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PAIN Management:  OPIOIDS, Antagonists, Other

Opiates

Codeine Fentanyl
Hydrocodone Hydromorphone (Dilaudid ® )
Levorphanol (Levo-Dromoran ®) Meperidine (Demerol ®)
Methadone (Dolophine ®) Morphine sulfate
Oxycodone (Roxicodone) Propoxyphene (Darvon ®)
tapentadol- NUCYNTA®  

Non-Narcotic analgesics:

Fioricet® Fiorinal®
Soma compound® Tramadol (Ultram®)

Agonist-Antagonists

Buprenorphene (Buprenex®), BELBUCA ™, PROBUPHINE ®  
Butorphanol (Stadol®) Dezocine (Dalgan®)
Nalbuphine (Nubain®) Pentazocine (Talwin®)

Antagonists

Nalmefene (Revex®) Naltrexone
Naloxone (Narcan®, EVZIO®)  

Other

Suboxone ® (Buprenorphine and naloxone) Ziconotide (Prialt ®)
Original table
Old table  
Please see package insert for additional information and possible updates. The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.    [  Read the disclaimer    |   <<Back     ]

Non-Narcotic analgesics:

Fioricet ®(apap 325mg + butalbital 50mg + caffeine 40mg) top of page

Dosing (Adults): Oral: 1-2 tablets or capsules (or 15-30 mL elixir) every 4 hours; not to exceed 6 tablets or capsules (or 180 mL elixir) daily.

Dosing interval in renal or hepatic impairment: Should be reduced

SUPPLIED:
Capsule:
Anolor 300, Esgic®, Medigesic®: Butalbital 50 mg, caffeine 40 mg, and acetaminophen 325 mg
Dolgic® Plus: Butalbital 50 mg, caffeine 40 mg, and acetaminophen 750 mg
Esgic-Plus™, Zebutal™: Butalbital 50 mg, caffeine 40 mg, and acetaminophen 500 mg

Elixir (Dolgic® LQ): Butalbital 50 mg, caffeine 40 mg, and acetaminophen 325 mg per 15 mL (480 mL)

Tablet: Butalbital 50 mg, caffeine 40 mg, and acetaminophen 325 mg;
            butalbital 50 mg, caffeine 40 mg, and acetaminophen 500 mg.
Esgic®, Fioricet®, Repan®: Butalbital 50 mg, caffeine 40 mg, and acetaminophen 325 mg

Fiorinal ®(ASA 325mg + butalbital 50mg + caffeine 40mg) top of page

Dosing (Adults):
Oral: 1-2 tablets or capsules every 4 hours; not to exceed 6/day

Dosing interval in renal or hepatic impairment: Should be reduced

SUPPLIED
:
Capsule (Fiorinal®): Butalbital 50 mg, caffeine 40 mg, and aspirin 325 mg

Soma compound ®(Carisoprodol 200mg + ASA 325mg) top of page

Dosing (Adults):  1-2 tabs orally four times daily.

SUPPLIED
:
Tablet: Carisoprodol 200 mg and aspirin 325 mg

Tramadol (Ultram®) top of page

Pharmacodynamics
ULTRAM® contains tramadol, a centrally acting synthetic opioid analgesic. Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to µ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin.

Opioid activity is due to both low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to µ-opioid receptors. In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in µ-opioid binding. Tramadol-induced analgesia is only partially antagonized by the opiate antagonist naloxone in several animal tests. The relative contribution of both tramadol and M1 to human analgesia is dependent upon the plasma concentrations of each compound.

Tramadol has been shown to inhibit reuptake of norepinephrine and serotonin in vitro, as have some other opioid analgesics. These mechanisms may contribute independently to the overall analgesic profile of ULTRAM®. Analgesia in humans begins approximately within one hour after administration and reaches a peak in approximately two to three hours.

Dosing (Adults):
Oral: Moderate to severe chronic pain: 50-100 mg every 4-6 hours, not to exceed 400 mg/day

For patients not requiring rapid onset of effect, tolerability may be improved by starting dose at 25 mg/day and titrating dose by 25 mg every 3 days, until reaching 25 mg 4 times/day. Dose may then be increased by 50 mg every 3 days as tolerated, to reach dose of 50 mg 4 times/day.

