Introduction

Opioid antagonist.

Uses for Naloxone (Systemic)

Opioid-induced Depression and Acute Opioid Overdosage

Treatment of opioid-induced depression, including respiratory depression, caused by natural and synthetic opioids (e.g., codeine, diphenoxylate, fentanyl, heroin, hydromorphone, levorphanol, meperidine, methadone, morphine, oxymorphone, concentrated opium alkaloids, propoxyphene).

Useful for treatment of opioid-induced depression, including respiratory depression, caused by certain opioid partial agonists including butorphanol, nalbuphine, and pentazocine. However, reversal of respiratory depression from overdosage of opioid partial agonists may be incomplete and require higher or more frequent naloxone doses.

May be used in community (nonmedical) settings for emergency treatment of known or suspected opioid overdosage, as manifested by respiratory and/or CNS depression. Availability as prefilled syringes and nasal spray facilitates administration by family members or other caregivers; such treatment is not a substitute for emergency medical care. When administering naloxone outside of a supervised medical setting, always seek emergency medical assistance after the first dose is administered.

Many experts including CDC, American Heart Association (AHA), and American Society of Addiction Medicine recommend administration of naloxone in the event of a known or suspected opioid overdose.

The 2022 CDC clinical practice guideline on prescribing opioids for pain recommends that clinicians discuss the risk of opioid-related harms with patients, including risk mitigation strategies such as naloxone for overdose reversal.

Clinicians should offer naloxone and provide overdose prevention education to patients receiving opioid analgesics who are at increased risk of opioid overdosage (e.g., those receiving concomitant therapy with benzodiazepines or other CNS depressants, those with a history of opioid or substance use disorder, those with medical conditions that could increase sensitivity to opioid effects, those who have experienced a prior opioid overdose, those taking higher dosages of opioids [e.g., ≥50 morphine mg equivalents/day, and those at risk of returning to a high dose to which they have lost tolerance [e.g., patients undergoing tapering or recently released from prison]). Naloxone also should be offered when patients receiving opioids have household members who are at risk for accidental ingestion or overdosage.

Diagnosis of Suspected or Known Acute Opioid Overdosage

Used for diagnosis of suspected or known acute opioid overdosage.

Septic Shock

Naloxone hydrochloride injection is FDA-labeled for adjunctive use in the management of septic shock. Has been used in a limited number of patients in this setting. Rise in BP may last up to several hours, but not shown to improve survival and associated with adverse effects (e.g., agitation, nausea, vomiting, pulmonary edema, hypotension, cardiac arrhythmias, seizures).

Use caution in patients with septic shock, particularly in patients who may have underlying pain or previously received opioid therapy and may have developed opioid tolerance. Naloxone therapy is not included in the current Surviving Sepsis Campaign International Guidelines for Management of Sepsis and Septic Shock; fluid resuscitation and vasopressors (e.g., norepinephrine, vasopressin) are used first-line in hemodynamic management.

Diagnosis of Chronic Opioid Abuse (Naloxone Challenge Test)

To avoid precipitating opioid withdrawal following administration of naltrexone, naloxone has been used as a screening test (naloxone challenge test^{† [off-label]}) to document the absence of physiological dependence and reduce the risk of precipitated withdrawal.

The naloxone challenge test is not recommended in pregnant patients.

Combination Therapies

A combination of pentazocine hydrochloride and naloxone hydrochloride in a ratio of 100:1 is commercially available for oral use as an analgesic.

Combinations of buprenorphine hydrochloride and naloxone hydrochloride in a ratio of 4:1 for sublingual administration or approximately 6:1 for intrabuccal administration are commercially available for use in the management of opioid dependence.

Opioid-Induced Pruritus

Prevention of opioid-induced pruritus^{† [off-label]} in children and adolescents.

Naloxone (Systemic) Dosage and Administration

General

Patient Monitoring

• Carefully monitor patients who have responded to naloxone; the duration of action of most opioids may exceed that of naloxone and may result in recurrent respiratory and CNS depression. Administer repeated doses of naloxone when necessary.

• Monitor pediatric patients who have responded to naloxone for at least 24 hours.

