OPIATE MEDICATIONS









Buprenorphine (Belbuca®)

Dosage forms

Buccal film
  • 75 mcg
  • 150 mcg
  • 300 mcg
  • 450 mcg
  • 600 mcg
  • 750 mcg
  • 900 mcg
  • Comes in carton of 60 films

Dosing

Severe pain requiring long-term treatment
  • Adults (opiate-naïve)
    • 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

Generic / Price

  • No generic
  • 60 films - $$$$

Other

  • DEA 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.

Buprenorphine hydrochloride (Subutex®)

Dosage forms

Sublingual tablet
  • 2 mg
  • 8 mg

Dosing

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]

Generic / Price

  • Generic (60 tablets) - $$

Other

  • DEA 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

Buprenorphine hydrochloride (Butrans®)

Dosage forms

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

Dosing

Severe pain
  • Adults (opiate-naïve)
    • 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
  • Initiate Butrans at the next dosing interval
  • Oral morphine equivalent < 30 mg/day: start with 5 mcg/hr
  • Oral morphine equivalent 30 - 80 mg/day: before beginning Butrans, taper current opioids for up to 7 days to no more than 30 mg oral morphine equivalent per day. Initiate Butrans at 10 mcg/hr.
  • Oral morphine equivalent > 80 mg/day: 20 mcg/hr may not provide adequate analgesia. Consider the use of an alternate analgesic.

Generic / Price

  • No generic
  • 4 patches - $$$$

Other

  • DEA 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.

Buprenorphine hydrochloride (Probuphine®)

Dosage forms

Subdermal implant
  • Each implant contains 80 mg of buprenorphine HCL
  • Comes in kit with 4 implants and disposable applicator

Dosing

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.

Efficacy

Generic / Price

  • No generic
  • 1 kit - $$$$

Other


Buprenorphine hydrochloride (Sublocade®)

Dosage forms

Prefilled syringe, single-dose
  • 100 mg/0.5 ml
  • 300 mg/1.5 ml

Dosing

Maintenance of opioid dependence
  • Indicated for patients who have initiated treatment with a transmucosal buprenorphine-containing product, followed by dose adjustment for a minimum of 7 days. Patients should be receiving the equivalent of 8 to 24 mg of buprenorphine daily.
  • For abdominal subcutaneous administration only
  • Should only be administered by healthcare provider
  • Dosing: 300 mg monthly for the first two months followed by a maintenance dose of 100 mg monthly
  • Maintenance dose may be increased to 300 mg monthly for patients who tolerate the 100 mg dose, but do not demonstrate a satisfactory clinical response
  • There should be a minimum of 26 days between doses
  • Occasional delays in dosing up to 2 weeks are not expected to have a clinically significant impact on treatment effect

Efficacy

Generic / Price

  • No generic
  • 1 syringe - $$$$

Other

  • DEA Schedule III
  • Subclocade is injected as a liquid, and the subsequent precipitation of the poly polymer creates a solid depot which contains buprenorphine. The depot disintegrates over time, but may be removed surgically before total disintegration.
  • After steady-state has been achieved (4-6 months), patients discontinuing Sublocade may have detectable plasma levels of buprenorphine for twelve months or longer
  • Providers must be certified in the Sublocade REMS program in order to prescribe Sublocade


Buprenorphine and Naloxone | Suboxone® | Zubsolv® | Bunavail®

Dosage forms

Suboxone® - sublingual tablet
  • Buprenorphine (mg) : Naloxone (mg)
    • 2 mg : 0.5 mg
    • 8 mg : 2.0 mg
Suboxone® - sublingual film
    Buprenorphine : Naloxone
    • 2 mg : 0.5 mg
    • 4 mg : 1.0 mg
    • 8 mg : 2 mg
    • 12 mg: 3 mg
Zubsolv® - sublingual tablet
  • Buprenorphine : Naloxone
    • 1.4 mg : 0.36 mg
    • 5.7 mg : 1.4 mg
    • 8.6 mg : 2.1 mg
    • 11.4 mg : 2.9 mg
Bunavail® - buccal film
  • Buprenorphine : Naloxone
    • 2.1 mg : 0.3 mg
    • 4.2 mg : 0.7 mg
    • 6.3 mg : 1.0 mg

Dosing

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).

Generic / Price

  • Suboxone generic (30 tablets) - $$
  • Suboxone generic (30 films) - $$
  • Zubsolv (30 tablets) - $$$$
  • Bunavail (30 films) - $$$$

Other

  • DEA 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


Butorphanol tartrate (Stadol®)

Dosage forms

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

Dosing

Adults
  • 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

Generic / Price

  • Generic (1 bottle) - $

Other

  • DEA Schedule IV
  • 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


Codeine - APAP | Tylenol #3 | Tylenol #4

Dosage forms

Tablet
  • Codeine phosphate : Acetaminophen
    • 15 mg : 300 mg
    • 30 mg: 300 mg (Tylenol® #3)
    • 60 mg : 300 mg (Tylenol® #4)

Dosing

Adults
  • 15 - 60 mg every 4 hours as needed
  • Do not exceed 360 mg in 24 hours
Children
  • Standard
    • 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

Generic / Price

  • Generic (30 tablets) - $

Other

  • DEA 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.

Codeine - APAP solution

Dosage forms

Solution
  • Codeine 12 mg and acetaminophen 120 mg per 5 ml

Dosing

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

Generic / Price

  • Generic (120 ml) - $

Other

  • DEA 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.

