OPIATE MEDICATIONS

P = drugs with pediatric dosing recommendations

PRICING INFO

$ = 0 - $50
$$ = $51 - $100
$$$ = $101 - $150
$$$$ = > $151

Pricing based on one month of therapy at standard dosing in an adult
Pricing based on information from GoodRX.com®
Pricing may vary by region and availability

References:

1 - Package insert for drug unless otherwise specified
2 - PMID 23720867 - WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses
3 - PMID 23946177 NCCN Adult Cancer Pain GL
4 - 24685458 - APS methadone GL
5 - 12362012 NEJM pediatric pain review
6 - Actiq PI
7 - Pentazocine PI
8 - CredibleMeds website
9 - PMID 27464203 - opiate withdrawal

OPIATE-TOLERANT DEFINITION

Opiate-tolerant is defined as receiving one of the following around-the-clock on a regular basis:

≥ 60 mg of oral morphine daily
≥ 30 mg of oral oxycodone daily
≥ 8 mg of oral hydromorphone daily
≥ 25 mcg/hour of transdermal fentanyl
≥ 25 mg of oral oxymorphone daily
An equianalgesic dose of another opioid for a week or longer [3,6]

FDA SCHEDULES

Schedule I

The drug or other substance has a high potential for abuse
The drug or other substance has no currently accepted medical use in treatment in the United States
There is a lack of accepted safety for use of the drug or other substance under medical supervision
Examples: cocaine, heroin, lsd, etc.

Schedule II

The drug or other substance has a high potential for abuse
The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions
Abuse of the drug or other substances may lead to severe psychological or physical dependence

Schedule III

The drug or other substance has a potential for abuse less than the drugs or other substances in schedules I and II
The drug or other substance has a currently accepted medical use in treatment in the United States
Abuse of the drug or other substance may lead to moderate or low physical dependence or high psychological dependence

Schedule IV

The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule III
The drug or other substance has a currently accepted medical use in treatment in the United States
Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule III

Schedule V

The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule IV
The drug or other substance has a currently accepted medical use in treatment in the United States
Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule IV

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
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

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

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 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) - $$ - $$$$, depending on the strength 37.5, 62.5, and 87.5 mcg/hour doses are much more expensive
Fentanyl Actiq®	Lozenge 200 mcg 400 mcg 600 mcg 800 mcg 1200 mcg 1600 mcg	Adult - opiate naïve Not recommended Should only be used in opiate-tolerant cancer patients for breakthrough pain Dosing in opioid-tolerant cancer patients The Actiq PI (sec 2) contains a dose titration schedule	Other Providers and patients must enroll in the TIRF REMS Access program for outpatient use Special lozenge disposal instructions are provided to prevent accidental exposures Fentanyl is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors. Price Generic (30 lozenges) - $$$$
Fentanyl Lazanda®	Nasal spray 100 mcg/100 mcL 400 mcg/100 mcL Each bottle contains 8 sprays of 100 mcL	Adult - opiate naïve Not recommended Should only be used in opiate-tolerant cancer patients for breakthrough pain Dosing in opioid-tolerant cancer patients The Lazanda PI (sec 2) contains a dose titration schedule	Other Providers and patients must enroll in the TIRF REMS Access program for outpatient use Special disposal instructions are provided to prevent accidental exposure Fentanyl is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors. Price No generic 1 bottle - $$$$
Fentanyl Subsys®	Sublingual spray 100 mcg 200 mcg 400 mcg 600 mcg 800 mcg 1200 mcg 1600 mcg Comes in cartons of 10 and 30 sprays	Adult - opiate naïve Not recommended Should only be used in opiate-tolerant cancer patients for breakthrough pain Dosing in opioid-tolerant cancer patients The Subsys PI (sec 2) contains a dose titration schedule	Other Providers and patients must enroll in the TIRF REMS Access program for outpatient use Each dose comes in an individual sprayer Special disposal instructions are provided to prevent accidental exposure Fentanyl is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors. Price No generic 30 sprays - $$$$
Fentanyl Fentora®	Buccal / sublingual tablet 100 mcg 200 mcg 400 mcg 600 mcg 800 mcg Comes in cartons containing 7 blister cards with 4 tablets per card	Adult - opiate naïve Not recommended Should only be used in opiate-tolerant cancer patients for breakthrough pain Dosing in opioid-tolerant cancer patients The Fentora PI (sec 2) contains a dose titration schedule	Other Providers and patients must enroll in the TIRF REMS Access program for outpatient use Tablet can be placed above a rear molar, between the upper cheek and gum, or under the tongue Special disposal instructions are provided to prevent accidental exposure Fentanyl is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors. Price No generic 30 tablets - $$$$
Fentanyl Abstral®	Sublingual tablet 100 mcg 200 mcg 300 mcg 400 mcg 600 mcg 800 mcg Comes in packets of 12 (100, 200, 300, 400 mcg strengths only) or 32 tablets (all strengths)	Adult - opiate naïve Not recommended Should only be used in opiate-tolerant cancer patients for breakthrough pain Dosing in opioid-tolerant cancer patients The Abstral PI (sec 2) contains a dose titration schedule	Other Providers and patients must enroll in the TIRF REMS Access program for outpatient use Tablet is placed under the tongue Special disposal instructions are provided to prevent accidental exposure Fentanyl is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors. Price No generic 30 tablets - $$$$

