramate (unii: 0h73wjj391) (topiramate - unii:0h73wjj391) - topiramate 50 mg - topiramate tablets, usp are indicated as initial monotherapy in patients 2 years of age and older with partial onset or primary generalized tonic-clonic seizures. safety and effectiveness in patients who were converted to monotherapy from a previous regimen of other anticonvulsant drugs have not been established in controlled trials [see clinical studies ( 14.1)] . topiramate tablets, usp are indicated as adjunctive therapy for adults and pediatric patients ages 2 to 16 years with partial onset seizures or primary generalized tonic-clonic seizures, and in patients 2 years of age and older with seizures associated with lennox-gastaut syndrome [see clinical studies ( 14.2)] . additional pediatric use information for patients ages 12 to 17 years is approved for janssen pharmaceuticals, inc.’s topamax (topiramate) tablets and sprinkle capsules. however, due to janssen pharmaceuticals, inc.’s marketing exclusivity rights,

Spojené štáty - angličtina - NLM (National Library of Medicine)

aidarex pharmaceuticals llc - topiramate (unii: 0h73wjj391) (topiramate - unii:0h73wjj391) - topiramate tablets usp are indicated as initial monotherapy in patients 2 years of age and older with partial onset or primary generalized tonic-clonic seizures. topiramate tablets are indicated as adjunctive therapy for adults and pediatric patients 2 to 16 years of age with partial onset seizures or primary generalized tonic-clonic seizures, and in patients 2 years of age and older with seizures associated with lennox-gastaut syndrome. topiramate tablets are indicated for patients 12 years of age and older for the prophylaxis of migraine headache. none pregnancy category d  [see  warnings and precautions 5.7 ] topiramate  can cause fetal harm when administered to a pregnant woman. data from pregnancy registries indicate that infants exposed to topiramate in utero have an increased risk for cleft lip and/or cleft palate (oral clefts). when multiple species of pregnant animals received topiramate at clinically relevant doses, structural malformations, including craniofacial defects, and reduced fetal weigh

Spojené štáty - angličtina - NLM (National Library of Medicine)

nucare pharmaceuticals, inc. - topiramate (unii: 0h73wjj391) (topiramate - unii:0h73wjj391) - topiramate tablets usp are indicated as initial monotherapy in patients 2 years of age and older with partial onset or primary generalized tonic-clonic seizures. safety and effectiveness in patients who were converted to monotherapy from a previous regimen of other anticonvulsant drugs have not been established in controlled trials [see clinical studies (14.1)] .                                                                  topiramate tablets usp are indicated as adjunctive therapy for adults and pediatric patients ages 2 to 16 years with partial onset seizures or primary generalized tonic-clonic seizures, and in patients 2 years of age and older with seizures associated with lennox-gastaut syndrome [see clinical studies (14.2)] . none pregnancy category d   [see   warnings and precautions 5.7 ] topiramate tablets can cause fetal harm when administered to a pregnant woman. data from pregnancy registries indicate that infants exposed to topiramate in utero have an increased risk for cleft lip and/or cleft palate (oral clefts). when multiple species of pregnant animals received topiramate at clinically relevant doses, structural malformations, including craniofacial defects, and reduced fetal weights occurred in offspring. topiramate tablets should be used during pregnancy only if the potential benefit outweighs the potential risk. if this drug 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 use in specific populations ( 8.9)] . pregnancy registry patients should be encouraged to enroll in the north american antiepileptic drug (naaed) pregnancy registry if they become pregnant. this registry is collecting information about the safety of antiepileptic drugs during pregnancy. to enroll, patients can call the toll-free number 1-888-233-2334. information about the north american drug pregnancy registry can be found at http://www.massgeneral.org/aed/ . human data data from the naaed pregnancy registry (425 prospective topiramate monotherapy-exposed pregnancies) indicate an increased risk of oral clefts in infants exposed during the first trimester of pregnancy. the prevalence of oral clefts among topiramate-exposed infants was 1.2% compared to a prevalence of 0.39% for infants exposed to a reference aed. in infants of mothers without epilepsy or treatment with