• Monitor for development of opioid withdrawal symptoms (e.g., abdominal cramps, body aches, diarrhea, fever, increased blood pressure, nausea or vomiting, nervousness, runny nose, piloerection, restlessness or irritability, shivering or trembling, sneezing, sweating, tachycardia, weakness, yawning).

Other General Considerations

• Resuscitative measures such as maintenance of a patent airway, artificial ventilation, cardiac massage, and vasopressor agents should be available and employed when necessary in the treatment of opioid overdose.

• State naloxone laws vary, and may permit prescribing and dispensation to patients with risk factors for overdose or to lay persons (including nonmedical first responders, potential bystanders, and family and friends of opioid users). Consult state law for further information.

• Carefully instruct patients and their family members or close contacts regarding clinical manifestations requiring naloxone administration, proper administration technique, and the importance of seeking emergency care immediately following administration of the initial dose. Advise caregivers, household members, and other close contacts of where naloxone is stored, and to ensure the location is easily accessible during an emergency (e.g., naloxone should not be stored in a locked container with the opioid).

• Advise patients taking doses of opioid analgesics when away from home to carry naloxone with them and to advise individuals who are with them of the availability of the drug and its proper use.

Administration

Administer by IV, sub-Q, or IM injection; by IV infusion; or intranasally.

The most rapid onset of action is achieved by IV administration, which is recommended in emergency situations in medically supervised settings. Because absorption may be erratic or delayed, AAP does not endorse sub-Q or IM injection for emergency medical management of opioid intoxication in children or neonates.

When IV access cannot be established in emergency situations, has been administered via an endotracheal tube^{† [off-label]} and by intraosseous^{† [off-label]} (IO) injection.

IV Infusion

Continuous IV infusions may be most appropriate in patients who require higher doses, continue to experience recurrent respiratory or CNS depression after effective therapy with repeated doses, and/or in whom the effects of long-acting opioids are being antagonized.

Dilution

For continuous IV infusion, dilute 2 mg of naloxone hydrochloride in 500 mL of 0.9% sodium chloride or 5% dextrose injection to produce a solution containing 0.004 mg/mL (4 mcg/mL). Other concentrations have been recommended in pediatric patients (see Standardize 4 Safety under Dosage and Administration).

Rate of Administration

Titrate in accordance with patient’s response.

IM or Sub-Q Injection

May be administered by family members or other caregivers prior to emergency medical response to individuals with known or suspected opioid overdosage. Caregivers should seek emergency medical care immediately after administering the initial dose.

May be administered by IM or sub-Q injection via prefilled syringes. Administer initial dose of naloxone prefilled syringes (Zimhi) IM or sub-Q into the anterolateral aspect of the thigh, through clothing if necessary. When administered to pediatric patients <1 year of age, pinch the thigh muscle while administering the drug.

Intranasal Administration

May be administered by family members or other caregivers prior to emergency medical response to individuals with known or suspected opioid overdosage.

Do not remove nasal spray units from carton until time of administration; do not prime or test units prior to administration.

Intranasal Administration Technique

Place the patient in a supine position. Remove the nasal spray unit from carton and blister package. Tilt patient’s head back, with one hand supporting the neck. Do not prime or test device prior to administration. Gently insert tip of nasal spray unit into one nostril until the fingers on either side of the nozzle are against the patient's nose; press device plunger firmly to administer dose.

Remove nozzle from nostril following administration, and place patient in recovery position; closely monitor patient.

If additional doses are required, administer into alternate nostrils using new nasal spray unit.

Standardize 4 Safety

Standardized concentrations for naloxone have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. For additional information on S4S (including updates that may be available), see [Web].

The panel recognizes that 40 and 400 mcg/mL concentrations are 10× different; however, these are the only two concentrations studied for stability.

Dosage

Available as naloxone hydrochloride; dosage expressed in terms of the salt.

Pediatric Patients

Opioid-induced Depression in Neonates

IV, IM, or Sub-Q

Usual initial dose is 0.01 mg/kg, administered at 2- to 3-minute intervals to the desired degree of reversal.

Opioid Overdosage in Children

Children may receive an initial IV naloxone hydrochloride dose of 0.01 mg/kg; if this dose does not produce the desired degree of response, a subsequent dose of 0.1 mg/kg may be administered.

