KLOXXADO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KLOXXADO (KLOXXADO).
KLOXXADO (flumazenil) is a benzodiazepine antagonist that competitively inhibits the activity at the benzodiazepine binding site on the GABA-A receptor, thereby reversing the effects of benzodiazepines.
| Metabolism | Hepatic metabolism via CYP1A2 and CYP3A4; undergoes extensive first-pass metabolism; major metabolites are inactive or less active. |
| Excretion | Hepatic metabolism primarily via CYP3A4 to inactive metabolites; renal excretion accounts for <1% of unchanged drug; fecal excretion accounts for approximately 50-60% of the dose as metabolites. |
| Half-life | Terminal elimination half-life is approximately 2 hours (range 1-4 hours); clinical context: short half-life supports rapid reversal of opioid effects but requires monitoring for renarcotization, especially with long-acting opioids. |
| Protein binding | Approximately 80% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 2-4 L/kg; high Vd indicates extensive tissue distribution, which is consistent with rapid redistribution from brain to peripheral tissues, contributing to its short duration of action. |
| Bioavailability | Intranasal bioavailability is approximately 40-50% relative to intravenous administration; gastrointestinal absorption is limited due to first-pass metabolism, so oral bioavailability is <1%. |
| Onset of Action | Intranasal administration: rapid absorption, with peak plasma concentrations achieved within 15-30 minutes; clinical onset of reversal of opioid effects is typically observed within 2-5 minutes. |
| Duration of Action | Duration of opioid reversal is approximately 30-60 minutes, depending on the dose and the amount and type of opioid; clinical note: shorter duration than most opioids, necessitating repeat doses or continuous monitoring for recurrence of respiratory depression. |
| Molecular Weight | 327.38 |
5 mg intranasally as a single dose; may repeat once after 2-3 minutes if response inadequate.
| Dosage form | SPRAY |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B); severe hepatic impairment (Child-Pugh C) has not been studied, use with caution. |
| Pediatric use | Weight ≥30 kg: 5 mg intranasally as single dose; weight 10-30 kg: 2.5 mg intranasally as single dose; may repeat once after 2-3 minutes if needed. |
| Geriatric use | No specific dose adjustment; elderly patients may be more sensitive to adverse effects, monitor for excessive sedation or respiratory depression. |
| 1st trimester | Limited data; animal studies show no teratogenicity at doses up to 10 mg/kg/day. Risk cannot be ruled out. Use only if benefit outweighs risk. |
| 2nd trimester | No increased risk of congenital anomalies reported. May increase risk of withdrawal in newborn after prolonged use. Use with caution. |
| 3rd trimester | Chronic use may lead to neonatal opioid withdrawal syndrome (NOWS). Risk of respiratory depression at delivery. Avoid prolonged use. |
Clinical note
Comprehensive clinical and safety monograph for KLOXXADO (KLOXXADO).
| Placental transfer | Naloxone crosses the placenta. Rapid distribution and elimination in fetus. Fetal/maternal ratio approximately 0.5-0.8. |
| Breastfeeding | Kloxxado (naloxone) is excreted in breast milk in low amounts (RID <2%). No adverse effects reported in infants. Consider benefit of maternal treatment vs. risk of infant exposure. Monitor for drowsiness or feeding difficulties. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to naloxone or any component of the formulationKnown history of hypersensitivity to naloxone hydrochloride
| Precautions | Risk of seizures, especially in patients with physical dependence on benzodiazepines, concurrent tricyclic antidepressant overdose, or history of seizures, Do not use for diagnostic purposes in suspected seizure disorders, May cause panic attacks in patients with anxiety disorders, Monitor for resedation due to shorter duration of action than benzodiazepines |
| Food/Dietary | No known food interactions with Kloxxado. Naloxone is not affected by food intake. Avoid alcohol or sedatives as they may exacerbate opioid effects. |
Loading safety data…
| Lactation Rating | L2 (Safer) for acute use; L3 (Moderately Safe) for chronic use per LactMed. |
| Teratogenic Risk | Pregnancy category D: Positive evidence of human fetal risk in first trimester (increased risk of oral clefts), second and third trimesters (risk of maternal and neonatal respiratory depression, neonatal withdrawal syndrome). Avoid in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal respiratory rate, sedation level, and oxygen saturation. Assess fetal heart rate patterns if used near term. Monitor neonate for respiratory depression, sedation, and withdrawal symptoms. |
| Fertility Effects | May impair fertility in males and females due to effects on hypothalamic-pituitary-gonadal axis. Reversible upon discontinuation. |
| Clinical Pearls |
| Kloxxado (naloxone) 8 mg nasal spray is FDA-approved for emergency treatment of opioid overdose. Use in patients with known or suspected opioid overdose, including respiratory depression. Onset within 2-3 minutes. May require repeat dosing due to shorter half-life than many opioids. Monitor for withdrawal precipitation. Store at room temperature; protect from light. Train caregivers and patients on proper administration. |
| Patient Advice | Administer as soon as opioid overdose is suspected: unresponsiveness, slow/stopped breathing, or pin-point pupils. · Spray one dose into one nostril; if no response in 2-3 minutes, give second dose in other nostril using a new device. · Call 911 immediately before or after administration; Kloxxado is a temporary measure. · Stay with patient until emergency help arrives; repeat doses may be needed if opioids are long-acting (e.g., fentanyl). · Side effects include acute withdrawal symptoms (nausea, vomiting, sweating, agitation, rapid heart rate). · Store at 68-77°F (20-25°C); do not freeze. Check expiration date. |