Elderly: >75 years: 50-100 mg every 4-6 hours (not to exceed 300 mg/day); see dosing adjustments for renal and hepatic impairment

Dosing adjustment in renal impairment: Clcr<30 mL/minute: Administer 50-100 mg dose every 12 hours (maximum: 200 mg/day)

Dosing adjustment in hepatic impairment: Cirrhosis: Recommended dose: 50 mg every 12 hours

SUPPLIED
::
Tablet, as hydrochloride: 50 mg

Agonist-Antagonists

Buprenorphine (Buprenex®) top of page

Dosing (Adults):
Long-term use is not recommended
Note: These are guidelines and do not represent the maximum doses that may be required in all patients. Doses should be titrated to pain relief/prevention. In high-risk patients (eg, elderly, debilitated, presence of respiratory disease) and/or concurrent CNS depressant use, reduce dose by one-half. Buprenorphine has an analgesic ceiling.

Acute pain (moderate to severe):

I.M.: Initial: Opiate-naive: 0.3 mg every 6-8 hours as needed; initial dose (up to 0.3 mg) may be repeated once in 30-60 minutes after the initial dose if needed; usual dosage range: 0.15-0.6 mg every 4-8 hours as needed

Slow I.V.: Initial: Opiate-naive: 0.3 mg every 6-8 hours as needed; initial dose (up to 0.3 mg) may be repeated once in 30-60 minutes after the initial dose if needed

Elderly: 0.15 mg every 6 hours; elderly patients are more likely to suffer from confusion and drowsiness compared to younger patients

Sublingual: Adults: Opioid dependence:
Induction: Range: 12-16 mg/day (doses during an induction study used 8 mg on day 1, followed by 16 mg on day 2; induction continued over 3-4 days). Treatment should begin at least 4 hours after last use of heroin or short-acting opioid, preferably when first signs of withdrawal appear. Titrating dose to clinical effectiveness should be done as rapidly as possible to prevent undue withdrawal symptoms and patient drop-out during the induction period.

Maintenance: Target dose: 16 mg/day; range: 4-24 mg/day; patients should be switched to the buprenorphine/naloxone combination product for maintenance and unsupervised therapy

Administration
I.V.: Administer slowly, over at least 2 minutes.

SUPPLIED:
Injection, solution (Buprenex®): 0.3 mg/mL (1 mL)
Tablet, sublingual (Subutex®): 2 mg, 8 mg

Drug UPDATESBELBUCA ™ (buprenorphine) buccal film CIII
[Drug information  /  PDF]    Click link for the latest monograph
Dosing:  Click (+) next to Dosage and Administration section (drug info link)

Initial U.S. Approval:  2015

Mechanism of Action: Buprenorphine is a partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor.

INDICATIONS AND USAGE:  BELBUCA is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

Limitations of Use
Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with long-acting opioid formulations, reserve BELBUCA for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
BELBUCA is not indicated as an as-needed (prn) analgesic.

HOW SUPPLIED: BELBUCA is a buccal film available in 7 dosage strengths: 75 mcg, 150 mcg, 300 mcg, 450 mcg, 600 mcg, 750 mcg, and 900 mcg buprenorphine per film.

Drug UPDATESPROBUPHINE ® (buprenorphine) implant for subdermal administration CIII
[Drug information  /  PDF]  
Package insert - Dosing:  Click (+) next to Dosage and Administration section (drug info link)

BOXED WARNING:
Risk Associated with Insertion and Removal Insertion and removal of PROBUPHINE are associated with the risk of implant migration, protrusion, and expulsion resulting from the ...

WARNING: IMPLANT MIGRATION, PROTRUSION, EXPULSION, and NERVE DAMAGE ASSOCIATED WITH INSERTION and REMOVAL

Risk Associated with Insertion and Removal

Insertion and removal of PROBUPHINE are associated with the risk of implant migration, protrusion, and expulsion resulting from the procedure. Rare but serious complications including nerve damage and migration resulting in embolism and death may result from improper insertion of drug implants inserted in the upper arm. Additional complications may include local migration, protrusion and expulsion.

Incomplete insertions or infections may lead to protrusion or expulsion. [see Warnings and Precautions (5.1)].

Because of the risks associated with insertion and removal, PROBUPHINE is available only through a restricted program called the PROBUPHINE REMS Program. All Healthcare Providers must successfully complete a live training program on the insertion and removal procedures and become certified, prior to performing insertions or prescribing PROBUPHINE implants. Patients must be monitored to ensure that PROBUPHINE is removed by a healthcare provider certified to perform insertions. [see Warnings and Precautions (5.2)].


