New Drugs in Palliative Care Dr Chloe Webb Palliative Care Registrar Beaumont Hospital

Drugs Covered Targin Pecfent Effentora Palexia Oxynorm Dispersa Relistor Durogesic Dtrans Buprenorphine Transtec Butrans

Targin

Targin Indication Opioid analgesic Combines oxycodone with opioid antagonist naloxone Naloxone is added to counteract opioid-induced constipation - Blocks the action of oxycodone at opioid receptors locally in the gut. Oral use Twice daily dose

Targin Recommended starting dose in opioid naïve patients - 10 mg/5 mg oxycodone/naloxone BD Max daily dose of Targin - 80 mg/40mg. If higher doses required – consider administration of supplemental oxycodone hydrochloride prolonged-release at the same time. Beneficial effect of naloxone hydrochloride on bowel function may be impaired with additional oxycodone

PecFent Fentanyl Nasal Spray Indication Management of breakthrough pain in adults already receiving maintenance opioid therapy for chronic cancer pain 60mg PO morphine daily, 25mcg/hr TD fentanyl, 30mg PO oxycodone daily, 8mg PO hydromorphone daily

PecFent Nasal mucosa is highly vascularised with a large surface area Lipophilic drugs such as fentanyl are rapidly and extensively absorbed Avoids first pass metabolism and issues with oral pathologies e.g. nausea / vomiting or dry / ulcerated buccal membrane

PecFent Yellow pack – 100mcg/spray strength Available in two strengths: Yellow pack – 100mcg/spray strength Violet pack – 400mcg/spray strength

Pecfent Starting dose of 100 mcg (one spray) Titrated to an “effective dose” At least 4 hours before further dose of PecFent can be used. Review background opioid treatment if >4 episodes of breakthrough pain/24hrs

Patient Instructions Blow your nose if you feel you need to Sit down with head upright Put the nozzle a short distance (about 1 cm) into your nostril Close the other nostril with a finger from your other hand Spray (listen for the click) Stay sitting for at least 1 minute after using the nasal spray Do not blow your nose straight after using the PecFent nasal spray

Effentora

Effentora Buccal Fentanyl Indication Treatment of breakthrough pain in patients with cancer already receiving maintenance opioid therapy for chronic cancer pain. 60mg PO morphine daily, 25mcg/hr TD fentanyl, 30mg PO oxycodone daily, 8mg PO hydromorphone daily

Effentora Individually titrated to an “effective”/maintenance dose The effective dose of Effentora is not predictable from the daily maintenance dose of opioid. At least 4 hours between doses May require readjustment of maintenance dose

Effentora - Titration 100mcg initially - If pain still present within 30mins - Give 2nd same strength Effentora tablet. Increase dose to the next strength to treat the next episode of pain. Multiple tablets may be used to treat a single episode of pain - up to four 100mcgs - up to four 200mcgs Doses >800mcgs were not evaluated in clinical studies.

Effentora – How to use it! Blister pack (peel open) Place tablet above an upper rear molar between cheek and the gum/sublingually Dissolves/disintergrates in ~15-25mins Shouldn’t be sucked or chewed If any tablet remains after 30mins – swallow with a glass of water

Palexia

Palexia Tapentadol Indication Relief of moderate to severe acute & chronic pain in adults µ-opioid receptor agonist & noradrenaline reuptake-inhibition Nociceptive, neuropathic, visceral and inflammatory pain Mainly evidence supports use in nociceptive pain conditions including postoperative orthopaedic & abdominal pain, also chronic pain due to osteoarthritis (hip/knee).

Palexia SR Starting dose - 50mg tapentadol BD (12hrs apart). Increase in increments of 50 mg tapentadol SR twice daily every 3 days Titrate dose to provide adequate analgesia with minimal undesirable effects Antiemetic prophylaxis is not usually required Laxative porphylaxis is not usually required

Palexia Non-Opioid Dose Independent Tramadol PO (mg/d) < 400mg Oxycodone PO (mg/d) < 40mg 40 – 60mg 60 – 80mg Morphine PO (mg/d) < 80mg 80 – 120mg 120 – 160mg Hydromorphone PO (mg/d) < 12mg 12 – 16mg 16 – 20mg Fentanyl TD (µg/h) < 37.5µg 37.5 – 50µg 50 – 75µg Buprenorphine TD (µg/h) < 35µg 35 – 52.5µg 52.5 – 70µg Palexia SR 50mg BD 100mg BD 150mg BD