other aeds. the prevalence was 0.12%. for comparison, the centers for disease control and prevention (cdc) reviewed available data on oral clefts in the united states and found a similar background rate of 0.17%. the relative risk of oral clefts in topiramate-exposed pregnancies in the naaed pregnancy registry was 9.6 (95% confidence interval [ci] 4.0 – 23.0) as compared to the risk in a background population of untreated women. the uk epilepsy and pregnancy register reported a similarly increased prevalence of oral clefts of 3.2% among infants exposed to topiramate monotherapy. the observed rate of oral clefts was 16 times higher than the background rate in the uk, which is approximately 0.2%. topiramate tablets treatment can cause metabolic acidosis [see warnings and precautions ( 5.4)] . the effect of topiramate-induced metabolic acidosis has not been studied in pregnancy; however, metabolic acidosis in pregnancy (due to other causes) can cause decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the fetus' ability to tolerate labor. pregnant patients should be monitored for metabolic acidosis and treated as in the nonpregnant state [see warnings and precautions ( 5.4)] . newborns of mothers treated with topiramate tablets should be monitored for metabolic acidosis because of transfer of topiramate to the fetus and possible occurrence of transient metabolic acidosis following birth. animal data topiramate has demonstrated selective developmental toxicity, including teratogenicity, in multiple animal species at clinically relevant doses. when oral doses of 20, 100, or 500 mg/kg were administered to pregnant mice during the period of organogenesis, the incidence of fetal malformations (primarily craniofacial defects) was increased at all doses. the low dose is approximately 0.2 times the recommended human dose (rhd) 400 mg/day on a mg/m 2 basis. fetal body weights and skeletal ossification were reduced at 500 mg/kg in conjunction with decreased maternal body weight gain. in rat studies (oral doses of 20, 100, and 500 mg/kg or 0.2, 2.5, 30, and 400 mg/kg), the frequency of limb malformations (ectrodactyly, micromelia, and amelia) was increased among the offspring of dams treated with 400 mg/kg (10 times the rhd on a mg/m 2 basis) or greater during the organogenesis period of pregnancy. embryotoxicity (reduced fetal body weights, increased incidence of structural variations) was observed at doses as low as 20 mg/kg (0.5 times the rhd on a mg/m 2 basis). clinical signs of maternal toxicity were seen at 400 mg/kg and above, and maternal body weight gain was reduced during treatment with 100 mg/kg or greater. in rabbit studies (20, 60, and 180 mg/kg or 10, 35, and 120 mg/kg orally during organogenesis), embryo/fetal mortality was increased at 35 mg/kg (2 times the rhd on a mg/m 2 basis) or greater, and teratogenic effects (primarily rib and vertebral malformations) were observed at 120 mg/kg (6 times the rhd on a mg/m 2 basis). evidence of maternal toxicity (decreased body weight gain, clinical signs, and/or mortality) was seen at 35 mg/kg and above. when female rats were treated during the latter part of gestation and throughout lactation (0.2, 4, 20, and 100 mg/kg or 2, 20, and 200 mg/kg), offspring exhibited decreased viability and delayed physical development at 200 mg/kg (5 times the rhd on a mg/m 2 basis) and reductions in preand/or postweaning body weight gain at 2 mg/kg (0.05 times the rhd on a mg/m 2 basis) and above. maternal toxicity (decreased body weight gain, clinical signs) was evident at 100 mg/kg or greater. in a rat embryo/fetal development study with a postnatal component (0.2, 2.5, 30, or 400 mg/kg during organogenesis; noted above), pups exhibited delayed physical development at 400 mg/kg (10 times the rhd on a mg/m 2 basis) and persistent reductions in body weight gain at 30 mg/kg (1 times the rhd on a mg/m 2 basis) and higher. although the effect of topiramate tablets on labor and delivery in humans has not been established, the development of topiramate-induced metabolic acidosis in the mother and/or in the fetus might affect the fetus' ability to tolerate labor [see   use   in   specific   populations   ( 8.1 )] . limited data on 5 breastfeeding infants exposed to topiramate showed infant plasma topiramate levels equal to 10–20% of the maternal plasma level. the effects of this exposure on infants are unknown. caution should be exercised when administered to a nursing woman. adjunctive treatment for partial onset epilepsy in infants and toddlers ( 1 to 24 months)             safety and effectiveness in patients below the age of 2 years have not