OPIATE MEDICATIONS

P = drugs with pediatric dosing recommendations | IR - immediate-release | ER - extended-release
SCHEDULE II MEDICATIONS
Codeine sulfate P Fentanyl (Abstral® sublingual tablet) Fentanyl (Actiq® lozenge) Fentanyl (Duragesic® patch) Fentanyl (Fentora® buccal tablet) Fentanyl (Lazanda® nasal spray) Fentanyl (Subsys® sublingual spray) Hydrocodone IR (Norco®, Vicodin®) P Hydrocodone ER (Hysingla® ER) Hydrocodone ER (Zohydro®) Hydrocodone cough meds P Hydromorphone IR (Dilaudid®) P Hydromorphone ER (Exalgo®) Meperidine (Demerol®) P Methadone P Morphine IR P
Morphine ER (Arymo® ER) Morphine ER (Avinza®) Morphine ER (Embeda®) Morphine ER (Kadian®) Morphine ER (Morphabond™ ER) Morphine ER (MS Contin®) P Oxycodone IR and ibuprofen Oxycodone IR (Percocet®, Roxicet®) Oxycodone IR (Percodan®) Oxycodone IR (Roxicodone®) P Oxycodone ER (Oxycontin®) P Oxycodone ER (Xtampza® ER) Oxymorphone IR (Opana®) Oxymorphone ER (Opana® ER) Tapentadol IR (Nucynta®) Tapentadol ER (Nucynta® ER)
SCHEDULE III AND V MEDICATIONS
Buprenorphine (Belbuca®) Buprenorphine (Buprenex®, Subutex®) Buprenorphine (Butrans®) Buprenorphine (Probuphine®) Buprenorphine (Sublocade™) Buprenorphine/Naloxone (Suboxone®,
Zubsolv®, Bunavail®) Codeine/APAP (Tylenol® #3/4) P Codeine (Fioricet®) Codeine (Fiorinal®) Codeine (Soma® compound) Codeine cough meds P Dihydrocodeine (Synalgos®-DC) Dihydrocodeine (Trezix®) Diphenoxylate (Lomotil®) P
SCHEDULE IV MEDICATIONS
Butorphanol (Stadol®) Pentazocine (Talwin NX®) Tramadol IR (Ultram®) Tramadol IR (Ultracet®) Tramadol ER (Ultram ER®) Tramadol ER (Conzip®)
OPIOID ANTAGONISTS
Methylnaltrexone (Relistor®) Naloxegol (Movantik®) Naloxone (Evzio® injection) Naloxone (Narcan® nasal spray) Naltrexone (Revia®) Naltrexone (Vivitrol®)
OTHER OPIATE INFORMATION
Opiate side effects Opiate precautions/contraindications Opiate drug interactions Opioid antagonists
Opiate-tolerant definition
Opioid analgesic equivalence table
Urinary metabolites of opiates
Opiate withdrawal treatment
FDA schedules
Pricing ($) info
References
PRICING INFO
References:
OPIATE-TOLERANT DEFINITION


FDA SCHEDULES


  • Reference [9]
TREATMENT OF OPIATE WITHDRAWAL
Symptoms Medication Dosing
Autonomic overactivity
(elevated pulse and blood pressure, anxiety, chills, piloerection)		 Clonidine
  • 0.1 - 0.2 mg every 4 hours; maximum of 1 mg/day; hold dose for SBP < 80 mmHg or DBP < 50 mmHg; on day 5, start to decrease dose by 0.2 mg/day
Lofexidine (Lucemyra™)
  • Lofexidine is another alpha-2 agonist that was FDA-approved for opiate withdrawal in 2018
  • Dosing: Three 0.18 mg tablets four times daily during the period of peak withdrawal symptoms. There should be 5 to 6 hours between each dose. Reduce dose over 2 - 4 days (e.g reduce 1 tablet per dose every 1 - 2 days)
  • See Lucemyra PI for full prescribing information
Insomnia Temazepam
  • 15 - 30 mg at bedtime as needed
Anxiety Diazepam
  • 2 - 10 mg every 4 hours as needed; maximum of 20 mg/day
Diarrhea Loperamide
(Imodium®)
  • 4 mg initially followed by 2 mg as needed for loose stools; maximum of 16 mg/day
Joint pain, body aches NSAIDs One of the following:
  • Naprosyn: 500 mg twice daily as needed
  • Ibuprofen 800 mg three times a day as needed
Nausea and vomiting Antiemetics
  • Ondansetron (Zofran®): 8 mg every 8 hours as needed
  • Prochlorperazine (Compazine®): 5 - 10 mg by mouth every 4 hours as needed; daily doses > 40 mg should only be used in severe cases
OPIOID ANALGESIC EQUIVALENCE TABLE

  • NOTE: THIS TABLE IS NOT FOR CONVERTING BETWEEN DOSES OF DIFFERENT OPIOIDS. There are no established conversion ratios for converting from one opioid to another. See individual drug package inserts for recommendations on converting between drugs.
  • Reference [3,7]
Analgesic equivalent doses for select opioids
Opioid Equivalent analgesic oral dose
Morphine 30 mg
Oxycodone 15 - 20 mg
Hydrocodone 30 - 45 mg
Hydromorphone 7.5 mg
Codeine 200 mg
Pentazocine 166 mg
Fentanyl (transdermal) every 2 mg/day of morphine is
approximately equivalent to 1 mcg/hr of transdermal fentanyl
Methadone See Methadone dosing in opiate table
  • PMID 29114811 - Interpretation of Urine Drug Screens: Metabolites and Impurities, JAMA (2017)
URINARY METABOLITES OF OPIATES
Opiate Urinary metabolite Comment
Codeine
  • Morphine
  • Hydrocodone (< 10%)
  • Norcodeine
  • Codeine is metabolized to morphine
Buprenorphine
  • Norbuprenorphine
Fentanyl
  • Norfentanyl
Heroin
  • 6-Monoacetylmorphine
  • Morphine
  • Normorphine
  • Morphine may be the only metabolite detected after heroin use
Hydrocodone
  • Hydromorphone
  • Norhydrocodone
  • Dihydrocodeine
Hydromorphone
  • Hydromorphone-3-glucuronide
Methadone
  • 2-Ethylidene-1
  • 5-dimethyl-3
  • 3-diphenylpyrrolidine
Morphine
  • Normorphine
  • Hydromorphone (< 10%)
  • Morphine-6-glucuronide
  • Morphine-3-glucuronide
  • Codeine is sometimes a contaminant of morphine during manufacturing
  • Codeine contamination is typically 0.04% - 0.5% of morphine concentrations
Oxycodone
  • Oxymorphone
  • Noroxycodone
  • Hydrocodone is sometimes a contaminant of oxycodone during manufacturing
  • Hydrocodone contamination is typically < 0.1% of oxycodone concentrations
Oxymorphone
  • Oxymorphone-3-glucuronide
  • 6-hydroxy-oxymorphone


Drug Dosage forms Dosing Other
Codeine Sulfate
 Tablet
  • 15 mg
  • 30 mg
  • 60 mg
 Adult - opiate naïve
  • 15 - 60 mg every 4 hours as needed
  • Do not exceed 360 mg in 24 hours
Children (> 6 months old)
  • < 50 kg: 0.5 - 1 mg/kg/dose every 3 - 4 hours [5]
  • ≥ 50 kg: 30 - 60 mg every 3 - 4 hours [5]

NOTE: In 2017, the FDA declared that all codeine products are contraindicated in children < 12 years old 		Other
  • Codeine has no analgesic activity unless it is metabolized into morphine by CYP2D6. Poor metabolizers may not receive any pain relief from codeine while rapid metabolizers may experience toxicity. Because of the risk for toxicity, codeine is contraindicated for postoperative pain in children.
  • Duration of action: 3 - 4 hours
Price
  • Generic (30 tablets) - $

Drug Dosage forms Dosing Other
Fentanyl

Abstral®
 Sublingual tablet
  • 100 mcg
  • 200 mcg
  • 300 mcg
  • 400 mcg
  • 600 mcg
  • 800 mcg


Comes in packets of 12 (100, 200, 300, 400 mcg strengths only) or 32 tablets (all strengths) 		Adult - opiate naïve
  • Not recommended
  • Should only be used in
    opiate-tolerant
    cancer patients for breakthrough pain
Dosing in opioid-tolerant cancer patients 		Other
  • Providers and patients must enroll in the TIRF REMS Access program for outpatient use
  • Tablet is placed under the tongue
  • Special disposal instructions are provided to prevent accidental exposure
  • Fentanyl is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
Price
  • No generic
  • 30 tablets - $$$$
Fentanyl

Actiq®
 Lozenge
  • 200 mcg
  • 400 mcg
  • 600 mcg
  • 800 mcg
  • 1200 mcg
  • 1600 mcg
 Adult - opiate naïve
  • Not recommended
  • Should only be used in
    opiate-tolerant
    cancer patients for breakthrough pain
Dosing in opioid-tolerant cancer patients 		Other
  • Providers and patients must enroll in the TIRF REMS Access program for outpatient use
  • Special lozenge disposal instructions are provided to prevent accidental exposures
  • Fentanyl is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
Price
  • Generic (30 lozenges) - $$$$
Fentanyl

Duragesic®
 Patch
Fentanyl delivered in mcg/hour
  • 12
  • 25
  • 37.5
  • 50
  • 62.5
  • 75
  • 87.5
  • 100
 Adult - opiate naïve
  • Not recommended
  • Should only be used in
    opiate-tolerant
    patients
Converting from other opiates
  • The Duragesic PI (sec 2) contains an extensive table for converting from other opioids to fentanyl patch
 Other
  • Old patch is removed and new patch is applied every 72 hours. Apply new patch to different skin site.
  • Apply to chest, back, flank, or upper arm. Hair at application site may be clipped (not shaved).
  • Flush used patches down the toilet to prevent accidental exposure
  • Do not expose patch to direct heat because absorption may be increased
  • Patients with fever may absorb more fentanyl from the patch
  • Fentanyl is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
Price
  • Generic (30 days) - $$ - $$$$, depending on the strength
  • 37.5, 62.5, and 87.5 mcg/hour doses are much more expensive
Fentanyl

Fentora®
 Buccal / sublingual tablet
  • 100 mcg
  • 200 mcg
  • 400 mcg
  • 600 mcg
  • 800 mcg


Comes in cartons containing 7 blister cards with 4 tablets per card 		Adult - opiate naïve
  • Not recommended
  • Should only be used in
    opiate-tolerant
    cancer patients for breakthrough pain
Dosing in opioid-tolerant cancer patients 		Other
  • Providers and patients must enroll in the TIRF REMS Access program for outpatient use
  • Tablet can be placed above a rear molar, between the upper cheek and gum, or under the tongue
  • Special disposal instructions are provided to prevent accidental exposure
  • Fentanyl is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
Price
  • No generic
  • 30 tablets - $$$$
Fentanyl

Lazanda®
 Nasal spray
  • 100 mcg/100 mcL
  • 400 mcg/100 mcL
  • Each bottle contains 8 sprays of 100 mcL
 Adult - opiate naïve
  • Not recommended
  • Should only be used in
    opiate-tolerant
    cancer patients for breakthrough pain
Dosing in opioid-tolerant cancer patients 		Other
  • Providers and patients must enroll in the TIRF REMS Access program for outpatient use
  • Special disposal instructions are provided to prevent accidental exposure
  • Fentanyl is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
Price
  • No generic
  • 1 bottle - $$$$
Fentanyl