Cheratussin DAC®

Dosage forms

Liquid
  • Codeine 10 mg, guaifenesin 100 mg, pseudoephedrine 30 mg per 5 ml
  • Contains 2.1% alcohol

Dosing

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

Generic / Price

  • Generic (120 ml) - $

Other

  • DEA Schedule V
  • Guaifenesin is an expectorant
  • Pseudoephedrine is a decongestant

Phenergan® with codeine

Dosage forms

Syrup
  • Codeine 10 mg and promethazine 6.25 mg per 5 ml
  • Contains 7% alcohol

Dosing

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

Generic / Price

  • Generic (120 ml) - $

Other

  • DEA Schedule V
  • Promethazine is an antihistamine/anticholinergic medication

Phenergan® VC with codeine

Dosage forms

Syrup
  • Codeine 10 mg, phenylephrine 5 mg, and promethazine 6.25 mg per 5 ml
  • Contains 7% alcohol

Dosing

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

Generic / Price

  • Generic (120 ml) - $

Other

  • DEA Schedule V
  • Phenylephrine is a decongestant
  • Promethazine is an antihistamine/anticholinergic medication

Robitussin® AC

Dosage forms

Liquid / solution
  • Codeine 10 and guaifenesin 100 per 5 ml
  • Solution is alcohol free
  • Liquid contains 3 - 4% alcohol

Dosing

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

Generic / Price

  • Generic (120 ml) - $

Other

  • DEA Schedule V
  • Guaifenesin is an expectorant
  • Other brand names: Cheratussin AC®, Guaiatussin AC®, Virtussin AC®

Tuzistra™ XR

Dosage forms

Suspension, extended-release
  • Codeine 14.7 mg and chlorpheniramine 2.8 mg per 5 ml

Dosing

Adults 18 years and older
  • 10 ml every 12 hours as needed
  • Do not exceed 20 ml in 24 hours

Generic / Price

  • No generic
  • Brand (120 ml) - $$$

Other

  • DEA Schedule III
  • Chlorpheniramine is an antihistamine

Codeine Sulfate (CII)

Dosage forms

Tablet
  • 15 mg
  • 30 mg
  • 60 mg

Dosing

Adults (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

Generic / Price

  • Generic (30 tablets) - $

Other

  • DEA Schedule II
  • 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

Fioricet® with codeine

Dosage forms

Capsule
  • Codeine 30 mg, acetaminophen 325 mg, butalbital 50 mg, caffeine 40 mg per capsule
Capsule
  • Codeine 30 mg, acetaminophen 300 mg, butalbital 50 mg, caffeine 40 mg per capsule

Dosing

Tension headache
  • 1 - 2 capsules every 4 hours as needed
  • Do not exceed 6 capsules in 24 hours

Generic / Price

  • Generic (30 capsules) - $
  • NOTE: product with 300 mg of acetaminophen is $$$$

Other

  • DEA Schedule III
  • 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.

Fiorinal® with codeine

Dosage forms

Capsule
  • Codeine 30 mg, aspirin 325 mg, butalbital 50 mg, caffeine 40 mg per capsule

Dosing

Tension headache
  • 1 - 2 capsules every 4 hours as needed
  • Do not exceed 6 capsules in 24 hours

Generic / Price

  • Generic (30 capsules) - $

Other

  • DEA Schedule III
  • 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.

Soma® Compound with codeine

Dosage forms

Tablet
  • Codeine 16 mg, aspirin 325 mg, and carisoprodol 200 mg per tablet

Dosing

Acute, painful musculoskeletal conditions
  • 1 - 2 tablets four times daily as needed

Generic / Price

  • Generic (30 capsules) - $ - $$

Other

  • DEA 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.


Synalgos®-DC

Dosage forms

Capsule
  • Dihydrocodeine 16 mg, Caffeine 30 mg, Aspirin 356.4 mg per capsule

Dosing

Moderate to severe pain
  • 2 capsules every 4 hours as needed for pain

Generic / Price

  • Generic (30 capsules) - $

Other

  • DEA 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.

Trezix®

Dosage forms

Capsule
  • Dihydrocodeine 16 mg, Caffeine 30 mg, Acetaminophen 320.5 mg per capsule

Dosing

Moderate to severe pain
  • 2 capsules every 4 hours as needed for pain
  • Do not exceed 10 capsules in 24 hours

Generic / Price

  • Generic (30 capsules) - $$

Other

  • DEA 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.


Diphenoxylate | Lomotil® | Lonox®

Dosage forms

Tablet
  • Diphenoxylate 2.5 mg and atropine 0.025 mg per tablet
Solution
  • Diphenoxylate 2.5 mg and atropine 0.025 mg per 5 ml

Dosing - Diarrhea

Adults
  • Tablet - 2 tablets four times daily as needed
  • Liquid - 10 ml four times daily as needed
Children 2 - 13 years
  • 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

Generic / Price

  • Generic (30 tablets or 120ml) - $

Other

  • DEA Schedule V
  • Atropine is added to discourage deliberate overdose. It has no effect in normal dosing.
  • Young children may be more susceptible to diphenoxylate and atropine side effects


Fentanyl (Abstral®)

Dosage forms

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)

Dosing

  • The Abstral PI (sec 2) contains a dose titration schedule
  • Fentanyl products are not recommended in opiate-naïve patients, and they should only be used in opiate-tolerant cancer patients for breakthrough pain
  • See opiate-tolerant definition for more

Generic / Price

  • No generic
  • 30 tablets - $$$$

Other

  • DEA Schedule II
  • 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.

Fentanyl (Actiq®)

Dosage forms

Lozenge
  • 200 mcg
  • 400 mcg
  • 600 mcg
  • 800 mcg
  • 1200 mcg
  • 1600 mcg

Dosing

Opioid-tolerant cancer patients
  • The Actiq PI (sec 2) contains a dose titration schedule
  • Fentanyl products are not recommended in opiate-naïve patients, and they should only be used in opiate-tolerant cancer patients for breakthrough pain
  • See opiate-tolerant definition for more

Generic / Price

  • Generic (30 lozenges) - $$$$

Other

  • DEA Schedule II
  • 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.

