clonazepam (Rx)

>10%

Somnolence (37%)

1-10%

Abnormal coordination (5-10%)

Ataxia (5-10%)

Depression (5-10%)

Dizziness (5-10%)

Fatigue (5-10%)

Memory impairment (5-10%)

Upper respiratory infection (5-10%)

Confusion (1-5%)

Dysarthria (1-5%)

Rhinitis (1-5%)

Coughing (1-5%)

Urinary frequency (1-5%)

Impotence (1-5%)

Decreased libido (1-5%)

Frequency Not Defined

Increased salivation

Worsening tonic-clonic seizures

Contraindications

Significant hepatic impairment

Documented hypersensitivity

Acute narrow angle glaucoma

Cautions

Withdraw gradually when used for panic disorder

Use caution in COPD, sleep apnea, renal/hepatic disease, open-angle glaucoma (questionable), depression, suicidal ideation

Not recommended in patients with depressed neuroses, psychotic reactions, severe respiratory depression, myasthenia gravis (allowable in limited circumstances), acute alcohol intoxication

Anterograde amnesia reported benzodiazepine use

May cause CNS depression and impairs ability to perform hazardous tasks

Hyperactive or aggressive behavior reported with benzodiazepines in pediatric/adolescent patients and in psychiatric patients

Increased risk of suicidal thoughts/behavior reported with antiepileptic agents; monitor patient for suicidal behavior and notify health-care provider immediately

Use with caution in patients with a history of drug abuse or acute alcoholism; drug dependency possible; prolonged use may result in psychological and physical dependence

Use with caution in patients with compromised respiratory function

May have porphyrogenic effect; use with caution in patients with porphyria

Not for concomitant administration with alcohol or other CNS-depressant drugs

When used in patients in whom several different types of seizure disorders coexist, clonazepam may increase incidence or precipitate onset of generalized tonic-clonic seizures (grand mal); may require addition of appropriate anticonvulsants or increase in dosages; concomitant use of valproic acid and clonazepam may produce absence status

Abrupt withdrawal, particularly in patients on long-term, high-dose therapy, may precipitate status epilepticus; when discontinuing clonazepam, gradual withdrawal essential; while being gradually withdrawn, simultaneous substitution of another anticonvulsant may be indicated

Use of drug, particularly in patients at elevated risk, necessitates counseling about risks and proper use of drug along with monitoring for signs and symptoms of abuse, misuse, and addiction; do not exceed recommended dosing frequency

Avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (eg, opioid analgesics, stimulants); advise patients on proper disposal of unused drug; if a substance use disorder is suspected, evaluate patient and institute (or refer them for) early treatment, as appropriate

For patients using treated more frequently than recommended, to reduce risk of withdrawal reactions, use a gradual taper to discontinue therapy (a patient-specific plan should be used to taper the dose)

Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use

In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months

May produce increase in salivation; consider before giving drug to patients who have difficulty handling secretions

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

Paradoxical reactions, such as agitation, irritability, aggression, anxiety, anger, nightmares, hallucinations, and psychoses may occur when using benzodiazepines; discontinue therapy, should this occur; paradoxical reactions are more likely to occur in children and in the elderly

Pregnancy

There are no adequate and well-controlled studies of Klonopin in pregnant women; available human data on risk of teratogenicity are inconclusive; there is insufficient evidence in humans to assess effect of benzodiazepine exposure during pregnancy on neurodevelopment; administration of benzodiazepines immediately prior to or during childbirth can result in a syndrome of hypothermia, hypotonia, respiratory depression, and difficulty feeding; in addition, infants born to mothers who have taken benzodiazepines during later stages of pregnancy can develop dependence, and subsequently withdrawal, during the postnatal period

Data for other benzodiazepines suggest possibility of adverse developmental effects (long-term effects on neurobehavioral and immunological function) in animals following prenatal exposure to benzodiazepines

Lactation

Effects on breastfed infant and on milk production are unknown; developmental and health benefits of breastfeeding should be considered along with mother's clinical need for therapy and any potential adverse effects on breastfed infant from drug or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Long-acting benzodiazepine that increases the presynaptic GABA inhibition and reduces the monosynaptic and polysynaptic reflexes. Suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters

Suppresses the spike-and-wave discharge in absence seizures by depressing nerve transmission in motor cortex

Absorption

Bioavailability: 90%

Onset: 20-40 min

Peak plasma time: 1-4 hr; 5-7 days (steady state)

Distribution

Protein bound: 85%

Vd: 1.5-3 L/kg

Metabolism

Metabolized by CYP3A4 (minor), glucuronic acid conjugation

Metabolites: Inactive

Elimination

Half-life: 17-60 hr (adults); 22-33 hr (children)

Excretion: Urine