Medications: Klonopin^® – clonazepam

MEDICATIONS

Klonopin^® – clonazepam (View the FDA label)

Uses
Side Effects
Precautions
Interactions
Overdose

INDICATION AND USES:

Klonopin is indicated for:

Seizure Disorders
Panic Disorder

DOSAGE AND ADMINISTRATION

Seizure Disorders:

The use of multiple anticonvulsants may result in an increase of CNS depressant adverse effects. This should be considered before adding Klonopin to an existing anticonvulsant regimen.

Adults: The initial dose for adults with seizure disorders should not exceed 1.5 mg/day divided into three doses. Dosage may be increased in increments of 0.5 to 1 mg every 3 days until seizures are adequately controlled or until side effects preclude any further increase. Maintenance dosage must be individualized for each patient depending upon response. Maximum recommended daily dose is 20 mg.

Pediatric Patients: Klonopin is administered orally. In order to minimize drowsiness, the initial dose for infants and children (up to 10 years of age or 30 kg of body weight) should be between 0.01 and 0.03 mg/kg/day but not to exceed 0.05 mg/kg/day given in two or three divided doses. Dosage should be increased by no more than 0.25 to 0.5 mg every third day until a daily maintenance dose of 0.1 to 0.2 mg/kg of body weight has been reached, unless seizures are controlled or side effects preclude further increase. Whenever possible, the daily dose should be divided into three equal doses. If doses are not equally divided, the largest dose should be given before retiring.

Geriatric Patients: There is no clinical trial experience with Klonopin in seizure disorder patients 65 years of age and older. In general, elderly patients should be started on low doses of Klonopin and observed closely (see PRECAUTIONS: Geriatric Use).

Panic Disorder:

Adults: The initial dose for adults with panic disorder is 0.25 mg bid. An increase to the target dose for most patients of 1 mg/day may be made after 3 days. The recommended dose of 1 mg/day is based on the results from a fixed dose study in which the optimal effect was seen at 1 mg/day. Higher doses of 2, 3 and 4 mg/day in that study were less effective than the 1 mg/day dose and were associated with more adverse effects. Nevertheless, it is possible that some individual patients may benefit from doses of up to a maximum dose of 4 mg/day, and in those instances, the dose may be increased in increments of 0.125 to 0.25 mg bid every 3 days until panic disorder is controlled or until side effects make further increases undesired. To reduce the inconvenience of somnolence, administration of one dose at bedtime may be desirable. Treatment should be discontinued gradually, with a decrease of 0.125 mg bid every 3 days, until the drug is completely withdrawn. There is no body of evidence available to answer the question of how long the patient treated with clonazepam should remain on it. Therefore, the physician who elects to use Klonopin for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

Pediatric Patients: There is no clinical trial experience with Klonopin in panic disorder patients under 18 years of age.

Geriatric Patients: There is no clinical trial experience with Klonopin in panic disorder patients 65 years of age and older. In general, elderly patients should be started on low doses of Klonopin and observed closely (see PRECAUTIONS: Geriatric Use).

SIDE EFFECTS:

The adverse experiences for Klonopin are provided separately for patients with seizure disorders and with panic disorder.

Seizure Disorders: 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, including those identified during postapproval use of Klonopin are:

Cardiovascular: Palpitations
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
Hematopoietic: Anemia, leukopenia, thrombocytopenia, eosinophilia
Hepatic: Hepatomegaly, transient elevations of serum transaminases and alkaline phosphatase
Musculoskeletal: Muscle weakness, pains
Miscellaneous: Dehydration, general deterioration, fever, lymphadenopathy, weight loss or gain
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, 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: irritability, aggression, agitation, nervousness, hostility, anxiety, sleep disturbances, nightmares, abnormal dreams, hallucinations.
Respiratory: Chest congestion, rhinorrhea, shortness of breath, hypersecretion in upper respiratory passages

Panic Disorder:

Treatment-Emergent Adverse Event Incidence in 6- to 9-week placebo controlled clinical trials:

