Naloxoneside effects

The following serious adverse reactions are discussed elsewhere in the labeling:

Recurrent Respiratory and Central Nervous System Depression

Precipitation of Severe Opioid Withdrawal The following adverse reactions were reported with KLOXXADO in two adult subjects each: abdominal pain, asthenia, dizziness, headache, nasal discomfort, and presyncope. To report SUSPECTED ADVERSE REACTIONS, contact Hikma Specialty USA Inc. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in practice. KLOXXADO nasal spray, 4 mg No adverse events were reported in a pharmacokinetic study of 72 healthy adult volunteers exposed to one spray of 4 mg KLOXXADO nasal spray in one nostril. KLOXXADO nasal spray, 8 mg In two pharmacokinetic studies a total of 47 healthy adult volunteers were exposed to a single dose of KLOXXADO nasal spray 8 mg, one spray in one nostril. The following adverse reactions were reported in two subjects each: abdominal pain, asthenia, dizziness, headache, nasal discomfort, and presyncope. On local tissue assessments for nasal irritation, signs of nasal inflammation and nasal congestion were observed.

6.2 Postmarketing

Experience The following adverse events have been identified during the post-approval use of naloxone hydrochloride injection in the postoperative setting. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea, pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. Excessive doses of naloxone hydrochloride in postoperative patients have resulted in significant reversal of analgesia and have caused agitation. Abrupt reversal of opioid effects in persons who were physically dependent on opioids has precipitated an acute withdrawal syndrome. Signs and symptoms have included: body aches, fever, sweating, runny nose, sneezing, piloerection, yawning, weakness, shivering or trembling, nervousness, restlessness or irritability, diarrhea, nausea or vomiting, abdominal cramps, increased blood pressure, tachycardia. In some patients, there was aggressive behavior upon abrupt reversal of an opioid overdose. In the neonate, opioid withdrawal has included: convulsions, excessive crying, hyperactive reflexes. The following most frequently reported events (in decreasing frequency) have been identified primarily during post-approval use of naloxone hydrochloride (all routes of administration): withdrawal syndrome, vomiting, nonresponsiveness to stimuli, drug ineffective, agitation, somnolence, and loss of consciousness.