been established for the adjunctive therapy treatment of partial onset seizures, primary generalized tonic-clonic seizures, or seizures associated with lennox-gastaut syndrome. in a single randomized, double-blind, placebo-controlled investigational trial, the efficacy, safety, and tolerability of topiramate oral liquid and sprinkle formulations as an adjunct to concurrent antiepileptic drug therapy in infants 1 to 24 months of age with refractory partial onset seizures were assessed. after 20 days of double-blind treatment, topiramate (at fixed doses of 5, 15, and 25 mg/kg/day) did not demonstrate efficacy compared with placebo in controlling seizures. in general, the adverse reaction profile in this population was similar to that of older pediatric patients, although results from the above controlled study and an open-label, long-term extension study in these infants/toddlers (1 to 24 months old) suggested some adverse reactions/toxicities (not previously observed in older pediatric patients and adults; i.e., growth/length retardation, certain clinical laboratory abnormalities, and other adverse reactions/toxicities that occurred with a greater frequency and/or greater severity than had been recognized previously from studies in older pediatric patients or adults for various indications. these very young pediatric patients appeared to experience an increased risk for infections (any topiramate dose 12%, placebo 0%) and of respiratory disorders (any topiramate dose 40%, placebo 16%). the following adverse reactions were observed in at least 3% of patients on topiramate and were 3% to 7% more frequent than in patients on placebo: viral infection, bronchitis, pharyngitis, rhinitis, otitis media, upper respiratory infection, cough, and bronchospasm. a generally similar profile was observed in older children [see adverse reactions ( 6)] . topiramate resulted in an increased incidence of patients with increased creatinine (any topiramate dose 5%, placebo 0%), bun (any topiramate dose 3%, placebo 0%), and protein (any topiramate dose 34%, placebo 6%), and an increased incidence of decreased potassium (any topiramate dose 7%, placebo 0%). this increased frequency of abnormal values was not dose-related. creatinine was the only analyte showing a noteworthy increased incidence (topiramate 25 mg/kg/day 5%, placebo 0%) of a markedly abnormal increase [see warnings and precautions ( 5.16)] . the significance of these findings is uncertain. topiramate treatment also produced a dose-related increase in the percentage of patients who had a shift from normal at baseline to high/increased (above the normal reference range) in total eosinophil count at the end of treatment. the incidence of these abnormal shifts was 6 % for placebo, 10% for 5 mg/kg/day, 9% for 15 mg/kg/day, 14% for 25 mg/kg/day, and 11% for any topiramate dose [see warnings and precautions ( 5.16)] . there was a mean dose-related increase in alkaline phosphatase. the significance of these findings is uncertain. topiramate produced a dose-related increased incidence of treatment-emergent hyperammonemia [see warnings and precautions ( 5.10)] . treatment with topiramate for up to 1 year was associated with reductions in z scores for length, weight, and head circumference [see warnings and precautions ( 5.4) and adverse reactions ( 6)] . in open-label, uncontrolled experience, increasing impairment of adaptive behavior was documented in behavioral testing over time in this population. there was a suggestion that this effect was dose-related. however, because of the absence of an appropriate control group, it is not known if this decrement in function was treatment-related or reflects the patient's underlying disease (e.g., patients who received higher doses may have more severe underlying disease) [see warnings and precautions ( 5.6)] . in this open-label, uncontrolled study, the mortality was 37 deaths/1000 patient years. it is not possible to know whether this mortality rate is related to topiramate treatment, because the background mortality rate for a similar, significantly refractory, young pediatric population (1-24 months) with partial epilepsy is not known. monotherapy treatment in partial onset epilepsy in patients <2 years old safety and effectiveness in patients below the age of 2 years have not been established for the monotherapy treatment of epilepsy. juvenile animal studies when topiramate (30, 90, or 300 mg/kg/day) was administered orally to rats during the juvenile period of development (postnatal days 12 to 50), bone growth plate thickness was reduced in males at the highest dose, which is approximately 5-8 