One spray (2, 4, or 8 mg [contents of one spray unit]); if patient fails to respond or responds but subsequently relapses into respiratory depression, repeat as necessary (if additional spray units available) at 2- to 3-minute intervals until emergency care arrives. Prescribe the 2-mg strength for opioid-dependent patients expected to be at risk for severe opioid withdrawal only when the risk for accidental or intentional opioid exposure by household contacts is low.

Children <5 years of age or weighing ≤20 kg: Some experts suggest dose of 0.1 mg/kg.

Children ≥5 years of age or weighing >20 kg: Some experts suggest dose of 2 mg.

Optimum dose for administration via an endotracheal tube^† not established (higher doses as compared with other routes may be necessary).

Diagnosis of Opioid Overdosage

No specific recommendations at this time. If no response observed after administration of 10 mg of naloxone, diagnosis of opioid-induced toxicity should be questioned.

Postoperative Opioid Depression

IV

For initial reversal of respiratory depression, naloxone hydrochloride should be administered in increments of 0.005–0.01 mg at 2- to 3-minute intervals until desired response (i.e., adequate ventilation and alertness without substantial pain or discomfort) is obtained.

Treatment of Opioid-Induced Pruritus

IV†

Dosages in children and adolescents ranged from 0.25–1.0 mcg/kg per hour via continuous IV infusion.

Adults

Postoperative Opioid Depression

IV

Initial dosage: Usually, 0.1–0.2 mg, given at 2- to 3-minute intervals until desired response (i.e., adequate ventilation and alertness without substantial pain or discomfort) is obtained; additional doses may be necessary at 1- to 2-hour intervals depending on response and dosage and duration of action of the opioid administered.

For continuous IV infusion, titrate rate of infusion in accordance with the patient’s response.

Opioid Overdosage

IV

Initial dosage: Usually, 0.4–2 mg IV, administered at 2- to 3-minute intervals if necessary; if no response is observed after a total of 10 mg of the drug has been administered, the depressive condition may be caused by a drug or disease process not responsive to naloxone.

Duration of opioid action often exceeds that of naloxone; opioid depressant effects may return as the effects of naloxone diminish, and additional naloxone doses may be required.

Carefully monitor patient for recurrence of opioid depressant effects.

IM or Sub-Q

2 mg (contents of one prefilled syringe) or 5 mg (contents of one prefilled syringe; Zimhi); if patient fails to respond or responds but subsequently relapses into respiratory depression, repeat as necessary at 2- to 3-minute intervals until emergency care arrives.

Intranasal

One spray (2, 4, or 8 mg [contents of one spray unit]); if patient fails to respond or responds but subsequently relapses into respiratory depression, repeat as necessary at 2- to 3-minute intervals until emergency care arrives. Prescribe the 2-mg strength for opioid-dependent patients expected to be at risk for severe opioid withdrawal only when the risk for accidental or intentional opioid exposure by household contacts is low.

IO† or Endotracheal†

Optimal dosage not established; typical dose given by the endotracheal route is 2–2.5 times the recommended IV dose.

Diagnosis of Opioid Overdosage

No specific recommendations at this time. If no response observed after administration of 10 mg of naloxone, diagnosis of opioid-induced toxicity should be questioned.

Naloxone Challenge Test

Administration of naloxone hydrochloride 0.4–0.8 mg before initiating treatment with naltrexone may assist in documenting the absence of physiological dependence and minimizing the risk for withdrawal.

Septic Shock

IV

Optimal dosage and treatment regimens not established.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendation; use caution when selecting dosage.

Contraindications

• Known hypersensitivity to the drug or any ingredient in the formulation.

Warnings/Precautions

Other Resuscitative Measures

When used in management of acute opioid overdosage, other resuscitative measures (e.g., maintenance of an adequate airway, artificial respiration, cardiac massage, vasopressor agents) should be readily available and used when necessary.

Excessive Doses in Postoperative Patients

Excessive doses in postoperative patients have resulted in agitation and reversal of analgesia.