Initial U.S. Approval:  2016

Mechanism of Action:
PROBUPHINE implants contain buprenorphine HCl. Buprenorphine is a partial agonist at the mu- opioid receptor and an antagonist at the kappa-opioid receptor.


INDICATIONS AND USAGE:
PROBUPHINE contains buprenorphine, a partial opioid agonist. PROBUPHINE is indicated for the maintenance treatment of opioid dependence in patients who have achieved and sustained prolonged clinical stability on low-to-moderate doses of a transmucosal buprenorphine- containing product (i.e., doses of no more than 8 mg per day of Subutex or Suboxone sublingual tablet or generic equivalent). (1)

PROBUPHINE should be used as part of a complete treatment program to include counseling and psychosocial support. (1)

PROBUPHINE is not appropriate for new entrants to treatment and patients who have not achieved and sustained prolonged clinical stability, while being maintained on buprenorphine 8 mg per day or less of a Subutex or Suboxone sublingual tablet or generic equivalent. (1)

DOSAGE AND ADMINISTRATION:
Prescription use of this product is limited under the Drug Addiction Treatment Act. (2.1)

Four PROBUPHINE implants are inserted subdermally in the upper arm for 6 months of treatment and are removed by the end of the sixth month. (2.2)

PROBUPHINE implants should not be used for additional treatment cycles after one insertion in each upper arm. (2.2)

PROBUPHINE implants must be inserted and removed by trained Healthcare Providers only. (2.3)

PROBUPHINE implants should be administered in patients who have achieved and sustained prolonged clinical stability on transmucosal buprenorphine. (2.4)

Examine the insertion site one week following insertion of PROBUPHINE implants for signs of infection or other problems. (2.5)


HOW SUPPLIED:
DOSAGE FORMS AND STRENGTHS
Each PROBUPHINE implant is an ethylene vinyl acetate (EVA) implant, 26 mm in length and 2.5 mm in diameter, containing 74.2 mg of buprenorphine (equivalent to 80 mg of buprenorphine hydrochloride).

Butorphanol (Stadol®) top of page

Dosing (Adults):
Note: These are guidelines and do not represent the maximum doses that may be required in all patients. Doses should be titrated to pain relief/prevention. Butorphanol has an analgesic ceiling.
Parenteral:
Acute pain (moderate to severe):
I.M.: Initial: 2 mg, may repeat every 3-4 hours as needed; usual range: 1-4 mg every 3-4 hours as needed.
I.V.: Initial: 1 mg, may repeat every 3-4 hours as needed; usual range: 0.5-2 mg every 3-4 hours as needed.

Preoperative medication: I.M.: 2 mg 60-90 minutes before surgery

Supplement to balanced anesthesia: I.V.: 2 mg shortly before induction and/or an incremental dose of 0.5-1 mg (up to 0.06 mg/kg), depending on previously administered sedative, analgesic, and hypnotic medications

Pain during labor (fetus >37 weeks gestation and no signs of fetal distress):
I.M., I.V.: 1-2 mg; may repeat in 4 hours.  Note: Alternative analgesia should be used for pain associated with delivery or if delivery is anticipated within 4 hours
-----------------------

Nasal spray:
Moderate to severe pain (including migraine headache pain): Initial: 1 spray (~1 mg per spray) in 1 nostril; if adequate pain relief is not achieved within 60-90 minutes, an additional 1 spray in 1 nostril may be given; may repeat initial dose sequence in 3-4 hours after the last dose as needed

Alternatively, an initial dose of 2 mg (1 spray in each nostril) may be used in patients who will be able to remain recumbent (in the event drowsiness or dizziness occurs); additional 2 mg doses should not be given for 3-4 hours

Note: In some clinical trials, an initial dose of 2 mg (as 2 doses 1 hour apart or 2 mg initially - 1 spray in each nostril) has been used, followed by 1 mg in 1 hour; side effects were greater at these dosages

Dosage adjustment in renal impairment:
I.M., I.V.: Initial dosage should generally be 1 /2 of the recommended dose; repeated dosing must be based on initial response rather than fixed intervals, but generally should be at least 6 hours apart

Nasal spray: Initial dose should not exceed 1 mg; a second dose may be given after 90-120 minutes

