Romazicon and Narcan

1. Romazicon � and Narcan � Nicole Clark PharmD, BCPS Hallmark Health System

2. Romazicon� (Flumazenil) Indication Benzodiazepine antagonist Reverses sedative effects of benzodiazepines used in conscious sedation and general anesthesia Treatment of benzodiazepine overdose

3. Mechanism of Action Competitively inhibits the activity at the benzodiazepine receptor site on the GABA/benzodiazepine receptor complex Does not antagonize the CNS effects of other GABA antagonists (ethanol, barbituates or general anesthetics) Does not reverse narcotics/opiods

4. Adult Dosing � Reversal of conscious sedation & general anesthesia Initial dose 0.2mg IV over 15 seconds Repeat dose (max 4 doses) 0.2mg may be repeated at 1 minute intervals Maximum total cumulative dose 1mg (usual dose: 0.6-1mg)

5. Adult Dosing � Suspected benzodiazepine overdose Initial dose 0.2 mg IV over 30 seconds if the desired level of consciousness is not obtained, 0.3 mg can be given over 30 seconds Repeat Dose 0.5 mg over 30 seconds repeated at 1-minute intervals

6. Adult Dosing � Suspected benzodiazepine overdose Maximum total cumulative dose 3 mg (usual dose: 1-3 mg) Patients with a partial response at 3 mg may require additional titration up to total dose of 5 mg If a patient has not responded 5 minutes after cumulative dose of 5 mg the major cause of sedation is unlikely to be due to benzodiazepines

7. Resedation Repeated doses may be given at 20 - minute intervals as needed Maximum of 1mg/dose (rate of 0.5mg/minute) Maximum of 3mg/hr

8. Special Populations Elderly No dose adjustments required Since generally will have received smaller doses of agonist, flumazenil should be adm slowly, in incremental doses of 0.1 mg, titrated to effect Renal impairment No dose adjustments required Hepatic impairment Due to the clearance being decreased, use caution with initial and/or repeated doses in patients with liver disease

9. Pregnancy/Lactation Pregnancy Risk Factor C Teratogenic effects not seen in animal studies � no adequate human studies Embryocidal effects seen at large doses Use only if clearly needed Lactation Excretion in breast milk unknown/use caution

10. Initial Response 1 �2 minutes Mean time from flumazenil administration to eye opening was 3.1 minutes and the mean time to self-identification was 4.4 minutes �Peak Response 6-10 minutes

11. Duration of Action Single dose 1 � 4 hours After intoxication with high doses of benzodiazepines the duration of a single dose of flumazenil is not expected to exceed 1 hour Most patients with a benzodiazepine overdose with respond to a cumulative dose of 1-3 mg and doses > 3 mg do not reliably produce additional effects

12. Black Box Warning May result in seizures in some patients Pts on benzodiazepines for long-term sedation Tricyclic antidepressant overdose pts Concurrent major sedative-hypnotic drug withdrawal Recent therapy with repeated doses of parenteral benzodiazepines Myoclonic jerking or seizure activity prior to flumazenil administrations Use caution of patients relying on a benzodiazepine for seizure control

13. Cautions/Concerns Does not consistently reverse amnesia Should not rely upon to reverse respiratory depression/hypoventilation Use with caution in pts with head injury May provoke panic attacks in patients with history of panic disorder Caution in pts with mixed drug overdoses; toxic effects of other drugs may emerge once benzodiazepine effects are reversed

14. Adverse Effects Most Frequent Ataxia, blurred vision, dizziness, feeling agitated, headache, hyperhidrosis, injection site sequelae, nausea, tonic clonic seizure, vertigo, visual changes, vomiting Less Frequent Hypertension, mood changes, paresthesia, sedation, skin rash

15. Adverse Effects Rare Conduction disorder of the heart, dysphasia, fatigue, flushing, general weakness, hallucinations, hearing disorder, hyperacusis, impaired cognition, malaise, panic disorder, pruritus of skin, seizure disorder, thrombophlebitis, urticaria

16. Physical Assesment/Monitoring Asses level of consciousness frequently Monitor vital signs and airways closely ECG monitoring & oxygentation via pulse oximetry is highly recommended Observe continually for resedation, respiratory depression, and preseizure activity May require pain medication soon after reversal Asses for nausea and vomiting

17. Narcan Indication Opiod Antagonist Complete or partial reversal of opioid drug effects, including respiratory depression Management of known or suspected overdose Diagnosis of suspected opioid dependence or acute opioid overdose Mechanism of action Pure opioid antagonist that competes and displaces narcotics at opioid receptor sites

18. Adult Dosing- Opioid intoxication: Respiratory Depression 0.4-2 mg IV (over 30 seconds) May need to repeat doses every 2-3 minutes After reversal may need to readminister at a later interval depending on type/duration of opioid (long acting opioids) If no response observed after 10 mg consider other causes of respiratory depression Opioid-dependent patients may require lower doses (0.1mg) titrated incrementally to avoid precipitating acute withdrawal

19. Continuous Infusion Calculate dosage/hour based on effective intermittent dose/duration of adequate response seen Typically 0.25 � 6.25mg/hr � of the initial bolus dose should be readministered after infusion started to prevent drop in levels To prepare infusion 2 mg naloxone in 500 mL of 0.9% sodium chloride or D5W (final concentration: 40 mcg/mL)

20. Adult Dosing: Postoperative reversal 0.1-0.2mg IV every 2-3 minutes until desired response Repeat doses may be needed within 1-2 hour intervals depending on type, dose and timing of last dose of opioid administered

21. Pregnacy/Lactation Pregnancy Risk Factor C Consider benefit to the mother and risk to the fetus before administering to a pregnant women who is opioid dependent May precipitate withdrawal in both the mother and fetus Lactation Excretion in breast milk unknown/not recommended

22. Cautions/Concerns Use caution in patients with cardiovascular disease or in patients receiving medications with potential adverse cardiovascular effects Use caution in patients with history of seizures

23. Adverse Reactions Adverse events occur secondarily to reversal of narcotic analgesia and sedation Less frequent Conduction disorder of the heart, excitement, hyperhidrosis, hypertension, hypotension, irritability, nausea, nervousness, tachyarrhythmia, tremors, vomiting

24. References Lexi Comp Micromedex Medscape/drug info