Malta - inglese - Medicines Authority

aurobindo pharma (malta) limited vault 14, level 2, valletta waterfront, floriana frn 1913, malta - orodispersible tablet - olanzapine 5 mg - psycholeptics

Malta - inglese - Medicines Authority

aurobindo pharma (malta) limited vault 14, level 2, valletta waterfront, floriana frn 1913, malta - orodispersible tablet - olanzapine 10 mg - psycholeptics

Malta - inglese - Medicines Authority

aurobindo pharma (malta) limited vault 14, level 2, valletta waterfront, floriana frn 1913, malta - orodispersible tablet - olanzapine 15 mg - psycholeptics

Malta - inglese - Medicines Authority

aurobindo pharma (malta) limited vault 14, level 2, valletta waterfront, floriana frn 1913, malta - orodispersible tablet - olanzapine 20 mg - psycholeptics

Stati Uniti - inglese - NLM (National Library of Medicine)

aurobindo pharma limited - zaleplon (unii: s62u433rmh) (zaleplon - unii:s62u433rmh) - zaleplon 5 mg - zaleplon capsules are indicated for the short-term treatment of insomnia. zaleplon capsules have been shown to decrease the time to sleep onset for up to 30 days in controlled clinical studies (see clinical trials  under clinical pharmacology ). they have not been shown to increase total sleep time or decrease the number of awakenings. the clinical trials performed in support of efficacy ranged from a single night to 5 weeks in duration. the final formal assessments of sleep latency were performed at the end of treatment. zaleplon capsules are contraindicated in patients: - who have experienced complex sleep behaviors after taking zaleplon capsules (see warnings ). - with hypersensitivity to zaleplon or any excipients in the formulation (see precautions ). zaleplon is classified as a schedule iv controlled substance by federal regulation.  abuse and addiction are separate and distinct from physical dependence and tolerance. abuse is characterized by misuse of the drug for non-medical purposes, often in

Stati Uniti - inglese - NLM (National Library of Medicine)

aurobindo pharma limited - clonazepam (unii: 5pe9fde8gb) (clonazepam - unii:5pe9fde8gb) - seizure disorders: clonazepam tablets are 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, clonazepam tablets may be useful. some loss of effect may occur during the course of clonazepam treatment (see precautions: loss of effect ). panic disorder: clonazepam tablets are 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 clonazepam tablets 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 tri

Stati Uniti - inglese - NLM (National Library of Medicine)