times the maximum recommended pediatric dose (9 mg/kg/day) on a body surface area (mg/m 2 ) basis. in clinical trials, 3% of patients were over 60. no age-related differences in effectiveness or adverse effects were evident. however, clinical studies of topiramate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. dosage adjustment may be necessary for elderly with impaired renal function (creatinine clearance rate <70 ml/min/1.73 m 2 ) due to reduced clearance of topiramate [see   clinical   pharmacology   ( 12.3 )   and   dosage   and   administration   ( 2.5 )] . evaluation of effectiveness and safety in clinical trials has shown no race- or gender-related effects. the clearance of topiramate was reduced by 42% in moderately renally impaired (creatinine clearance 30 to 69 ml/min/1.73m 2 ) and by 54% in severely renally impaired subjects (creatinine clearance <30 ml/min/1.73m 2 ) compared to normal renal function subjects (creatinine clearance >70 ml/min/1.73m 2 ). one-half the usual starting and maintenance dose is recommended in patients with moderate or severe renal impairment [see dosage and administration ( 2.6) and clinical pharmacology ( 12.3)] . topiramate is cleared by hemodialysis at a rate that is 4 to 6 times greater than in a normal individual. accordingly, a prolonged period of dialysis may cause topiramate concentration to fall below that required to maintain an anti-seizure effect. to avoid rapid drops in topiramate plasma concentration during hemodialysis, a supplemental dose of topiramate tablets may be required. the actual adjustment should take into account the duration of dialysis period, the clearance rate of the dialysis system being used, and the effective renal clearance of topiramate in the patient being dialyzed [see   dosage   and   administration   ( 2.4 )   and   clinical   pharmacology   ( 12.3 )]   data from pregnancy registries indicate that infants exposed to topiramate tablets in utero have an increased risk for cleft lip and/or cleft palate (oral clefts) [see warnings and precautions ( 5.7) and use in specific populations (8.1)] . consider the benefits and the risks of topiramate tablets when prescribing this drug to women of childbearing potential, particularly when topiramate tablets is considered for a condition not usually associated with permanent injury or death. because of the risk of oral clefts to the fetus, which occur in the first trimester of pregnancy before many women know they are pregnant, all women of childbearing potential should be apprised of the potential hazard to the fetus from exposure to topiramate tablets. if the decision is made to use topiramate tablets, women who are not planning a pregnancy should use effective contraception [see drug interactions ( 7.3)] . women who are planning a pregnancy should be counselled regarding the relative risks and benefits of topiramate tablets use during pregnancy, and alternative therapeutic options should be considered for these patients [see patient counseling information ( 17)] .

Spojené štáty - angličtina - NLM (National Library of Medicine)

jazz pharmaceuticals, inc. - cannabidiol (unii: 19gbj60sn5) (cannabidiol - unii:19gbj60sn5) - epidiolex is indicated for the treatment of seizures associated with lennox-gastaut syndrome (lgs), dravet syndrome (ds), or tuberous sclerosis complex (tsc) in patients 1 year of age and older. epidiolex is contraindicated in patients with a history of hypersensitivity to cannabidiol or any of the ingredients in the product [see description (11) and warnings and precautions (5.4)].   pregnancy surveillance program and pregnancy exposure registry there are two programs, an epidiolex pregnancy surveillance program and an antiepileptic drug (aed) pregnancy exposure registry, that monitor pregnancy outcomes.  encourage women who are taking epidiolex during pregnancy to enroll in both, by calling the toll free numbers or visiting the websites below: risk summary there are no adequate data on the developmental risks associated with the use of epidiolex in pregnant women.  administration of cannabidiol to pregnant animals produced evidence of developmental toxicity (increased embryofetal mortality in rats and decreased fetal body weights in rabbits; decreased growth, delayed sexual maturation, long-term neurobehavioral changes, and adverse effects on the reproductive system in rat offspring) at maternal plasma exposures similar to (rabbit) or greater than (rat) that in humans at therapeutic doses (see animal data).   