Fentanyl (Duragesic®)

Dosage forms

Patch
  • 12 mcg/hour
  • 25 mcg/hour
  • 37.5 mcg/hour
  • 50 mcg/hour
  • 62.5 mcg/hour
  • 75 mcg/hour
  • 87.5 mcg/hour
  • 100 mcg/hour

Dosing

Opioid-tolerant cancer patients
  • The Duragesic PI (sec 2) contains an extensive table for converting from other opioids to fentanyl patch
  • Fentanyl products are not recommended in opiate-naïve patients, and they should only be used in opiate-tolerant cancer patients for breakthrough pain
  • See opiate-tolerant definition for more

Generic / Price

  • Generic available
  • 12 mcg/hr, 50 mcg/hr, 75 mcg/hr, 100 mcg/hr (10 patches) - $$-$$$
  • 25 mcg/hr (10 patches) - $
  • 37.5 mcg/hr, 62.5 mcg/hr, 87.5 mcg/hr (10 patches) - $$$$

Other

  • DEA Schedule II
  • 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.

Fentanyl (Fentora®)

Dosage forms

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

Dosing

Opioid-tolerant cancer patients
  • The Fentora PI (sec 2) contains a dose titration schedule
  • Fentanyl products are not recommended in opiate-naïve patients, and they should only be used in opiate-tolerant cancer patients for breakthrough pain
  • See opiate-tolerant definition for more

Generic / Price

  • No generic
  • 30 tablets - $$$$

Other

  • DEA Schedule II
  • 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.

Fentanyl (Lazanda®)

Dosage forms

Nasal spray
  • 100 mcg/100 mcL
  • 400 mcg/100 mcL
  • Each bottle contains 8 sprays of 100 mcL

Dosing

Opioid-tolerant cancer patients
  • The Lazanda PI (sec 2) contains a dose titration schedule
  • Fentanyl products are not recommended in opiate-naïve patients, and they should only be used in opiate-tolerant cancer patients for breakthrough pain
  • See opiate-tolerant definition for more

Generic / Price

  • No generic
  • 1 bottle - $$$$

Other

  • DEA Schedule II
  • 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.

Fentanyl (Subsys®)

Dosage forms

Sublingual spray
  • 100 mcg
  • 200 mcg
  • 400 mcg
  • 600 mcg
  • 800 mcg
  • 1200 mcg
  • 1600 mcg
  • Comes in cartons of 10 and 30 sprays

Dosing

Opioid-tolerant cancer patients
  • The Subsys PI (sec 2) contains a dose titration schedule
  • Fentanyl products are not recommended in opiate-naïve patients, and they should only be used in opiate-tolerant cancer patients for breakthrough pain
  • See opiate-tolerant definition for more

Generic / Price

  • No generic
  • 30 sprays - $$$$

Other

  • DEA Schedule II
  • 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.


Hydrocodone - APAP | Vicodin® | Norco® | Lortab®

Dosage forms

Tablet
  • Hydrocodone : Acetaminophen
    • 2.5 mg : 325 mg
    • 5.0 mg : 325 mg
    • 7.5 mg : 325 mg
    • 10 mg : 325 mg
    • 5.0 mg : 300 mg
    • 7.5 mg : 300 mg
    • 10 mg : 300 mg
Solution
  • Hydrocodone 7.5 mg and acetaminophen 325 mg per 15ml

Dosing

Adults (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*)

Generic / Price

  • Hydrocodone/APAP tab #30 - $
  • Hydrocodone/APAP solution #240 ml - $

Other

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

Hydrocodone - Ibuprofen (Vicoprofen®)

Dosage forms

Tablet
  • Hydrocodone : Ibuprofen
    • 2.5 mg : 200 mg
    • 5.0 mg : 200 mg
    • 7.5 mg : 200 mg
    • 10 mg : 200 mg

Dosing

Adults (opiate-naïve)
  • 5 - 10 mg every 4 - 6 hours as needed
  • Do not to exceed 50 mg a day

Generic / Price

  • Generic available
  • Hydrocodone/Ibuprofen tab #30: $-$$

Other

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

Flowtuss®

Dosage forms

Solution
  • Hydrocodone 2.5 mg and guaifenesin 200 mg per 5 ml

Dosing

  • 10 ml every 4 - 6 hours as needed
  • Do not exceed 60 ml in 24 hours

Generic / Price

  • No generic
  • 120 ml - $$$

Other

  • DEA Schedule II
  • Guaifenesin is an expectorant

Hycodan® syrup

Dosage forms

Syrup
  • Hydrocodone 5 mg and homatropine 1.5 mg per 5 ml

Dosing

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

Generic / Price

  • Generic 120 ml - $

Other

  • DEA Schedule II
  • Homatropine is an anticholinergic medication that is included to discourage overdose

Hycodan® tablets

Dosage forms

Tablet
  • Hydrocodone 5 mg and homatropine 1.5 mg per tablet

Dosing

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

Generic / Price

  • Generic 30 tablets - $

Other

  • DEA Schedule II
  • Homatropine is an anticholinergic medication that is included to discourage overdose

Hycofenix®

Dosage forms

Solution
  • Hydrocodone 2.5 mg, pseudoephedrine 30 mg, and guaifenesin 200 mg per 5 ml

Dosing

  • 10 ml every 4 - 6 hours as needed
  • Do not exceed 40 ml in 24 hours

Generic / Price

  • No generic
  • 120 ml - $$$

Other

  • DEA Schedule II
  • Guaifenesin is an expectorant
  • Pseudoephedrine is a decongestant