Use in Patients with Cardiovascular Disorders

Hypotension, hypertension, ventricular tachycardia/fibrillation, pulmonary edema, and cardiac arrest reported in postoperative patients receiving naloxone, sometimes resulting in death, coma, or encephalopathy. Reported mainly in patients with preexisting cardiovascular disorders or receiving other drugs with similar adverse cardiovascular effects.

Use with caution in patients with preexisting cardiovascular disease or in those receiving potentially cardiotoxic drugs; monitor such patients for hypotension, ventricular tachycardia or fibrillation, and pulmonary edema.

Limited Efficacy with Partial Agonists or Mixed Agonist/Antagonists

Reversal of respiratory depression resulting from overdosage of opioid partial agonists (e.g., buprenorphine, pentazocine) may be incomplete and require higher or repeated doses of naloxone.

Precipitation of Severe Opioid Withdrawal

May precipitate severe opioid withdrawal symptoms. Abrupt postoperative reversal of opioid effects may result in nausea, vomiting, sweating, tremor, tachycardia, hypotension, hypertension, seizures, ventricular tachycardia/ fibrillation, pulmonary edema, and cardiac arrest, which may result in death.

Administer with caution to patients known or suspected to be physically dependent on opioids (including neonates born to women who are opioid dependent), particularly in patients with cardiovascular disease. (See Use in Patients with Cardiovascular Disorders under Cautions.)

Risk of Recurrent Respiratory and CNS Depression

Duration of action of most opioids may exceed that of naloxone resulting in a return of respiratory and/or CNS depression after an initial improvement. Monitor patients closely and administer repeated doses of naloxone when necessary. Patients with life-threatening overdosage of a long-acting or extended-release opioid may require longer periods of observation. Monitor pediatric patients who have responded to naloxone for at least 24 hours.

Risk of Accidental Needlestick Injury

A needlestick injury could occur in emergency situations with use of naloxone prefilled syringes (Zimhi). If an accidental needlestick occurs, seek medical attention. Stress to patients the importance of familiarizing themselves with the device prior to emergency situation.

Specific Populations

Pregnancy

Limited data on use in pregnant women. Use only when clearly needed. Consider risk-benefit ratio before administering naloxone to a pregnant woman with known or suspected opioid dependence. Naloxone crosses the placenta; risk of opioid withdrawal in both the pregnant woman and fetus. Monitor for fetal distress.

Lactation

Not known whether naloxone is distributed into milk or has any effect on the breast-fed infant or on milk production, use naloxone with caution in nursing women. Does not affect prolactin or oxytocin concentrations in nursing women, and oral bioavailability is minimal.

Females and Males of Reproductive Potential

Animal studies revealed no evidence of impaired fertility.

Pediatric Use

Naloxone may be used to reverse effects of opioids in infants and children. Safety and efficacy of prefilled syringes for IM or Sub-Q use (Zimhi) or nasal spray (e.g., Narcan, Kloxxado) established in pediatric patients of all ages for emergency treatment of known or suspected opioid overdosage. Such use in pediatric patients supported by adult bioequivalence studies and evidence from other naloxone products.

Absorption following intranasal administration or IM or sub-Q injection in pediatric patients may be erratic or delayed; carefully monitor pediatric patients ≥24 hours.

Safety and efficacy in management of hypotension associated with septic shock not established in pediatric patients. In a study of 2 neonates with septic shock, treatment with naloxone produced positive pressor response; however, one patient subsequently died after intractable seizures.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults. Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.

Hepatic Impairment

Safety and efficacy not established; use with caution.

Renal Impairment

Safety and efficacy not established; use with caution.

Common Adverse Effects

Intranasal naloxone: abdominal pain, asthenia, dizziness, headache, increased blood pressure, constipation, toothache, muscle spasms, musculoskeletal pain, nasal congestion, nasal discomfort, nasal dryness, nasal edema, nasal inflammation, presyncope, rhinalgia, xeroderma.

Parenteral naloxone (postoperative use): Hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea, pulmonary edema, and cardiac arrest reported; sequelae include death, coma, and encephalopathy. Cardiovascular effects most common in patients with preexisting cardiovascular disease or in those receiving other drugs that produce similar adverse cardiovascular effects.

Naloxone injection for IM or sub-Q use (Zimhi): dizziness, elevated bilirubin, lightheadedness, and nausea.

