KLONOPIN TABLETS (clonazepam) KLONOPIN WAFERS(clonazepam orally disintegrating tablets) | KLONOPIN
Klonopin, a benzodiazepine, is available as scored tablets with a K-shaped perforation containing 0.5 mg of clonazepam and unscored tablets with a K-shaped perforation containing 1 mg or 2 mg of clonazepam. Each tablet also contains lactose, magnesium stearate, microcrystalline cellulose and corn starch, with the following colorants: 0.5 mg—FD&C Yellow No. 6 Lake; 1 mg—FD&C Blue No. 1 Lake and FD&C Blue No. 2 Lake.
Klonopin is also available as an orally disintegrating tablet containing 0.125 mg, 0.25 mg, 0.5 mg, 1 mg or 2 mg clonazepam. Each orally disintegrating tablet also contains gelatin, mannitol, methylparaben sodium, propylparaben sodium and xanthan gum.
Chemically, clonazepam is 5-(2-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has a molecular weight of 315.72 and the following structural formula:
The precise mechanism by which clonazepam exerts its antiseizure and antipanic effects is unknown, although it is believed to be related to its ability to enhance the activity of gamma aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Convulsions produced in rodents by pentylenetetrazol or, to a lesser extent, electrical stimulation are antagonized, as are convulsions produced by photic stimulation in susceptible baboons. A taming effect in aggressive primates, muscle weakness and hypnosis are also produced. In humans, clonazepam 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.
Clonazepam is rapidly and completely absorbed after oral administration. The absolute bioavailability of clonazepam is about 90%. Maximum plasma concentrations of clonazepam are reached within 1 to 4 hours after oral administration. Clonazepam is approximately 85% bound to plasma proteins. Clonazepam is highly metabolized, with less than 2% unchanged clonazepam being excreted in the urine. Biotransformation occurs mainly by reduction of the 7-nitro group to the 4-amino derivative. This derivative can be acetylated, hydroxylated and glucuronidated. Cytochrome P-450 including CYP3A, may play an important role in clonazepam reduction and oxidation. The elimination half-life of clonazepam is typically 30 to 40 hours. Clonazepam pharmacokinetics are dose-independent throughout the dosing range. There is no evidence that clonazepam induces its own metabolism or that of other drugs in humans.
Controlled studies examining the influence of gender and age on clonazepam pharmacokinetics have not been conducted, nor have the effects of renal or liver disease on clonazepam pharmacokinetics been studied. Because clonazepam undergoes hepatic metabolism, it is possible that liver disease will impair clonazepam elimination. Thus, caution should be exercised when administering clonazepam to these patients.
The effectiveness of Klonopin in the treatment of panic disorder was demonstrated in two double-blind, placebo-controlled studies of adult outpatients who had a primary diagnosis of panic disorder (DSM-IIIR) with or without agoraphobia. In these studies, Klonopin was shown to be significantly more effective than placebo in treating panic disorder on change from baseline in panic attack frequency, the Clinician's Global Impression Severity of Illness Score and the Clinician's Global Impression Improvement Score.
Study 1 was a 9-week, fixed-dose study involving Klonopin doses of 0.5, 1, 2, 3 or 4 mg/day or placebo. This study was conducted in four phases: a 1-week placebo lead-in, a 3-week upward titration, a 6-week fixed dose and a 7-week discontinuance phase. A significant difference from placebo was observed consistently only for the 1 mg/day group. The difference between the 1 mg dose group and placebo in reduction from baseline in the number of full panic attacks was approximately 1 panic attack per week. At endpoint, 74% of patients receiving clonazepam 1 mg/day were free of full panic attacks, compared to 56% of placebo-treated patients.
Study 2 was a 6-week, flexible-dose study involving Klonopin in a dose range of 0.5 to 4 mg/day or placebo. This study was conducted in three phases: a 1-week placebo lead-in, a 6-week optimal-dose and a 6-week discontinuance phase. The mean clonazepam dose during the optimal dosing period was 2.3 mg/day. The difference between Klonopin and placebo in reduction from baseline in the number of full panic attacks was approximately 1 panic attack per week. At endpoint, 62% of patients receiving clonazepam were free of full panic attacks, compared to 37% of placebo-treated patients.
Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of race or gender.
Klonopin is 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, Klonopin may be useful.
In some studies, up to 30% of patients have shown a loss of anticonvulsant activity, often within 3 months of administration. In some cases, dosage adjustment may reestablish efficacy.
Klonopin is indicated for the treatment of panic disorder, with or without agoraphobia, as defined in DSM-IV. 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 Klonopin 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 Trials).