Obredon®

Dosage forms

Solution
  • Hydrocodone 2.5 mg and guaifenesin 200 mg per 5 ml

Dosing

  • 10 ml every 4 - 6 hours as needed
  • Do not exceed 60 ml in 24 hours

Generic / Price

  • No generic
  • 120 ml - $$$

Other

  • DEA Schedule II
  • Guaifenesin is an expectorant

Rezira®

Dosage forms

Solution
  • Hydrocodone 5 mg and pseudoephedrine 60 mg per 5 ml

Dosing

  • 5 ml every 4 - 6 hours as needed
  • Do not exceed 20 ml in 24 hours

Generic / Price

  • No generic
  • 120 ml - $

Other

  • DEA Schedule II
  • Pseudoephedrine is a decongestant

Tussicaps®

Dosage forms

Capsule, extended-release
  • Hydrocodone 5 mg and chlorpheniramine 4 mg per capsule
  • Hydrocodone 10 mg and chlorpheniramine 8 mg per capsule

Dosing

Adults and children ≥ 12 years
  • 1 capsule (hydrocodone 10 mg) every 12 hours as needed
  • Do not exceed 2 capsules in 24 hours
Children 6 - 11 years
  • 1 capsule (hydrocodone 5 mg) every 12 hours as needed
  • Do not exceed 2 capsules in 24 hours
  • Only hydrocodone 5 mg capsule should be used in this age group
NOTE: In 2018, the FDA declared that all opiate-containing cough/cold medications should not be used in patients < 18 years old

Generic / Price

  • No generic
  • 30 capsules - $$$$

Other

  • DEA Schedule II
  • Chlorpheniramine is an antihistamine

Tussionex®

Dosage forms

Suspension, extended-release
  • Hydrocodone 10 mg and chlorpheniramine 8 mg per 5 ml

Dosing

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

Generic / Price

  • Generic 120ml - $

Other

  • DEA Schedule II
  • Chlorpheniramine is an antihistamine

Vituz®

Dosage forms

Solution
  • Hydrocodone 5 mg and chlorpheniramine 4 mg per 5 ml

Dosing

  • 5 ml every 4 - 6 hours as needed
  • Do not exceed 20 ml in 24 hours

Generic / Price

  • No generic
  • 120 ml - $

Other

  • DEA Schedule II
  • Chlorpheniramine is an antihistamine

Zutripro®

Dosage forms

Solution
  • Hydrocodone 5 mg, chlorpheniramine 4 mg, pseudoephedrine 60 mg per 5 ml

Dosing

  • 5 ml every 4 - 6 hours as needed
  • Do not exceed 20 ml in 24 hours

Generic / Price

  • Generic (120 ml) - $-$$

Other

  • DEA Schedule II
  • Chlorpheniramine is an antihistamine
  • Pseudoephedrine is a decongestant

Hydrocodone (Hysingla® ER)

Dosage forms

Tablet, extended-release
  • 20 mg
  • 30 mg
  • 40 mg
  • 60 mg
  • 80 mg
  • 100 mg
  • 120 mg

Dosing

Adults (opiate-naïve)
  • 20 mg once daily
  • Increase dose by 10 - 20 mg every 3 - 5 days as needed
Converting other hydrocodone formulations to Hysingla
  • Total daily hydrocodone dose is given as once daily Hysingla dose
Converting from other opioids

Generic / Price

  • No generic
  • 30 tablets - $$$$

Other

  • DEA Schedule II
  • 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

Hydrocodone (Zohydro® ER)

Dosage forms

Capsule, extended-release
  • 10 mg
  • 15 mg
  • 20 mg
  • 30 mg
  • 40 mg
  • 50 mg

Dosing

Adults (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 hydrocodone dose is divided by 2 and given once every 12 hours
Converting from other opioids

Generic / Price

  • No generic
  • 30 capsules - $$$$

Other

  • DEA Schedule II
  • 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


Hydromorphone IR (Dilaudid®)

Dosage forms

Tablet
  • 2 mg
  • 4 mg
  • 8 mg
Solution
  • 5 mg/5 ml

Dosing

Adults (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]

Generic / Price

  • Generic (30 tablets) - $
  • Generic (200 ml) - $$

Other

  • DEA Schedule II
  • Solution and tablet are bioequivalent

Hydromorphone ER (Exalgo®)

Dosage forms

Tablet - extended-release
  • 8 mg
  • 12 mg
  • 16 mg
  • 32 mg

Dosing

Adults (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

Generic / Price

  • No generic
  • 30 tablets, 12mg - $$$$

Other

  • DEA Schedule II
  • May take without regard to food
  • Do not crush, cut, or chew tablets


Meperidine hydrochloride (Demerol®)

Dosage forms

Tablet
  • 50 mg
  • 100 mg
Solution
  • 50 mg/5 ml

Dosing

Adults (opiate-naïve)
  • 50 - 150 mg every 3 - 4 hours as needed
Children ≥ 6 months
  • Standard
    • 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]

Generic / Price

  • Generic (30 tablets) - $

Other

  • DEA Schedule II
  • 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.