aurobindo pharma limited - vigabatrin (unii: gr120krt6k) (vigabatrin - unii:gr120krt6k) - vigabatrin for oral solution is indicated as adjunctive therapy for adults and pediatric patients 2 years of age and older with refractory complex partial seizures who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss [see warnings and precautions (5.1)]. vigabatrin for oral solution is not indicated as a first line agent for complex partial seizures. vigabatrin for oral solution is indicated as monotherapy for pediatric patients with infantile spasms 1 month to 2 years of age for whom the potential benefits outweigh the potential risk of vision loss [see warnings and precautions (5.1)]. none. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, including vigabatrin, during pregnancy. encourage women who are taking vigabatrin during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry. this can be done by calling the toll-free number 1-888-233-2334 or visiting the website, http://www.aedpregnancyregistry.org/ . this must be done by the patient herself. risk summary there are no adequate data on the developmental risk associated with the use of vigabatrin in pregnant women. limited available data from case reports and cohort studies pertaining to vigabatrin use in pregnant women have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. however, based on animal data, vigabatrin use in pregnant women may result in fetal harm. when administered to pregnant animals, vigabatrin produced developmental toxicity, including an increase in fetal malformations and offspring neurobehavioral and neurohistopathological effects, at clinically relevant doses. in addition, developmental neurotoxicity was observed in rats treated with vigabatrin during a period of postnatal development corresponding to the third trimester of human pregnancy (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 administration of vigabatrin (oral doses of 50 to 200 mg/kg/day) to pregnant rabbits throughout the period of organogenesis was associated with an increased incidence of malformations (cleft palate) and embryofetal death; these findings were observed in two separate studies. the no-effect dose for adverse effects on embryofetal development in rabbits (100 mg/kg/day) is approximately 1/2 the maximum recommended human dose (mrhd) of 3 g/day on a body surface area (mg/m2 ) basis. in rats, oral administration of vigabatrin (50, 100, or 150 mg/kg/day) throughout organogenesis resulted in decreased fetal body weights and increased incidences of fetal anatomic variations. the no-effect dose for adverse effects on embryo-fetal development in rats (50 mg/kg/day) is approximately 1/5 the mrhd on a mg/m2 basis. oral administration of vigabatrin (50, 100, 150 mg/kg/day) to rats from the latter part of pregnancy through weaning produced long-term neurohistopathological (hippocampal vacuolation) and neurobehavioral (convulsions) abnormalities in the offspring. a no-effect dose for developmental neurotoxicity in rats was not established; the low-effect dose (50 mg/kg/day) is approximately 1/5 the mrhd on a mg/m2 basis. in a published study, vigabatrin (300 or 450 mg/kg) was administered by intraperitoneal injection to a mutant mouse strain on a single day during organogenesis (day 7, 8, 9, 10, 11, or 12). an increase in fetal malformations (including cleft palate) was observed at both doses. oral administration of vigabatrin (5, 15, or 50 mg/kg/day) to young rats during the neonatal and juvenile periods of development (postnatal days 4 to 65) produced neurobehavioral (convulsions, neuromotor impairment, learning deficits) and neurohistopathological (brain vacuolation, decreased myelination, and retinal dysplasia) abnormalities in treated animals. the early postnatal period in rats is generally thought to correspond to late pregnancy in humans in terms of brain development. the no-effect dose for developmental neurotoxicity in juvenile rats (5 mg/kg/day) was associated with plasma vigabatrin exposures (auc) less than 1/30 of those measured in pediatric patients receiving an oral dose of 50 mg/kg. risk summary vigabatrin is excreted in human milk. the effects of vigabatrin on the breastfed infant and on milk production are unknown. because of the potential for serious adverse reactions from vigabatrin in nursing infants, breastfeeding is not recommended. if exposing a breastfed infant to vigabatrin, observe for any potential adverse effects [see warnings and precautions (5.1, 5.3, 5.4, 5.8)] . the safety and effectiveness of vigabatrin as adjunctive treatment of refractory complex partial seizures in pediatric patients 2 to 16 years of age have been established and is supported by three double-blind, placebo-controlled studies in patients 3 to 16 years of age, adequate and well-controlled studies in adult patients, pharmacokinetic data from patients 2 years of age and older, and additional safety information in patients 2 years of age [see clinical pharmacology (12.3) and clinical studies (14.1)]. the dosing recommendation in this population varies according to age group and is weight-based [see dosage and administration (2.2)]. adverse reactions in this pediatric population are similar to those observed in the adult population [see adverse reactions (6.1)]. the safety and effectiveness of vigabatrin as monotherapy for pediatric patients with infantile spasms (1 month to 2 years of age) have been established [see dosage and administration (2.3) and clinical studies (14.2)]. safety and effectiveness as adjunctive treatment of refractory complex