Panic disorder (DSM-IV) is characterized by recurrent unexpected panic attacks, ie, a discrete period of intense fear or discomfort in which four (or more) of the following symptoms develop abruptly and reach a peak within 10 minutes: (1) palpitations, pounding heart or accelerated heart rate; (2) sweating; (3) trembling or shaking; (4) sensations of shortness of breath or smothering; (5) feeling of choking; (6) chest pain or discomfort; (7) nausea or abdominal distress; (8) feeling dizzy, unsteady, lightheaded or faint; (9) derealization (feelings of unreality) or depersonalization (being detached from oneself); (10) fear of losing control; (11) fear of dying; (12) paresthesias (numbness or tingling sensations); (13) chills or hot flushes.
The effectiveness of Klonopin in long-term use, that is, for more than 9 weeks, has not been systematically studied in controlled clinical trials. The physician who elects to use Klonopin for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient (see DOSAGE AND ADMINISTRATION).
Klonopin should not be used in patients with a history of sensitivity to benzodiazepines, nor 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 contraindicated 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 PRECAUTIONS: Drug Interactions and Information for Patients).
Antiepileptic drugs (AEDs), including Klonopin, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43% compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed.
Table 1 shows absolute and relative risk by indication for all evaluated AEDs.
The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing Klonopin or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
|Indication||Placebo Patients with Events Per 1000 Patients||Drug Patients with Events Per 1000 Patients||Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients||Risk Difference: Additional Drug Patients with Events per 1000 Patients|
Data from several sources raise concerns about the use of Klonopin during pregnancy.
In three studies in which Klonopin was administered orally to pregnant rabbits at doses of 0.2, 1, 5 or 10 mg/kg/day (low dose approximately 0.2 times the maximum recommended human dose of 20 mg/day for seizure disorders and equivalent to the maximum dose of 4 mg/day for panic disorder, on a mg/m basis) during the period of organogenesis, a similar pattern of malformations (cleft palate, open eyelid, fused sternebrae and limb defects) was observed in a low, non-dose-related incidence in exposed litters from all dosage groups. Reductions in maternal weight gain occurred at dosages of 5 mg/kg/day or greater and reduction in embryo-fetal growth occurred in one study at a dosage of 10 mg/kg/day. No adverse maternal or embryo-fetal effects were observed in mice and rats following administration during organogenesis of oral doses up to 15 mg/kg/day or 40 mg/kg/day, respectively (4 and 20 times the maximum recommended human dose of 20 mg/day for seizure disorders and 20 and 100 times the maximum dose of 4 mg/day for panic disorder, respectively, on a mg/m basis).
Recent reports suggest an association between the use of anticonvulsant drugs by women with epilepsy and an elevated incidence of birth defects in children born to these women. Data are more extensive with respect to diphenylhydantoin and phenobarbital, 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.
In children of women treated with drugs for epilepsy, reports suggesting an elevated incidence of birth defects 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 (eg, 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 medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy; however, it cannot be said with any confidence that even mild seizures do not pose some hazards to the developing embryo or fetus.
An increased risk of congenital malformations associated with the use of benzodiazepine drugs has been suggested in several studies.
There may also be non-teratogenic risks associated with the use of benzodiazepines during pregnancy. There have been reports of neonatal flaccidity, respiratory and feeding difficulties, and hypothermia in children born to mothers who have been receiving benzodiazepines late in pregnancy. In addition, children born to mothers receiving benzodiazepines late in pregnancy may be at some risk of experiencing withdrawal symptoms during the postnatal period.
In general, the use of Klonopin in women of childbearing potential, and more specifically during known pregnancy, should be considered only when the clinical situation warrants the risk to the fetus.
The specific considerations addressed above regarding the use of anticonvulsants for epilepsy in women of childbearing potential should be weighed in treating or counseling these women.
Because of experience with other members of the benzodiazepine class, Klonopin is assumed to be capable of causing an increased risk of congenital abnormalities when administered to a pregnant woman during the first trimester. Because use of these drugs is rarely a matter of urgency in the treatment of panic disorder, their use during the first trimester should almost always be avoided. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Patients should also be advised that if they become pregnant during therapy or intend to become pregnant, they should communicate with their physician about the desirability of discontinuing the drug.
Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines (see DRUG ABUSE AND DEPENDENCE).
When used in patients in whom several different types of seizure disorders coexist, Klonopin may increase the incidence or precipitate the onset of generalized tonic-clonic seizures (grand mal). This may require the addition of appropriate anticonvulsants or an increase in their dosages. The concomitant use of valproic acid and Klonopin may produce absence status.
