Duloxetine (Cymbalta®)
VERDICT & SUMMARY Duloxetine (Cymbalta®)
For the treatment of diabetic peripheral neuropathic pain Committee’s Verdict: CATEGORY A (Q1) BNF: 4.3.4 Duloxetine is suitable for prescribing in primary care for the treatment of peripheral neuropathic pain associated with diabetes. Category A: suitable for prescribing in primary care Q1 rating: The evidence for comparative efficacy and safety of duloxetine for diabetic neuropathic pain was considered to be relatively strong. Three double-blind randomised controlled trials found significantly greater Q2 Q1 efficacy of duloxetine than placebo using pain scores and other pain- higher place higher place related tools, that was considered to be clinically important. A dose of 120 weaker evidence stronger evidence mg per day was not found to be superior to 60 mg per day. There were no comparisons with other agents. NICE guidance gives duloxetine a high place in therapy for this specific indication. Q4 Q3 lower place lower place The Q rating relates to the drug’s position on the effectiveness indicator weaker evidence stronger evidence grid. The strength of the evidence is determined by the quality and quantity of studies that show significant efficacy of the drug compared with placebo or in primary care therapy Place in alternative therapy. Its place in therapy in primary care takes into account safety Strength of evidence for efficacy and practical aspects of using the drug in primary care, alternative options, relevant NICE guidance, and the need for secondary care input.
MTRAC reviewed this drug because of an additional licensed indication.
Licensed indication considered Agents used in the control of diabetic neuropathic pain include amitriptyline and nortriptyline (although these Duloxetine is indicated for the treatment of diabetic 1 are not licensed for this indication), duloxetine, peripheral neuropathic pain in adults. gabapentin and pregabalin.2 Opioids (morphine, Background information methadone, tramadol and oxycodone) are tried when other measures fail. Neuropathic pain, caused by damage in the peripheral or central nervous system, may be more difficult to Duloxetine, a selective serotonin and noradrenaline treat than other types of pain because standard reuptake inhibitor, was launched in the UK in 2004 as analgesics often do not provide sufficient relief. It is Yentreve for the treatment of stress urinary syndrome associated with a significant impairment of quality of and later as Cymbalta for the treatment of major life and a large cost burden on healthcare services.2 depression, diabetic peripheral neuropathic pain in adults, and generalized anxiety disorder. Different disease processes may produce neuropathic pain syndromes. Diabetes is associated with NICE guidance generalised polyneuropathy of the peripheral nervous The NICE guideline for the management of type 2 system. An age-standardised incidence rate of 27 per 4 diabetes (CG87, published in May 2009) included a 100,000 patient years was reported in 2008 for painful 2 section on the management of diabetic neuropathic diabetic neuropathy, rising with age and severity. pain. The guideline recommended a trial of The symptoms of diabetic neuropathy include initial duloxetine, gabapentin or pregabalin (whichever is the loss of ability to sense pain and temperature cheapest at the maximum dose), when standard sensation, followed by the development of pain in the analgesic measures or a tricyclic drug have not fingers and toes that progresses along the limbs. The controlled the symptoms.4 pain has been described as burning, stabbing, and A draft NICE guideline on the management of tingling, and can lead to depression, anxiety, neuropathic pain was published in October 2009 for interference with sleep, and severe functional 5 consultation. It recommended the use of duloxetine disability. Abnormal thermal sensations (burning or as first-line treatment for painful diabetic neuropathy. ice-cold) are also reported by patients. The final guideline is expected in March 2010.
October 2009 Page 1 of 2 Clinical efficacy Adverse effects Three published, multicentre, double-blind The percentage of patients who withdrew from the randomized controlled trials have assessed the studies because of adverse events was greater in efficacy and safety of duloxetine compared with those groups taking duloxetine (4% to 19% for both placebo (n = 457, 348, 334).6-8 All three studies were doses across the studies) than placebo (3% to 7%). sponsored by the manufacturer of duloxetine. The difference was significant for both doses in one Included patients were aged ≥ 18 years with type 1 or study6 and for the higher dose in all studies.6-8 type 2 diabetes, and had confirmed daily bilateral Adverse events included somnolence, dizziness, neuropathic pain for at least six months. Patients fatigue and gastrointestinal disturbances. See the having any of a number of co-morbid conditions, Summary of Product Characteristics (SPC) for further including depression and anxiety, were excluded. details.1 After a two- to three-week screening period, patients Additional information were randomized to treatment with either duloxetine 60 mg/day, duloxetine 120 mg/day or placebo for 12 • The recommended dose of duloxetine for weeks. Patients completed a daily diary of pain neuropathic pain is 60 to 120 mg daily. scores on an 11-point Likert scale. The primary • Duloxetine is contraindicated in patients with liver outcome was the change in the weekly mean of the disease resulting in hepatic impairment. average 24-hour pain score from baseline to endpoint. • The current cost of one year’s treatment with Use of paracetamol or aspirin was allowed during the duloxetine 60 mg/day is £361. study, but no other medication for neuropathic pain. References In all three studies, the 24-hour average pain scores were significantly more reduced by duloxetine than by 1. Cymbalta 30 mg & 60 mg hard gastro-resistant placebo (p < 0.01).6-8 The changes in the scores capsules. Summary of Product Characteristics. Eli Lilly. across the three studies ranged from -2.50 to -2.89 for 2009. www.emc.medicines.org.uk/
Launch date: 2004 Manufacturer: Eli Lilly EU/1/04/296/001-9 WARNING: This sheet should be read in conjunction with the Summary of Product Characteristics This guidance is based upon the published information available in English at the time the drug was considered. It remains open to review in the event of significant new evidence emerging. MTRAC can be contacted at Medicines Management, School of Pharmacy, Keele University, Keele, Staffodshire ST5 5BG Tel: 01782 734131 Fax: 01782 713586 Email: [email protected] Web: www.mtrac.co.uk
Date: October 2009 ©Midlands Therapeutics Review & Advisory Committee VS09/14