partial seizures in pediatric patients below the age of 2 and as monotherapy for the treatment of infantile spasms in pediatric patients below the age of 1 month have not been established. duration of therapy for infantile spasms was evaluated in a post hoc analysis of a canadian pediatric epilepsy network (cpen) study of developmental outcomes in infantile spasms patients. this analysis suggests that a total duration of 6 months of vigabatrin therapy is adequate for the treatment of infantile spasms. however, prescribers must use their clinical judgment as to the most appropriate duration of use [see clinical studies (14.2)]. abnormal mri signal changes and intramyelinic edema (ime) in infants and young children being treated with vigabatrin have been observed [see warnings and precautions (5.3, 5.4)]. juvenile animal toxicity data oral administration of vigabatrin (5, 15, or 50 mg/kg/day) to young rats during the neonatal and juvenile periods of development (postnatal days 4 to 65) produced neurobehavioral (convulsions, neuromotor impairment, learning deficits) and neurohistopathological (brain gray matter vacuolation, decreased myelination, and retinal dysplasia) abnormalities. the no-effect dose for developmental neurotoxicity in juvenile rats (the lowest dose tested) was associated with plasma vigabatrin exposures (auc) substantially less than those measured in pediatric patients at recommended doses. in dogs, oral administration of vigabatrin (30 or 100 mg/kg/day) during selected periods of juvenile development (postnatal days 22 to 112) produced neurohistopathological abnormalities (brain gray matter vacuolation). neurobehavioral effects of vigabatrin were not assessed in the juvenile dog. a no-effect dose for neurohistopathology was not established in juvenile dogs; the lowest effect dose (30 mg/kg/day) was associated with plasma vigabatrin exposures lower than those measured in pediatric patients at recommended doses [see warnings and precautions (5.4)]. clinical studies of vigabatrin did not include sufficient numbers of patients aged 65 and over to determine whether they responded differently from younger patients. vigabatrin is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. oral administration of a single dose of 1.5 g of vigabatrin to elderly (≥65 years) patients with reduced creatinine clearance (<50 ml/min) was associated with moderate to severe sedation and confusion in 4 of 5 patients, lasting up to 5 days. the renal clearance of vigabatrin was 36% lower in healthy elderly subjects (≥65 years) than in young healthy males. adjustment of dose or frequency of administration should be considered. such patients may respond to a lower maintenance dose [see dosage and administration (2.4) and clinical pharmacology (12.3)]. other reported clinical experience has not identified differences in responses between the elderly and younger patients. dose adjustment, including initiating treatment with a lower dose, is necessary in pediatric patients 2 years of age and older and adults with mild (creatinine clearance >50 to 80 ml/min), moderate (creatinine clearance >30 to 50 ml/min) and severe (creatinine clearance >10 to 30 ml/min) renal impairment [see dosage and administration (2.4) and clinical pharmacology (12.3)]. vigabatrin is not a controlled substance. vigabatrin did not produce adverse events or overt behaviors associated with abuse when administered to humans or animals. it is not possible to predict the extent to which a cns active drug will be misused, diverted, and/or abused once marketed. consequently, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of vigabatrin (e.g., incrementation of dose, drug-seeking behavior). following chronic administration of vigabatrin to animals, there were no apparent withdrawal signs upon drug discontinuation. however, as with all aeds, vigabatrin should be withdrawn gradually to minimize increased seizure frequency [see warnings and precautions (5.6)]. vigabatrin for oral solution, usp (vye ga' ba trin) read this instructions for use before your child starts taking vigabatrin for oral solution and each time you get a refill. there may be new information. this information does not take the place of talking with your healthcare provider about your child’s medical condition or treatment. talk to your healthcare provider if you have any questions about the right dose of medicine to give your child or how to mix it. important note: - vigabatrin for oral solution comes in a packet - each vigabatrin packet contains 500 mg of powder - vigabatrin for oral solution must be mixed with water only. the water may be cold or at room temperature. - your healthcare provider will tell you: how many packets of vigabatrin for oral solution you will need for each dose how many milliliters (ml) of water to use to mix one dose of vigabatrin for oral solution how many milliliters (ml) of the powder and water mixture you will need for each dose of medicine - how many packets of vigabatrin for oral solution you will need for each dose - how many milliliters (ml) of water to use to mix one dose of vigabatrin for oral solution - how many milliliters (ml) of the powder and water mixture you will need for each dose of medicine - vigabatrin for oral solution should be given right away after it is mixed - use the oral syringes, provided by the pharmacy, to measure and give the correct dose. do not use a household teaspoon or tablespoon. supplies you will need to mix 1 dose of vigabatrin for oral solution:   - the number of packets of vigabatrin for oral solution needed for each dose - 2 clean cups: 1 for mixing and 1 for water. the cup used for mixing vigabatrin for oral solution should be clear so you can see if the powder is dissolved - water to mix with the vigabatrin for oral solution powder - one small 3 ml oral syringe and one large 10 ml oral syringe which are provided by the pharmacy - small spoon or other clean utensil to stir the mixture - scissors   step 1: start with 1 of the empty cups and the total number of packets you will need for 1 dose. step 2: before you open the packet, tap it to settle all the powder to the bottom of the packet. step 3: use a pair of scissors to cut open the vigabatrin for oral solution packet along the dotted line. step 4: empty the entire contents of the vigabatrin for oral solution packet into 1 of the clean empty cups (see figure a ).   - repeat steps 2 to 4 above to open all of the packets needed for 1 dose of vigabatrin for oral solution. step 5: take the second cup and fill it half way with water (see figure b ).          do not mix vigabatrin for oral solution with anything other than water.   - you will use the larger oral syringe (10 ml) to draw up the water needed to mix with the powder from the packets. you will need 10 ml of water for each packet of vigabatrin for oral solution. for example: - if you are using 1 packet of vigabatrin for oral solution, you will need to use 10 ml of water (fill the 10 ml oral syringe 1 time) - if you are using 2 packets of vigabatrin for oral solution, you will need to use 20 ml of water (fill the 10 ml oral syringe 2 times) - if you are using 3 packets of vigabatrin for oral solution, you will need to use 30 ml of water (fill the 10 ml oral syringe 3 times) step 6: use the 10 ml oral syringe to draw up 10 ml of water. to do this, put the tip of the oral syringe all the way into the water in your cup. then pull the plunger up towards you until the edge of the white plunger is at the 10 ml line on the barrel of the oral syringe (see figure c ).   - if you see bubbles of air in the oral syringe after drawing up the water, turn the oral syringe so the tip is pointing up (see figure d ). the air will move to the top of the oral syringe. pull the plunger back towards you and then push it back gently into the oral syringe to get rid of the bubbles. tiny bubbles are normal.   step 7: check the oral syringe to make sure it is filled with water up to the 10 ml line (see figure e ). step 8: get the second cup that contains the vigabatrin for oral solution needed for your dose. step 9: hold the 10 ml oral syringe that is filled with water with the tip pointing down over the vigabatrin for oral solution. step 10: slowly push the oral syringe plunger all the way down to empty the water from the oral syringe straight into the cup containing the vigabatrin for oral solution (see figure f ).   repeat steps 6 through 10 until all of the water that is needed to mix 1 dose of vigabatrin for oral solution has been added to the cup containing the powder. step 11: stir the mixture with the small spoon or other clean utensil until the solution is clear (see figure g ). this means that all of the powder is dissolved and ready for use.   - to give a dose of vigabatrin for oral solution to your child, you should use the oral syringe to draw up the total number of mls of the mixture that your healthcare provider tells you to. if you are giving 3 ml or less of the mixture, use the smaller 3 ml oral syringe. if you are giving more than 3 ml of the mixture, use the larger 10 ml oral syringe (this is the oral syringe that you just used to add the water). - if you are giving 3 ml or less of the mixture, use the smaller 3 ml oral syringe. - if you are giving more than 3 ml of the mixture, use the larger 10 ml oral syringe (this is the oral syringe that you just used to add the water). step 12: put the tip of the oral syringe all the way into the mixture. pull the plunger up towards you to draw up the mixture. stop when the edge of the white plunger lines up with markings on the barrel of the oral syringe that matches the number of mls of mixture your healthcare provider told you to give (see figure h ).   • if you see bubbles of air in the oral syringe after drawing up the mixture, turn the oral syringe so the tip is pointing up (see figure i ). the air will move to the top of the oral syringe. pull the plunger back towards you and then gently push it back in the oral syringe in order to get rid of the bubbles. tiny bubbles are normal.   step 13: place the tip of the oral syringe into your child’s mouth and point the oral syringe towards either cheek (see figure j ). push on the plunger slowly, a small amount at a time, until all of the mixture in the oral syringe is given. - if the dose you are giving your child is more than 10 mls, repeat steps 12 and 13 until you give the total dose of mixture prescribed by your healthcare provider. step 14: throw away any mixture that is left over. do not save or reuse any leftover mixture. step 15: wash the oral syringes and mixing cups in warm water. to clean the oral syringes, remove the plunger by gently pulling it straight out of the barrel. the barrel and plunger can be hand washed with soap and water, rinsed, and allowed to dry. this instructions for use has been approved by the u.s. food and drug administration. dispense with medication guide available at: www.aurobindousa.com/medication-guides . distributed by: aurobindo pharma usa, inc. 279 princeton-hightstown road east windsor, nj 08520 manufactured by: aurobindo pharma limited hyderabad-500 032, india revised: 11/2021

