Frisium 10

Anxiety, tension, irritability, restlessness, epilepsy.

May be taken with or without food. Individualize weight-based dose according to clinical efficacy and tolerability Doses above 5 mg/day should be administered in divided doses twice daily (5 mg dose can be administered as a single daily dose) May be administered whole, or crushed and mixed in applesauce When discontinuing, withdraw gradually; taper by decreasing the total daily dose by 5-10 mg/day on a weekly basis until discontinued

Seizures Indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged 2 years or older >30 kg: Initiate at 5 mg PO q12hr; may titrate as tolerated up to 40 mg/day divided q12hr Dose escalation should not proceed more rapidly than once weekly Hepatic impairment Limited data to characterize the effect of hepatic impairment on the pharmacokinetics; proceed with low and slow titration Mild-to-moderate (Child-Pugh 5-9): Starting dose should be 5 mg/day and titrated according to weight, but to half the typical adult dose; additional titration to the maximum dose (20 mg/day or 40 mg/day), depending on the weight group may be started on day 21 Severe hepatic impairment: Not recommended

Seizures Indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged 2 years or older <30 kg Starting dose: 5 mg PO qDay; titrate as tolerated up to 20 mg PO daily After 7 days, may increase to 5 mg PO q12hr; if needed, may increase to 10 mg PO q12hr after an additional 7 days >30 kg Starting dose: 5 mg PO q12hr; titrate as tolerated up to 40 mg PO daily After 7 days, may increase to 10 mg PO q12hr; if needed, may increase to 20 mg PO q12hr after an additional 7 days

Renal impairment Mild or moderate renal impairment: No dose adjustment required Severe renal impairment or ESRD: No experience

Hypersensitivity; history of drug dependence; myasthaenia gravis; pregnancy (1st trimester), lactation; serious liver damage; sleep apnoea syndrome; impaired respiratory function.

Clobazam binds to one or more specific GABA receptors at several sites within the CNS including the limbic system and reticular formation. Increased permeability of neuronal membrane to chloride ions results in GABA's inhibitory effect leading to hyperpolarisation and stabilisation.

May impair ability to perform skilled tasks and hazardous activities; elderly; renal or hepatic impairment; alcoholics; obesity; withdrawal should be gradual. Lactation: Excreted in breast milk; effects of exposure on infants unknown

>10% Somnolence or sedation (26%),Somnolence (22%),Pyrexia (13%),Upper respiratory tract infection (12%) 1-10% Drooling (9%),Aggression (8%),Irritability (7%),Vomiting (7%),Insomnia (5%),Ataxia (5%),Sedation (5%),Constipation (5%),Fatigue (5%),Cough (5%),Psychomotor hyperactivity (4%),Pneumonia (4%),Urinary tract infection (4%),Dysarthria (3%),Decreased appetite (3%),Increased appetite (3%),Bronchitis (2%),Dysphagia (2%) Potentially Fatal: Respiratory depression.

Pregnancy There are no adequate and well-controlled studies in pregnant women; available data suggest that the class of benzodiazepines is not associated with marked increases in risk for congenital anomalies; although some early epidemiological studies suggested a relationship between benzodiazepine drug use in pregnancy and congenital anomalies such as cleft lip and or palate, these studies had considerable limitations; more recently completed studies of benzodiazepine use in pregnancy have not consistently documented elevated risks for specific congenital anomalies; there is insufficient evidence to assess effect of benzodiazepine pregnancy exposure on neurodevelopment There are clinical considerations regarding exposure to benzodiazepines during second and third trimester of pregnancy or immediately prior to or during childbirth; these risks include decreased fetal movement and/or fetal heart rate variability, “floppy infant syndrome,” dependence, and withdrawal Administration of clobazam to pregnant rats and rabbits during 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; data for other benzodiazepines suggest possibility of long-term effects on neurobehavioral and immunological function in animals following prenatal exposure to benzodiazepines at clinically relevant doses; drug should be used during pregnancy only if potential benefit to mother justifies potential risk to fetus; advise a pregnant woman and women of childbearing age of potential risk to a fetus Infants born to mothers who have taken benzodiazepines during later stages of pregnancy can develop dependence, and subsequently withdrawal, during postnatal period; clinical manifestations of withdrawal or neonatal abstinence syndrome may include hypertonia, hyperreflexia, hypoventilation, irritability, tremors, diarrhea, and vomiting; these complications can appear shortly after delivery to 3 weeks after birth and persist from hours to several months depending on degree of dependence and pharmacokinetic profile of the benzodiazepine; symptoms may be mild and transient or severe; standard management for neonatal withdrawal syndrome has not yet been defined; observe newborns who are exposed to drug in utero during later stages of pregnancy for symptoms of withdrawal and manage accordingly Laber and delivery Administration of benzodiazepines immediately prior to or during childbirth can result in a floppy infant syndrome, which is characterized by lethargy, hypothermia, hypotonia, respiratory depression, and difficulty feeding; floppy infant syndrome occurs mainly within first hours after birth and may last up to 14 days; observe exposed newborns for these symptoms and manage accordingly Lactation Drug is excreted in human milk; postmarketing experience suggests that breastfed infants of mothers taking benzodiazepines, may have effects of lethargy, somnolence and poor sucking; effect of drug on milk production is unknown; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for drug and any potential adverse effects on breastfed infant from drug or from underlying maternal condition; if exposing a breastfed infant to drug, observe for any potential adverse effects

Increased hepatic clearance of clobazam when administered with phenytoin, phenobarbital or carbamazepine. Cimetidine may increase levels of clobazam. Potentially Fatal: Concurrent alcohol, hypnotics and sedative antidepressants can potentiate CNS side effects of clobazam