Oxynorm Dispersa Orodispersible oxycodone Indication Treatment of severe pain/breakthrough pain Oral use Taken every 4-6hours as needed Dissolves on tongue

Relistor Methylnaltrexone bromide Subcutaneous injection Indication Treatment of opioid-induced constipation in palliative care patients when response to usual laxative therapy has not been sufficient Given on top of usual laxatives

Relistor Dose Recommended dose - 8 mg (0.4 ml) for patients weighing 38-61 kg - 12 mg (0.6 ml) for patients weighing 62-114 kg - Patients whose weight falls outside these ranges should be dosed at 0.15 mg/kg. Induces prompt bowel motion Single dose alternate days. Doses may also be given with longer intervals, as per clinical need. Rotate injection sites (upper arms & legs, abdomen)

Relistor Use with caution in patients with known or suspected GI lesions. - Increased risk of GI perforation Advise patients to discontinue and consult their doctor if they develop severe, persistent, and/or worsening abdominal symptoms (GI perforation). Note concomitant medications [e.g. bevacizumab (AVASTIN), NSAIDs and steroids]

Durogesic

Durogesic Transdermal fentanyl patch Indication Management of chronic intractable pain in patients requiring opioid analgesia Reapplied every 72hours Initial dose - based on the patient's current opioid use. Recommended that Durogesic DTrans be used in opioid tolerant patients

Durogesic DTrans Opioid-tolerant patients Use Equianalgesic potency conversion chart to convert from PO/parenteral opioids to Durogesic Dtrans. Dose may be titrated up or down - increments of 12/25 µg/h - achieve the lowest appropriate dose of Durogesic Dtrans - depends on response and supplementary analgesic requirements.

Oral 24hr Morphine (mg/day) Durogesic Dtrans Dose (µg/h) 4 hourly PO morphine (mg) breakthrough < 44 12 < 7.5 45-89 25 10-15 90-134 37 15-20 135-189 50 25-30 190-224 62 35 225-314 75 40-50 315-404 100 55-65 405-494 125 70-80 495-584 150 85-95 585-674 175 100-110 675-764 200 115-125 765-854 225 130-140 855-944 250 145-155 945-1034 275 160-170 1035-1124 300 175-185

Durogesic DTrans Opioid-naïve patients The normal initial Durogesic DTrans dosage should not exceed 25 µg/h. Recommended that patients be titrated with low doses of immediate-release opioids (e.g., morphine, oxycodone) to attain equianalgesic dose relative to Durogesic 12/25 µg/h TD fentanyl is licensed for use as a 1st line strong opioid severe dysphagia, renal failure high risk of diversion and tablet misuse.

Durogesic – Patient Instruction Apply to upper arm or chest area Don’t apply patch in same place twice in a row Clean and dry skin Takes 18-24hr to become therapeutic intially Open the pouch – tear off edge of pouch Mind not to tear patch Peel off backing – try not to touch sticky side Press onto skin firmly (hold for 30secs) Wash your hands

Butrans & Transtec Transdermal Buprenorphine Indication Pain of moderate to severe intensity Alternative to both weak opioids and morphine Not suitable for the treatment of acute pain Take into account previous opioid history Opioid naive pts – prescribe lowest strength (5mcg/h)

Buprenorphine Butrans Transtec 7 day patch Doses available 5, 10 and 20mcg/h Onset of action 18–24h Peak plasma concentration 3 days 4 day patch Doses available 35, 52.5, 70mcg/h Onset of action 21h for 35mcg/h patch; 11h for 70mcg/h patch Peak plasma concentration 60 hrs

Butrans vs Morphine Buprenorphine Morphine 5µg/hr 10mg/24hrs 10µg/hr

References Palliative Care Formulary 3 - Robert Twycross and Andrew Wilcock www.palliativedrugs.com www.medicines.ie Archimedes Pharma Cephalon JanssenCilag Grunenthal Mundipharma Wyeth