Clonazepam Maximum Daily Dose
Adverse Event by Body System	<1mg n=96 %	1- <2mg n=129 %	2- <3mg n=113 %	>3mg n=235 %	All Klonopin Groups N=574 %	Placebo N=294 %
Central & Peripheral Nervous System Somnolence^† Dizziness Coordination Abnormal^† Ataxia^† Dysarthria^†	26 5 1 2 0	35 5 2 1 0	50 12 7 8 4	36 8 9 8 3	37 8 6 5 2	10 4 0 0 0
Psychiatric Depression Memory Disturbance Nervousness Intellectual Ability Reduced Emotional Lability Libido Decreased Confusion	7 2 1 0 0 0 0	6 5 4 2 1 1 2	8 2 3 4 2 3 2	8 5 4 3 2 1 1	7 4 3 2 1 1 1	1 2 2 0 1 0 0
Respiratory System Upper Respiratory Tract Infection^† Sinusitis Rhinitis Coughing Pharyngitis Bronchitis	10 4 3 2 1 1	10 2 2 2 1 0	7 8 4 4 3 2	6 4 2 0 2 2	8 4 2 2 2 1	4 3 1 0 1 1
Gastrointestinal System Constipation^† Appetite Decreased Abdominal Pain^†	0 1 2	1 1 2	5 0 2	3 3 0	2 1 1	2 1 1
Body as a Whole Fatigue Allergic Reaction	9 3	6 1	7 4	7 2	7 2	4 1
Musculoskeletal Myalgia	2	1	4	0	1	1
Resistance Mechanism Disorders Inflenza	3	2	5	5	4	3
Urinary System Micturition Frequency Urinary Tract Infection^†	1 0	2 0	2 2	1 2	1 1	0 0
Vision Disorders Blurred Vision	1	2	3	0	1	1
Reproductive Disorders^† Female Dysmenorrhea Colpitis Male Ejaculation Delayed Impotence	0 40 3	6 00 0	5 22 2	2 12 1	3 11 1	2 10 0

Following is a list of modified CIGY terms that reflect treatment-emergent adverse events reported by patients treated with Klonopin at multiple doses during clinical trials. All reported events are included except those already listed in Table above.

Body as a Whole: weight increase, accident, weight decrease, wound, edema, fever, shivering, abrasions, ankle edema, edema foot, edema periorbital, injury, malaise, pain, cellulitis, inflammation localized
Cardiovascular Disorders: chest pain, hypotension postural
Central and Peripheral Nervous System Disorders: migraine, paresthesia, drunkenness, feeling of enuresis, paresis, tremor, burning skin, falling, head fullness, hoarseness, hyperactivity, hypoesthesia, tongue thick, twitching
Gastrointestinal System Disorders: abdominal discomfort, gastrointestinal inflammation, stomach upset, toothache, flatulence, pyrosis, saliva increased, tooth disorder, bowel movements frequent, pain pelvic, dyspepsia, hemorrhoids
Hearing and Vestibular Disorders: vertigo, otitis, earache, motion sickness
Heart Rate and Rhythm Disorders: palpitation
Metabolic and Nutritional Disorders: thirst, gout
Musculoskeletal System Disorders: back pain, fracture traumatic, sprains and strains, pain leg, pain nape, cramps muscle, cramps leg, pain ankle, pain shoulder, tendinitis, arthralgia, hypertonia, lumbago, pain feet, pain jaw, pain knee, swelling knee
Platelet, Bleeding and Clotting Disorders: bleeding dermal
Psychiatric Disorders: insomnia, organic disinhibition, anxiety, depersonalization, dreaming excessive, libido loss, appetite increased, libido increased, reactions decreased, aggression, apathy, disturbance in attention, excitement, anger, hunger abnormal, illusion, nightmares, sleep disorder, suicide ideation, yawning
Reproductive Disorders, Female: breast pain, menstrual irregularity
Reproductive Disorders, Male: ejaculation decreased
Resistance Mechanism Disorders: infection mycotic, infection viral, infection streptococcal, herpes simplex infection, infectious mononucleosis, moniliasis
Respiratory System Disorders: sneezing excessive, asthmatic attack, dyspnea, nosebleed, pneumonia, pleurisy
Skin and Appendages Disorders: acne flare, alopecia, xeroderma, dermatitis contact, flushing, pruritus, pustular reaction, skin burns, skin disorder
Special Senses Other, Disorders: taste loss
Urinary System Disorders: dysuria, cystitis, polyuria, urinary incontinence, bladder dysfunction, urinary retention, urinary tract bleeding, urine discoloration
Vascular (Extracardiac) Disorders: thrombophlebitis leg
Vision Disorders: eye irritation, visual disturbance, diplopia, eye twitching, styes, visual field defect, xerophthalmia

CONTRAINDICATIONS:

Klonopin is contraindicated in patients with the following conditions:

History of sensitivity to benzodiazepines
Clinical or biochemical evidence of significant liver disease
Acute narrow angle glaucoma (it may be used in patients with open angle glaucoma who are receiving appropriate therapy).