Methadone | Methadose® | Dolophine®

Dosage forms

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

Dosing - Children 1 - 12 years

Chronic pain, opiate-naïve
  • 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

Dosing - Adults

Chronic pain, opiate-naïve
  • 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
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

Generic / Price

  • Generic (90 tablets) - $
  • Generic (500 ml) - $

Other

  • DEA Schedule II
  • 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


Morphine sulfate IR

Dosage forms

Tablet
  • 15 mg
  • 30 mg
Solution
  • 10 mg/5 ml
  • 20 mg/5 ml
  • 100 mg/5 ml

Dosing

Adults (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)
  • Standard
    • 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]
Discontinuation
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal
  • Do not discontinue abruptly

Generic / Price

  • Generic (30 tablets or 120 ml) - $

Other

  • DEA Schedule II
  • Duration of action: 3 - 4 hours

Morphine sulfate (Arymo® ER)

Dosage forms

Tablet, extended-release
  • 15 mg
  • 30 mg
  • 60 mg

Dosing

Adults (opiate-naïve)
  • 15 mg every 8 - 12 hours
  • Increase dose every 1 - 2 days as needed
Converting from other oral morphine meds
  • Total daily morphine dose will remain the same. Dose may given in halves every twelve hours or thirds every 8 hours.
Converting from parenteral morphine to oral
  • Between 2 to 6 mg of oral morphine may be required to provide analgesia equivalent to 1 mg of parenteral morphine. Typically, a dose of morphine that is approximately three times the previous daily parenteral morphine requirement is sufficient.
  • In chronic dosing, 3 mg of oral morphine for every 1 mg of parenteral morphine may be sufficient [3]
Discontinuation
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal
  • Do not discontinue abruptly

Generic / Price

  • No generic
  • 30 tablets - $$$$

Other

  • DEA Schedule II
  • Do not crush, cut, dissolve, or chew tablets. Swallow tablets whole.

Morphine sulfate ER (Avinza®)

Dosage forms

Capsule, extended-release
  • 30 mg
  • 45 mg
  • 60 mg
  • 75 mg
  • 90 mg
  • 120 mg

Dosing

Adults (opiate-naïve)
  • 30 mg once daily
  • Increase in increments not greater than 30 mg every 4 days
Converting from other oral morphine meds
  • Total daily morphine dose can be given as once daily Avinza dose
Converting from parenteral morphine to oral
  • Anywhere from 3 to 6 mg of oral morphine sulfate may be required to provide pain relief equivalent to 1 mg of parenteral morphine
  • In chronic dosing, 3 mg of oral morphine for every 1 mg of parenteral morphine may be sufficient [3]
Discontinuation
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal
  • Do not discontinue abruptly

Generic / Price

  • Generic (30 capsules) - $$$

Other

  • DEA Schedule II
  • 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

Morphine sulfate - Naltrexone ER (Embeda®)

Dosage forms

Capsule, extended-release
  • Morphine : Naltrexone
    • 20 mg: 0.8 mg
    • 30 mg: 1.2 mg
    • 50 mg: 2 mg
    • 60 mg: 2.4 mg
    • 80 mg: 3.2 mg
    • 100 mg: 4 mg

Dosing

Adults (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]
Discontinuation
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal
  • Do not discontinue abruptly

Generic / Price

  • No generic
  • 30 capsules - $$$$

Other

  • DEA Schedule II
  • 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.

Morphine sulfate ER (Kadian®)

Dosage forms

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

Dosing

Adults (opiate-naïve)
  • 30 mg once daily
  • Kadian daily dose may also be divided in half and given every 12 hours
  • Increase dose at intervals of every 1 - 2 days
Converting from other oral morphine meds
  • Total daily morphine dose can be given as once daily Kadian dose or divided by 2 and given every 12 hours
Converting from parenteral morphine to oral
  • Anywhere from 3 to 6 mg of oral morphine sulfate may be required to provide pain relief equivalent to 1 mg of parenteral morphine
  • In chronic dosing, 3 mg of oral morphine for every 1 mg of parenteral morphine may be sufficient [3]
Discontinuation
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal
  • Do not discontinue abruptly

Generic / Price

  • Generic (30 capsules) - $$-$$$$ depending on strength

Other

  • DEA Schedule II
  • Kadian may be opened and sprinkled on applesauce. Swallow whole. Do not chew or crush beads.

Morphine sulfate (Morphabond™ ER)

Dosage forms

Tablet, extended-release
  • 15 mg
  • 30 mg
  • 60 mg
  • 100 mg

Dosing

Adults (opiate-naïve)
  • 15 mg every 8 - 12 hours
  • Increase dose every 1 - 2 days as needed
Converting from other oral morphine meds
  • Total daily morphine dose will remain the same. Dose may given in halves every twelve hours or thirds every 8 hours.
Converting from parenteral morphine to oral
  • Between 2 to 6 mg of oral morphine may be required to provide analgesia equivalent to 1 mg of parenteral morphine. Typically, a dose of morphine that is approximately three times the previous daily parenteral morphine requirement is sufficient.
  • In chronic dosing, 3 mg of oral morphine for every 1 mg of parenteral morphine may be sufficient [3]
Discontinuation
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal
  • Do not discontinue abruptly

Generic / Price

  • No generic
  • 30 tablets - $$$$

Other

  • DEA Schedule II
  • Do not crush, cut, chew, or dissolve tablets. Swallow tablets whole.
  • Tablet shell containing inactive ingredients may be seen in stool

Morphine sulfate ER (MS Contin®)

Dosage forms

Tablet, extended-release
  • 15 mg
  • 30 mg
  • 60 mg
  • 100 mg
  • 200 mg

Dosing

Adults (opiate-naïve)
  • 15 mg every 12 hours
  • Increase dose at intervals of every 1 - 2 days
Children 1 - 12 years (opiate-naïve)
  • 0.2 - 0.8 mg/kg every 12 hours [2]
Converting from other oral morphine meds
  • Total daily morphine dose can be divided in half and given every 12 hours
  • Total daily morphine dose may also be divided into thirds and given every 8 hours
Converting from parenteral morphine to oral
  • Anywhere from 3 to 6 mg of oral morphine sulfate may be required to provide pain relief equivalent to 1 mg of parenteral morphine
  • In chronic dosing, 3 mg of oral morphine for every 1 mg of parenteral morphine may be sufficient [3]
Discontinuation
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal
  • Do not discontinue abruptly

Generic / Price

  • Generic (60 tablets) - $-$$$ depending on strength

Other

  • DEA Schedule II
  • Do not crush, cut, or chew tablets


Methylnaltrexone (Relistor®)

Dosage forms

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

Dosing

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

  • Give dose every other day as needed
Weight Dose
< 38 kg 0.15 mg/kg
38 to < 62 kg 8 mg
62 to 114 kg 12 mg
> 114 kg 0.15 mg/kg

Generic / Price

  • No generic
  • 28 syringes or 90 tablets - $$$$

Other

  • Injection is given in upper arm, abdomen, or thigh. Rotate injection sites.
  • Contraindicated in patients with GI obstruction and in those at increased risk of obstruction
  • May increase risk of gastrointestinal perforation
  • Discontinue all laxatives before starting. Laxatives may be added after 3 days if response to Relistor is suboptimal

Mechanism of action

  • 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.

