Drug-Specific Therapies Unit 6 Joseph Shega, MD

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

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

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

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.

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, 10-35 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 10-24 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.

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

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

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

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

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

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

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

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

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

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

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

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

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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