WARNINGS AND PRECAUTIONS:

Risks from Concomitant Use with Opioids
Interference with Cognitive and Motor Performance
Suicidal Behavior and Ideation
Withdrawal Symptoms
Worsening of Seizures: 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.
Loss of Effect: In some studies, up to 30% of patients who initially responded have shown a loss of anticonvulsant activity, often within 3 months of administration. In some cases, dosage adjustment may reestablish efficacy.
Laboratory Testing During Long-Term Therapy: Periodic blood counts and liver function tests are advisable during long-term therapy with Klonopin.
Psychiatric and Paradoxical Reactions: Paradoxical reactions, such as agitation, irritability, aggression, anxiety, anger, nightmares, hallucinations, and psychoses are known to occur when using benzodiazepines (see ADVERSE REACTIONS: Psychiatric). Should this occur, the use of the drug should be discontinued gradually (see PRECAUTIONS: Risks of Abrupt Withdrawal and DRUG ABUSE AND DEPENDENCE: Physical and Psychological Dependence). Paradoxical reactions are more likely to occur in children and in the elderly.
Risks of Abrupt Withdrawal: 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.
Caution in Renally Impaired Patients: 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.
Hypersalivation: Klonopin may produce an increase in salivation. This should be considered before giving the drug to patients who have difficulty handling secretions.
Respiratory Depression: Klonopin may cause respiratory depression and should be used with caution in patients with compromised respiratory function (e.g., chronic obstructive pulmonary disease, sleep apnea).
Porphyria: Klonopin may have a porphyrogenic effect and should be used with care in patients with porphyria.
Dose Changes
Interference With Cognitive and Motor Performance: 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.
Suicidal Thinking and Behavior: 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.
Pregnancy: Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy with Klonopin (see PRECAUTIONS: Pregnancy). 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).
Nursing: Patients should be advised to notify their physician if they are breastfeeding or intend to breastfeed during therapy.
Concomitant Medication: 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.
Alcohol: Patients should be advised to avoid alcohol while taking Klonopin.
Pediatric Use: Safety and effectiveness in pediatric patients with panic disorder below the age of 18 have not been established
Geriatric Use: 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.
Physical and Psychological Dependence

DRUG INTERACTIONS:

Effect of Concomitant Use of Benzodiazepines and Opioids: The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABAA sites, and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and follow patients closely for respiratory depression and sedation.

Effect of Clonazepam on the Pharmacokinetics of Other Drugs: Clonazepam does not appear to alter the pharmacokinetics of carbamazepine or phenobarbital. Clonazepam has the potential to influence concentrations of phenytoin. Monitoring of phenytoin concentration is recommended when clonazepam is co-administrated with phenytoin. The effect of clonazepam on the metabolism of other drugs has not been investigated.

Effect of Other Drugs on the Pharmacokinetics of Clonazepam: 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 Cmax of clonazepam was 20% lower when the orally disintegrating tablet was given with propantheline compared to when it was given alone. The selective serotonin reuptake inhibitors sertraline (weak CYP3A4 inducer) and fluoxetine (CYP2D6 inhibitor), and the anti-epileptic drug felbamate (CYP2C19 inhibitor and CYP3A4 inducer) do not affect the pharmacokinetics of clonazepam. Cytochrome P450 inducers, such as phenytoin, carbamazepine, lamotrigine, and phenobarbital induce clonazepam metabolism, causing an approximately 38% 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 (e.g., fluconazole), should be used cautiously in patients receiving clonazepam because they may impair the metabolism of clonazepam leading to exaggerated concentrations and effects.

Pharmacodynamic Interactions: 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.

OVERDOSE:

Symptoms of clonazepam overdosage, like those produced by other CNS depressants, include somnolence, confusion, coma, and diminished reflexes.

Overdose Management: Treatment includes monitoring of respiration, pulse and blood pressure, general supportive measures and immediate gastric lavage. Intravenous fluids should be administered and an adequate airway maintained. Hypotension may be combated by the use of levarterenol or metaraminol. Dialysis is of no known value. Flumazenil, a specific benzodiazepine-receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with a benzodiazepine is known or suspected. Prior to the administration of flumazenil, necessary measures should be instituted to secure airway, ventilation and intravenous access. Flumazenil is intended as an adjunct to, not as a substitute for, proper management of benzodiazepine overdose. Patients treated with flumazenil should be monitored for resedation, respiratory depression and other residual benzodiazepine effects for an appropriate period after treatment. The prescriber should be aware of a risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine users and in cyclic antidepressant overdose. The complete flumazenil package insert, including CONTRAINDICATIONS, WARNINGS and PRECAUTIONS, should be consulted prior to use. Flumazenil is not indicated in patients with epilepsy who have been treated with benzodiazepines. Antagonism of the benzodiazepine effect in such patients may provoke seizures. Serious sequelae are rare unless other drugs or alcohol have been taken concomitantly.

