Clonazepam

Benzodiazepines have been associated with anterograde amnesia (Nelson 1999).

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving); increased risk may occur with the use of multiple anticonvulsants.

Paradoxical reactions, including hyperactive or aggressive behavior, hallucinations, nightmares, anger, anxiety, irritability, agitation, and psychoses, have been reported with benzodiazepines, particularly in pediatric or elderly patients. Gradually discontinue therapy if such reactions occur (Mancuso 2004).

An increased risk for hazardous sleep-related activities such as sleep-driving; cooking and eating food, and making phone calls while asleep have also been noted with benzodiazepines (Dolder 2008).

Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify healthcare provider immediately if symptoms occur. Disease-related concerns:

Use caution in patients with depression, particularly if suicidal risk may be present.

Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.

May be used in patients with open angle glaucoma who are receiving appropriate therapy; contraindicated in acute narrow angle glaucoma.

Use with caution in patients with hepatic impairment; accumulation likely to occur. Contraindicated in patients with significant hepatic impairment.

Use with caution in patients with porphyria; may have a porphyrogenic effect.

Use with caution in patients with renal impairment; clonazepam metabolites are renally eliminated.

Clonazepam may cause respiratory depression and may produce an increase in salivation; use with caution in patients with compromised respiratory function (eg, chronic obstructive pulmonary disease, sleep apnea) and in patients who have difficulty handling secretions. Concurrent drug therapy issues:

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Use with caution in debilitated patients.

Use with extreme caution in patients who are at risk of falls; benzodiazepines have been associated with falls and traumatic injury. Other warnings/precautions:

Does not have analgesic, antidepressant, or antipsychotic properties. Worsening of seizures may occur when added to patients with multiple seizure types. Loss of anticonvulsant activity may occur (typically within 3 months of initiation); dose adjustment may be necessary. Periodically reevaluate the long-term usefulness of clonazepam for the individual patient.

Clonazepam is a long half-life benzodiazepine. Duration of action after a single dose is determined by redistribution rather than metabolism. Tolerance develops to the anticonvulsant effects. It does not develop to the anxiolytic effects (Vinkers 2012). Chronic use of this agent may increase the perioperative benzodiazepine dose needed to achieve desired effect.

Rebound or withdrawal symptoms may occur following abrupt discontinuation or large decreases in dose. Use caution when reducing dose or withdrawing therapy; decrease slowly and monitor for withdrawal symptoms. Flumazenil may cause withdrawal in patients receiving long-term benzodiazepine therapy (Brogden 1988).