Dosage adjustment in hepatic impairment:
I.M., I.V.: Initial dosage should generally be 1 /2 of the recommended dose; repeated dosing must be based on initial response rather than fixed intervals, but generally should be at least 6 hours apart

Nasal spray: Initial dose should not exceed 1 mg; a second dose may be given after 90-120 minutes

Elderly:
I.M., I.V.: Initial dosage should generally be 1 /2 of the recommended dose; repeated dosing must be based on initial response rather than fixed intervals, but generally should be at least 6 hours apart

Nasal Spray: Initial dose should not exceed 1 mg; a second dose may be given after 90-120 minutes

SUPPLIED:
Injection, solution, as tartrate [preservative free] (Stadol®): 1 mg/mL (1 mL); 2 mg/mL (1 mL, 2 mL)
Injection, solution, as tartrate [with preservative] (Stadol®): 2 mg/mL (10 mL)
Solution, intranasal spray, as tartrate: 10 mg/mL (2.5 mL) [14-15 doses]

Dezocine (Dalgan®) top of page

Dosing (Adults):
2.5 to 10 mg IV every 2 to 4 hours or 5-20mg IM every 3 to 6 hours as needed.

Nalbuphine (Nubain®) top of page

Dosing (Adults):
I.M., I.V., SubQ:
10 mg/70 kg every 3-6 hours; maximum single dose: 20 mg; maximum daily dose: 160 mg

Dosing adjustment/comments in hepatic impairment:
Use with caution and reduce dose

SUPPLIED:
Injection, solution, as hydrochloride: 10 mg/mL (10 mL); 20 mg/mL (10 mL)
Injection, solution, as hydrochloride [preservative free]: 10 mg/mL (1 mL); 20 mg/mL (1 mL)

Pentazocine (Talwin®) top of page

Partial agonist-antagonist.

Dosing (Adults):
Oral: 50 mg every 3-4 hours; may increase to 100 mg/dose if needed, but should not exceed 600 mg/day

I.M., SubQ: 30-60 mg every 3-4 hours, not to exceed total daily dose of 360 mg

I.V.: 30 mg every 3-4 hours (maximum: 360 mg/day)

Elderly: Elderly patients may be more sensitive to the analgesic and sedating effects. The elderly may also have impaired renal function. If needed, dosing should be started at the lower end of dosing range and adjust dose for renal function.

Dosing adjustment in renal impairment:
Clcr 10-50 mL/minute: Administer 75% of normal dose
Clcr<10 mL/minute: Administer 50% of normal dose

Dosing adjustment in hepatic impairment:
Reduce dose or avoid use in patients with liver disease

SUPPLIED:
Injection, solution (Talwin®): 30 mg/mL (1 mL, 10 mL)
Tablet (Talwin® NX): Pentazocine 50 mg and naloxone 0.5 mg

Antagonists

Nalmefene (Revex) top of page

Dosing (Adults):
Reversal of postoperative opioid depression: Blue labeled product (100 mcg/mL): Titrate to reverse the undesired effects of opioids; initial dose for nonopioid dependent patients: 0.25 mcg/kg followed by 0.25 mcg/kg incremental doses at 2- to 5-minute intervals; after a total dose >1 mcg/kg, further therapeutic response is unlikely

Management of known/suspected opioid overdose: Green labeled product (1000 mcg/mL): Initial dose: 0.5 mg/70 kg; may repeat with 1 mg/70 kg in 2-5 minutes; further increase beyond a total dose of 1.5 mg/70 kg will not likely result in improved response and may result in cardiovascular stress and precipitated withdrawal syndrome. (If opioid dependency is suspected, administer a challenge dose of 0.1 mg/70 kg; if no withdrawal symptoms are observed in 2 minutes, the recommended doses can be administered.)

Note: If recurrence of respiratory depression is noted, dose may again be titrated to clinical effect using incremental doses.

Note: If I.V. access is lost or not readily obtainable, a single SubQ or I.M. dose of 1 mg may be effective in 5-15 minutes.

Dosing adjustment in renal or hepatic impairment: Not necessary with single uses, however, slow administration (over 60 seconds) of incremental doses is recommended to minimize hypertension and dizziness

SUPPLIED:
Injection, solution: 100 mcg/mL (1 mL); 1000 mcg/mL (2 mL)

Naltrexone (ReVia® ) top of page

INDICATIONS:
Treatment of ethanol dependence; blockade of the effects of exogenously administered opioids

Pharmacodynamic Actions: REVIA is a pure opioid antagonist. It markedly attenuates or completely blocks, reversibly, the subjective effects of intravenously administered opioids.