Subsys®
 Sublingual spray
  • 100 mcg
  • 200 mcg
  • 400 mcg
  • 600 mcg
  • 800 mcg
  • 1200 mcg
  • 1600 mcg


Comes in cartons of 10 and 30 sprays 		Adult - opiate naïve
  • Not recommended
  • Should only be used in
    opiate-tolerant
    cancer patients for breakthrough pain
Dosing in opioid-tolerant cancer patients 		Other
  • Providers and patients must enroll in the TIRF REMS Access program for outpatient use
  • Each dose comes in an individual sprayer
  • Special disposal instructions are provided to prevent accidental exposure
  • Fentanyl is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
Price
  • No generic
  • 30 sprays - $$$$

Drug Dosage forms Dosing Other
Hydrocodone (HC)

Vicodin®
Norco®
Vicoprofen®
 Tablet
HC (mg) : Acetaminophen (mg)
  • 2.5 : 325
  • 5.0 : 325
  • 7.5 : 325
  • 10 : 325
  • 5.0 : 300
  • 7.5 : 300
  • 10 : 300

HC (mg) : Ibuprofen (mg)
  • 2.5 : 200
  • 5.0 : 200
  • 7.5 : 200
  • 10 : 200
Solution
HC (mg) : Acetaminophen (mg)
  • 7.5 : 325 per 15ml
 Adult - opiate naïve
  • 5 - 10 mg every 4 - 6 hours as needed
  • Do not to exceed 50 mg a day
Children (≥ 2 years) - opiate naïve
  • 0.135 mg/kg/dose every 4 - 6 hours as needed
  • Do not exceed 6 doses a day

    • *Based on 7.5 mg/15 ml solution
    Weight (kg) Dose every 4 - 6 hours
    12 - 15 1.875 mg (3.75 ml*)
    16 - 22 2.5 mg (5 ml*)
    23 - 31 3.75 mg (7.5 ml*)
    32 - 45 5 mg (10 ml*)
Other
Brand names
  • HC : acetaminophen - Norco®, Vicodin® Lortab®, Anexsia®
  • HC : ibuprofen - Vicoprofen®, Reprexain®
Price (30 tablets)
  • HC : acetaminophen - $
  • HC : ibuprofen - $ - $$$, depending on strength
Hydrocodone (HC)

Hysingla® ER
 Tablet, extended-release
  • 20 mg
  • 30 mg
  • 40 mg
  • 60 mg
  • 80 mg
  • 100 mg
  • 120 mg
 Adult - opiate naïve
  • 20 mg once daily
  • Increase dose by 10 - 20 mg every 3 - 5 days as needed
Converting other HC formulations to Hysingla
  • Total daily HC dose is given as once daily Hysingla dose
Converting from other opioids 		Other
  • Do not crush, cut, chew, or dissolve tablet
  • Abuse-deterrent properties - when tablet is crushed and mixed with water, it forms a gel that is difficult to pull through a needle
  • Hydrocodone is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
  • Prolonged QT interval has been seen with Hysingla doses of ≥ 160 mg
Price
  • No generic
  • 30 tablets - $$$$
Hydrocodone (HC)

Zohydro® ER
 Capsule, extended-release
  • 10 mg
  • 15 mg
  • 20 mg
  • 30 mg
  • 40 mg
  • 50 mg
 Adult - opiate naïve
  • 10 mg every 12 hours
  • Increase dose by 10 mg every 3 - 7 days as needed
Converting other HC formulations to Zohydro
  • Total daily HC dose is divided by 2 and given once every 12 hours
Converting from other opioids
  • A conversion table is available in the Zohydro PI
 Other
Price
  • No generic
  • 30 capsules - $$$$
Hydrocodone (HC)
cough/cold preparations

Flowtuss®
 Solution
  • HC 2.5 mg and guaifenesin 200 mg per 5 ml
 Adults
  • 10 ml every 4 - 6 hours as needed
  • Do not exceed 60 ml in 24 hours
 Other
  • Guaifenesin is an expectorant
Price
  • No generic
  • 120 ml - $$$
Hydrocodone (HC)
cough/cold preparations

Hycodan®
 Syrup
  • HC 5 mg and homatropine 1.5 mg per 5 ml
 Adults
  • 5 ml every 4 - 6 hours as needed
  • Do not exceed 30 ml in 24 hours
Children 6 - 12 years
  • 2.5 ml every 4 - 6 hours as needed
  • Do not exceed 15 ml in 24 hours

NOTE: In 2018, the FDA declared that all opiate-containing cough/cold medications should not be used in patients < 18 years old 		Other
  • Homatropine is an anticholinergic medication that is included to discourage overdose
Price
  • Generic 120ml - $
Hydrocodone (HC)
cough/cold preparations

Hycodan® tablets
 Tablet
  • HC 5 mg and homatropine 1.5 mg per tablet
 Adults
  • 1 tablet every 4 - 6 hours as needed
  • Do not exceed 6 tablets in 24 hours
Children 6 - 12 years
  • One-half (1/2) tablet every 4 - 6 hours as needed
  • Do not exceed 3 tablets in 24 hours

NOTE: In 2018, the FDA declared that all opiate-containing cough/cold medications should not be used in patients < 18 years old 		Other
  • Homatropine is an anticholinergic medication that is included to discourage overdose
  • Trade names: Hycodan®, Tussigon®
Price
  • Generic 30 tablets - $
Hydrocodone (HC)
cough/cold preparations

Hycofenix®
 Solution
  • HC 2.5 mg, pseudoephedrine 30 mg, and guaifenesin 200 mg per 5 ml
 Adults
  • 10 ml every 4 - 6 hours as needed
  • Do not exceed 40 ml in 24 hours
 Other
  • Guaifenesin is an expectorant
  • Pseudoephedrine is a decongestant
Price
  • No generic
  • 120 ml - $$$
Hydrocodone (HC)
cough/cold preparations

Obredon®
 Solution
  • HC 2.5 mg and guaifenesin 200 mg per 5 ml
 Adults
  • 10 ml every 4 - 6 hours as needed
  • Do not exceed 60 ml in 24 hours
 Other
  • Guaifenesin is an expectorant
Price
  • No generic
  • 120 ml - $$$ - $$$$
Hydrocodone (HC)
cough/cold preparations

Rezira®
 Solution
  • HC 5 mg and pseudoephedrine 60 mg per 5 ml
 Adults
  • 5 ml every 4 - 6 hours as needed
  • Do not exceed 20 ml in 24 hours
 Other
  • Pseudoephedrine is a decongestant
Price
  • No generic
  • 120 ml - $$$
Hydrocodone (HC)
cough/cold preparations

Tussicaps®
 Capsule, extended-release
  • HC 5 mg and chlorpheniramine 4 mg per capsule
  • HC 10 mg and chlorpheniramine 8 mg per capsule
 Adults and children ≥ 12 years
  • 1 capsule (HC 10 mg) every 12 hours as needed
  • Do not exceed 2 capsules in 24 hours
Children 6 - 11 years
  • 1 capsule (HC 5 mg) every 12 hours as needed
  • Do not exceed 2 capsules in 24 hours

NOTE: In 2018, the FDA declared that all opiate-containing cough/cold medications should not be used in patients < 18 years old 		Other
  • Chlorpheniramine is an antihistamine
Price
  • No generic
  • 30 capsules - $$$$
Hydrocodone (HC)
cough/cold preparations

Tussionex® Pennkinetic
 Suspension, extended-release
  • HC 10 mg and chlorpheniramine 8 mg per 5 ml
 Adults and adolescents ≥ 12 years
  • 5 ml every 12 hours
  • Do not exceed 10 ml in 24 hours
Children 6 - 11 years
  • 2.5 ml every 12 hours
  • Do not exceed 5 ml in 24 hours

NOTE: In 2018, the FDA declared that all opiate-containing cough/cold medications should not be used in patients < 18 years old 		Other
  • Chlorpheniramine is an antihistamine
Price
  • Generic 120ml - $-$$
Hydrocodone (HC)
cough/cold preparations

Vituz®
 Solution
  • HC 5 mg and chlorpheniramine 4 mg per 5 ml
 Adults
  • 5 ml every 4 - 6 hours as needed
  • Do not exceed 20 ml in 24 hours
 Other
  • Chlorpheniramine is an antihistamine
Price
  • No generic
  • 120 ml - $$$
Hydrocodone (HC)
cough/cold preparations

Zutripro®
 Solution
  • HC 5 mg, chlorpheniramine 4 mg, pseudoephedrine 60 mg per 5 ml
 Adults
  • 5 ml every 4 - 6 hours as needed
  • Do not exceed 20 ml in 24 hours
 Other
  • Chlorpheniramine is an antihistamine
  • Pseudoephedrine is a decongestant
Price
  • Generic (120 ml) - $$ - $$$

Drug Dosage forms Dosing Other
Hydromorphone

Dilaudid®
 Tablet
  • 2 mg
  • 4 mg
  • 8 mg
Solution
  • 5 mg/5 ml
 Adult - opiate naïve
  • 2 - 4 mg every 4 - 6 hours as needed
Children (≥ 6 months) - opiate naïve
  • < 50 kg: 0.040 - 0.080 mg/kg every 3 - 4 hours as needed
  • ≥ 50 kg: 2 - 4 mg every 3 - 4 hours as needed [2]
 Other
  • Solution and tablet are bioequivalent
Price
  • Generic (30 tablets) - $
  • Generic (200 ml) - $$
Hydromorphone

Exalgo®
 Tablet - extended-release
  • 8 mg
  • 12 mg
  • 16 mg
  • 32 mg
 Adult - opiate naïve
  • Not recommended
Converting from other oral hydromorphone products
  • Give total daily dose of hydromorphone as once daily Exalgo® dose
Converting from other opioids 		Other
  • May take without regard to food
  • Do not crush, cut, or chew tablets
Price
  • 30 tablets, 12mg - $$$$
  • No generic


Drug Dosage forms Dosing Other
Meperidine hydrochloride

Demerol®
 Tablet
  • 50 mg
  • 100 mg
Solution
  • 50 mg/5 ml
 Adult - opiate naïve
  • 50 - 150 mg every 3 - 4 hours as needed
Children (≥ 6 months)
  • 1.1 - 1.8 mg/kg (max 150 mg/dose) every 3 - 4 hours as needed [dosing from package insert]
Alternative
  • < 50 kg: 2 - 3 mg/kg every 3 - 4 hours [5]
  • ≥ 50 kg: 100 - 150 mg every 3 - 4 hours [5]
 Other
  • Prolonged use of meperidine may cause accumulation of its metabolite, normeperidine. Normeperidine has been associated with an increased risk of seizures.
  • Meperidine should only be used for acute pain. It should not be used for chronic pain.
Price
  • Generic (30 tablets) - $

