With either drug, a severe allergic reaction is unlikely. However, if a person develops any symptoms of a reaction — such as a rash, difficulty breathing, itching, or swelling — they need emergency help.
People taking Xanax or clonazepam should not mix them with alcohol or opioid medication. Doing so can cause dangerous side effects that could be fatal. Other CNS depressants can also interact with Xanax or clonazepam and change the way they work.
Such changes can also lead to severe side effects. Before starting to take a new medication, a person should tell their doctor or pharmacist about any other drugs that they are taking or planning to take. Off-label uses are uses that are not indicated on the Food and Drug Administration FDA -approved packaging but for which a doctor might still prescribe the drug. Although clonazepam and Xanax are similar types of drug, there are times when one might be better to use than the other.
Xanax is not a seizure medication. Therefore, a person trying to control and treat seizures may find clonazepam more useful. People with anxiety disorders should make an appointment with their doctor to discuss the various treatment options and the pros and cons of each. They will consider any current medication the individual is taking before advising which prescription is most suitable. If this is the case, a person should talk to their doctor, who can make an alternative recommendation.
Following a ruling by the Affordable Care Act, Medicare now includes coverage for Xanax in their prescription drug coverage. Read more here. Adderall and Xanax are two medications that affect the central nervous system in opposite ways. Learn about whether it is safe to take them together…. Anxiety and related mental health conditions can cause ear ringing or tinnitus, and tinnitus can exacerbate existing anxiety.
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What is the difference between clonazepam and Xanax? Medically reviewed by Alan Carter, Pharm. What do people use them for? How do they differ?
Dosage comparison. Forms comparison. Side effects. Off-label uses. In addition, the use of clobazam appeared to be associated with less neurotoxicity than was observed for the 1,4-benzodiazepines clonazepam and nitrazepam. Another Canadian study, involving adult patients with different types of epilepsy, observed that those who had achieved a sustained response to clobazam differed from those who had developed tolerance in duration of epilepsy and the clobazam concentrations that had been maintained [ 20 ].
Sustained responders had experienced a shorter duration of epilepsy mean In a subset of patients in that study for whom data were available for up to 5 years, the mean modal clobazam dosage was 0. Similar results were found in a single-center study of clobazam with children from Seoul, Korea, with LGS, which reported retention rates of The switch from clonazepam to clobazam should be considered in light of relevant pharmacokinetic and pharmacodynamic factors of these compounds.
One of the important determinants of brain uptake is relative lipophilicity, often estimated by the octanol-to-water partition ratios. Via this in vitro measure, clobazam is much less lipophilic than diazepam ratio of 9 for clobazam versus for diazepam.
Similar data for clonazepam are not readily available [ 22 , 23 ]. However, the retention times for diazepam, clonazepam, and clobazam in a reverse-phase, high-performance liquid chromatography HPLC system using a neutral mobile phase are The retention time for N -desmethylclobazam is 12, again not far from the times for clonazepam or clobazam. Of the in vitro estimates, available data [ 22 , 23 ] suggest that HPLC retention times correlated better with in vivo unbound volumes of distribution for a series of benzodiazepines.
Unfortunately, data were not provided for clonazepam in this report. Thus, based on a combination of lipophilicity and protein binding, the central nervous system penetration of clonazepam and clobazam should be comparable. The binding affinities K i in nM for clonazepam, clobazam, and N -desmethylclobazam to rat brain homogenates have been determined to be 0.
In the same report, Jensen et al. These data would explain, at least in part, why clobazam may be much less sedating than clonazepam, as observed by Nicholson [ 16 ] nearly 35 years ago. For drug disposition, clobazam estimated half-life of 36 hours undergoes hepatic metabolism to N -desmethylclobazam estimated half-life of 80 hours. Because of the lower clearance, the latter achieves an approximately to fold steady concentration by approximately 4 weeks after initiation of therapy [ 26 ].
Thus, under clinical conditions, N - desmethylclobazam can appear less potent. The important finding, however, is that the concentration of N -desmethylclobazam stabilizes 4 weeks after initiation of therapy. The authors concluded that clobazam may be administered safely as adjunctive therapy in patients with LGS, without meaningful changes in clobazam pharmacokinetics that would require dosage adjustments.
The literature reviewed thus supports the transition strategies highlighted in the cases described. A rough estimate of the final dosage of clobazam for each mg of clonazepam under substitution is likely to be at least fold, probably closer to fold for many patients, and as high as fold for a few. While there is prudent caution in delaying the weaning of clonazepam until significant clobazam is already onboard from the point of view of breakthrough seizures, patients — as well as their families and caregivers — should be counseled to expect increased sedation transiently with that approach.
These guidelines are general, because if the patient is also receiving other medications acting via GABA mechanisms, the removal of clonazepam is likely to be tolerated slightly better and breakthrough seizures are less likely or may be milder should such seizures intervene. Written informed consent was obtained from both of the adult patients and the parents of the child for publication in this case series. Copies of the written consents are available for review by the Editor-in-Chief of this journal.
Writing assistance and editorial support during manuscript preparation and revision were provided by Michael A. Editorial support and article processing fees were funded by Lundbeck LLC. Competing interests. The authors received no compensation to prepare this article. RS chaired the meeting and drafted the Introduction and Discussion sections. All authors read and approved the final manuscript. Raman Sankar, Email: ude.
Steve Chung, Email: gro. Michael Scott Perry, Email: gro. Ruben Kuzniecky, Email: gro. Saurabh Sinha, Email: ude. National Center for Biotechnology Information , U. J Med Case Rep. Published online Dec Author information Article notes Copyright and License information Disclaimer.