When co-administered with morphine, on a chronic basis, REVIA blocks the physical dependence to morphine, heroin and other opioids.

REVIA has few, if any, intrinsic actions besides its opioid blocking properties. However, it does produce some pupillary constriction, by an unknown mechanism.

The administration of REVIA is not associated with the development of tolerance or dependence. In subjects physically dependent on opioids, REVIA will precipitate withdrawal symptomatology.

Dosing (Adults):
Do not give until patient is opioid-free for 7-10 days as determined by urine analysis
Adults: Oral: 25 mg; if no withdrawal signs within 1 hour give another 25 mg; maintenance regimen is flexible, variable and individualized (50 mg/day to 100-150 mg 3 times/week for 12 weeks); up to 800 mg/day has been tolerated in adults without an adverse effect

Dosing cautions in renal/hepatic impairment: Caution in patients with renal and hepatic impairment. An increase in naltrexone AUC of approximately five- and 10-fold in patients with compensated or decompensated liver cirrhosis respectively, compared with normal liver function has been reported.

Administration
If there is any question of occult opioid dependence, perform a naloxone challenge test; do not attempt treatment until naloxone challenge is negative.
Naltrexone is administered orally; to minimize adverse gastrointestinal effects, administer with food or antacids or after meals; advise patient not to self-administer opiates while receiving naltrexone therapy

SUPPLIED:
Tablet, as hydrochloride: 50 mg


##########################################
DOSAGE AND ADMINISTRATION
IF THERE IS ANY QUESTION OF OCCULT OPIOID DEPENDENCE, PERFORM A NALOXONE CHALLENGE TEST AND DO NOT INITIATE REVIA THERAPY UNTIL THE NALOXONE CHALLENGE IS NEGATIVE.

Treatment of Alcoholism:
A dose of 50 mg once daily is recommended for most patients (see Individualization of Dosage ). The placebo-controlled studies that demonstrated the efficacy of REVIA as an adjunctive treatment of alcoholism used a dose regimen of REVIA 50 mg once daily for up to 12 weeks. Other dose regimens or durations of therapy were not evaluated in these trials.

A patient is a candidate for treatment with REVIA if:
The patient is willing to take a medicine to help with alcohol dependence.
The patient is opioid free for 7-10 days.
The patient does not have severe or active liver or kidney problems (Typical guidelines suggest liver function tests no greater than 3 times the upper limits of normal, and bilirubin normal.)
The patient is not allergic to REVIA , and no other contraindications are present. 

REVIA should be considered as only one of many factors determining the success of treatment of alcoholism. Factors associated with a good outcome in the clinical trials with REVIA were the type, intensity, and duration of treatment; appropriate management of comorbid conditions; use of community-based support groups; and good medication compliance. To achieve the best possible treatment outcome, appropriate compliance-enhancing techniques should be implemented for all components of the treatment program, especially medication compliance.

Treatment of Opioid Dependence:
Initiate treatment with REVIA using the following guidelines:
1.) Treatment should not be attempted unless the patient has remained opioid-free for at least 7-10 days. Self-reporting of abstinence from opioids in opioid addicts should be verified by analysis of the patient's urine for absence of opioids. The patient should not be manifesting withdrawal signs or reporting withdrawal symptoms.
2.) If there is any question of occult opioid dependence, perform a naloxone challenge test. If signs of opioid withdrawal are still observed following naloxone challenge, treatment with REVIA should not be attempted. The naloxone challenge can be repeated in 24 hours.
3.) Treatment should be initiated carefully, with an initial dose of 25 mg of REVIA. If no withdrawal signs occur, the patient may be started on 50 mg a day thereafter.

Naloxone Challenge Test: The naloxone challenge test should not be performed in a patient showing clinical signs or symptoms of opioid withdrawal, or in a patient whose urine contains opioids. The naloxone challenge test may be administered by either the intravenous or subcutaneous routes.

Intravenous:
Inject 0.2 mg naloxone.
Observe for 30 seconds for signs or symptoms of withdrawal.
If no evidence of withdrawal, inject 0.6 mg of naloxone.
Observe for an additional 20 minutes.

Subcutaneous:
Administer 0.8 mg naloxone.

