Boxed Warning: FDA's Most Serious Warning

Clonazepam carries the FDA's most serious warning (Boxed Warning) regarding three major risks :

1. Risks from Concomitant Use with Opioids

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone .

Get emergency help right away if any of the following happens:

• Shallow or slowed breathing

• Breathing stops (which may lead to the heart stopping)

• Excessive sleepiness (sedation)

2. Abuse, Misuse, and Addiction

The use of benzodiazepines, including clonazepam, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes .

Important facts:

• You can develop an addiction even if you take clonazepam as prescribed

• Serious side effects including coma and death have happened in people who have abused or misused benzodiazepines

• Do not share your clonazepam with other people

• Selling or giving away clonazepam may harm others and is against the law 

3. Dependence and Withdrawal Reactions

The continued use of benzodiazepines may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose .

Do not suddenly stop taking clonazepam. Stopping clonazepam suddenly can cause serious and life-threatening side effects, including:

• Unusual movements, responses, or expressions

• Seizures

• Sudden and severe mental or nervous system changes

• Depression

• Seeing or hearing things that others do not see or hear

• An extreme increase in activity or talking

• Losing touch with reality

• Suicidal thoughts or actions 

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

• Anxiety, trouble remembering, learning, or concentrating

• Depression, problems sleeping

• Feeling like insects are crawling under your skin

• Weakness, shaking, muscle twitching

• Burning or prickling feeling in your hands, arms, legs, or feet

• Ringing in your ears

Acute Withdrawal Signs and Symptoms: More severe acute withdrawal signs, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, hallucinations, mania, psychosis, seizures, and suicidality .

Physical dependence is not the same as drug addiction. Your healthcare provider can tell you more about the differences .

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Suicidal Thoughts and Behavior

Like other antiepileptic drugs, clonazepam may cause suicidal thoughts or actions in a very small number of people, about 1 in 500. Pooled analyses of 199 placebo-controlled clinical trials showed that patients randomized to antiepileptic drugs had approximately twice the risk of suicidal thinking or behavior compared to patients randomized to placebo .

Call your healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:

• Thoughts about suicide or dying

• Attempts to commit suicide

• New or worse depression, anxiety, or irritability

• Panic attacks

• Trouble sleeping (insomnia)

• Acting aggressive, being angry, or violent

• Acting on dangerous impulses

• An extreme increase in activity and talking (mania)

• Other unusual changes in behavior or mood 

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Contraindications

Do not take clonazepam if you :

• Are allergic to benzodiazepines

• Have significant liver disease (severe hepatic impairment)

• Have acute narrow angle glaucoma

• Have acute pulmonary insufficiency

• Have myasthenia gravis

• Have severe respiratory insufficiency

• Have sleep apnoea syndrome

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Common Side Effects

The most common side effects of clonazepam include :

• Drowsiness

• Problems with walking and coordination

• Dizziness

• Depression

• Fatigue

• Problems with memory

Clonazepam can also make your seizures happen more often or make them worse. Call your healthcare provider right away if your seizures get worse while taking clonazepam .

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What to Avoid While Taking Clonazepam

• Do not drive, operate heavy machinery, or do other dangerous activities until you know how clonazepam affects you 

• Do not drink alcohol — when taken with alcohol, clonazepam may make your sleepiness or dizziness much worse 

• Do not stop taking clonazepam suddenly without talking to your healthcare provider 

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Pregnancy and Breastfeeding

Pregnancy

Taking clonazepam late in pregnancy may cause your baby to have symptoms of sedation (breathing problems, sluggishness, low muscle tone), and/or withdrawal symptoms (jitteriness, irritability, restlessness, shaking, excessive crying, feeding problems). Some babies may need to spend time in the neonatal intensive care unit (NICU) .

A study of 314 children exposed to clonazepam during pregnancy found an increased chance of intellectual disability and delayed developmental milestones .

If you become pregnant while taking clonazepam, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry at 1-888-233-2334 .

Breastfeeding

Clonazepam can pass into breast milk in small amounts. Breastfeeding during treatment may cause your baby to have sleepiness (sedation), feeding problems, and decreased weight gain . The product label for clonazepam recommends women who are breastfeeding not use this medication . However, the benefit of using clonazepam along with the benefits of breastfeeding may outweigh the possible risks — discuss with your healthcare provider .

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Drug Interactions

CYP3A4 Inhibitors (Increase Clonazepam Levels)

CYP3A4 inhibitors can increase clonazepam serum concentration :

• Bicalutamide

• Erythromycin

• High dose fluconazole

• Haloperidol

• Isavuconazole (moderate inhibitor)

CYP3A4 Inducers (Decrease Clonazepam Levels)

CYP3A4 inducers can reduce clonazepam concentration :

• Carbamazepine

• High dose dexamethasone

• Phenobarbital

Phenytoin Interaction

Clonazepam and phenytoin have unpredictable effects on each other's plasma concentrations. Monitor the phenytoin plasma level if given concurrently with clonazepam .

Major Interactions

• Opioids — Concomitant use may result in profound sedation, respiratory depression, coma, and death 

• Alcohol — Increased CNS depression 

• Other CNS Depressants — Concurrent use leads to increased sedation 

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⚠️ Critical Safety Notice

Clonazepam is a Schedule IV controlled substance. It is illegal to purchase or possess clonazepam without a valid prescription from a licensed healthcare provider. Legitimate online pharmacies will always require a valid prescription and must have a valid U.S. DEA Registration. Websites offering clonazepam without a prescription are illegal and likely fraudulent. Always obtain clonazepam through licensed healthcare providers and verified pharmacies.