Naloxegol (Movantik®)

Dosage forms

Tablet
  • 12.5 mg
  • 25 mg

Dosing

Opioid-induced constipation in patients with chronic non-cancer pain
  • Dosing: 25 mg once daily in the morning. Patients who cannot tolerate 25 mg may try 12.5 mg once daily.
  • Take on an empty stomach at least 1 hour prior to the first meal of the day or 2 hours after the meal
  • Kidney disease (CrCl < 60 ml/min: start with 12.5 mg once daily. If well tolerated, may increase to 25 mg once daily.
  • Strong CYP3A4 inhibitors: DO NOT COMBINE
  • Moderate CYP3A4 inhibitors: Not recommended. If must combine, use 12.5 mg once daily.

Generic / Price

  • No generic
  • 30 tablets - $$$$

Other

  • Tablet may be crushed and mixed with 120 ml of water
  • Contraindicated in patients with GI obstruction and in those at increased risk of obstruction
  • May increase risk of gastrointestinal perforation
  • Discontinue all laxatives before starting. Laxatives may be added after 3 days if response to Movantik is suboptimal
  • Patients receiving opioids for less than 4 weeks may be less responsive

Mechanism of action

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

Naloxone (Evzio®)

Dosage forms

Injection
  • Prefilled, single-use autoinjector pen containing 0.4 mg of naloxone per injection
  • Comes in carton that contains 2 pens

Dosing

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

Generic / Price

  • No generic
  • Carton of 2 syringes - $$$$

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

Mechanism of action

  • 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 (Narcan®)

Dosage forms

Nasal spray
  • 4 mg single-use spray
  • Comes in a carton with 2 single-use sprays

Dosing

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

Generic / Price

  • No generic
  • Carton of 2 sprays - $$$

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

Mechanism of action

  • 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.

Naltrexone (Revia®)

Dosage forms

Tablet
  • 50 mg

Dosing

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

Generic / Price

  • Generic - $

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

Mechanism of action

  • Naltrexone is an opioid antagonist. Naltrexone binds to opiate receptors and blocks the effects of opioid medications.
  • The mechanism of action of naltrexone hydrochloride in alcoholism is not understood; however, involvement of the endogenous opioid system is suggested by preclinical data. Naltrexone hydrochloride, an opioid receptor antagonist, competitively binds to such receptors and may block the effects of endogenous opioids.

Naltrexone (Vivitrol®)

Dosage forms

Injectable suspension
  • 380 mg vial
  • Carton comes with vial, diluent, special needle and syringe

Dosing

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

Generic / Price

  • No generic
  • One injection - $$$$

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

Mechanism of action

  • Naltrexone is an opioid antagonist. Naltrexone binds to opiate receptors and blocks the effects of opioid medications.
  • The mechanism of action of naltrexone hydrochloride in alcoholism is not understood; however, involvement of the endogenous opioid system is suggested by preclinical data. Naltrexone hydrochloride, an opioid receptor antagonist, competitively binds to such receptors and may block the effects of endogenous opioids.

Studies



Oxycodone IR (Roxicodone®)

Dosage forms

Tablet
  • 5 mg
  • 10 mg
  • 15 mg
  • 20 mg
  • 30 mg
Capsule
  • 5 mg
Solution
  • 5 mg/5 ml
  • 100 mg/5 ml

Dosing

Adults (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]
Discontinuing therapy
  • If patients have been taking regularly, taper the dose gradually, by 25% to 50% every 2 to 4 days and monitor for withdrawal symptoms

Generic / Price

  • Generic solution (120 ml) - $
  • Generic capsules/tablets (#30) - $

Other

  • DEA Schedule II
  • Duration of action: 3 - 5 hours
  • Oxycodone is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.

Oxycodone - APAP IR | Percocet® | Roxicet®

Dosage forms

Tablet
  • Oxycodone : Acetaminophen
    • 2.5 mg: 325 mg
    • 5.0 mg: 325 mg
    • 7.5 mg: 325 mg
    • 10 mg: 325 mg
    • 2.5 mg: 300 mg
    • 5.0 mg: 300 mg
    • 7.5 mg: 300 mg
    • 10 mg: 300 mg
Solution
  • Oxycodone 5 mg and acetaminophen 325 mg per 5 ml

Dosing

Adults (opiate-naïve)
  • 2.5 - 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
Discontinuing therapy
  • If patients have been taking regularly, taper the dose gradually, by 25% to 50% every 2 to 4 days and monitor for withdrawal symptoms

Generic / Price

  • Generic tablets (#30), solution (120ml) - $

Other

  • DEA Schedule II
  • Duration of action: 3 - 5 hours
  • Oxycodone is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.

Oxycodone - Aspirin IR (Percodan®)

Dosage forms

Tablet
  • Oxycodone : Aspirin
    • 4.8355 mg : 325 mg

Dosing

Adults (opiate-naïve)
  • One tablet 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
Discontinuing therapy
  • If patients have been taking regularly, taper the dose gradually, by 25% to 50% every 2 to 4 days and monitor for withdrawal symptoms

Generic / Price

  • Generic tablets (#30) - $

Other

  • DEA Schedule II
  • Duration of action: 3 - 5 hours
  • Oxycodone is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.