Drug Dosage forms Dosing Other
Methadone

Methadose®
Dolophine®
 Tablet
  • 5 mg
  • 10 mg
Tablet for suspension (dispersible)
  • 40 mg
Solution
  • 5 mg/5 ml
  • 10 mg/5 ml
Concentrate
  • 10 mg/1 ml
 Adult - opiate naïve - chronic pain
  • 2.5 mg every 8 hours
  • Increase dose no more than 5 mg/day every 5 - 7 days [4]
  • May also be dosed every 12 hours
Children (1 - 12 years) - opiate naïve - chronic pain
  • 0.100 mg/kg (max 5 mg/dose) every 6 - 8 hours
  • Increase dose every 5 - 7 days [4]
  • May also be dosed every 12 hours
Converting from other opiates to methadone (chronic pain)

Patients taking < 40 – 60 mg/day of morphine or equivalent:
  • Start methadone 2.5 mg three times a day
  • Increase dose no more than 5 mg/day every 5 to 7 days
Patients taking > 60 mg/day of morphine or equivalent:
  • Start methadone therapy at a dose 75 to 90% less than the calculated equianalgesic dose and at no higher than 30 to 40 mg/day
  • Increases dose no more than 10 mg/day every 5 to 7 days [4]
Maintenance therapy in opiate dependence
  • Start with 15 - 30 mg/day and increase by 10 - 15 mg every 3 - 5 days up to 50 - 80 mg/day
  • At weeks 3 - 6, dose may need to be increased to 80 - 100 mg/day if tolerance develops and cravings increase
  • Consider tapering after 1 year [9]
Discontinuing methadone

Patients taking > 100 mg/day
  • Reduce dose by 5 mg/day down to 100 mg, then reduce by 3 mg/day to 0 mg
  • Based on PMID 26028120
Patients taking ≤ 100 mg/day 		Other
  • Methadone has a long half-life. Typical range is 15 - 60 hours, but may be as long as 120 hours in some individuals.
  • Risk of adverse events is higher during first 4 - 5 days of therapy
  • Doses above 30 mg/day should only be done in appropriate settings
  • Methadone may prolong the QT interval. (see prolonged QT interval). Baseline and periodic EKG may be appropriate in patients at increased risk. [3,4]
  • Methadone is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
  • Tablets for suspension are intended for dispersion in a liquid immediately prior to observed intake
Price
  • Generic (90 tablets) - $
  • Generic (500 ml) - $

Drug Dosage forms Dosing Other
Morphine sulfate
immediate-release
 Tablet
  • 15 mg
  • 30 mg
Solution
  • 10 mg/5 ml
  • 20 mg/5 ml
  • 100 mg/5 ml
 Adult - opiate naïve
  • Tablet: 15 - 30 mg every 4 hours as needed
  • Solution: 10 - 20 mg every 4 hours as needed
Children (1 - 12 years) - opiate naïve
  • 0.2 - 0.5 mg/kg every 4 hours as needed (max 5 mg) [2]
Alternative
  • < 50 kg: 0.3 mg/kg every 3 - 4 hours as needed [5]
  • ≥ 50 kg: 15 - 20 mg every 3 - 4 hours as needed [5]
Converting from parenteral to oral
  • Anywhere from 3 to 6 mg of oral morphine sulfate may be required to provide pain relief equivalent to 1 mg of parenteral morphine
  • In chronic dosing, 3 mg of oral morphine for every 1 mg of parenteral morphine may be sufficient [3]
 Other
  • Duration of action: 3 - 4 hours
Price
  • Generic (30 tablets or 120 ml) - $
Morphine sulfate
extended-release

Arymo® ER
 Tablet, extended-release
  • 15 mg
  • 30 mg
  • 60 mg
 Adult - opiate naïve
  • 15 mg every 8 - 12 hours
  • Increase dose every 1 - 2 days as needed
Converting from other oral morphine meds
  • Total daily morphine dose will remain the same. Dose may given in halves every twelve hours or thirds every 8 hours.
Converting from parenteral morphine to oral
  • Between 2 to 6 mg of oral morphine may be required to provide analgesia equivalent to 1 mg of parenteral morphine. Typically, a dose of morphine that is approximately three times the previous daily parenteral morphine requirement is sufficient.
  • In chronic dosing, 3 mg of oral morphine for every 1 mg of parenteral morphine may be sufficient [3]
Discontinuation
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal
  • Do not discontinue abruptly
 Other
  • Do not crush, cut, dissolve, or chew tablets. Swallow tablets whole.
Price
  • No generic
  • 30 tablets - $$$$
Morphine sulfate
extended-release

Avinza®
 Capsule, extended-release
  • 30 mg
  • 45 mg
  • 60 mg
  • 75 mg
  • 90 mg
  • 120 mg
 Adult - opiate naïve
  • 30 mg once daily
  • Increase in increments not greater than 30 mg every 4 days
Converting from other oral morphine meds
  • Total daily morphine dose can be given as once daily Avinza dose
Converting from parenteral morphine to oral
  • Anywhere from 3 to 6 mg of oral morphine sulfate may be required to provide pain relief equivalent to 1 mg of parenteral morphine
  • In chronic dosing, 3 mg of oral morphine for every 1 mg of parenteral morphine may be sufficient [3]
 Other
  • Avinza may be opened and sprinkled on applesauce. Swallow whole. Do not chew or crush beads.
  • Daily dose should not exceed 1600 mg because of fumaric acid content of drug
Price
  • Generic (30 capsules) - $$-$$$$ depending on strength
Morphine sulfate
extended-release

Embeda®
 Capsule, extended-release
Morphine (mg) : Naltrexone (mg)
  • 20 : 0.8
  • 30 : 1.2
  • 50 : 2
  • 60 : 2.4
  • 80 : 3.2
  • 100 : 4
 Adult - opiate naïve
  • 20/0.8 mg every 24 hours
  • Embeda daily dose may also be divided in half and given every 12 hours
  • Increase dose at intervals of every 1 - 2 days
Converting from other oral morphine meds
  • Total daily morphine dose can be given as once daily Embeda dose or divided by 2 and given every 12 hours
Converting from parenteral to oral
  • Anywhere from 3 to 6 mg of oral morphine sulfate may be required to provide pain relief equivalent to 1 mg of parenteral morphine
  • In chronic dosing, 3 mg of oral morphine for every 1 mg of parenteral morphine may be sufficient [3]
 Other
  • Embeda may be opened and sprinkled on applesauce. Swallow whole. Do not chew or crush pellets.
  • Naltrexone is an opioid antagonist that is added as an abuse-deterrent. When pellets are crushed, naltrexone is released and the euphoric effect of the drug is reduced. If pellets are not crushed, naltrexone remains sequestered and inactive.
Price
  • No generic
  • 30 capsules - $$$$
Morphine sulfate
extended-release

Kadian®
 Capsule, extended-release
  • 10 mg
  • 20 mg
  • 30 mg
  • 40 mg
  • 50 mg
  • 60 mg
  • 70 mg
  • 80 mg
  • 100 mg
  • 130 mg
  • 150 mg
  • 200 mg
 Adult - opiate naïve
  • 30 mg once daily
  • Kadian daily dose may also be divided in half and given every 12 hours
  • Increase dose at intervals of every 1 - 2 days
Converting from other oral morphine meds
  • Total daily morphine dose can be given as once daily Kadian dose or divided by 2 and given every 12 hours
Converting from parenteral morphine to oral
  • Anywhere from 3 to 6 mg of oral morphine sulfate may be required to provide pain relief equivalent to 1 mg of parenteral morphine
  • In chronic dosing, 3 mg of oral morphine for every 1 mg of parenteral morphine may be sufficient [3]
 Other
  • Kadian may be opened and sprinkled on applesauce. Swallow whole. Do not chew or crush beads.
Price
  • Generic (30 capsules) - $$$-$$$$ depending on strength
Morphine sulfate
extended-release

Morphabond™ ER
 Tablet, extended-release
  • 15 mg
  • 30 mg
  • 60 mg
  • 100 mg
 Adult - opiate naïve
  • 15 mg every 8 - 12 hours
  • Increase dose every 1 - 2 days as needed
Converting from other oral morphine meds
  • Total daily morphine dose will remain the same. Dose may given in halves every twelve hours or thirds every 8 hours.
Converting from parenteral morphine to oral
  • Between 2 to 6 mg of oral morphine may be required to provide analgesia equivalent to 1 mg of parenteral morphine. Typically, a dose of morphine that is approximately three times the previous daily parenteral morphine requirement is sufficient.
  • In chronic dosing, 3 mg of oral morphine for every 1 mg of parenteral morphine may be sufficient [3]
Discontinuation
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal
  • Do not discontinue abruptly
 Other
  • Do not crush, cut, chew, or dissolve tablets. Swallow tablets whole.
Price
  • No generic
  • 30 tablets - $$$$
Morphine sulfate
extended-release

MS Contin®
 Tablet, extended-release
  • 15 mg
  • 30 mg
  • 60 mg
  • 100 mg
  • 200 mg
 Adult - opiate naïve
  • 15 mg every 12 hours
  • Increase dose at intervals of every 1 - 2 days
Children (1 - 12 years) - opiate naïve
  • 0.2 - 0.8 mg/kg every 12 hours [2]
Converting from other oral morphine meds
  • Total daily morphine dose can be divided in half and given every 12 hours
  • Total daily morphine dose may also be divided into thirds and given every 8 hours
Converting from parenteral morphine to oral
  • Anywhere from 3 to 6 mg of oral morphine sulfate may be required to provide pain relief equivalent to 1 mg of parenteral morphine
  • In chronic dosing, 3 mg of oral morphine for every 1 mg of parenteral morphine may be sufficient [3]
 Other
  • Do not crush, cut, or chew tablets
Price
  • Generic (60 tablets) - $-$$$ depending on strength

Drug Dosage forms Dosing Other
Oxycodone hydrochloride (OC) and ibuprofen

 Tablet
Oxycodone : Ibuprofen
  • 5 mg : 400 mg
 Adult - opiate naïve
  • 5 mg every 6 hours as needed
  • Do not exceed 4 tablets in 24 hours
 Other
Price
  • Generic tablets (#30) - $
Oxycodone hydrochloride (OC)

Percocet®
Roxicet®
 Tablet
OC (mg) : Acetaminophen (mg)
  • 2.5 : 325
  • 5.0 : 325
  • 7.5 : 325
  • 10 : 325
  • 2.5 : 300
  • 5.0 : 300
  • 7.5 : 300
  • 10 : 300
Solution
Oxycodone : Acetaminophen
  • 5 mg : 325 mg per 5 ml
 Adult - opiate naïve
  • 5 mg every 6 hours as needed
  • Do not exceed 60 mg of oxycodone in 24 hours
  • Do not exceed 4000 mg of acetaminophen in 24 hours
 Other
  • Duration of action: 3 - 5 hours
  • Oxycodone is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
  • Trade names: Percocet®, Roxicet®
Price
  • Generic tablets (#30), solution (120ml) - $
Oxycodone hydrochloride (OC)

Percodan®
 Tablet
Oxycodone : Aspirin
  • 4.8355 mg : 325 mg
 Adult - opiate naïve
  • 5 mg every 6 hours as needed
  • Do not exceed 60 mg of oxycodone in 24 hours
  • Do not exceed 4000 mg of aspirin in 24 hours
 Other
  • Duration of action: 3 - 5 hours
  • Oxycodone is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
  • Trade names: Percodan®
Price
  • Generic tablets (#30) - $
Oxycodone hydrochloride (OC)

