1. Drug-Specific Therapies
Unit 6
Joseph Shega, MD

2. Product Specific Information
Dosing interval
Key instructions
Drug interactions common (in the class)
Opioid tolerant patients
Contraindications
Product specific safety

3. Morphine Sulfate ER (Avinza)
Dose- Once daily
Instructions-
Non-tolerant initial dose 30mg
3 day titration intervals minimum
swallow whole; do not chew pellets
Max dose 1600mg, renal toxicity fumaric acid
Interactions- Alcoholic beverages rapid release and absorption of potentially fatal dose
Tolerant Patients- 90mg capsules and up
Capsules 30mg, 45mg, 60mg, 75mg, 90mg, 120mg
Contains fumarate
Immediate release and delayed release component
DI- Dosing Interval
KI Key Instructions
SPI- Specific drug interactions
OTP- opioid tolerant patients
PSS- Product specific safety

4. Butrans (Buprenorphine)
Dosing- one transdermal system every 7 days
Instructions-
5mcg/hr opioid non-tolerant, <30mg oral morphine, or mild to moderate hepatic impairment
10mcg/hr, 30 to 80mg oral morphine, taper to 30mg dose first then initiate dose
Minimum 72hrs prior to dose adjustment
Max dose 20mcg/hr, QTc prolongation
Dispose by folding patch and flush down toilet
Transdermal system- 5mcg/hr, 10mcg/hr, 20mcg/hr

5. Butrans (Buprenorphine)…
Apply non irritated skin
Clip hair and wash water only
Rotate site every 3 weeks before reapply
Do not cut patch
Butrans should be applied to the upper outer arm, upper chest, upper back, or the side of the chest (See Figure 1). These 4 sites (located on both sides of the body) provide 8 possible Butrans application sites. You should change the skin site where you apply Butrans each week, making sure that at least 3 weeks (21 days) pass before you re-use the same skin site.
Apply Butrans to a hairless or nearly hairless skin site. If needed, you can clip the hair at the skin site (See Figure 2). Do not shave the area. The skin site should not be irritated. Use only water to clean the application site. You should not use soaps, alcohol, oils, lotions, or abrasive devices. Allow the skin to dry before you apply the patch.

6. Butrans (Buprenorphine)…
Interactions-
CYP34A inhibitors increase levels and inducers decrease levels
Benzodiazepine may increase respiratory depression
Class IA and III antiarythmics and other arrythmogenic agents increase risk QTc prolongation and torsade
Tolerant patients- 10mcg/hr and 20mcg/hr
Safety- QTc and torsade, hepatotoxicity, application site skin reactions
Equivalency to oral morphine has not been established
In case of overdose, priorities are the re-establishment of a patent and protected airway and institution of assisted or controlled ventilation if needed. Employ other supportive measures (including oxygen, vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life support techniques.
Naloxone may not be effective in reversing any respiratory depression produced by buprenorphine. High doses of naloxone, mg/70 kg, may be of limited value in the management of buprenorphine overdose. The onset of naloxone effect may be delayed by 30 minutes or more. Doxapram hydrochloride (a respiratory stimulant) has also been used.
Remove BUTRANS immediately. Because the duration of reversal would be expected to be less than the duration of action of buprenorphine from BUTRANS, carefully monitor the patient until spontaneous respiration is reliably re-established. Even in the face of improvement, continued medical monitoring is required because of the possibility of extended effects as buprenorphine continues to be absorbed from the skin. After removal of BUTRANS, the mean buprenorphine concentrations decrease approximately 50% in 12 hours (range hours) with an apparent terminal half-life of approximately 26 hours. Due to this long apparent terminal half-life, patients may require monitoring and treatment for at least 24 hours.

7. Methadone Hydrocholide (Dolophine)
Dosing- Every 8 to 12 hours
Instructions-
Non-tolerant patients 2.5 to 10mg
Equianalgesic conversions using tables can result in overdose and death, use lower estimate
Inter-patient variability in absorption, metabolism, and relative potency
Opioid detoxification only provided by certified addiction program
5mg and 10mg tabs

8. Methadone Hydrocholide (Dolophine)…
Interactions-
CYP450 inhibitors increase levels and inducers decrease levels
Anti-retrovirals mixed effects
Drug-drug interactions are complex
Benzodiazepine may increase respiratory depression
Arrythmogenic; QTc prolongation and torsade (>200mg daily)
Tolerant pts- See full prescribing information
Safety-
QTc prolongation and torsade
Peak respiratory depression later and persists longer than other opiods
Clearance may increase during pregnancy
False positive urine drug screen possible
Relative potency to morphine varies

9. Duragesic (Fentanyl) Dosing- Every 72 hours Instructions -
product specific conversion information
50% dose in mild to moderate hepatic/renal impairment
Avoid in severe hepatic/renal impairment
Application: as with other patch
72 hour titration intervals
Avoid heat exposure
Avoid accidental contact when holding kids
Fold and flush down toilet
Contraindications: opioid non-tolerant, acute pain or short use duration, management post-op pain, and mild pain
12, 25, 50, 75, and 100mcg

