One double-blind study assessed infusion-site tolerance of equivalent loading doses (15 to 20 mg PE/kg) of Cerebyx infused at 150 mg PE/min or phenytoin infused at 50 mg/min. An increased risk of heart defects, facial clefts, and digital hypoplasia has been reported. Therapeutic effect without clinical signs of toxicity occurs more often with serum total phenytoin concentrations between 10 and 20 mcg/mL (unbound phenytoin concentrations of 1 to 2 mcg/mL), although some mild cases of tonic-clonic (grand mal) epilepsy may be controlled with lower serum levels of phenytoin.

Differences in the 7.5 mg/kg twice daily treatment groups, respectively.The efficacy and safety of CELEBREX for JRA have not been studied beyond six months. This may or may not be associated with extravasation. CELEBREX doses of 100 mg twice daily and 200 mg twice daily were similar in effectiveness and both were comparable to naproxen 500 mg twice daily.Although CELEBREX 100 mg twice daily and 200 mg twice daily provided similar overall effectiveness, some patients derived additional benefit from the 200 mg twice daily dose. Kaplan-Meier cumulative rates for investigator-reported serious cardiovascular thromboembolic adverse events (including MI, The correlation between findings of short-term endoscopic studies with CELEBREX and the relative incidence of clinically significant serious upper GI events with long-term use has not been established. Median exposures for CELEBREX (n = 3,987) and diclofenac It is a colorless crystalline compound, insoluble in water, with the following molecular structure:In animals, diazepam appears to act on parts of the limbic system, the thalamus and hypothalamus, and induces calming effects. Reduction in rate of administration or discontinuation of dosing may be needed.Antiepileptic drugs should not be abruptly discontinued because of the possibility of increased seizure frequency, including status epilepticus. There are no specific antidotes. Vials that develop particulate matter should not be used.Injection vials are single-dose only. However, cardiac events have also been reported in adults and children without underlying cardiac disease or comorbidities and at recommended doses and infusion rates.The rate of intravenous Cerebyx administration should not exceed 150 mg phenytoin sodium equivalents (PE) per minute in adults and 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower) in pediatric patients Although the risk of cardiovascular toxicity increases with infusion rates above the recommended infusion rate, these events have also been reported at or below the recommended infusion rate.As non-emergency therapy, intravenous Cerebyx should be administered more slowly.

Metabolites of diazepam are excreted by the kidney; to avoid their excess accumulation, caution should be exercised in the administration to patients with compromised kidney function.Since an increase in cough reflex and laryngospasm may occur with peroral endoscopic procedures, the use of a topical anesthetic agent and the availability of necessary countermeasures are recommended.Propylene glycol toxicity has been reported in patients treated with Diazepam Injection at doses significantly greater than recommended. Periodic measurement of serum phenytoin concentrations may be valuable in the management of pregnant women as a guide to appropriate adjustment of dosage A potentially life-threatening bleeding disorder related to decreased levels of vitamin K-dependent clotting factors may occur in newborns exposed to phenytoin Meta-analyses using data from published observational studies and registries have estimated an approximately 2.4-fold increased risk for any major malformation in children with prenatal phenytoin exposure compared to controls. Studies have therefore empirically determined an infusion rate for Cerebyx that gives a rate and extent of phenytoin systemic availability similar to that of a 50 mg/min phenytoin sodium infusion. Diazepam Injection BP contains propylene glycol. Cerebyx dose reduction is indicated if serum levels are excessive; if symptoms persist, administration of Cerebyx should be discontinued.The following serious adverse reactions are described elsewhere in the labeling:Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.The more important adverse clinical reactions caused by the IV use of Cerebyx or phenytoin are cardiovascular collapse and/or CNS depression. The syndrome may not develop for several days after injection.The phosphate load provided by Cerebyx (0.0037 mmol phosphate/mg PE Cerebyx) should be considered when treating patients who require phosphate restriction, such as those with severe renal impairment.Because the fraction of unbound phenytoin (the active metabolite of Cerebyx) is increased in patients with renal or hepatic disease, or in those with hypoalbuminemia, the monitoring of phenytoin serum levels should be based on the unbound fraction in those patients.

Although a cause and effect relationship has not been established, the occurrence of lymphadenopathy indicates the need to differentiate such a condition from other types of lymph node pathology.

This has the potential to increase the frequency and severity of adverse events.In view of isolated reports associating phenytoin (the active metabolite of Cerebyx) with exacerbation of porphyria, caution should be exercised in using Cerebyx in patients suffering from this disease.Cerebyx may cause fetal harm when administered to a pregnant woman. The background risk of major birth defects and miscarriage for the indicated population is unknown.An increase in seizure frequency may occur during pregnancy because of altered phenytoin pharmacokinetics. Propylene glycol toxicity can cause acute tubular necrosis (which can progress to multi-organ failure), mental status changes, hypotension, seizures, and cardiac arrhythmias.