Roxicodone®
 Tablet
  • 5 mg
  • 10 mg
  • 15 mg
  • 20 mg
  • 30 mg
Capsule
  • 5 mg
Solution
  • 5 mg/5 ml
  • 100 mg/5 ml
 Adult - opiate naïve
  • 5 - 15 mg every 4 - 6 hours as needed
  • Do not exceed 60 mg in 24 hours
Children (1 - 12 years) - opiate naïve
  • 0.125 - 0.200 mg/kg every 4 hours as needed (max 5 mg/dose) [2]
 Other
  • Duration of action: 3 - 5 hours
  • Brand names: Roxicodone®
  • Oxycodone is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
Price
  • Generic solution (120 ml) - $
  • Generic capsules/tablets (#30) - $
Oxycodone hydrochloride (OC)

Oxycontin®
 Tablet, extended-release
  • 10 mg
  • 15 mg
  • 20 mg
  • 30 mg
  • 40 mg
  • 60 mg
  • 80 mg
 Adult - opiate naïve
  • 10 mg every 12 hours
  • Increase dose every 1 - 2 days in increments of 25 - 50% of the current dose
Converting from other oxycodone meds
  • Total daily oxycodone dose can be divided in half and given every 12 hours
Children ≥ 11 years - opiate naïve
  • Not recommended

Children ≥ 11 years - opiate-tolerant
  • Patients must be receiving opioids for at least 5 consecutive days
  • Patients must be receiving ≥ 20 mg/day of oxycodone or its equivalent for the 2 days prior to starting
  • See Oxycontin PI sec 2.4 for dose conversion table from other opioids
 Other
  • Abuse-deterrent properties - when tablet is crushed and mixed with water, it forms a gel that is difficult to pull through a needle
  • Oxycodone is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
Price
  • No generic
  • Tablets (#30) - $$$ - $$$$, depending on the strength
Oxycodone hydrochloride (OC)

Xtampza® ER
 Capsule, extended-release
  • 9 mg (equivalent to 10 mg OC)
  • 13.5 mg (equivalent to 15 mg OC)
  • 18 mg (equivalent to 20 mg OC)
  • 27 mg (equivalent to 30 mg OC)
  • 36 mg (equivalent to 40 mg OC)
 Adult - opiate naïve
  • Starting dose is 9 mg every 12 hours with food
  • Increase dose every 1 - 2 days in increments of 25 - 50% of the current dose
  • Maximum daily dose is 288 mg/day
Converting from other oxycodone meds
  • Total daily oxycodone dose can be divided in half and given every 12 hours
 Other
  • Each dose of Xtampza should be taken with approximately the same amount of food in order to ensure consistent plasma levels are achieved. Food increases absorption, and absorption is higher with high-fat, high-calorie foods.
  • Capsules may be opened and sprinkled on a small amount of soft food (e.g. applesauce, pudding). Swallow whole and do not chew. Rinse mouth.
  • Contents of capsule may be given through feeding tube
  • Abuse-deterrent properties - microspheres are difficult to manipulate for misuse and abuse
  • Oxycodone is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
Price
  • No generic
  • Capsules (#30) - $$$-$$$$, depending on the strength

Drug Dosage forms Dosing Other
Oxymorphone

Opana®
 Tablet
  • 5 mg
  • 10 mg
 Adult - opiate naïve
  • 10 - 20 mg every 4 - 6 hours as needed
  • Take on an empty stomach, at least one hour prior to or two hours after eating
  • Kidney disease (CrCl < 50 ml/min): Use caution. Start with 5 mg dose.
  • Liver disease (Child-Pugh A): Use caution. Start with 5 mg dose.
  • Liver disease (Child-Pugh B/C): DO NOT USE
Converting from parenteral oxymorphone
  • Given Opana’s absolute oral bioavailability of approximately 10%, patients receiving parenteral oxymorphone may be converted to oral Opana by administering 10 times the patient’s total daily parenteral oxymorphone dose as Opana, in four or six equally divided doses (e.g., [IV dose x 10] divided by 4 or 6)
  • For example, approximately 10 mg of Opana four times daily may be required to provide pain relief equivalent to a total daily IM dose of 4 mg oxymorphone
Discontinuation
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal
  • Do not discontinue abruptly
 Other
  • Half-life: 9 - 11 hours
Price
  • Generic (30 tablets) - $$$-$$$$
Oxymorphone

Opana® ER
 Tablet, extended-release
  • 5 mg
  • 7.5 mg
  • 10 mg
  • 15 mg
  • 20 mg
  • 30 mg
  • 40 mg
 Adult - opiate naïve
  • 5 mg every 12 hours
  • Adjust dose in increments of 5 - 10 mg every 12 hours, every 3 to 7 days
  • Take on an empty stomach, at least one hour prior to or two hours after eating
  • Kidney disease (CrCl < 50 ml/min): Use caution. Start with 5 mg dose. For patients on prior opioid therapy, start Opana ER at 50% lower than the starting dose for a patient with normal renal function.
  • Liver disease (Child-Pugh A): Use caution. Start with 5 mg dose. For patients on prior opioid therapy, start Opana ER at 50% lower than the starting dose for a patient with normal hepatic function.
  • Liver disease (Child-Pugh B/C): DO NOT USE
Converting from Opana® to Opana® ER
  • Total daily dose remains the same. Administer half the total daily Opana dose as Opana ER, every 12 hours.
Converting from parenteral oxymorphone
  • The absolute oral bioavailability of Opana ER is approximately 10%. Convert patients receiving parenteral oxymorphone to Opana ER by administering 10 times the patient's total daily parenteral oxymorphone dose as Opana ER in two equally divided doses (e.g., [IV dose x 10] divided by 2).
Converting from other opioids to Opana ER
Discontinuation
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal
  • Do not discontinue abruptly
 Other
  • Do not crush, cut, chew, or dissolve tablets
Price
  • No generic
  • 60 tablets - $$$$

Drug Dosage forms Dosing Other
Tapentadol

Nucynta®
 Tablet
  • 50 mg
  • 75 mg
  • 100 mg
 Adult - opiate naïve
  • 50 - 100 mg every 4 - 6 hours as needed
  • On the first day of dosing, the second dose may be administered as soon as one hour after the first dose if adequate pain relief is not attained with the first dose. Subsequent dosing is 50 mg, 75 mg, or 100 mg every 4 to 6 hours and should be adjusted to maintain adequate analgesia with acceptable tolerability.
  • Do not exceed 700 mg on the first day of therapy, and do not exceed 600 mg/day on subsequent days
 Other
  • Tapentadol is a centrally-acting synthetic analgesic. Although its exact mechanism is unknown, analgesic efficacy is thought to be due to mu-opioid agonist activity and the inhibition of norepinephrine reuptake.
  • The minimum effective plasma concentration of tapentadol for analgesia varies widely among patients
  • Tapentadol should not be consumed with alcohol. Alcohol increases blood levels and can lead to overdose.
Price
  • No generic
  • 30 tablets - $$$$
Tapentadol

Nucynta® ER
 Tablet, extended-release
  • 50 mg
  • 100 mg
  • 150 mg
  • 200 mg
  • 250 mg
 Adult - opiate naïve
  • 50 mg every 12 hours
  • Increase dose in increments of 50 mg at intervals of ≥ 3 days
  • Do not exceed 500 mg/day
Converting from Nucynta® to Nucynta® ER
  • Total daily dose of Nucynta® can be divided in half and given every 12 hours as Nucynta® ER
  • Do not exceed 500 mg/day of Nucynta® ER
 Other
  • Do not crush, cut, chew, or dissolve tablets
  • Tapentadol is a centrally-acting synthetic analgesic. Although its exact mechanism is unknown, analgesic efficacy is thought to be due to mu-opioid agonist activity and the inhibition of norepinephrine reuptake.
  • The minimum effective plasma concentration of tapentadol for analgesia varies widely among patients
  • Tapentadol should not be consumed with alcohol. Alcohol increases blood levels and can lead to overdose.
Price
  • No generic
  • 60 tablets - $$$$

Drug Dosage forms Dosing Other
Buprenorphine hydrochloride

Belbuca®
 Buccal film
  • 75 mcg
  • 150 mcg
  • 300 mcg
  • 450 mcg
  • 600 mcg
  • 750 mcg
  • 900 mcg


Comes in carton of 60 films 		Adults - opiate-naïve - severe pain
  • Approved to treat severe pain that requires long-term treatment
  • 75 mcg once daily or 75 mcg every 12 hours (if tolerated) for at least 4 days
  • Increase to 150 mcg every 12 hours after 4 days
  • Further dose increases should be in increments of 150 mcg every 12 hours at intervals of no less than 4 days
  • Doses up to 450 mcg every 12 hours were studied in opiate-naïve patients in clinical trials
Converting from other opiates
  • To reduce the risk of opioid withdrawal, taper patients to no more than 30 mg of oral morphine sulfate equivalent (MSE) daily before beginning Belbuca
  • Dose increases should be in increments of no more than 150 mcg every 12 hours at intervals of no less than 4 days
  • Do not exceed 900 mcg every 12 hours due to potential for QT prolongation

  • MSE - morphine sulfate equivalent
Prior daily dose of MSE before taper to 30 mg MSE Initial Belbuca dose
< 30 mg 75 mcg once daily or every 12 hours
30 - 89 mg 150 mcg every 12 hours
90 - 160 mg 300 mcg every 12 hours
> 160 mg Consider alternative
Other
  • Schedule III
  • Buprenorphine is a partial agonist at mu opioid receptors
  • FDA-approved for the treatment of severe pain requiring long-term treatment
  • Belbuca is placed against the inside of the cheek
  • Belbuca film dissolves within 30 minutes
  • Do not eat or drink until film is dissolved
  • Buprenorphine is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
Price
  • No generic
  • 60 films - $$$$
Buprenorphine hydrochloride

Buprenex®
Subutex®
 Sublingual tablet  
  • 2 mg
  • 8 mg
 Adults - opiate withdrawal and maintenance
  • Used to prevent withdrawal symptoms in patients who are being treated for opiate addiction
  • Dosage will vary depending on the patient and their addiction characteristics
  • Given as a once daily dose
  • Initial dose is usually 4 - 8 mg on Day 1 given 12 - 48 hours after most recent opioid use while patient is having withdrawal symptoms
  • On Day 2, dose may be increased up to 16 mg. On days 3 - 7, dose may be increased up to 30 mg.
  • Maintenance dose is typically 16 - 24 mg/day
  • During maintenance phase, patients should be switched to a buprenorphine-naloxone product
  • Consider weaning after 1 year [9]
 Other
  • Schedule III
  • Buprenorphine is an opioid partial agonist. It prevents symptoms of opiate withdrawal, but its maximal effects are less than those seen with heroin, methadone, etc.
  • Buprenorphine has been associated with liver toxicity, especially in high-risk patients (alcoholism, hepatitis C, etc). Baseline and periodic LFTs are recommended.
  • Buprenorphine is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
  • Providers must obtain waiver and complete special training in order to prescribe - see SAMHSA website
Price
  • Generic (30 tablets) - $$
Buprenorphine hydrochloride