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. the background risks of major birth defects and miscarriage for the indicated populations are unknown. data animal data oral administration of cannabidiol (0, 75, 150, or 250 mg/kg/day) to pregnant rats throughout the period of organogenesis resulted in embryofetal mortality at the highest dose tested.  there were no other drug-related maternal or developmental effects.  the highest no-effect dose for embryofetal toxicity in rats was associated with maternal plasma cannabidiol exposures (auc) approximately 16 and 9 times that in humans at the recommended human doses (rhd) of 20 and 25 mg/kg/day, respectively. oral administration of cannabidiol (0, 50, 80, or 125 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in decreased fetal body weights and increased fetal structural variations at the highest dose tested, which was also associated with maternal toxicity.  maternal plasma cannabidiol exposures at the no-effect level for embryofetal developmental toxicity in rabbits were less than that in humans at the rhds. when cannabidiol (75, 150, or 250 mg/kg/day) was orally administered to rats throughout pregnancy and lactation, decreased growth, delayed sexual maturation, neurobehavioral changes (decreased activity), and adverse effects on male reproductive organ development (small testes in adult offspring) and fertility were observed in the offspring at the mid and high dose.  these effects occurred in the absence of maternal toxicity.  the no-effect dose for pre- and post-natal developmental toxicity in rats was associated with maternal plasma cannabidiol exposures approximately 9 and 5 times that in humans at the rhds of 20 and 25 mg/kg/day, respectively. risk summary there are no data on the presence of cannabidiol or its metabolites in human milk, the effects 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 epidiolex and any potential adverse effects on the breastfed infant from epidiolex or from the underlying maternal condition. safety and effectiveness of epidiolex for the treatment of seizures associated with lgs, ds, or tsc have been established in patients 1 year of age and older.  the use of epidiolex in these indications is supported by adequate and well-controlled studies in patients 2 years of age and older with lgs and ds and in patients 1 year of age and older with tsc [see clinical studies (14.1, 14.2, 14.3)]. safety and effectiveness of epidiolex in pediatric patients below 1 year of age have not been established. juvenile animal data administration of cannabidiol (subcutaneous doses of 0 or 15 mg/kg on postnatal days (pnds) 4-6 followed by oral administration of 0, 100, 150, or 250 mg/kg on pnds 7-77) to juvenile rats for 10 weeks resulted in increased body weight, delayed male sexual maturation, neurobehavioral effects (decreased locomotor activity and auditory startle habituation), increased bone mineral density, and liver hepatocyte vacuolation.  a no-effect dose was not established.  the lowest dose causing developmental toxicity in juvenile rats (15 sc/100 po mg/kg) was associated with cannabidiol exposures (auc) approximately 15 and 8 times that in humans at the rhds of 20 and 25 mg/kg/day, respectively. clinical trials of epidiolex in the treatment of lgs, ds, and tsc did not include a sufficient number of patients aged above 55 years to determine whether or not they respond differently from younger patients.  in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see dosage and administration (2.6), warnings and precautions (5.1), and clinical pharmacology (12.3)] . because of an increase in exposure to epidiolex, dosage adjustments are necessary in patients with moderate or severe hepatic impairment [see dosage and administration (2.6), warnings and precautions (5.1), and clinical pharmacology (12.3)] .  epidiolex does not require dosage adjustments in patients with mild hepatic impairment. epidiolex is not a controlled substance. animal abuse-related studies show that cannabidiol does not produce cannabinoid-like behavioral responses, including generalization to delta-9-tetrahydrocannabinol (thc) in a drug discrimination study. cannabidiol also does not produce animal self-administration, suggesting it does not produce rewarding effects.  in a human abuse potential study, acute administration of cannabidiol to non-dependent adult recreational drug users at therapeutic and supratherapeutic doses of 750, 1500, and 4500 mg in the fasted state (equivalent respectively to 10, 20, and 60 mg/kg in a 75 kg adult) produced responses on positive subjective measures such as drug liking and take drug again that were within the acceptable placebo range.  