Malta - inglese - Medicines Authority

aurobindo pharma (malta) limited vault 14, level 2, valletta waterfront, floriana frn 1913, malta - tablet - olanzapine 5 mg - psycholeptics

Malta - inglese - Medicines Authority

aurobindo pharma (malta) limited vault 14, level 2, valletta waterfront, floriana frn 1913, malta - tablet - olanzapine 10 mg - psycholeptics

Stati Uniti - inglese - NLM (National Library of Medicine)

aurobindo pharma limited - clobazam (unii: 2mro291b4u) (clobazam - unii:2mro291b4u) - clobazam oral suspension is indicated for the adjunctive treatment of seizures associated with lennox-gastaut syndrome (lgs) in patients 2 years of age or older. clobazam oral suspension is contraindicated in patients with a history of hypersensitivity to the drug or its ingredients. hypersensitivity reactions have included serious dermatological reactions [see warnings and precautions (5.6, 5.7)]. pregnancy registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, such as clobazam, during pregnancy. healthcare providers are encouraged to recommend that pregnant women taking clobazam enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling 1-888-233-2334 or online at http://www.aedpregnancyregistry.org/. risk summary neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal [see warnings and precautions (5.9) and clinical considerations]. available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects (see data ). administration of clobazam to pregnant rats and rabbits during the period of organogenesis or to rats throughout pregnancy and lactation resulted in developmental toxicity, including increased incidences of fetal malformations and mortality, at plasma exposures for clobazam and its major active metabolite, n-desmethylclobazam, below those expected at therapeutic doses in patients [see animal data]. data for other benzodiazepines suggest the possibility of long-term effects on neurobehavioral and immunological function in animals following prenatal exposure to benzodiazepines at clinically relevant doses. clobazam should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. advise a pregnant woman and women of childbearing age of the potential risk to a fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions benzodiazepines cross the placenta and may produce respiratory depression, hypotonia, and sedation in neonates. monitor neonates exposed to clobazam during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. monitor neonates exposed to clobazam during pregnancy for signs of withdrawal. manage these neonates accordingly [see warnings and precautions (5.9)]. data human data published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. in addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol, tobacco and other medications, have not confirmed these findings. animal data in a study in which clobazam (0, 150, 450, or 750 mg/kg/day) was orally administered to pregnant rats throughout the period of organogenesis, embryofetal mortality and incidences of fetal skeletal variations were increased at all doses. the low-effect dose for embryofetal developmental toxicity in rats (150 mg/kg/day) was associated with plasma exposures (auc) for clobazam and its major active metabolite, n-desmethylclobazam, lower than those in humans at the maximum recommended human dose (mrhd) of 40 mg/day. oral administration of clobazam (0, 10, 30, or 75 mg/kg/day) to pregnant rabbits throughout the period of organogenesis resulted in decreased fetal body weights, and increased incidences of fetal malformations (visceral and skeletal) at the mid and high doses, and an increase in embryofetal mortality at the high dose. incidences of fetal variations were increased at all doses. the highest dose tested was associated with maternal toxicity (ataxia and decreased activity). the low-effect dose for embryofetal developmental toxicity in rabbits (10 mg/kg/day) was associated with plasma exposures for clobazam and n-desmethylclobazam lower than those in humans at the mrhd. oral administration of clobazam (0, 50, 350, or 750 mg/kg/day) to rats throughout pregnancy and lactation resulted in increased embryofetal mortality at the high dose, decreased pup survival at the mid and high doses and alterations in offspring behavior (locomotor activity) at all doses. the low-effect dose for adverse effects on pre- and postnatal development in rats (50 mg/kg/day) was associated with plasma exposures for clobazam and n-desmethylclobazam lower than those in humans at the mrhd. risk summary clobazam is excreted in human milk (see data ). there are reports of sedation, poor feeding and poor weight gain in infants exposed to benzodiazepines through breast milk. there are no data on the effects of clobazam on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for clobazam and any potential adverse effects on the breastfed infant from clobazam or from the underlying maternal condition. clinical considerations adverse reactions such as somnolence and difficulty feeding have been reported in infants during breastfeeding in postmarketing experience with clobazam. infants exposed to clobazam through breast milk should be monitored for sedation, poor feeding and poor weight gain. data scientific literature on clobazam use during lactation is limited. after short-term administration, clobazam and n-desmethylclobazam are transferred into breast milk. administration of clobazam to rats prior to and during mating and early gestation resulted in adverse effects on fertility and early embryonic development at plasma exposures for clobazam and its major active metabolite, n-desmethylclobazam, below those in humans at the mrhd [see nonclinical toxicology (13.1)] . safety and effectiveness in patients less than 2 years of age have not been established. in a study in which clobazam (0, 4, 36, or 120 mg/kg/day) was orally administered to rats during the juvenile period of development (postnatal days 14 to 48), adverse effects on growth (decreased bone density and bone length) and behavior (altered motor activity and auditory startle response; learning deficit) were observed