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

Duration of action: 3 - 5 hours
Hydrocodone is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.

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

A conversion table is available in the Hysingla PI

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

Do not crush, open, chew, or dissolve capsules
Hydrocodone is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.
Extended-release hydrocodone products have been associated with prolonged QT interval

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

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
Trade names: Hycodan®

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

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

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) - $$ - $$$

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

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 - $$$ - $$$$

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) - $$
Hydromorphone Exalgo®	Tablet - extended-release 8 mg 12 mg 16 mg 32 mg	Adult - opiate naïve Not recommended Converting from other oral hydromorphone products Give total daily dose of hydromorphone as once daily Exalgo® dose Converting from other opioids The Exalgo® PI sec 2.1 contains information on converting from other opioids	Other May take without regard to food Do not crush, cut, or chew tablets Price 30 tablets, 12mg - $$$$ No generic

Drug

Dosage forms

Dosing

Other

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

The Exalgo® PI sec 2.1 contains information on 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

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 Reduce dose by 3 mg/day down to 0 mg Based on PMID 26028120	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

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

Reduce dose by 3 mg/day down to 0 mg
Based on PMID 26028120

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 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 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) - $$-$$$$ depending on strength
Morphine sulfate extended-release Kadian®	Capsule, extended-release 10 mg 20 mg 30 mg 40 mg 50 mg 60 mg 70 mg 80 mg 100 mg 130 mg 150 mg 200 mg	Adult - opiate naïve 30 mg once daily Kadian daily dose may also be divided in half and given every 12 hours Increase dose at intervals of every 1 - 2 days Converting from other oral morphine meds Total daily morphine dose can be given as once daily Kadian dose or divided by 2 and given every 12 hours Converting from parenteral to oral Anywhere from 3 to 6 mg of oral morphine sulfate may be required to provide pain relief equivalent to 1 mg of parenteral morphine In chronic dosing, 3 mg of oral morphine for every 1 mg of parenteral morphine may be sufficient [3]	Other Kadian may be opened and sprinkled on applesauce. Swallow whole. Do not chew or crush beads. Price Generic (30 capsules) - $$$-$$$$ depending on strength
Morphine sulfate extended-release MS Contin®	Tablet, extended-release 15 mg 30 mg 60 mg 100 mg 200 mg	Adult - opiate naïve 15 mg every 12 hours Increase dose at intervals of every 1 - 2 days Children (1 - 12 years) - opiate naïve 0.2 - 0.8 mg/kg every 12 hours [2] Converting from other oral morphine meds Total daily morphine dose can be divided in half and given every 12 hours Total daily morphine dose may also be divided into thirds and given every 8 hours Converting from parenteral to oral Anywhere from 3 to 6 mg of oral morphine sulfate may be required to provide pain relief equivalent to 1 mg of parenteral morphine In chronic dosing, 3 mg of oral morphine for every 1 mg of parenteral morphine may be sufficient [3]	Other Do not crush, cut, or chew tablets Price Generic (60 tablets) - $-$$$ depending on strength
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 - $$$$