Observe for 20 minutes for signs or symptoms of withdrawal.

Note: Individual patients, especially those with opioid dependence, may respond to lower doses of naloxone. In some cases, 0.1 mg IV naloxone has produced a diagnostic response.

 Interpretation of the Challenge: Monitor vital signs and observe the patient for signs and symptoms of opioid withdrawal. These may include, but are not limited to: nausea, vomiting, dysphoria, yawning, sweating, tearing, rhinorrhea, stuffy nose, craving for opioids, poor appetite, abdominal cramps, sense of fear, skin erythema, disrupted sleep patterns, fidgeting, uneasiness, poor ability to focus, mental lapses, muscle aches or cramps, pupillary dilation, piloerection, fever, changes in blood pressure, pulse or temperature, anxiety, depression, irritability, back ache, bone or joint pains, tremors, sensations of skin crawling or fasciculations. If signs or symptoms of withdrawal appear, the test is positive and no additional naloxone should be administered.

Warning: If the test is positive, do NOT initiate REVIA therapy. Repeat the challenge in 24 hours. If the test is negative, REVIA therapy may be started if no other contraindictions are present. If there is any doubt about the result of the test, hold REVIA and repeat the challenge in 24 hours.

Alternative Dosing Schedules:
Once the patient has been started on REVIA, 50 mg every 24 hours will produce adequate clinical blockade of the actions of parenterally administered opioids (i.e., this dose will block the effects of a 25 mg intravenous heroin challenge). A flexible approach to a dosing regimen may need to be employed in cases of supervised administration. Thus, patients may receive 50 mg of REVIA every weekday with a 100 mg dose on Saturday, 100 mg every other day, or 150 mg every third day. The degree of blockade produced by REVIA may be reduced by these extended dosing intervals.

There may be a higher risk of hepatocellular injury with single doses above 50 mg, and use of higher doses and extended dosing intervals should balance the possible risks against the probable benefits.

Naloxone (Narcan®): top of page

CLINICAL PHARMACOLOGY
Complete or Partial Reversal of Opioid Depression
NARCAN prevents or reverses the effects of opioids including respiratory depression, sedation and hypotension. Also, NARCAN can reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine.

NARCAN is an essentially pure opioid antagonist, i.e., it does not possess the "agonistic" or morphine-like properties characteristic of other opioid antagonists. When administered in usual doses and in the absence of opioids or agonistic effects of other opioid antagonists, it exhibits essentially no pharmacologic activity.

NARCAN has not been shown to produce tolerance or cause physical or psychological dependence. In the presence of physical dependence on opioids, NARCAN will produce withdrawal symptoms. However, in the presence of opioid dependence, opiate withdrawal symptoms may appear within minutes of NARCAN administration and subside in about 2 hours. The severity and duration of the withdrawal syndrome are related to the dose of NARCAN and to the degree and type of opioid dependence.

While the mechanism of action of NARCAN is not fully understood, in vitro evidence suggests that NARCAN antagonizes opioid effects by competing for the µ, kappa and sigma opiate receptor sites in the CNS, with the greatest affinity for the µ receptor.

Dosing (Adults):
I.M., I.V. (preferred), intratracheal, SubQ:

Narcotic overdose: Adults: I.V.: 0.4-2 mg every 2-3 minutes as needed; may need to repeat doses every 20-60 minutes, if no response is observed after 10 mg, question the diagnosis. Note: Use 0.1-0.2 mg increments in patients who are opioid dependent and in postoperative patients to avoid large cardiovascular changes.

Adults: Continuous infusion: I.V.: If continuous infusion is required, calculate dosage/hour based on effective intermittent dose used and duration of adequate response seen, titrate dose 0.04-0.16 mg/kg/hour for 2-5 days in children, adult dose typically 0.25-6.25 mg/hour (short-term infusions as high as 2.4 mg/kg/hour have been tolerated in adults during treatment for septic shock); alternatively, continuous infusion utilizes 2 /3 of the initial naloxone bolus on an hourly basis; add 10 times this dose to each liter of D5W and infuse at a rate of 100 mL/hour; 1 /2 of the initial bolus dose should be readministered 15 minutes after initiation of the continuous infusion to prevent a drop in naloxone levels; increase infusion rate as needed to assure adequate ventilation

SUPPLIED:
Injection, solution, as hydrochloride: 0.4 mg/mL (1 mL, 10 mL)

Drug UPDATES:  EVZIO® (naloxone hydrochloride injection) Auto-Injector for intramuscular or subcutaneous use
Initial U.S. Approval: 1971
[Drug information  /  PDF]  
Dosing:  Click (+) next to Dosage and Administration section (drug info link)

U.S. Approval:  2014

Mechanism of Action: Naloxone hydrochloride is an opioid antagonist that antagonizes opioid effects by competing for the same receptor sites.
Naloxone hydrochloride reverses the effects of opioids, including respiratory depression, sedation, and hypotension. Also, it can reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine.

