Klonopin is available as scored tablets containing 0.5 mg, 1 mg or 2 mg clonazepam/Roche. Each tablet also contains lactose, magnesium stearate, microcrystalline cellulose and corn starch, with the following dye systems: 0.5 mg - FD& C Yellow No. 6; 1 mg - FD& C Blue No. 1 and FD& C Blue No. 2. Chemically, clonazepam is 5-(2-chlorophenyl)-1,3-dihydo-7-nitro-2H-1, 4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has a molecular weight of 315.7.
In laboratory animals, Klonopin exhibits several pharmacologic properties which are characteristic of the benzodiazepine class of drugs. Convulsions produced in rodents by pentylenetetrazol or electrical stimulation are antagonized, as are convulsions produced by photic stimulation in susceptible baboons. A taming effect in aggressive primates, muscle weakness an hypnosis are likewise produced by Klonopin. In humans it is capable of suppressing the spike and wave discharge in absence seizures (petit mal) and decreasing the frequency, amplitude, duration and spread of discharge in minor motor seizures. Single oral dose administration of Klonopin to humans gave maximum blood levels of drug, in most cases within one to two hours. The half-life of the parent compound varied from approximately 18 to 50 hours, and the major route of excretion was in the urine. In humans, five metabolites have been identified. In general, the biotransformation of clonazepam followed two pathways: oxidative hydroxylation at the C-3 position and reduction of the 7-nitro function to form 7-amino and/or 7-acetyl-amino derivatives.
Klonopin should not be used in patients with a history of sensitivity to benzodiazepines, not in patients with clinical or biochemical evidence of significant liver disease. It may be used in patients with open angle glaucoma who are receiving appropriate therapy, but is contraindicted in acute narrow angle glaucoma.
Since Klonopin produces CNS depression, patients receiving this drug should be cautioned against engaging in hazardous occupations requiring mental alertness, such as operating machinery or driving a motor vehicle. They should also be warned about the concomitant use of alcohol or other CNS-depressant drugs during Klonopin therapy (see Drug Interactions).
The effects of Klonopin in human pregnancy and nursing infants are unknown. Recent reports suggest an association between the use of anticonvulsant drugs by women with epilepsy and an elevated incidence of bith defects in children born to these women. Data are more extensive with respect to diphenyl-hydantoin and phenobarbitol, but these are also the most commonly prescribed anticonvulsants; less systematic or anecdotal reports suggest a possible similar association with the use of all known anticonvulsant drugs. The reports suggesting an elevated incidence of birth defects in children of drug-treated epileptic women cannot be regarded as adequate to prove a definite cause and effect relationship. There are intrinsic methodologic problems in obtaining adequate data on drug teratogenicity in humans; the possibility also exists that other factors, e.g., genetic factors or the epileptic condition itself, may be more important than drug therapy in leading to birth defects. The great majority of mothers on anticonvulsant medication deliver normal infants. It is important to note that anticonvulsant drugs should not be discontinued in patients in whom the drug is administered to prevent seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorder are such that the removal of the medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even mild seizures do not pose some hazards to the developing embryo or fetus. These considerations should be weighed in treating or counseling epileptic women of childbearing potential. Use of Klonopin in women of childbearing potential should be considered only when the clinical situation warrants the risk. Mothers receiving Klonopin should not breast feed their infants. In a two-generation reproduction study with Klonopin given orally to rats at 10 or 100 mg/kg/day, there was a decrease in the number of pregnancies and a decrease in the number of offspring surviving until weaning. When Klonopin was administered orally to pregnant rabbits at 0.2, 1.0, 5.0 or 10.0 mg/kg/day, a nondose-related incidence of cleft palates, open eyelids, fused sternebrae and limb defects was observed at the 0.2 and 5.0 mg/kg/day levels. Nearly all of the malformations were seen from one dam in each of the affected dosages.
Because of the possibility that adverse effects on physical or mental development could become apparent only after many years, a benefit-risk consideration of the long-term use of Klonopin is important in pediatric patients. Withdrawl symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines.
Scored tablets - 0.5 mg, orange; 1 mg, blue; 2 mg, white - bottles of 100; Tel-E-Dose packages of 100, available in boxes of four reverse-numbered cards of 25.
Distributed by Hoffmann-La Roche Inc. Nutley, New Jersey 07110-1199. Manufactured by Roche Pharma, Inc. Manati, Puerto Rico 00674.
Roche Laboratories a division of Hoffmann-La Roche Inc. 340 Kingsland Street Nutley, New Jersey 07110-1199