10. Duragesic (Fentanyl)…
Interactions- CYP34A inhibitors increase levels and inducers decrease levels
Opioid tolerant persons only
Safety- Accidental exposure secondary exposure unwashed/unclothed application site
Increased exposure with increased core body temp
Bradycardia
Application site skin reactions
Relative potency to morphine see individual product information

11. Morphine Sulfate ER-Naltrexone (Embeda)
Dosing Interval: Daily or every 12 hours
Instructions:
Initial dose as first opioid 20mg/0.8mg
Titrate minimum 3 day interval
Swallow capsules whole, NO CRUSH/CHEW; releases morphine (OD) and naltrexone (withdrawal)
Open capsule and sprinkle pellets, swallow no chew
Specific Drug Interactions
Alcoholic beverages may result in rapid release and absorption morphine
PGP inhibitors (quinidine) may increase absorption/exposure morphine 2-fold
Opioid tolerant only 100mg/4mg
Doses 20mg/0.8mg, 30mg/1.2mg, 50mg/2mg, 60mg/2.4mg, 80mg/3.2mg, 100mg/4mg
Not been shown to decrease abuse potential

12. Hydromorphone Hydrochloride (Exalgo)
Dosing- Once daily
Instructions-
Conversions in product information
Moderate hepatic impairment 25% usual dose
Moderate renal impairment 50% and severe 25% of usual dose
Titrate every 3-4 days
Do not crush or chew, swallow whole
Opioid tolerant only
Safety- Allergic manifestations sulfa
Oral morphine to hydromorphone 5:1
XR 8mg,12mg,16mg
Peak plasma level at 16hours, elimination half life 24 hours

13. Morphine Sulfate ER Capsules (Kadian)
Dosing- Daily or every 12 hours
Instructions-
Not recommended as first opioid
Titrate minimum of 2 day interval
Open capsule/sprinkle pellets
Swallow capsule whole
Interactions-
Alcohol may result in rapid release and absorption of morphine
PGP inhibitors (quinidine) may increase absorption 2-fold
Tolerant pts- 100mg capsules and higher
10mg. 20mg, 30mg, 50mg, 60mg, 80mg, 100mg, 200mg

14. Morphine Sulfate ER Capsules (Kadian)…
Kadian can be administered through a 16 french gastrostomy tube
Flush g-tube with water to ensure wet
Sprinkle Kadian pellets into 10cc water
Use a swirling motion to pour pellets and water into G-tube through a funnel
Rinse the beaker with a further 10cc of water and pour this into the funnel
Repeat rinsing until no pellets remain in the beaker
Do not administer Kadian pellets through NG tube

15. Morphine Sulfate CR (MS Contin)
Dosing- every 8 or 12 hours
Instructions-
Not recommended as first opioid
Titrate minimum 2 day interval
Swallow whole, no crush/chew
Interactions- PGP inhibitors (quinidine) increase absorption/exposure 2-fold
Tolerant pts- 100mg tablets and higher
15mg, 30mg, 60mg, 100mg, 200mg

16. Tapentadol (Nucynta ER)
Dosing- Every 12 hours
Instructions-
50mg every 12 hours initial dose in opioid nontolerant
Titrate 50mg increments, every 3 days
Maximum daily dose 500mg
Swallow whole, no crush/chew
One tablet at a time with enough water to immediately swallow
Moderate liver impairment, maximum dose 100mg daily
Avoid use severe liver/renal impairment
50mg, 100mg, 150mg, 200mg, 250mg

17. Tapentadol (Nucynta ER)…
Interactions-
Alcohol may result in rapid release and absorption
Contraindication MAOIs
Tolerant pts- No product-specific considerations
Safety-
Risk serotonin syndrome
Angioedema
Hallucinations/Suicidal Ideation
Equipotency to oral morphine has not been established

18. Oxymorphone hydrochloride (Opana ER)
Dosing- Every 12 hours, benefit asymmetric dosing
Instructions-
5mg every 12 hrs opioid non-tolerant, mild hepatic and renal impairment, and persons over the of 65
Swallow whole, no crush/chew
One tablet at a time with enough water to immediately swallow
Titrate 2-day intervals
Contraindicated moderate to severe hepatic/renal impairment
Interactions- Alcohol may result in rapid release and absorption
Relative potency 3:1 oral morphine to oxymorphone
ER 5mg, 7.5mg, 10mg, 15mg, 20mg, 30mg, 40mg

19. Oxycodone Hydrochloride (OxyContin)
Dosing - Every 12 hours
Interactions-
Opioid naive 10mg every 12 hours
Titrate at a minimum of 1-2 day intervals
Hepatic impairment 1/3 to ½ usual dose
Renal impairment ½ usual dose
Consider other analgesic in patients difficulty swallowing or GI disorder predispose obstruction
Swallow whole, no crush/chew
One tablet at a time with enough water to immediately swallow
Interactions- CYP34A inhibitors increase levels and inducers decrease levels
Tolerant pts- single dose 40mg, daily dose 80mg opioid tolerant only
Safety-
choking, gagging, and tablets stuck back throat; difficulty swallowing
Contraindication GI obstruction
Relative potency 2:1 oral morphine to oxycodone
CR 10mg, 15mg, 20mg, 30mg, 40mg, 60mg, 80mg

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21. Thank You!