Barrow Neurological Institute, W. Corresponding author. Received Aug 18; Accepted Oct This article is published under license to BioMed Central Ltd. This article has been cited by other articles in PMC. Case presentations The following three case reports provide insight into the transition from clonazepam to clobazam.
Conclusions From these cases, we observe that a rough estimate of final clobazam dosage for each mg of clonazepam under substitution is likely to be at least fold, probably closer to fold for many patients, and as high as fold for a few.
Keywords: Clobazam, Clonazepam, Switching, Transition. Introduction Benzodiazepines have been used to treat seizures since , when a group from Marseilles, led by Henri Gastaut, reported on the successful use of diazepam to treat non-convulsive mainly absence seizures [ 1 ] and its utility in the treatment of status epilepticus [ 2 ].
Case 2 year-old, left-handed, White Hispanic man with moderate mental retardation and medically refractory seizures Case 2 is a year-old, left-handed, White Hispanic man with moderate mental retardation and medically refractory seizures that he began experiencing at age 1 year, secondary to tuberous sclerosis.
Table 1 Dosing transition from clonazepam to clobazam in a year-old, left-handed White Hispanic man with moderate mental retardation and medically refractory seizures.
Open in a separate window. Case 3 year-old Korean woman with convulsive seizures Case 3 is a year-old Korean woman who had been quite healthy until she had a stroke in , with subsequent right hemiparesis. Table 2 Dosing transition from clonazepam to clobazam in a year-old Korean woman who had experienced a stroke in and subsequent right hemiparesis leading to convulsive seizures.
Discussion The three cases represent distinct patterns of a clonazepam to clobazam transition. Figure 1. Conclusions The literature reviewed thus supports the transition strategies highlighted in the cases described. Consent Written informed consent was obtained from both of the adult patients and the parents of the child for publication in this case series.
Acknowledgments Writing assistance and editorial support during manuscript preparation and revision were provided by Michael A. Contributor Information Raman Sankar, Email: ude.
References 1. Rev Neurol Paris ; — Patients must be 2 years of age or older. Onfi is available in a number of dose sizes. It should be started slowly in a divided dose twice daily, and it should be done according to body weight. Serum levels of clobazam and its metabolites require days to reach a steady state level. Onfi, produced by Lundbeck , is available in the United States as 10 mg and 20 mg scored tablets, as well as 2.
The dose of Onfi depends on patient's weight. The total daily dose should be divided into 2 daily doses. For patients at or less than 30 kilograms of body weight, start Onfi at 5 milligrams daily and slowly increase the medication up to 20 milligrams a day as tolerated by the patient. For patients more than 30 kilograms of body weight, start Onfi at 10 milligrams daily and increase the dose up to 40 milligrams a day as tolerated by the patient.
You need to adjust the dose in older patients, patients who are known to slowly metabolize medications through the liver known CYP2C19 metabolizers and individuals with liver disease or problems. It's OK to take clobazam either with food or without food. To give it to small children or others who cannot swallow tablets, you can crush it and mix it with a spoonful of soft food such as applesauce, yogurt, or ice cream or use the suspension. Measure your dose of Onfi oral suspension using the bottle adapter and dosing syringes that are given with the suspension.
Use Onfi oral suspension within 90 days of first opening the bottle. Throw away any unused Onfi suspension after this time. In general, a forgotten dose should be taken right away. If it is almost time for the next dose, just take one dose, not a double dose, and call the doctor's office for more advice.
Do your best to follow the doctor's directions. If you forget doses often, it may be a good idea to get a special pillbox or watch with an alarm to remind you. Taking the right amount of seizure medicine on time every single day is the most important step in preventing seizures! The mechanism of action for clobazam is not fully understood but is thought to involve what is known as potentiation of GABAergic neurotransmission resulting from binding at a benzodiazepine site at the GABA A receptor.
It is bioavailable. Food does not affect absorption. It can be easily crushed in items such as apple sauce or other foods. The main metabolite of the drug is the major circulating metabolite in humans, and at therapeutic doses, plasma concentrations of this can be 3 times higher than its parent compound. There is no specific recommendation from the company as to what should be done with people who have kidney or renal problems.
Clobazam is being marketed in the United States under the trade name of Onfi. The FDA indication for clobazam is strictly for add-on therapy for treatment of seizures associated with Lennox-Gastaut syndrome in children from age 2 and older. Both studies were similar in terms of the patient populations that were studied. The first study was a randomized, double-blind, placebo-controlled study that looked at patients who were aged 2 to 54 years with a current or prior diagnosis of Lennox-Gastaut syndrome.
The patients were divided into 2 groups by weight, those who were less than 30 kg and those who were greater than 30 kg, and then they were randomized to 1 of 3 maintenance doses of the medication 5 mg- Low, 10 mg Medium and 20 mg High doses. The primary measure for the study was the percent seizure reduction and weekly frequency of various seizures that typify the syndrome, primarily drop, tonic, or myoclonic seizures over a 4-week baseline to a week period of observation on the medication.
In the low-dose group, there was a In the medium-dose group, there was a The placebo group showed only a Because this is a drug in the benzodiazepine family, they also looked at the issue of tolerance which is common to this drug group. Tolerance is defined as whether a drug maintains its effectiveness over time at a given dose.
In other benzodiazepines, one often needs to take more of a given drug in order to maintain effectiveness. There was no significant development of tolerance over a 3-month period of observation. In the high dose group, the target daily dose of 20 mg for less than 30 kg body weight vs. Based on these analyses, the drug was approved. However, excitement over these findings has been tempered by the fact that the benefits can often be short-lived. The most commonly reported side effect with this drug includes tiredness and sedation.
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