Oxycodone - Ibuprofen IR

Dosage forms

Tablet
  • Oxycodone : Ibuprofen
    • 5 mg : 400 mg

Dosing

Adults (opiate-naïve)
  • 5 mg every 6 hours as needed
  • Do not exceed 4 tablets in 24 hours
Discontinuing therapy
  • If patients have been taking regularly, taper the dose gradually, by 25% to 50% every 2 to 4 days and monitor for withdrawal symptoms

Generic / Price

  • Generic tablets (#30) - $

Other

  • DEA Schedule II
  • Duration of action: 3 - 5 hours
  • Oxycodone is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.

Oxycodone IR (Oxaydo®)

Dosage forms

Tablet
  • 5 mg
  • 7.5 mg

Dosing

Adults (opiate-naïve)
  • 5 - 15 mg every 4 - 6 hours as needed
  • Do not exceed 60 mg in 24 hours
Discontinuing therapy
  • If patients have been taking regularly, taper the dose gradually, by 25% to 50% every 2 to 4 days and monitor for withdrawal symptoms

Generic / Price

  • No generic
  • Tablets (#30) - $$$$

Other

  • DEA Schedule II
  • Duration of action: 3 - 4 hours
  • Oxycodone is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.

Oxycodone ER (Oxycontin®)

Dosage forms

Tablet, extended-release
  • 10 mg
  • 15 mg
  • 20 mg
  • 30 mg
  • 40 mg
  • 60 mg
  • 80 mg

Dosing

Adults (opiate-naïve)
  • 10 mg every 12 hours
  • Increase dose every 1 - 2 days in increments of 25 - 50% of the current dose
Children ≥ 11 years
  • Opiate-naïve
    • Not recommended
  • 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
Converting from other oxycodone products
  • Total daily oxycodone dose can be divided in half and given every 12 hours
Discontinuing therapy
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days and monitor for withdrawal symptoms

Generic / Price

  • Generic (30 tablets) - $-$$$$, depending on the strength

Other

  • DEA Schedule II
  • 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.

Oxycodone ER (Xartemis® XR)

Dosage forms

Tablet, extended-release
  • Oxycodone : Acetaminophen
    • 7.5 mg: 325 mg

Dosing

Adults (opiate-naïve)
  • Starting: 2 tablets every 12 hours
  • The second dose of 2 tablets may be given as early as 8 hours after the initial dose in patients without adequate relief. Subsequent doses are to be administered 2 tablets every 12 hours.
  • May take without regard to food
  • In patients with renal and/or hepatic impairment, start with 1 tablet every 12 hours and titrate as needed
Discontinuing therapy
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days and monitor for withdrawal symptoms

Generic / Price

  • No generic
  • Tablet (#30) - $$

Other

  • DEA Schedule II
  • Xartemis is not interchangeable with other oxycodone products
  • Do not break, chew, crush, cut, dissolve or split the tablets
  • Do not exceed 4000 mg of acetaminophen/day
  • Oxycodone is a sensitive CYP3A4 substrate. Use caution with CYP3A4 inducers and inhibitors.

Oxycodone ER (Xtampza® ER)

Dosage forms

Capsule, extended-release
  • 9 mg (equivalent to 10 mg oxycodone)
  • 13.5 mg (equivalent to 15 mg oxycodone)
  • 18 mg (equivalent to 20 mg oxycodone)
  • 27 mg (equivalent to 30 mg oxycodone)
  • 36 mg (equivalent to 40 mg oxycodone)

Dosing

Adults (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
Discontinuing therapy
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days and monitor for withdrawal symptoms

Generic / Price

  • No generic
  • Capsules (#30) - $$$-$$$$, depending on the strength

Other

  • DEA Schedule II
  • 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.


Oxymorphone IR (Opana®)

Dosage forms

Tablet
  • 5 mg
  • 10 mg

Dosing

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

Generic / Price

  • Generic (30 tablets) - $$

Other

  • DEA Schedule II
  • Half-life: 9 - 11 hours

Oxymorphone ER (Opana® ER)

Dosage forms

Tablet, extended-release
  • 5 mg
  • 7.5 mg
  • 10 mg
  • 15 mg
  • 20 mg
  • 30 mg
  • 40 mg

Dosing

Adults (opiate-naïve)
  • 5 mg every 12 hours
  • Adjust dose in increments of 5 - 10 mg every 12 hours, every 3 to 7 days
  • Take on an empty stomach, at least one hour prior to or two hours after eating
  • Kidney disease (CrCl < 50 ml/min): Use caution. Start with 5 mg dose. For patients on prior opioid therapy, start Opana ER at 50% lower than the starting dose for a patient with normal renal function.
  • Liver disease (Child-Pugh A): Use caution. Start with 5 mg dose. For patients on prior opioid therapy, start Opana ER at 50% lower than the starting dose for a patient with normal hepatic function.
  • Liver disease (Child-Pugh B/C): DO NOT USE
Converting from Opana® to Opana® ER
  • Total daily dose remains the same. Administer half the total daily Opana dose as Opana ER, every 12 hours.
Converting from parenteral oxymorphone
  • The absolute oral bioavailability of Opana ER is approximately 10%. Convert patients receiving parenteral oxymorphone to Opana ER by administering 10 times the patient's total daily parenteral oxymorphone dose as Opana ER in two equally divided doses (e.g., [IV dose x 10] divided by 2).
Converting from other opioids to Opana ER
Discontinuation
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal
  • Do not discontinue abruptly

Generic / Price

  • No generic
  • 60 tablets - $$-$$$$, depending on strength

Other

  • DEA Schedule II
  • Do not crush, cut, chew, or dissolve tablets


Pentazocine (Talwin NX®)

Dosage forms

Tablet
  • Pentazocine 50 mg and naloxone 0.5 mg per tablet

Dosing

Adults
  • One tablet every 3 - 4 hours
  • May increase to 2 tablets when needed
  • Do not exceed 12 tablets in 24 hours

Generic / Price

  • Generic (30 tablets) - $

Other

  • DEA Schedule IV
  • 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.