in contrast, 10 and 30 mg of dronabinol (synthetic thc) and 2 mg alprazolam produced large increases on positive subjective measures compared to placebo that were statistically significantly greater than those produced by cannabidiol.  in other phase 1 clinical studies conducted with cannabidiol, there were no reports of abuse-related adverse events. in a human physical dependence study, administration of cannabidiol 1500 mg/day (750 mg twice daily) to adults for 28 days did not produce signs or symptoms of withdrawal over a 6-week assessment period  beginning three days after drug discontinuation.  this suggests that cannabidiol likely does not produce physical dependence. instructions for use epidiolex® (eh-peh-dye-oh-lex) (cannabidiol) oral solution 100 mg/ml be sure that you read, understand and follow these instructions carefully to ensure proper dosing of the oral solution. important: each package contains: child-resistant cap 2 bottle adapters 1 bottle of epidiolex oral solution (100 mg/ml) 2  reusable 1 ml oral syringes and 2 reusable 5 ml oral syringes: if your dose of epidiolex is 1 ml or less , use the 1 ml syringes to take your medicine. for each syringe size:                            note: if you lose or damage an oral syringe, or cannot read the markings, use the spare syringe. prepare the bottle- to use epidiolex for the first time              note: do not remove the bottle adapter from the bottle after it is inserted. prepare the dose your healthcare provider will tell you how much epidiolex to take or give.               dose                                                                     how to measure                1 ml or less                                                           use the 1 ml oral syringe 1 time                more than 1 ml and less than 5 ml                        use the 5 ml oral syringe 1 time                more than 5 ml                                                     use the 5 ml oral syringe more than 1 time              line up the end of the plunger with the marking for your dose of epidiolex.                if there are air bubbles in the oral syringe, keep the bottle upside down and push the plunger so that all of the                liquid flows back into the bottle. repeat step 5 until the air bubbles are gone. give epidiolex              do not forcefully push on the plunger.              do not direct the medicine to the back of the mouth or throat. this may cause choking.              if the dose of epidiolex prescribed by the healthcare provider is more than 5 ml, repeat steps 4 through 8  to complete the dose.                 for example:                 if your dose of epidiolex is 8 ml, withdraw 5 ml of medicine into the syringe and give the medicine.                 insert the tip of the oral syringe back into the bottle adapter and withdraw 3 ml of medicine. give the                 medicine to receive a total dose of 8 ml. clean up                do not remove the bottle adapter. the cap will fit over it.                do not wash the oral syringe in the dishwasher.           do not throw away the oral syringe. how should i store epidiolex? helpline details for additional assistance, call the toll-free helpline at 1-833-426-4243. hours: monday-friday                                       08:00am – 08:00pm est frequently asked questions q:  what if there are air bubbles in the oral syringe? a:   push the liquid back into the bottle and repeat step 5 until the air bubbles are gone. q:  what should i do if the liquid in the bottle has turned cloudy? a:  the liquid in the bottle may turn cloudy if water gets in the bottle. this does not change the safety or how well the medicine works. continue to use the cloudy liquid as prescribed by your healthcare provider. always make sure the oral syringes are completely dry before each use. q:  what should i do if the oral syringe is not completely dry before use? a:  if the oral syringe is not completely dry, use the spare syringe provided in the pack.  distributed by: jazz pharmaceuticals, inc. palo alto, ca 94304 epidiolex® is a registered trademark of jazz pharmaceuticals plc or its subsidiaries. © 2023 jazz pharmaceuticals, inc. this instructions for use has been approved by the u.s. food and drug administration. revised: 01/2023

Európska únia - angličtina - EMA (European Medicines Agency)

jazz pharmaceuticals ireland limited - cannabidiol - lennox gastaut syndrome; epilepsies, myoclonic - antiepileptics, - epidyolex is indicated for use as adjunctive therapy of seizures associated with lennox gastaut syndrome (lgs) or dravet syndrome (ds), in conjunction with clobazam, for patients 2 years of age and older.