Butrans®
 Transdermal patch
  • 5.0 mcg/hr
  • 7.5 mcg/hr
  • 10 mcg/hr
  • 15 mcg/hr
  • 20 mcg/hr

Comes in carton of 4 patches 		Adults - opiate-naïve - severe pain
  • Approved to treat severe pain that requires long-term treatment
  • One 5 mcg/hour patch every 7 days
  • Increase dose at an interval of ≥ 72 hours
  • Maximum dose is 20 mcg/hour because of prolonged QT interval risk
Converting from other opiates 		Other
  • Schedule III
  • Buprenorphine is a partial agonist at mu opioid receptors
  • FDA-approved for the treatment of severe pain requiring long-term treatment
  • Buprenorphine is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
  • Apply to upper outer arm, upper chest, upper back or the side of the chest. These 4 sites (each present on both sides of the body) provide 8 possible application sites. Rotate Butrans among the 8 described skin sites. After Butrans removal, wait a minimum of 21 days before reapplying to the same skin site.
  • Apply Butrans to a hairless or nearly hairless skin site. If none are available, the hair at the site should be clipped, not shaven.
  • Do not expose patch to direct heat because absorption may be increased
  • Patients with fever may absorb more buprenorphine from the patch
  • Special disposal instructions are provided to prevent accidental exposure. Used patches may be flushed down toilet.
Price
  • No generic
  • 4 patches - $$$$
Buprenorphine hydrochloride

Probuphine®
 Subdermal implant
  • Each implant contains 80 mg of buprenorphine HCL
  • Comes in kit with 4 implants and disposable applicator
 Adults - maintenance of opioid dependence
  • Approved for the maintenance treatment of opioid dependence
  • Four implants inserted subdermally in the inner side of the upper arm every 6 months
  • Patients should be on stable (≥ 3 months) maintenance doses of ≤ 8 mg/day of Subutex or Suboxone. For Bunavail, stable maintenance doses should be ≤ 4.2 mg/0.7 mg. For Zubsolv, stable maintenance doses should be ≤ 5.7 mg/1.4 mg.
  • If another insertion is desired after 6 months, the opposite arm should be used
  • After one insertion in each arm, patients should be transitioned back to transmucosal buprenorphine. Reinserting Probuphine in a previously-treated arm has not been studied.
 Other
Price
  • No generic
  • 1 kit - $$$$
Studies
  • Probuphine vs Sublingual Buprenorphine, JAMA (2016) - randomized, placebo-controlled trial in outpatient opioid-dependent patients (n=177)
    PRIMARY OUTCOME: ≥ 4 out of 6 months without opioid-positive urine test
    RESULTS: Primary outcome occurred in 86% of probuphine-treated patients and 72% of sublingual-treated patients (p=0.03). [PMID 27434441]
Buprenorphine hydrochloride

Sublocade®
 Prefilled syringe, single-dose
  • 100 mg/0.5 ml
  • 300 mg/1.5 ml
 Adults - maintenance of opioid dependence
  • Indicated for patients who have initiated treatment with a transmucosal buprenorphine-containing product, followed by dose adjustment for a minimum of 7 days. Patients should be receiving the equivalent of 8 to 24 mg of buprenorphine daily.
  • For abdominal subcutaneous administration only
  • Should only be administered by healthcare provider
  • Dosing: 300 mg monthly for the first two months followed by a maintenance dose of 100 mg monthly
  • Maintenance dose may be increased to 300 mg monthly for patients who tolerate the 100 mg dose, but do not demonstrate a satisfactory clinical response
  • There should be a minimum of 26 days between doses
  • Occasional delays in dosing up to 2 weeks are not expected to have a clinically significant impact on treatment effect
 Other
  • Schedule III
  • Subclocade is injected as a liquid, and the subsequent precipitation of the poly polymer creates a solid depot which contains buprenorphine. The depot disintegrates over time, but may be removed surgically before total disintegration.
  • After steady-state has been achieved (4-6 months), patients discontinuing Sublocade may have detectable plasma levels of buprenorphine for twelve months or longer
  • Providers must be certified in the Sublocade REMS program in order to prescribe Sublocade
Price
  • No generic
  • 1 syringe - $$$$
Buprenorphine and Naloxone

Suboxone®
Zubsolv®
Bunavail®
 Suboxone® - sublingual tablet
Buprenorphine (mg) : Naloxone (mg)
  • 2 : 0.5
  • 8 : 2.0

Suboxone® - sublingual film
Buprenorphine (mg) : Naloxone (mg)
  • 2 : 0.5
  • 4 : 1.0
  • 8 : 2
  • 12 : 3


Zubsolv® - sublingual tablet
Buprenorphine (mg) : Naloxone (mg)
  • 1.4 : 0.36
  • 5.7 : 1.4
  • 8.6 : 2.1
  • 11.4 : 2.9


Bunavail® - buccal film
Buprenorphine (mg) : Naloxone (mg)
  • 2.1 : 0.3
  • 4.2 : 0.7
  • 6.3 : 1.0
 Adults - opiate withdrawal and maintenance
  • Used to prevent withdrawal symptoms in patients who are being treated for opiate addiction
  • Buprenorphine/naloxone is preferred after induction with buprenorphine alone
  • Naloxone is included to deter injection of buprenorphine. Naloxone has no effect when taken orally, but acts as an opioid antagonist when injected.
  • Dosage will vary depending on the patient and their addiction characteristics
  • Given as once daily dose
  • Maintenance dose is typically 4 - 24 mg/day of buprenorphine, except for Zubsolv and Bunavail which have slightly different conversion ratios. See Zubsolv PI (sec 2) and Bunavail PI (sec 2).
 Other
  • Schedule III
  • Buprenorphine is an opioid partial agonist. It prevents symptoms of opiate withdrawal, but its maximal effects are less than those seen with heroin, methadone, etc.
  • Naloxone is an opioid antagonist. It has no effect when taken orally, but acts as an opioid antagonist when injected.
  • Buprenorphine has been associated with liver toxicity, especially in high-risk patients (alcoholism, hepatitis C, etc). Baseline and periodic LFTs are recommended.
  • Buprenorphine is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
  • Providers must obtain waiver and complete special training in order to prescribe - see SAMHSA website
Price
  • Suboxone generic (30 tablets) - $$-$$$
  • Suboxone (30 films) - $$$$
  • Zubsolv (30 tablets) - $$$$
  • Bunavail (30 films) - $$$$

Drug Dosage forms Dosing Other
Codeine phosphate (CP)

Tylenol #3
Tylenol #4
 Tablet
CP (mg) : Acetaminophen (mg)
  • 15 : 300
  • 30 : 300
  • 60 : 300
 Adults
  • 15 - 60 mg every 4 hours as needed
  • Do not exceed 360 mg in 24 hours
Children
  • 0.5 mg/kg/dose every 4 hours as needed
Alternative
  • < 50 kg: 0.5 - 1 mg/kg every 3 - 4 hours [5]
  • ≥ 50 kg: 30 - 60 mg every 3 - 4 hours [5]

NOTE: In 2017, the FDA declared that all codeine products are contraindicated in children < 12 years old 		Other
  • Schedule III
  • Codeine has no analgesic activity unless it is metabolized into morphine by CYP2D6. Poor metabolizers may not receive any pain relief from codeine while rapid metabolizers may experience toxicity. Because of the risk for toxicity, codeine is contraindicated for postoperative pain in children.
Trade names
  • Tylenol® No 3 - 30 mg/300 mg
  • Tylenol® No 4 - 60 mg/300 mg
Price
  • Generic (30 tablets) - $
Codeine phosphate (CP)
solution
 Solution
  • Codeine 12 mg and acetaminophen 120 mg per 5 ml
 Adults
  • 15 ml every 4 hours as needed
Children
  • 3 - 6 years: 5 ml three to four times daily
  • 7 - 12 years: 10 ml three to four times daily

NOTE: In 2017, the FDA declared that all codeine products are contraindicated in children < 12 years old 		Other
  • Schedule V
  • Codeine has no analgesic activity unless it is metabolized into morphine by CYP2D6. Poor metabolizers may not receive any pain relief from codeine while rapid metabolizers may experience toxicity. Because of the risk for toxicity, codeine is contraindicated for postoperative pain in children.
Price
  • Generic (120 ml) - $
Codeine phosphate (CP)

Fioricet® with codeine
 Capsule
  • Fioricet® with codeine
    • Codeine 30 mg, acetaminophen 325 mg, butalbital 50 mg, caffeine 40 mg per capsule

  • Other
    • Codeine 30 mg, acetaminophen 300 mg, butalbital 50 mg, caffeine 40 mg per capsule
 Adults
  • 1 - 2 capsules every 4 hours as needed
  • Do not exceed 6 capsules in 24 hours
 Other
  • Schedule III
  • FDA-approved for tension headaches
  • Butalbital is a barbiturate
  • Codeine has no analgesic activity unless it is metabolized into morphine by CYP2D6. Poor metabolizers may not receive any pain relief from codeine while rapid metabolizers may experience toxicity.
Price
  • Generic (30 capsules) - $
  • NOTE: product with 300 mg of acetaminophen is $$$$
Codeine phosphate (CP)

Fiorinal® with codeine
 Capsule
  • Codeine 30 mg, aspirin 325 mg, butalbital 50 mg, caffeine 40 mg per capsule
 Adults
  • 1 - 2 capsules every 4 hours as needed
  • Do not exceed 6 capsules in 24 hours
 Other
  • Schedule III
  • FDA-approved for tension headaches
  • Butalbital is a barbiturate
  • Codeine has no analgesic activity unless it is metabolized into morphine by CYP2D6. Poor metabolizers may not receive any pain relief from codeine while rapid metabolizers may experience toxicity.
Price
  • Generic (30 capsules) - $ - $$
Codeine phosphate (CP)

Soma® compound with codeine
 Tablet
  • Codeine 16 mg, aspirin 325 mg, carisoprodol 200 mg per tablet
 Adults
  • 1 - 2 tablets four times daily as needed
 Other
  • Schedule III
  • Carisoprodol is a centrally-acting muscle relaxant. See carisoprodol for more.
  • Codeine has no analgesic activity unless it is metabolized into morphine by CYP2D6. Poor metabolizers may not receive any pain relief from codeine while rapid metabolizers may experience toxicity.
Price
  • Generic (30 capsules) - $ - $$
Codeine cough/cold preparations

Cheratussin DAC®
 Liquid
  • Codeine 10 mg, guaifenesin 100 mg, pseudoephedrine 30 mg per 5 ml
  • Contains 2.1% alcohol
 Adults and children ≥ 12 years
  • 10 ml every 4 hours as needed
  • Do not take more than 4 doses in 24 hours
Children 6 - 11 years old
  • 5 ml every 4 hours as needed
  • Do not take more than 4 doses in 24 hours

NOTE: In 2018, the FDA declared that all opiate-containing cough/cold medications should not be used in patients < 18 years old 		Other
  • Schedule V
  • Guaifenesin is an expectorant
  • Pseudoephedrine is a decongestant
Price
  • Generic (120 ml) - $
Codeine cough/cold preparations