Periodic blood counts and liver function tests are advisable during long-term therapy with Klonopin.
The abrupt withdrawal of Klonopin, particularly in those patients on long-term, high-dose therapy, may precipitate status epilepticus. Therefore, when discontinuing Klonopin, gradual withdrawal is essential. While Klonopin is being gradually withdrawn, the simultaneous substitution of another anticonvulsant may be indicated.
Metabolites of Klonopin are excreted by the kidneys; to avoid their excess accumulation, caution should be exercised in the administration of the drug to patients with impaired renal function.
Klonopin may produce an increase in salivation. This should be considered before giving the drug to patients who have difficulty handling secretions. Because of this and the possibility of respiratory depression, Klonopin should be used with caution in patients with chronic respiratory diseases.
Patients should be instructed to take Klonopin only as prescribed. Physicians are advised to discuss the following issues with patients for whom they prescribe Klonopin:
To assure the safe and effective use of benzodiazepines, patients should be informed that, since benzodiazepines may produce psychological and physical dependence, it is advisable that they consult with their physician before either increasing the dose or abruptly discontinuing this drug.
Because benzodiazepines have the potential to impair judgment, thinking or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that Klonopin therapy does not affect them adversely.
Patients, their caregivers, and families should be counseled that AEDs, including Klonopin, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy with Klonopin (see WARNINGS: Pregnancy Risks). Patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 (see PRECAUTIONS: Pregnancy).
Patients should be advised not to breastfeed an infant if they are taking Klonopin.
Patients should be advised to inform their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions.
Patients should be advised to avoid alcohol while taking Klonopin.
Clonazepam does not appear to alter the pharmacokinetics of phenytoin, carbamazepine or phenobarbital. The effect of clonazepam on the metabolism of other drugs has not been investigated.
Literature reports suggest that ranitidine, an agent that decreases stomach acidity, does not greatly alter clonazepam pharmacokinetics.
In a study in which the 2 mg clonazepam orally disintegrating tablet was administered with and without propantheline (an anticholinergic agent with multiple effects on the GI tract) to healthy volunteers, the AUC of clonazepam was 10% lower and the C of clonazepam was 20% lower when the orally disintegrating tablet was given with propantheline compared to when it was given alone.
Fluoxetine does not affect the pharmacokinetics of clonazepam. Cytochrome P-450 inducers, such as phenytoin, carbamazepine and phenobarbital, induce clonazepam metabolism, causing an approximately 30% decrease in plasma clonazepam levels. Although clinical studies have not been performed, based on the involvement of the cytochrome P-450 3A family in clonazepam metabolism, inhibitors of this enzyme system, notably oral antifungal agents, should be used cautiously in patients receiving clonazepam.
The CNS-depressant action of the benzodiazepine class of drugs may be potentiated by alcohol, narcotics, barbiturates, nonbarbiturate hypnotics, antianxiety agents, the phenothiazines, thioxanthene and butyrophenone classes of antipsychotic agents, monoamine oxidase inhibitors and the tricyclic antidepressants, and by other anticonvulsant drugs.
Carcinogenicity studies have not been conducted with clonazepam.
The data currently available are not sufficient to determine the genotoxic potential of clonazepam.
In a two-generation fertility study in which clonazepam was given orally to rats at 10 and 100 mg/kg/day (low dose approximately 5 times and 24 times the maximum recommended human dose of 20 mg/day for seizure disorder and 4 mg/day for panic disorder, respectively, on a mg/m basis), there was a decrease in the number of pregnancies and in the number of offspring surviving until weaning.
(see WARNINGS: Pregnancy Risks).
To provide information regarding the effects of in utero exposure to Klonopin, physicians are advised to recommend that pregnant patients taking Klonopin enroll in the NAAED Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on this registry can also be found at the website http://www.aedpregnancyregistry.org/.
The effect of Klonopin on labor and delivery in humans has not been specifically studied; however, perinatal complications have been reported in children born to mothers who have been receiving benzodiazepines late in pregnancy, including findings suggestive of either excess benzodiazepine exposure or of withdrawal phenomena (see WARNINGS: Pregnancy Risks).
Mothers receiving Klonopin should not breastfeed their infants.
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 being treated for seizure disorder (see INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION).
Safety and effectiveness in pediatric patients with panic disorder below the age of 18 have not been established.