Drug	Dosage forms	Dosing	Other
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) 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) 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 Duration of action: 3 - 5 hours Oxycodone is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors. Price Generic 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
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

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
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) - $ - $$
Codeine cough/cold preparations Robitussin® AC	Liquid/solution Codeine (mg) : Guaifenesin (mg) 10 : 100 per 5 ml Solution is alcohol free Liquid contains 3 - 4% alcohol	Adults and children ≥ 12 years 10 ml every 4 hours as needed Do not take more than 6 doses in 24 hours Children 6 - 11 years old 5 ml every 4 hours as needed Do not take more than 6 doses in 24 hours NOTE: In 2018, the FDA declared that all opiate-containing cough/cold medications should not be used in patients < 18 years old	Other Schedule V Guaifenesin is an expectorant Other brand names: Cheratussin AC®, Guaiatussin AC®, Virtussin AC® Price Generic (120 ml) - $
Codeine cough/cold preparations Cheratussin DAC®	Liquid Codeine 10 mg, guaifenesin 100 mg, pseudoephedrine 30 mg per 5 ml Contains 2.1% alcohol	Adults and children ≥ 12 years 10 ml every 4 hours as needed Do not take more than 4 doses in 24 hours Children 6 - 11 years old 5 ml every 4 hours as needed Do not take more than 4 doses in 24 hours NOTE: In 2018, the FDA declared that all opiate-containing cough/cold medications should not be used in patients < 18 years old	Other Schedule V Guaifenesin is an expectorant Pseudoephedrine is a decongestant Price Generic (120 ml) - $
Codeine cough/cold preparations Tuzistra™ XR	Suspension, extended-release Codeine 14.7 mg and chlorpheniramine 2.8 mg per 5 ml	Adults 18 years and older 10 ml every 12 hours as needed Do not exceed 20 ml in 24 hours	Other Schedule III Chlorpheniramine is an antihistamine Price No generic Brand (120 ml) - $$$
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) - $

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

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

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 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) - $$$$
Zubsolv (30 tablets) - $$$$
Bunavail (30 films) - $$$$

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

The Butrans PI (sec 2) contains information for 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

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

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

Schedule III
Providers must be certified in the Probuphine REMS program in order to prescribe Probuphine

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]

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 overdosage. 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
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
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

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
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

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
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

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 to prevent opiate abuse-relapse, NEJM (2016) - open-label study that compared Vivitrol to usual care in 308 convicts who abused opioids PRIMARY OUTCOME: time to an opioid-relapse event 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). In a secondary outcome, Vivitrol did not have a significant effect on alcohol abuse. [PMID 27028913]

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 to prevent opiate abuse-relapse, NEJM (2016) - open-label study that compared Vivitrol to usual care in 308 convicts who abused opioids
PRIMARY OUTCOME: time to an opioid-relapse event
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). In a secondary outcome, Vivitrol did not have a significant effect on alcohol abuse. [PMID 27028913]

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
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

Tablets should be taken with water on an empty stomach at least 30 minutes before the first meal of the day
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 - $$$$

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. Methylnaltrexone (Relistor®) has been FDA-approved to treat opiate-induced constipation. 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

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. Methylnaltrexone (Relistor®) has been FDA-approved to treat opiate-induced constipation.
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

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

Fentanyl

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

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 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 P-glycoprotein inhibitors - p-glycoprotein inhibitors may increase exposure to morphine. Use caution when combining. 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.

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

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

P-glycoprotein inhibitors - p-glycoprotein inhibitors may increase exposure to morphine. Use caution when combining.

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 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®

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

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®