Phenergan® with codeine
 Syrup
Codeine (mg) : Promethazine (mg)
  • 10 : 6.25 per 5 ml
  • Contains 7% alcohol
 Adults and children ≥ 12 years
  • 5 ml every 4 - 6 hours as needed
  • Do not take more than 30 ml in 24 hours
Children 6 - 11 years old
  • 2.5 - 5 ml every 4 - 6 hours as needed
  • Do not take more than 30 ml in 24 hours

NOTE: In 2018, the FDA declared that all opiate-containing cough/cold medications should not be used in patients < 18 years old 		Other
  • Schedule V
  • Promethazine is an antihistamine/anticholinergic medication
Price
  • Generic (120 ml) - $
Codeine cough/cold preparations

Phenergan® VC with codeine
 Syrup
  • Codeine 10 mg, phenylephrine 5 mg, promethazine 6.25 mg per 5 ml
  • Contains 7% alcohol
 Adults and children ≥ 12 years
  • 5 ml every 4 - 6 hours as needed
  • Do not take more than 30 ml in 24 hours
Children 6 - 11 years old
  • 2.5 - 5 ml every 4 - 6 hours as needed
  • Do not take more than 30 ml in 24 hours

NOTE: In 2018, the FDA declared that all opiate-containing cough/cold medications should not be used in patients < 18 years old 		Other
  • Schedule V
  • Phenylephrine is a decongestant
  • Promethazine is an antihistamine/anticholinergic medication
Price
  • Generic (120 ml) - $
Codeine cough/cold preparations

Robitussin® AC
 Liquid/solution
Codeine (mg) : Guaifenesin (mg)
  • 10 : 100 per 5 ml
  • Solution is alcohol free
  • Liquid contains 3 - 4% alcohol
 Adults and children ≥ 12 years
  • 10 ml every 4 hours as needed
  • Do not take more than 6 doses in 24 hours
Children 6 - 11 years old
  • 5 ml every 4 hours as needed
  • Do not take more than 6 doses in 24 hours

NOTE: In 2018, the FDA declared that all opiate-containing cough/cold medications should not be used in patients < 18 years old 		Other
  • Schedule V
  • Guaifenesin is an expectorant
  • Other brand names: Cheratussin AC®, Guaiatussin AC®, Virtussin AC®
Price
  • Generic (120 ml) - $
Codeine cough/cold preparations

Tuzistra™ XR
 Suspension, extended-release
  • Codeine 14.7 mg and chlorpheniramine 2.8 mg per 5 ml
 Adults 18 years and older
  • 10 ml every 12 hours as needed
  • Do not exceed 20 ml in 24 hours
 Other
  • Schedule III
  • Chlorpheniramine is an antihistamine
Price
  • No generic
  • Brand (120 ml) - $$$

Drug Dosage forms Dosing Other
Dihydrocodeine bitartrate

Synalgos®-DC
 Capsule
  • Dihydrocodeine 16 mg, Caffeine 30 mg, Aspirin 356.4 mg per capsule
 Adult - moderate to severe pain
  • 2 capsules every 4 hours as needed for pain
 Other
  • Schedule III
  • Dihydrocodeine has no analgesic activity unless it is metabolized into dihydromorphine by CYP2D6. Poor metabolizers may not receive any pain relief from dihydrocodeine while rapid metabolizers may experience toxicity.
Price
  • Generic (30 capsules) - $
Dihydrocodeine bitartrate

Trezix®
 Capsule
  • Dihydrocodeine 16 mg, Caffeine 30 mg, Acetaminophen 320.5 mg per capsule
 Adult - moderate to severe pain
  • 2 capsules every 4 hours as needed for pain
  • Do not exceed 10 capsules in 24 hours
 Other
  • Schedule III
  • Dihydrocodeine has no analgesic activity unless it is metabolized into dihydromorphine by CYP2D6. Poor metabolizers may not receive any pain relief from dihydrocodeine while rapid metabolizers may experience toxicity.
Price
  • Generic (30 capsules) - $$-$$$

Drug Dosage forms Dosing Other
Diphenoxylate

(Lomotil®)
(Lonox®)
 Tablet
  • Diphenoxylate 2.5 mg and atropine 0.025 mg per tablet
Liquid
  • Diphenoxylate 2.5 mg and atropine 0.025 mg per 5 ml
 Adults - diarrhea
  • Tablet - 2 tablets four times daily as needed
  • Liquid - 10 ml four times daily as needed
Children (2 - 13 years) - diarrhea
  • Use liquid in children
  • 0.3 - 0.4 mg/kg/day (diphenoxylate component) given in 4 divided doses

Age (years) Weight (kg) Weight (pounds) Dose in milliliters
(4 times daily as needed)
2 11 - 14 24 - 31 1.5 - 3.0
3 12 - 16 26 - 35 2.0 - 3.0
4 14 - 20 31 - 44 2.0 - 4.0
5 16 - 23 35 - 51 2.5 - 4.5
6 - 8 17 - 32 38 - 71 2.5 - 5.0
9 - 12 23 - 55 51 - 121 3.5 - 5.0

Other
  • Schedule V
  • FDA-approved to treat diarrhea
  • Atropine is added to discourage deliberate overdose. It has no effect in normal dosing.
  • Young children may be more susceptible to diphenoxylate and atropine side effects
Price
  • Generic (30 tablets or 120ml) - $

Drug Dosage forms Dosing Other
Butorphanol tartrate

Stadol®
 Nasal spray
  • 1 mg/spray
  • Comes in 2.5 ml bottle at a concentration of 10 mg/ml
  • On average, one bottle delivers 14 - 15 one milligram doses
 Adults - pain
  • 1 - 2 mg (one or two sprays)
  • May repeat in 3 - 4 hours as needed
  • When giving more than 1 spray, give in separate nostrils

Elderly or patients with renal or hepatic impairment
  • 1 mg (one spray)
  • May give an additional 1 mg in 90 - 120 minutes
  • May repeat in 6 hours as needed

Discontinuation after chronic dosing
  • Reduce dose by 25 - 50% every 2 - 4 days to prevent withdrawal
 Other
  • Butorphanol is a partial opioid agonist at the mu opioid receptor and a full agonist at the kappa opioid receptor
  • Butorphanol is a CYP3A4 sensitive substrate
  • Store at room temperature
  • Bottle must be primed if not used for ≥ 48 hours
Price
  • Generic (1 bottle) - $

Drug Dosage forms Dosing Other
Pentazocine

Talwin NX®
 Tablet
  • Pentazocine 50 mg and naloxone 0.5 mg per tablet
 Adults
  • One tablet every 3 - 4 hours
  • May increase to 2 tablets when needed
  • Do not exceed 12 tablets in 24 hours
 Other
  • Pentazocine is an opioid agonist/antagonist
  • Pentazocine may antagonize the effects of stronger opiates (e.g. morphine, methadone)
  • Pentazocine 50 mg is equivalent in analgesic activity to 60 mg of codeine
  • Naloxone is an opioid antagonist. It has no effect when taken orally, but acts as an opioid antagonist when injected.
Price
  • Generic (30 tablets) - $

Drug Dosage forms Dosing Other
Tramadol

Ultram®
 Tablet
  • 50 mg
 Adults
  • 50 - 100 mg every 4 - 6 hours as needed
  • Do not exceed 400 mg in 24 hours
 Other
  • Tablets are scored so they can be halved
  • Tramadol is a synthetic opioid that acts at opiate receptors in the central nervous system
  • Tramadol has been shown to inhibit reuptake of norepinephrine and serotonin. Tramadol should be used with caution when taken with other serotonergic drugs (see serotonin syndrome for more).
  • Patients who are allergic to opiates should not receive tramadol
  • Tramadol lowers the seizure threshold and increases the risk of seizures. Seizure risk may also be increased when taken with SSRIs, TCAs, other opioids, MAO inhibitors, and neuroleptics.
Price
  • Generic (30 tablets) - $
Tramadol

Ultracet®
 Tablet
  • Tramadol 37.5 mg and acetaminophen 325 mg per tablet
 Adults
  • 2 tablets every 4 - 6 hours as needed
  • Do not exceed 8 tablets in 24 hours
 Other
  • Tramadol is a synthetic opioid that acts at opiate receptors in the central nervous system
  • Tramadol has been shown to inhibit reuptake of norepinephrine and serotonin. Tramadol should be used with caution when taken with other serotonergic drugs (see serotonin syndrome for more).
  • Patients who are allergic to opiates should not receive tramadol
  • Tramadol lowers the seizure threshold and increases the risk of seizures. Seizure risk may also be increased when taken with SSRIs, TCAs, other opioids, MAO inhibitors, and neuroleptics.
Price
  • Generic (30 tablets) - $
Tramadol

Ultram® ER
 Tablet, extended-release
  • 100 mg
  • 200 mg
  • 300 mg
 Adults
  • 100 mg once daily
  • Increase dose in 100 mg increments every 5 days as needed
  • Do not exceed 300 mg once daily
 Other
  • Do not crush, cut, or chew tablet
  • Tramadol is a synthetic opioid that acts at opiate receptors in the central nervous system
  • Tramadol has been shown to inhibit reuptake of norepinephrine and serotonin. Tramadol should be used with caution when taken with other serotonergic drugs (see serotonin syndrome for more).
  • Patients who are allergic to opiates should not receive tramadol
  • Tramadol lowers the seizure threshold and increases the risk of seizures. Seizure risk may also be increased when taken with SSRIs, TCAs, other opioids, MAO inhibitors, and neuroleptics.
Price
  • Generic (30 tablets) - $$-$$$
Tramadol

Conzip®
 Capsule, extended-release
  • 100 mg
  • 200 mg
  • 300 mg
 Adults
  • 100 mg once daily
  • Increase dose in 100 mg increments every 5 days as needed
  • Do not exceed 300 mg once daily
 Other
  • Do not crush, cut, chew, or open capsule
  • Tramadol is a synthetic opioid that acts at opiate receptors in the central nervous system
  • Tramadol has been shown to inhibit reuptake of norepinephrine and serotonin. Tramadol should be used with caution when taken with other serotonergic drugs (see serotonin syndrome for more).
  • Patients who are allergic to opiates should not receive tramadol
  • Tramadol lowers the seizure threshold and increases the risk of seizures. Seizure risk may also be increased when taken with SSRIs, TCAs, other opioids, MAO inhibitors, and neuroleptics.
Price
  • No Generic
  • Price (30 capsules) - $$$$

Drug Dosage forms Dosing Other
Methylnaltrexone

Relistor®
 Tablet
  • 150 mg
Prefilled syringe
  • 8 mg/0.4 ml
  • 12 mg/0.6 ml
  • Comes in carton of 7 syringes
Single-dose vial
  • 12 mg/0.6 ml
 Opioid-induced constipation in patients with chronic non-cancer pain
  • Tablet: 450 mg once daily in the morning
  • Injection: 12 mg subcutaneously once daily
  • Tablets should be taken with water on an empty stomach at least 30 minutes before the first meal of the day
  • Kidney and liver disease - see Relistor PI for dosing
Opioid-induced constipation in patients with advanced illness
  • Only the injection is approved for advanced illness
  • Dosing is weight-based (see table)
  • Dose in given every other day as needed
  • Use single-dose vial for doses other than 8 and 12 mg
  • Kidney and liver disease - see Relistor PI for dosing