at the high dose. the effect on bone density, but not on behavior, was reversible when drug was discontinued. the no-effect level for juvenile toxicity (36 mg/kg/day) was associated with plasma exposures (auc) to clobazam and its major active metabolite, n-desmethylclobazam, less than those expected at therapeutic doses in pediatric patients. clinical studies of clobazam did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. however, elderly subjects appear to eliminate clobazam more slowly than younger subjects based on population pharmacokinetic analysis. for these reasons, the initial dose in elderly patients should be 5 mg/day. patients should be titrated initially to 10 to 20 mg/day. patients may be titrated further to a maximum daily dose of 40 mg if tolerated [see dosage and administration (2.4), clinical pharmacology (12.3)] . concentrations of clobazam’s active metabolite, n-desmethylclobazam, are higher in cyp2c19 poor metabolizers than in extensive metabolizers. for this reason, dosage modification is recommended [see dosage and administration (2.5), clinical pharmacology (12.3)] . the pharmacokinetics of clobazam were evaluated in patients with mild and moderate renal impairment. there were no significant differences in systemic exposure (auc and cmax ) between patients with mild or moderate renal impairment and healthy subjects. no dose adjustment is required for patients with mild and moderate renal impairment. there is essentially no experience with clobazam in patients with severe renal impairment or esrd. it is not known if clobazam or its active metabolite, n-desmethylclobazam, is dialyzable [see dosage and administration (2.6), clinical pharmacology (12.3)] . clobazam is hepatically metabolized; however, there are limited data to characterize the effect of hepatic impairment on the pharmacokinetics of clobazam. for this reason, dosage adjustment is recommended in patients with mild to moderate hepatic impairment (child-pugh score 5 to 9). there is inadequate information about metabolism of clobazam in patients with severe hepatic impairment [see dosage and administration (2.7), clinical pharmacology (12.3)] . clobazam oral suspension contains clobazam, a schedule iv controlled substance. clobazam 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 and precautions (5.2)] . 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). the world health organization epidemiology database contains reports of drug abuse, misuse, and overdoses associated with clobazam. physical dependence clobazam 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 and precautions (5.3)]. in clinical trials, cases of dependency were reported following abrupt discontinuation of clobazam. to reduce the risk of withdrawal reactions, use a gradual taper to discontinue clobazam or reduce the dosage [see dosage and administration (2.2) and warnings and precautions (5.3)].   acute withdrawal signs and symptoms 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 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 tolerance to clobazam 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 clobazam may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines. clobazam (kloe′ ba zam) oral suspension, civ   read this instructions for use before using clobazam oral suspension and each time you get a refill. there may be new information. this leaflet does not take the place of talking with your healthcare provider about your medical condition or treatment. prepare clobazam oral suspension dose you will need the following supplies: see figure a - clobazam oral suspension bottle - bottle adapter - oral dosing syringe (2 dosing syringes are included in the clobazam oral suspension box). - use only 1 syringe to take your dose of clobazam oral suspension. if you lose or damage the syringe, or cannot read the markings, use the other syringe. figure a step 1. remove the clobazam oral suspension bottle, bottle adapter, and 1 syringe from the box. step 2. shake the bottle well before each use. see figure b figure b step 3. uncap the bottle and firmly insert the bottle adapter into the bottle until the adapter top is even with the bottle top. see figure c figure c once the bottle adapter is in place, it should not be removed. step 4. check your dose in milliliters (ml) as prescribed by your healthcare provider. find this number on the syringe. do not take more than the prescribed total dose in 1 day. see figure d figure d step 5. push the plunger all the way down and then insert the syringe into the upright bottle through the opening in the bottle adapter. see figure e figure e step 6. with the syringe in place, turn the bottle upside down. pull the plunger to the number of mls needed (the amount of liquid medicine in step 4). see figure f figure f measure the mls of medicine using the edge of the violet plunger. see figure g figure g step 7. remove the syringe from the bottle adapter. slowly squirt clobazam oral suspension directly into the corner of your mouth or your child’s mouth until all of the liquid medicine in the syringe is given. see figure h figure h step 8. cap the bottle tightly with the adapter in place. if the cap does not fit securely, check to see if the adapter is fully inserted. see figure i - store and dispense clobazam oral suspension in its original bottle in an upright position at 68°f to 77°f (20°c to 25°c). - use clobazam oral suspension within 90 days of first opening bottle. - after 90 days safely throw away any clobazam oral suspension that has not been used. figure i step 9. wash the oral syringe after each use. - to clean the oral syringe, take apart by removing the plunger completely. pull plunger straight out of the barrel. - the barrel and plunger can be washed with soap and water, rinsed, and allowed to dry. - do not wash the oral syringe in the dishwasher. this instruction for use has been approved by the u.s. food and drug administration. distributed by: aurobindo pharma usa, inc. 279 princeton-hightstown road east windsor, nj 08520 manufactured by: aurobindo pharma limited hyderabad-500 032, india revised: 04/2024