Clinical studies of Klonopin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Because clonazepam undergoes hepatic metabolism, it is possible that liver disease will impair clonazepam elimination. Metabolites of Klonopin are excreted by the kidneys; to avoid their excess accumulation, caution should be exercised in the administration of the drug to patients with impaired renal function. Because elderly patients are more likely to have decreased hepatic and/or renal function, care should be taken in dose selection, and it may be useful to assess hepatic and/or renal function at the time of dose selection.
Sedating drugs may cause confusion and over-sedation in the elderly; elderly patients generally should be started on low doses of Klonopin and observed closely.
The adverse experiences for Klonopin are provided separately for patients with seizure disorders and with panic disorder.
The most frequently occurring side effects of Klonopin are referable to CNS depression. Experience in treatment of seizures has shown that drowsiness has occurred in approximately 50% of patients and ataxia in approximately 30%. In some cases, these may diminish with time; behavior problems have been noted in approximately 25% of patients. Others, listed by system, are:
Neurologic: Abnormal eye movements, aphonia, choreiform movements, coma, diplopia, dysarthria, dysdiadochokinesis, ''glassy-eyed'' appearance, headache, hemiparesis, hypotonia, nystagmus, respiratory depression, slurred speech, tremor, vertigo
Psychiatric: Confusion, depression, amnesia, hallucinations, hysteria, increased libido, insomnia, psychosis (the behavior effects are more likely to occur in patients with a history of psychiatric disturbances). The following paradoxical reactions have been observed: excitability, irritability, aggressive behavior, agitation, nervousness, hostility, anxiety, sleep disturbances, nightmares and vivid dreams
Respiratory: Chest congestion, rhinorrhea, shortness of breath, hypersecretion in upper respiratory passages
Dermatologic: Hair loss, hirsutism, skin rash, ankle and facial edema
Gastrointestinal: Anorexia, coated tongue, constipation, diarrhea, dry mouth, encopresis, gastritis, increased appetite, nausea, sore gums
Genitourinary: Dysuria, enuresis, nocturia, urinary retention
Musculoskeletal: Muscle weakness, pains
Miscellaneous: Dehydration, general deterioration, fever, lymphadenopathy, weight loss or gain
Hematopoietic: Anemia, leukopenia, thrombocytopenia, eosinophilia
Hepatic: Hepatomegaly, transient elevations of serum transaminases and alkaline phosphatase
Adverse events during exposure to Klonopin were obtained by spontaneous report and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and tabulations that follow, CIGY dictionary terminology has been used to classify reported adverse events, except in certain cases in which redundant terms were collapsed into more meaningful terms, as noted below.
The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.
Overall, the incidence of discontinuation due to adverse events was 17% in Klonopin compared to 9% for placebo in the combined data of two 6- to 9-week trials. The most common events (≥1%) associated with discontinuation and a dropout rate twice or greater for Klonopin than that of placebo included the following:
|Adverse Event||Klonopin (N=574)||Placebo (N=294)|
|Intellectual Ability Reduced||1%||0%|
Table 3 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred during acute therapy of panic disorder from a pool of two 6- to 9-week trials. Events reported in 1% or more of patients treated with Klonopin (doses ranging from 0.5 to 4 mg/day) and for which the incidence was greater than that in placebo-treated patients are included.
The prescriber should be aware that the figures in Table 3 cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence in the population studied.
|Clonazepam Maximum Daily Dose|
by Body System
All Klonopin Groups
|Central & Peripheral Nervous System|
| Coordination Abnormal
|Intellectual Ability Reduced||0||2||4||3||2||0|
| Upper Respiratory Tract
| Abdominal Pain
|Body as a Whole|
|Resistance Mechanism Disorders|
| Urinary Tract Infection
(Genentech Preferred Term)
In the pool of two short-term placebo-controlled trials, adverse events classified under the preferred term "depression" were reported in 7% of Klonopin-treated patients compared to 1% of placebo-treated patients, without any clear pattern of dose relatedness. In these same trials, adverse events classified under the preferred term "depression" were reported as leading to discontinuation in 4% of Klonopin-treated patients compared to 1% of placebo-treated patients. While these findings are noteworthy, Hamilton Depression Rating Scale (HAM-D) data collected in thes
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Drugs and Medications
KLONOPIN TABLETS (clonazepam) KLONOPIN WAFERS(clonazepam orally disintegrating tablets)
KLONOPIN TABLETS CIV(clonazepam)KLONOPIN WAFERS CIV(clonazepam orally disintegrating tablets)
To compare the single-dose bioavailability of Clonazepam ODT 1 mg and Klonopin Wafers 1 mg ODT
To compare the single-dose bioavailability of Clonazepam tablets 1 mg and Klonopin tablets 1 mg
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