Abrupt reversal of opiate effects may precipitate acute withdrawal and aggressive behavior.

General

Patient Monitoring

• Carefully monitor patients who have responded to naloxone; the duration of action of most opioids may exceed that of naloxone and may result in recurrent respiratory and CNS depression. Administer repeated doses of naloxone when necessary.

• Monitor pediatric patients who have responded to naloxone for at least 24 hours.

• Monitor for development of opioid withdrawal symptoms (e.g., abdominal cramps, body aches, diarrhea, fever, increased blood pressure, nausea or vomiting, nervousness, runny nose, piloerection, restlessness or irritability, shivering or trembling, sneezing, sweating, tachycardia, weakness, yawning).

Other General Considerations

• Resuscitative measures such as maintenance of a patent airway, artificial ventilation, cardiac massage, and vasopressor agents should be available and employed when necessary in the treatment of opioid overdose.

• State naloxone laws vary, and may permit prescribing and dispensation to patients with risk factors for overdose or to lay persons (including nonmedical first responders, potential bystanders, and family and friends of opioid users). Consult state law for further information.

• Carefully instruct patients and their family members or close contacts regarding clinical manifestations requiring naloxone administration, proper administration technique, and the importance of seeking emergency care immediately following administration of the initial dose. Advise caregivers, household members, and other close contacts of where naloxone is stored, and to ensure the location is easily accessible during an emergency (e.g., naloxone should not be stored in a locked container with the opioid).

• Advise patients taking doses of opioid analgesics when away from home to carry naloxone with them and to advise individuals who are with them of the availability of the drug and its proper use.

Administration

Administer by IV, sub-Q, or IM injection; by IV infusion; or intranasally.

The most rapid onset of action is achieved by IV administration, which is recommended in emergency situations in medically supervised settings. Because absorption may be erratic or delayed, AAP does not endorse sub-Q or IM injection for emergency medical management of opioid intoxication in children or neonates.

When IV access cannot be established in emergency situations, has been administered via an endotracheal tube^{† [off-label]} and by intraosseous^{† [off-label]} (IO) injection.

IV Infusion

Continuous IV infusions may be most appropriate in patients who require higher doses, continue to experience recurrent respiratory or CNS depression after effective therapy with repeated doses, and/or in whom the effects of long-acting opioids are being antagonized.

Dilution

For continuous IV infusion, dilute 2 mg of naloxone hydrochloride in 500 mL of 0.9% sodium chloride or 5% dextrose injection to produce a solution containing 0.004 mg/mL (4 mcg/mL). Other concentrations have been recommended in pediatric patients (see Standardize 4 Safety under Dosage and Administration).

Rate of Administration

Titrate in accordance with patient’s response.

IM or Sub-Q Injection

May be administered by family members or other caregivers prior to emergency medical response to individuals with known or suspected opioid overdosage. Caregivers should seek emergency medical care immediately after administering the initial dose.

May be administered by IM or sub-Q injection via prefilled syringes. Administer initial dose of naloxone prefilled syringes (Zimhi) IM or sub-Q into the anterolateral aspect of the thigh, through clothing if necessary. When administered to pediatric patients <1 year of age, pinch the thigh muscle while administering the drug.

Intranasal Administration

May be administered by family members or other caregivers prior to emergency medical response to individuals with known or suspected opioid overdosage.

Do not remove nasal spray units from carton until time of administration; do not prime or test units prior to administration.

Intranasal Administration Technique

Place the patient in a supine position. Remove the nasal spray unit from carton and blister package. Tilt patient’s head back, with one hand supporting the neck. Do not prime or test device prior to administration. Gently insert tip of nasal spray unit into one nostril until the fingers on either side of the nozzle are against the patient's nose; press device plunger firmly to administer dose.

Remove nozzle from nostril following administration, and place patient in recovery position; closely monitor patient.

If additional doses are required, administer into alternate nostrils using new nasal spray unit.

Standardize 4 Safety

Standardized concentrations for naloxone have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. For additional information on S4S (including updates that may be available), see [Web].

The panel recognizes that 40 and 400 mcg/mL concentrations are 10× different; however, these are the only two concentrations studied for stability.