Uses

INDICATION AND USES:

Klonopin is indicated for:

Seizure Disorders
Panic Disorder

DOSAGE AND ADMINISTRATION

Seizure Disorders:

The use of multiple anticonvulsants may result in an increase of CNS depressant adverse effects. This should be considered before adding Klonopin to an existing anticonvulsant regimen.

Panic Disorder:

Pediatric Patients: There is no clinical trial experience with Klonopin in panic disorder patients under 18 years of age.

Side Effects

SIDE EFFECTS:

The adverse experiences for Klonopin are provided separately for patients with seizure disorders and with panic disorder.

Cardiovascular: Palpitations
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
Hematopoietic: Anemia, leukopenia, thrombocytopenia, eosinophilia
Hepatic: Hepatomegaly, transient elevations of serum transaminases and alkaline phosphatase
Musculoskeletal: Muscle weakness, pains
Miscellaneous: Dehydration, general deterioration, fever, lymphadenopathy, weight loss or gain
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, 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: irritability, aggression, agitation, nervousness, hostility, anxiety, sleep disturbances, nightmares, abnormal dreams, hallucinations.
Respiratory: Chest congestion, rhinorrhea, shortness of breath, hypersecretion in upper respiratory passages

Panic Disorder:

Treatment-Emergent Adverse Event Incidence in 6- to 9-week placebo controlled clinical trials:

Clonazepam Maximum Daily Dose
Adverse Event by Body System	<1mg n=96 %	1- <2mg n=129 %	2- <3mg n=113 %	>3mg n=235 %	All Klonopin Groups N=574 %	Placebo N=294 %
Central & Peripheral Nervous System Somnolence^† Dizziness Coordination Abnormal^† Ataxia^† Dysarthria^†	26 5 1 2 0	35 5 2 1 0	50 12 7 8 4	36 8 9 8 3	37 8 6 5 2	10 4 0 0 0
Psychiatric Depression Memory Disturbance Nervousness Intellectual Ability Reduced Emotional Lability Libido Decreased Confusion	7 2 1 0 0 0 0	6 5 4 2 1 1 2	8 2 3 4 2 3 2	8 5 4 3 2 1 1	7 4 3 2 1 1 1	1 2 2 0 1 0 0
Respiratory System Upper Respiratory Tract Infection^† Sinusitis Rhinitis Coughing Pharyngitis Bronchitis	10 4 3 2 1 1	10 2 2 2 1 0	7 8 4 4 3 2	6 4 2 0 2 2	8 4 2 2 2 1	4 3 1 0 1 1
Gastrointestinal System Constipation^† Appetite Decreased Abdominal Pain^†	0 1 2	1 1 2	5 0 2	3 3 0	2 1 1	2 1 1
Body as a Whole Fatigue Allergic Reaction	9 3	6 1	7 4	7 2	7 2	4 1
Musculoskeletal Myalgia	2	1	4	0	1	1
Resistance Mechanism Disorders Inflenza	3	2	5	5	4	3
Urinary System Micturition Frequency Urinary Tract Infection^†	1 0	2 0	2 2	1 2	1 1	0 0
Vision Disorders Blurred Vision	1	2	3	0	1	1
Reproductive Disorders^† Female Dysmenorrhea Colpitis Male Ejaculation Delayed Impotence	0 40 3	6 00 0	5 22 2	2 12 1	3 11 1	2 10 0