  • Give dose every other day as needed
Weight Dose
< 38 kg 0.15 mg/kg
38 to < 62 kg 8 mg
62 to 114 kg 12 mg
> 114 kg 0.15 mg/kg
Other
  • Injection is given in upper arm, abdomen, or thigh. Rotate injection sites.
  • Contraindicated in patients with GI obstruction and in those at increased risk of obstruction
  • May increase risk of gastrointestinal perforation
  • Discontinue all laxatives before starting. Laxatives may be added after 3 days if response to Relistor is suboptimal
  • See opioid antagonists for a review of how these drugs work
Price
  • No generic
  • 28 syringes or 90 tablets - $$$$

Drug Dosage forms Dosing Other
Naloxegol

Movantik®
 Tablet
  • 12.5 mg
  • 25 mg
 Opioid-induced constipation in patients with chronic non-cancer pain
  • Dosing: 25 mg once daily in the morning. Patients who cannot tolerate 25 mg may try 12.5 mg once daily.
  • Take on an empty stomach at least 1 hour prior to the first meal of the day or 2 hours after the meal
  • Kidney disease (CrCl < 60 ml/min: start with 12.5 mg once daily. If well tolerated, may increase to 25 mg once daily.
  • Strong CYP3A4 inhibitors: DO NOT COMBINE
  • Moderate CYP3A4 inhibitors: Not recommended. If must combine, use 12.5 mg once daily.
 Other
  • Tablet may be crushed and mixed with 120 ml of water
  • Contraindicated in patients with GI obstruction and in those at increased risk of obstruction
  • May increase risk of gastrointestinal perforation
  • Discontinue all laxatives before starting. Laxatives may be added after 3 days if response to Movantik is suboptimal
  • Patients receiving opioids for less than 4 weeks may be less responsive
  • See opioid antagonists for a review of how these drugs work
Price
  • No generic
  • 30 tablets - $$$$

Drug Dosage forms Dosing Other
Naloxone

Evzio®
 Injection
  • Prefilled, single-use autoinjector pen containing 0.4 mg of naloxone per injection
  • Comes in carton that contains 2 pens
 Acute opiate overdose
  • May be given intramuscularly or subcutaneously
  • Injection device comes with speaker that gives audio instructions when activated
  • Inject into anterolateral thigh. May be given through clothes.
  • Dose may be repeated after 2 - 3 minutes
  • If given to infant < 1 year old, pinch middle of outer thigh before giving
 Other
  • Seek immediate medical help. Naloxone may wear off and opiate-induced respiratory depression may return.
  • Reversal of buprenorphine and pentazocine may require higher doses
  • Time to max blood concentration is about 15 minutes
  • Average naloxone half-life is about 1.3 hours
  • See opioid antagonists for a review of how these drugs work
Price
  • No generic
  • Carton of 2 syringes - $$$$
Naloxone

Narcan®
 Nasal spray
  • 4 mg single-use spray
  • Comes in a carton with 2 single-use sprays
 Acute opiate overdose
  • Initial: administer one spray in one nostril
  • May give an additional spray every 2 - 3 minutes depending on response. Alternate nostrils.
  • Use each nasal spray only one time
  • Lay patient on their back and provide support to the back of the neck to allow the head to tilt back before giving
  • Lay patient on side after giving
 Other
  • Seek immediate medical help. Naloxone may wear off and opiate-induced respiratory depression may return.
  • Reversal of buprenorphine and pentazocine may require higher doses
  • Median time to max blood concentration:
    • One spray (4 mg): 30 minutes
    • Two sprays (8 mg): 20 minutes
  • Average naloxone half-life is about 2 hours
  • See opioid antagonists for a review of how these drugs work
Price
  • No generic
  • Carton of 2 sprays - $$$$

Drug Dosage forms Dosing Other
Naltrexone

Revia®
 Tablet
  • 50 mg
 Alcohol dependence
  • 50 mg once daily
  • Has been used for up to 12 weeks in trials
Opiate dependence
  • Start with 25 mg once daily
  • If no withdrawal signs occur, the dose may be increased to 50 mg once daily
  • Naltrexone should not be used during acute opiate withdrawal
 Other
  • Naltrexone 50 mg a day should block the action of most parenterally administered opiates
  • After stopping naltrexone, patients may be more sensitive to opioids and at greater risk for adverse events
  • See opioid antagonists for a review of how these drugs work
  • Brand name: Revia®
Price
  • Generic - $$
Naltrexone

Vivitrol®
 Injectable suspension
  • 380 mg vial
  • Carton comes with vial, diluent, special needle and syringe
 Alcohol dependence
  • 380 mg intramuscularly every 4 weeks
Opiate dependence
  • 380 mg intramuscularly every 4 weeks
  • Naltrexone should not be used during acute opiate withdrawal
 Other
  • Dose should be administered by a healthcare provider
  • Dose is given in the gluteus. Alternate buttocks with each injection.
  • Vivitrol should only be administered with the needle and diluent that comes with it
  • Allow Vivitrol to reach room temperature before injecting
  • Vivitrol should be refrigerated. Vivitrol is good for 7 days when kept at room temperature.
  • After stopping naltrexone, patients may be more sensitive to opioids and at greater risk for adverse events
  • See opioid antagonists for a review of how these drugs work
Price
  • No generic
  • One injection - $$$$
Studies
  • Vivitrol vs Buprenorphine to Prevent Opiate Relapse, Lancet (2018) - Randomized, open-label trial (N=570) in opiate-addicted patients. Results: 24-week relapse events were greater for Buprenorphine (65%) than for Vivitrol (57%). [PMID 29150198]
  • Vivitrol vs Buprenorphine to Prevent Opiate Relapse, JAMA Psych (2017) - Randomized, open-label trial (N=159) in opiate-dependent patients. Results: Vivitrol was as effective as buprenorphine-naloxone in maintaining short-term abstinence from heroin and other illicit substances. [PMID 29049469]
  • Vivitrol vs Usual Care to Prevent Opiate Relapse, NEJM (2016) - Randomized, open-label trial (N=308) in convicts who abused opioids. Results: The vivitrol group had a longer median time to relapse than did those assigned to usual treatment (10.5 vs. 5.0 weeks, p<0.001). [PMID 27028913]


OPIATE SIDE EFFECTS
  • Respiratory depression - all opiates can suppress respiratory drive which can lead to death in overdose
  • Constipation - most common side effect of opiates. Typically does not improve with continued use. Increased fiber, stool softeners, and laxatives may be necessary in some patients.
  • Nausea and vomiting - common side effect. Typically diminishes with continued use.
  • Urinary retention - occurs through both central and peripheral mechanism. Naltrexone reverses opioid-induced urinary retention.
  • Pruritus (itching) - thought to occur through central mu-opioid receptor-mediated mechanisms. Presence of rash or hives may indicate true opiate allergy as opposed to side effect. May treat with antihistamines, promethazine, or naloxone in severe cases.
  • Mental status changes - delirium, sedation, confusion, and impaired cognitive function may occur with all opiates. Elderly patients may be more susceptible.
  • Male hypogonadism - chronic opiate use suppresses GnRH synthesis and may lead to hypogonadism in males (low testosterone)
  • Hypotension (low blood pressure) - opiates may lower blood pressure in some patients
  • Adrenal insufficiency - cases of adrenal insufficiency have been associated with opiate use, particularly chronic use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure.

OPIATE PRECAUTIONS / CONTRAINDICATIONS
    All opiates
    • Drug addiction and abuse - opiates are both physically and psychologically addictive. Use with caution in susceptible patients.
    • Pulmonary disease - opiates suppress respiratory drive and may lead to hypoxia and even death in patients with respiratory disease. Use with caution in susceptible patients.
    • Intestinal disorders - opiates inhibit bowel peristalsis and can worsen some bowel conditions. Use with caution in patients with intestinal disorders.
    • Withdrawal syndrome - abruptly stopping opiates after chronic therapy may lead to withdrawal reactions including diarrhea, nausea and vomiting, confusion, somnolence, visual hallucinations, and dysphoria. Taper dose slowly depending on the situation and medication.
    • Head injury and increased intracranial pressure - use caution in patients with head injuries or increased intracranial pressure. Opiates may suppress respiratory drive causing CO₂ retention which increases intracranial pressure.
    • Elderly patients - elderly patients are more susceptible to the side effects of opiates. Use caution.
    • Hypotension - opiates may cause severe hypotension. Use caution in susceptible patients (e.g. dehydration, heart disease, etc.).
    • Pregnancy - prolonged use of opioids in pregnancy can lead to neonatal opioid withdrawal syndrome which may be life-threatening
    • Seizure disorders - opiates may lower the seizure threshold in some patients
    • Biliary disease - opiates may cause spasm of the sphincter of Oddi. Use caution in patients with biliary disease or pancreatitis. Meperidine and pentazocine may not have this effect.
    • Kidney disease - opiate clearance is decreased in kidney disease. Use caution.
    • Liver disease - opiate clearance is decreased in liver disease. Use caution.

    Buprenorphine (Butrans®, Belbuca®, etc.)
    • Prolonged QT interval - buprenorphine can prolong the QT interval, particularly at higher doses. Use caution in patients at increased risk for QT prolongation (e.g. heart disease, hypokalemia, hypomagnesemia). Do not use in patients with history of Long QT Syndrome or an immediate family member with this condition.
    • Oral mucositis (Belbuca®) - patients with oral mucositis from chemotherapy may absorb Belbuca more rapidly. Reduce starting dose and titration dose by half, from 150 mcg to 75 mcg.
    • Hepatotoxicity - buprenorphine has been associated with liver toxicity, especially in high-risk patients (e.g. alcoholism, hepatitis C, etc.). Baseline and periodic LFTs are recommended in susceptible patients.
    • Liver disease (Belbuca®)
      • Severe liver disease (Child-Pugh C): reduce starting dose and titration dose by half, from 150 mcg to 75 mcg

    Codeine
    • Children < 12 years old - DO NOT USE. May cause breathing difficulties and death.
    • Adolescents 12 - 18 years old who are obese or have conditions such as obstructive sleep apnea or severe lung disease - Not recommended. May cause breathing problems.
    • Nursing mothers - Not recommended. May cause somnolence and breathing issues in breastfed infants.
    • CYP2D6 poor/rapid metabolizers - Codeine has no analgesic activity unless it is metabolized into morphine by CYP2D6. Poor metabolizers may not receive any pain relief from codeine while rapid metabolizers may experience toxicity. Because of the risk for toxicity, codeine is contraindicated for postoperative pain in children.

    Dihydrocodeine
    • Dihydrocodeine has no analgesic activity unless it is metabolized into dihydromorphine by CYP2D6. Poor metabolizers may not receive any pain relief from codeine while rapid metabolizers may experience toxicity. Because of the risk for toxicity, dihydrocodeine is contraindicated for postoperative pain in children.

    Fentanyl
    • Bradycardia (slow heart rate) - fentanyl may cause bradycardia. Use caution in at-risk patients.