INDICATIONS AND USAGE:
EVZIO is an opioid antagonist indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression.
EVZIO is intended for immediate administration as emergency therapy in settings where opioids may be present.
EVZIO is not a substitute for emergency medical care.
HOW SUPPLIED: Injection: 0.4 mg/0.4 mL naloxone hydrochloride solution in a pre-filled auto-injector.

Other

Suboxone ® (Buprenorphine and naloxone) top of page

Dosing (Adults):
Treatment of opioid dependence. Not recommended for use during the induction period. Initial treatment should begin using buprenorphine oral tablets. Patients should be switched to the combination product for maintenance and unsupervised therapy. Maintenance: Target dose (based on buprenorphine content): 16 mg/day - range: 4-24 mg/day.

Supplied: sublingual tablet: Buprenorphine 2 mg and naloxone 0.5 mg; buprenorphine 8 mg and naloxone 2 mg.

Ziconotide (Prialt ®) top of page

CLINICAL PHARMACOLOGY
Mechanism of Action
Ziconotide binds to N-type calcium channels located on the primary nociceptive (A-delta and C) afferent nerves in the superficial layers (Rexed laminae I and II) of the dorsal horn in the spinal cord. Although the mechanism of action of ziconotide has not been established in humans, results in animals suggest that its binding blocks N-type calcium channels, which leads to a blockade of excitatory neurotransmitter release from the primary afferent nerve terminals and antinociception.

Dosage (adults):
I.T.:  Chronic pain: Initial dose: 2.4 mcg/day (0.1 mcg/hour)

Dose may be titrated by </= 2.4 mcg/day (0.1 mcg/hour) at intervals >/= 2-3 times/week to a maximum dose of 19.2 mcg/day (0.8 mcg/hour) by day 21; average dose at day 21: 6.9 mcg/day (0.29 mcg/hour). A faster titration should be used only if the urgent need for analgesia outweighs the possible risk to patient safety.

Administration
Not for I.V. administration. For I.T. administration only using a Medtronic SynchroMed® EL, SynchroMed® II Infusion System or Simms Deltec Cadd Micro® External Microinfusion Device and Catheter.
Medtronic SynchroMed® EL or SynchroMed® II Infusion Systems:

Naive pump priming (first time use with ziconotide): Use 2mL of undiluted ziconotide 25 mcg/mL solution to rinse the internal surfaces of the pump; repeat twice for a total of 3 rinses

Initial pump fill: Use only undiluted 25 mcg/mL solution and fill pump after priming. Following the initial fill only, adsorption on internal device surfaces will occur, requiring the use of the undiluted solution and refill within 14 days.

Pump refills: Contents should be emptied prior to refill. Subsequent pump refills should occur at least every 40 days if using diluted solution or every 60 days if using undiluted solution

Simms Deltec Cadd Micro® External Microinfusion Device and Catheter: Refer to manufacturers' manual for initial fill and refill instructions

Elderly: Refer to Adults dosing; use with caution

Dosage adjustment for toxicity: Cognitive impairment: Reduce dose or discontinue; effects are generally reversible within 2 weeks of discontinuation

Supplied: Injection (soln): 100 mcg/ml (1 ml, 2 ml, 5 ml).
25 mcg/ml (20 ml).

 ® top of page

 

Reference(s)

National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
Provides access to the latest drug monographs submitted to the Food and Drug Administration (FDA). Please review the latest applicable package insert for additional information and possible updates.  A local search option of this data can be found here.

Disclaimer

Listed dosages are for - Adult patients ONLY. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. GlobalRPH does not directly or indirectly practice medicine or provide medical services and therefore assumes no liability whatsoever of any kind for the information and data accessed through the Service or for any diagnosis or treatment made in reliance thereon.
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Medical Calculators - A thru Z
Lab Values - A thru Z