Body as a Whole: weight increase, accident, weight decrease, wound, edema, fever, shivering, abrasions, ankle edema, edema foot, edema periorbital, injury, malaise, pain, cellulitis, inflammation localized
Cardiovascular Disorders: chest pain, hypotension postural
Central and Peripheral Nervous System Disorders: migraine, paresthesia, drunkenness, feeling of enuresis, paresis, tremor, burning skin, falling, head fullness, hoarseness, hyperactivity, hypoesthesia, tongue thick, twitching
Gastrointestinal System Disorders: abdominal discomfort, gastrointestinal inflammation, stomach upset, toothache, flatulence, pyrosis, saliva increased, tooth disorder, bowel movements frequent, pain pelvic, dyspepsia, hemorrhoids
Hearing and Vestibular Disorders: vertigo, otitis, earache, motion sickness
Heart Rate and Rhythm Disorders: palpitation
Metabolic and Nutritional Disorders: thirst, gout
Musculoskeletal System Disorders: back pain, fracture traumatic, sprains and strains, pain leg, pain nape, cramps muscle, cramps leg, pain ankle, pain shoulder, tendinitis, arthralgia, hypertonia, lumbago, pain feet, pain jaw, pain knee, swelling knee
Platelet, Bleeding and Clotting Disorders: bleeding dermal
Psychiatric Disorders: insomnia, organic disinhibition, anxiety, depersonalization, dreaming excessive, libido loss, appetite increased, libido increased, reactions decreased, aggression, apathy, disturbance in attention, excitement, anger, hunger abnormal, illusion, nightmares, sleep disorder, suicide ideation, yawning
Reproductive Disorders, Female: breast pain, menstrual irregularity
Reproductive Disorders, Male: ejaculation decreased
Resistance Mechanism Disorders: infection mycotic, infection viral, infection streptococcal, herpes simplex infection, infectious mononucleosis, moniliasis
Respiratory System Disorders: sneezing excessive, asthmatic attack, dyspnea, nosebleed, pneumonia, pleurisy
Skin and Appendages Disorders: acne flare, alopecia, xeroderma, dermatitis contact, flushing, pruritus, pustular reaction, skin burns, skin disorder
Special Senses Other, Disorders: taste loss
Urinary System Disorders: dysuria, cystitis, polyuria, urinary incontinence, bladder dysfunction, urinary retention, urinary tract bleeding, urine discoloration
Vascular (Extracardiac) Disorders: thrombophlebitis leg
Vision Disorders: eye irritation, visual disturbance, diplopia, eye twitching, styes, visual field defect, xerophthalmia

Precautions

CONTRAINDICATIONS:

Klonopin is contraindicated in patients with the following conditions:

History of sensitivity to benzodiazepines
Clinical or biochemical evidence of significant liver disease
Acute narrow angle glaucoma (it may be used in patients with open angle glaucoma who are receiving appropriate therapy).

WARNINGS AND PRECAUTIONS:

Risks from Concomitant Use with Opioids
Interference with Cognitive and Motor Performance
Suicidal Behavior and Ideation
Withdrawal Symptoms
Worsening of Seizures: 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.
Loss of Effect: In some studies, up to 30% of patients who initially responded have shown a loss of anticonvulsant activity, often within 3 months of administration. In some cases, dosage adjustment may reestablish efficacy.
Laboratory Testing During Long-Term Therapy: Periodic blood counts and liver function tests are advisable during long-term therapy with Klonopin.
Psychiatric and Paradoxical Reactions: Paradoxical reactions, such as agitation, irritability, aggression, anxiety, anger, nightmares, hallucinations, and psychoses are known to occur when using benzodiazepines (see ADVERSE REACTIONS: Psychiatric). Should this occur, the use of the drug should be discontinued gradually (see PRECAUTIONS: Risks of Abrupt Withdrawal and DRUG ABUSE AND DEPENDENCE: Physical and Psychological Dependence). Paradoxical reactions are more likely to occur in children and in the elderly.
Risks of Abrupt Withdrawal: 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.
Caution in Renally Impaired Patients: 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.
Hypersalivation: Klonopin may produce an increase in salivation. This should be considered before giving the drug to patients who have difficulty handling secretions.
Respiratory Depression: Klonopin may cause respiratory depression and should be used with caution in patients with compromised respiratory function (e.g., chronic obstructive pulmonary disease, sleep apnea).
Porphyria: Klonopin may have a porphyrogenic effect and should be used with care in patients with porphyria.
Dose Changes
Interference With Cognitive and Motor Performance: 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.
Suicidal Thinking and Behavior: 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.
Pregnancy: Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy with Klonopin (see PRECAUTIONS: Pregnancy). 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).
Nursing: Patients should be advised to notify their physician if they are breastfeeding or intend to breastfeed during therapy.
Concomitant Medication: 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.
Alcohol: Patients should be advised to avoid alcohol while taking Klonopin.
Pediatric Use: Safety and effectiveness in pediatric patients with panic disorder below the age of 18 have not been established
Geriatric Use: 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.
Physical and Psychological Dependence

Interactions