Tapentadol IR (Nucynta®)

Dosage forms

Tablet
  • 50 mg
  • 75 mg
  • 100 mg

Dosing

Adults (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
Discontinuation
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal
  • Do not discontinue abruptly

Generic / Price

  • No generic
  • 30 tablets - $$$$

Other

  • DEA Schedule II
  • 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.

Tapentadol ER (Nucynta® ER)

Dosage forms

Tablet, extended-release
  • 50 mg
  • 100 mg
  • 150 mg
  • 200 mg
  • 250 mg

Dosing

Adults (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
Discontinuation
  • Taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal
  • Do not discontinue abruptly

Generic / Price

  • No generic
  • 60 tablets - $$$$

Other

  • DEA Schedule II
  • 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.


Tramadol IR (Ultram®)

Dosage forms

Tablet
  • 50 mg

Dosing

  • 50 - 100 mg every 4 - 6 hours as needed
  • Do not exceed 400 mg in 24 hours

Generic / Price

  • Generic (30 tablets) - $

Other

  • DEA Schedule IV
  • 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.

Tramadol - APAP IR (Ultracet®)

Dosage forms

Tablet
  • Tramadol 37.5 mg and acetaminophen 325 mg per tablet

Dosing

  • 2 tablets every 4 - 6 hours as needed
  • Do not exceed 8 tablets in 24 hours

Generic / Price

  • Generic (30 tablets) - $

Other

  • DEA Schedule IV
  • 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.

Tramadol ER (Ultram® ER)

Dosage forms

Tablet, extended-release
  • 100 mg
  • 200 mg
  • 300 mg

Dosing

  • 100 mg once daily
  • Increase dose in 100 mg increments every 5 days as needed
  • Do not exceed 300 mg once daily

Generic / Price

  • Generic (30 tablets) - $

Other

  • DEA Schedule IV
  • 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.

Tramadol ER (Conzip®)

Dosage forms

Capsule, extended-release
  • 100 mg
  • 200 mg
  • 300 mg

Dosing

  • 100 mg once daily
  • Increase dose in 100 mg increments every 5 days as needed
  • Do not exceed 300 mg once daily

Generic / Price

  • No Generic
  • Price (30 capsules) - $$$$

Other

  • DEA Schedule IV
  • 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.




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

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

Codeine

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

Dihydrocodeine

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

Fentanyl

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

Hydrocodone

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

Hydromorphone (Dilaudid®, Exalgo®)

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

Meperidine

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

Methadone

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

Naltrexone

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

Oxycodone

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

Pentazocine

  • Hypertension - pentazocine may raise blood pressure in some patients

Tramadol

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


Drug interactions

All opiates

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

Buprenorphine

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

Butorphanol

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

Codeine

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

Dihydrocodeine

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

Fentanyl

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

Hydrocodone

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

Meperidine

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

Methadone

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

Morphine

Oxycodone

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

Tapentadol

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

Tramadol

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




  • NOTE: THIS TABLE IS NOT FOR CONVERTING BETWEEN DOSES OF DIFFERENT OPIOIDS. There are no established conversion ratios for converting from one opioid to another. See individual drug package inserts for recommendations on converting between drugs.
  • Reference [3,7]
Analgesic equivalent doses for select opioids
Opioid Equivalent analgesic oral dose
Morphine 30 mg
Oxycodone 15 - 20 mg
Hydrocodone 30 - 45 mg
Hydromorphone 7.5 mg
Codeine 200 mg
Pentazocine 166 mg
Fentanyl (transdermal) every 2 mg/day of morphine is
approximately equivalent to 1 mcg/hr of transdermal fentanyl
Methadone See Methadone dosing in opiate table


  • PMID 29114811 - Interpretation of Urine Drug Screens: Metabolites and Impurities, JAMA (2017)
URINARY METABOLITES OF OPIATES
Opiate Urinary metabolite Comment
Codeine
  • Morphine
  • Hydrocodone (< 10%)
  • Norcodeine
  • Codeine is metabolized to morphine
Buprenorphine
  • Norbuprenorphine
Fentanyl
  • Norfentanyl
Heroin
  • 6-Monoacetylmorphine
  • Morphine
  • Normorphine
  • Morphine may be the only metabolite detected after heroin use
Hydrocodone
  • Hydromorphone
  • Norhydrocodone
  • Dihydrocodeine
Hydromorphone
  • Hydromorphone-3-glucuronide
Methadone
  • 2-Ethylidene-1
  • 5-dimethyl-3
  • 3-diphenylpyrrolidine
Morphine
  • Normorphine
  • Hydromorphone (< 10%)
  • Morphine-6-glucuronide
  • Morphine-3-glucuronide
  • Codeine is sometimes a contaminant of morphine during manufacturing
  • Codeine contamination is typically 0.04% - 0.5% of morphine concentrations
Oxycodone
  • Oxymorphone
  • Noroxycodone
  • Hydrocodone is sometimes a contaminant of oxycodone during manufacturing
  • Hydrocodone contamination is typically < 0.1% of oxycodone concentrations
Oxymorphone
  • Oxymorphone-3-glucuronide
  • 6-hydroxy-oxymorphone


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




Pricing legend
  • $ = 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