    Hydrocodone
    • Prolonged QT interval - extended-release hydrocodone products (e.g. Hysingla, Zohydro) may cause QT prolongation. Do not use in patients with congenital long QT syndrome. [8]

    Hydromorphone (Dilaudid®, Exalgo®)
    • Sulfites - hydromorphone contains sulfites. Do not use in sulfite-sensitive patients.
    • Liver disease (Exalgo®)
      • Moderate liver disease (Child-Pugh B): start with 25% of the usual Exalgo dose; titrate slowly and monitor closely
      • Severe liver disease (Child-Pugh C): consider alternative
    • Kidney disease (Exalgo®)
      • Moderate kidney disease (CrCl 40 - 60 ml/min): start with 50% of the usual Exalgo dose; titrate slowly and monitor closely
      • Severe kidney disease (CrCl < 30 ml/min): start with 25% of the usual Exalgo dose; titrate slowly and monitor closely

    Meperidine
    • Seizures - prolonged use of meperidine may cause accumulation of its metabolite, normeperidine. Normeperidine has been associated with an increased risk of seizures.
    • Serotonin syndrome - meperidine has serotonergic activity. Use caution in susceptible patients.
    • Supraventricular tachycardia (SVT) - meperidine may increase the ventricular response rate in patients with SVTs. Use caution.

    Methadone
    • Prolonged QT interval - methadone can prolong the QT interval. Baseline and periodic EKG may be indicated in patients at increased risk.

    Naltrexone
    • Liver toxicity - naltrexone has been associated with cases of hepatitis. Patients with liver disease (hepatitis C, alcoholism, etc.) may be at greater risk.

    Oxycodone
    • Liver disease - clearance is decreased. Use 1/3 to 1/2 the recommended starting dose.

    Pentazocine
    • Hypertension - pentazocine may raise blood pressure in some patients

    Tramadol
    • Children < 12 years old - DO NOT USE. May cause breathing difficulties and death.
    • Children < 18 years old to treat pain after surgery to remove the tonsils and/or adenoids - DO NOT USE. May cause breathing difficulties and death.
    • Adolescents 12 - 18 years old who are obese or have conditions such as obstructive sleep apnea or severe lung disease - Not recommended. May cause breathing problems.
    • Nursing mothers - Not recommended. May cause somnolence and breathing issues in breastfed infants.
    • Seizure risk - tramadol lowers the seizure threshold and increases the risk of seizures. Seizure risk may also be increased when taken with SSRIs, TCAs, other opioids, MAO inhibitors, and neuroleptics.
    • Serotonin syndrome - tramadol has been shown to inhibit reuptake of norepinephrine and serotonin. Tramadol should be used with caution when taken with other serotonergic drugs.
    • Kidney disease - CrCl < 30 ml/min: increase dosing interval to every 12 hours, max dose is 200 mg/day (standard-release products only, do not use extended-release products)
    • Cirrhosis - recommended dose in 50 mg every 12 hours (standard-release products only, do not use extended-release products)

OPIATE DRUG INTERACTIONS
    All opiates
    • Central Nervous System (CNS) Depressants - opiates may potentiate the effects of other CNS depressants (e.g., sedatives, alcohol, anxiolytics, hypnotics, neuroleptics, other opioids)
    • Anticholinergic medications - opiates may potentiate the urinary retention and constipating effects of anticholinergic medications
    • MAO inhibitors - MAO inhibitors may potentiate the effects of opiates and vice versa
    • Tricyclic antidepressants - tricyclic antidepressants may potentiate the effects of opiates and vice versa
    • Diuretics - opiates may reduce the efficacy of diuretics by inducing ADH release
    • Serotonergic drugs - opiates may potentiate the effects of serotonergic medications and increase the risk of serotonin syndrome
    • Cimetidine (Tagamet®) - cimetidine may potentiate the respiratory depression seen with opiate medications. Use caution.

    Buprenorphine
    • CYP3A4 inhibitors and inducers - buprenorphine is a CYP3A4 sensitive substrate. CYP3A4 inhibitors may raise blood levels of buprenorphine and increase the risk of adverse effects. CYP3A4 inducers may decrease blood levels of buprenorphine. Stopping concomitant CYP3A4 inducers may raise buprenorphine blood levels and increase the risk of adverse effects.
    • Benzodiazepines - benzodiazepines may potentiate the respiratory-depressing effects of buprenorphine. Deaths have been reported when combined. Use caution.
    • Drugs that prolong the QT interval - buprenorphine may prolong the QT interval. Do not take buprenorphine with other medications that may prolong the QT interval.

    Butorphanol
    • CYP3A4 inhibitors and inducers - butorphanol is a CYP3A4 sensitive substrate. CYP3A4 inhibitors may raise blood levels of butorphanol and increase the risk of adverse effects. CYP3A4 inducers may decrease blood levels of butorphanol. Stopping concomitant CYP3A4 inducers may raise butorphanol blood levels and increase the risk of adverse effects.
    • Benzodiazepines - benzodiazepines may potentiate the respiratory-depressing effects of butorphanol. Deaths have been reported when combined. Use caution.

    Codeine
    • CYP3A4 inducers - may decrease effectiveness of codeine
    • CYP2D6 inhibitors - codeine is metabolized by CYP2D6 to morphine. CYP2D6 inhibitors may decrease the effectiveness of codeine.

    Dihydrocodeine
    • CYP2D6 inhibitors - dihydrocodeine is metabolized by CYP2D6 to dihydromorphine. CYP2D6 inhibitors may decrease the effectiveness of dihydrocodeine.

    Fentanyl
    • CYP3A4 inhibitors and inducers - fentanyl is a CYP3A4 sensitive substrate. CYP3A4 inhibitors may increase blood levels and the risk of adverse effects. CYP3A4 inducers may decrease blood levels. Stopping concomitant CYP3A4 inducers may increase fentanyl blood levels.

    Hydrocodone
    • CYP3A4 inhibitors and inducers - hydrocodone is a CYP3A4 sensitive substrate. CYP3A4 inhibitors may increase blood levels and the risk of adverse effects. CYP3A4 inducers may decrease blood levels. Stopping concomitant CYP3A4 inducers may increase hydrocodone blood levels.
    • Drugs that prolong the QT interval - extended-release hydrocodone products (e.g. Hysingla, Zohydro) may cause QT prolongation. Use caution if combining with other QT interval prolonging drugs. [8]

    Meperidine
    • Serotonergic drugs - meperidine has serotonergic activity. Use caution when combining with other serotonergic medications.
    • Acyclovir - acyclovir may increase blood levels of meperidine
    • Cimetidine (Tagamet®) - cimetidine may reduce the clearance of meperidine
    • Phenytoin - phenytoin may increase the clearance of meperidine and increase levels of normeperidine
    • Ritonavir - ritonavir may increase exposure to normeperidine

    Methadone
    • CYP3A4 inhibitors and inducers - methadone is a CYP3A4 sensitive substrate. CYP3A4 inhibitors may increase blood levels and the risk of adverse effects. CYP3A4 inducers may decrease blood levels. Stopping concomitant CYP3A4 inducers may increase methadone blood levels.
    • Drugs that prolong the QT interval - methadone may prolong the QT interval. Use caution if prescribed with other QT-prolonging drugs
    • Antiretroviral agents - abacavir, amprenavir, efavirenz, nelfinavir, nevirapine, ritonavir, lopinavir+ritonavir combination - may increase the clearance of methadone; didanosine and stavudine - methadone may decrease levels; zidovudine - methadone may increase levels

    Morphine
    Oxycodone
    • CYP3A4 inhibitors and inducers - oxycodone is a CYP3A4 sensitive substrate. CYP3A4 inhibitors may increase blood levels and the risk of adverse effects. CYP3A4 inducers may decrease blood levels. Stopping concomitant CYP3A4 inducers may increase oxycodone blood levels.
    • CYP2D6 inhibitors - oxycodone is a minor substrate of CYP2D6. If oxycodone is taken with a CYP2D6 inhibitor and a CYP3A4 inhibitor, exposure may be increased. Use caution.

    Tapentadol
    • Alcohol - do not consume alcohol with tapentadol. Alcohol can increase blood levels of tapentadol leading to overdose
    • Serotonergic drugs - serotonin syndrome has occurred in patients taking tapentadol with other serotonergic drugs. Use caution.

    Tramadol
    • CYP3A4 inhibitors and inducers - tramadol is a CYP3A4 substrate. CYP3A4 inhibitors and inducers may affect tramadol levels.
    • CYP2D6 inhibitors and inducers - tramadol is a CYP2D6 substrate. CYP2D6 inhibitors and inducers may affect tramadol levels.
    • Drugs that lower seizure threshold - tramadol lowers the seizure threshold and increases the risk of seizures. Seizure risk may also be increased when taken with SSRIs, TCAs, other opioids, MAO inhibitors, and neuroleptics.
    • Drugs with serotonergic activity - tramadol has been shown to inhibit reuptake of norepinephrine and serotonin. Tramadol should be used with caution when taken with other serotonergic drugs.

OPIOID ANTAGONISTS
Naloxone
  • Naloxone is an opioid antagonist. Naloxone binds to opiate receptors blocking the effects of opioid medications.
  • Naloxone can be used in emergency situations to reverse the respiratory depression that occurs in opiate overdose. Naloxone is available by prescription as an injection (Evzio®) and a nasal spray (Narcan®) to treat accidental opiate overdoses.
  • Naloxone is also included in several oral medications (e.g. buprenorphine, pentazocine) to deter patients from crushing the pills and injecting them. When consumed orally, naloxone has no measurable opiate antagonist activity, but when it is crushed and injected, it will block opiate receptors.

Naltrexone
  • Naltrexone is an opioid antagonist. Naltrexone binds to opiate receptors and blocks the effects of opioid medications.
  • Naltrexone is included in Embeda®, an extended-release morphine product. Naltrexone acts as an abuse-deterrent. When Embeda pellets are crushed, naltrexone is released and the euphoric effect of the drug is reduced. If pellets are not crushed, naltrexone remains sequestered and inactive.
  • Naltrexone is FDA-approved for the treatment of alcohol dependence and opiate dependence. It is available as a tablet (Revia®) and an injection (Vivitrol®).
  • Naltrexone is also combined with the antidepressant bupropion in the diet pill Contrave®. The mechanism by which naltrexone suppresses appetite is not completely understood.

Methylnaltrexone (Relistor®)
  • Methylnaltrexone is a selective opioid antagonist. It binds and blocks mu-opioid receptors in the periphery, but it does not cross the blood-brain barrier.
  • Methylnaltrexone can help alleviate opioid-induced constipation by blocking mu-opioid receptors in the gastrointestinal tract. Since it does not enter the central nervous system, it does not affect the analgesic properties of opioids.
  • Methylnaltrexone is available as a pill and subcutaneous injection under the trade name Relistor®

Naloxegol (Movantik®)
  • Naloxegol is a selective opioid antagonist. It binds and blocks mu-opioid receptors in the periphery, but its central nervous system (CNS) penetration is negligible.
  • Naloxegol can help alleviate opioid-induced constipation by blocking mu-opioid receptors in the gastrointestinal tract. Since it does not penetrate the CNS well at recommended doses, it does not affect the analgesic properties of opioids.
  • Naloxegol is available as a pill under the trade name Movantik®