Dosage

Available as naloxone hydrochloride; dosage expressed in terms of the salt.

Pediatric Patients

Opioid-induced Depression in Neonates

IV, IM, or Sub-Q

Usual initial dose is 0.01 mg/kg, administered at 2- to 3-minute intervals to the desired degree of reversal.

Opioid Overdosage in Children

Children may receive an initial IV naloxone hydrochloride dose of 0.01 mg/kg; if this dose does not produce the desired degree of response, a subsequent dose of 0.1 mg/kg may be administered.

One spray (2, 4, or 8 mg [contents of one spray unit]); if patient fails to respond or responds but subsequently relapses into respiratory depression, repeat as necessary (if additional spray units available) at 2- to 3-minute intervals until emergency care arrives. Prescribe the 2-mg strength for opioid-dependent patients expected to be at risk for severe opioid withdrawal only when the risk for accidental or intentional opioid exposure by household contacts is low.

Children <5 years of age or weighing ≤20 kg: Some experts suggest dose of 0.1 mg/kg.

Children ≥5 years of age or weighing >20 kg: Some experts suggest dose of 2 mg.

Optimum dose for administration via an endotracheal tube^† not established (higher doses as compared with other routes may be necessary).

Diagnosis of Opioid Overdosage

No specific recommendations at this time. If no response observed after administration of 10 mg of naloxone, diagnosis of opioid-induced toxicity should be questioned.

Postoperative Opioid Depression

IV

For initial reversal of respiratory depression, naloxone hydrochloride should be administered in increments of 0.005–0.01 mg at 2- to 3-minute intervals until desired response (i.e., adequate ventilation and alertness without substantial pain or discomfort) is obtained.

Treatment of Opioid-Induced Pruritus

IV†

Dosages in children and adolescents ranged from 0.25–1.0 mcg/kg per hour via continuous IV infusion.

Adults

Postoperative Opioid Depression

IV

Initial dosage: Usually, 0.1–0.2 mg, given at 2- to 3-minute intervals until desired response (i.e., adequate ventilation and alertness without substantial pain or discomfort) is obtained; additional doses may be necessary at 1- to 2-hour intervals depending on response and dosage and duration of action of the opioid administered.

For continuous IV infusion, titrate rate of infusion in accordance with the patient’s response.

Opioid Overdosage

IV

Initial dosage: Usually, 0.4–2 mg IV, administered at 2- to 3-minute intervals if necessary; if no response is observed after a total of 10 mg of the drug has been administered, the depressive condition may be caused by a drug or disease process not responsive to naloxone.

Duration of opioid action often exceeds that of naloxone; opioid depressant effects may return as the effects of naloxone diminish, and additional naloxone doses may be required.

Carefully monitor patient for recurrence of opioid depressant effects.

IM or Sub-Q

2 mg (contents of one prefilled syringe) or 5 mg (contents of one prefilled syringe; Zimhi); if patient fails to respond or responds but subsequently relapses into respiratory depression, repeat as necessary at 2- to 3-minute intervals until emergency care arrives.

Intranasal

One spray (2, 4, or 8 mg [contents of one spray unit]); if patient fails to respond or responds but subsequently relapses into respiratory depression, repeat as necessary at 2- to 3-minute intervals until emergency care arrives. Prescribe the 2-mg strength for opioid-dependent patients expected to be at risk for severe opioid withdrawal only when the risk for accidental or intentional opioid exposure by household contacts is low.

IO† or Endotracheal†

Optimal dosage not established; typical dose given by the endotracheal route is 2–2.5 times the recommended IV dose.

Diagnosis of Opioid Overdosage

No specific recommendations at this time. If no response observed after administration of 10 mg of naloxone, diagnosis of opioid-induced toxicity should be questioned.

Naloxone Challenge Test

Administration of naloxone hydrochloride 0.4–0.8 mg before initiating treatment with naltrexone may assist in documenting the absence of physiological dependence and minimizing the risk for withdrawal.

Septic Shock

IV

Optimal dosage and treatment regimens not established.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendation; use caution when selecting dosage.

Metabolized in the liver primarily by glucuronide conjugation.

Specific Drugs