Estimated impact for the NHS | Narcolepsy with or without cataplexy in adults: pitolisant | Advice

Other treatments

Managing narcolepsy involves implementing good sleep hygiene and accessing counselling and support. Medicines used to treat the symptoms of narcolepsy include stimulants such as modafinil, dexamfetamine or methylphenidate (off-label), and sodium oxybate. Antidepressants such as selective serotonin reuptake inhibitors (SSRIs; for example fluoxetine), serotonin-noradrenaline reuptake inhibitors (SNRIs; for example venlafaxine) or tricyclic antidepressants (for example clomipramine) are also used off-label (Narcolepsy: NHS Choices).

Costs of other medicines

See table 3 for details.

Table 3 Costs of other medicines used in narcolepsy: stimulants and sodium oxybate

Medicine	Usual dose ^a	Cost per 30 days treatment, excluding VAT
Pitolisant tablets	4.5 mg to 36 mg once daily^b	£310.00 to £620.00^c
Modafinil tablets	Initially 200 mg (elderly 100 mg) daily, either in 2 divided doses morning and at noon or as a single dose in the morning, adjusted according to response to 200 mg to 400 mg daily in 2 divided doses or as a single dose^d	£6.59 to £32.38^e
Methylphenidate tablets	10 mg to 60 mg (usually 20 mg to 30 mg) daily in divided doses before meals^f	£6.06 to £32.76^e
Dexamfetamine tablets	Initially 10 mg (elderly 5 mg) daily in divided doses increased at weekly intervals by 10 mg (elderly 5 mg) daily to a maximum of 60 mg daily^g	£26.52 to £318.24^e
Sodium oxybate oral solution 500 mg/ml	Initially 2.25 g on retiring and repeated 2.5 to 4 hours later, increased according to response in steps of 1.5 g daily in 2 divided doses at intervals of 1 to 2 weeks to a maximum of 9 g daily in 2 divided doses^h	£540.00 to £1,080.00^e,i
^a These directions do not represent the full range that can be used and they do not imply therapeutic equivalence. ^b From pitolisant summary of product characteristics. Pitolisant is licensed in adults for the treatment of narcolepsy with or without cataplexy. ^c Costs taken from MIMS, February 2017 (excluding VAT). ^d From BNF and modafinil summary of product characteristics. Modafinil is licensed in adults for the treatment of excessive sleepiness associated with narcolepsy with or without cataplexy. ^e Costs taken from Drug Tariff, February 2017 (excluding VAT). ^f From BNF. Methylphenidate is not licensed for narcolepsy (methylphenidate summaries of product characteristics). ^g From BNF and dexamfetamine summaries of product characteristics. Dexamfetamine is licensed for narcolepsy. ^h From BNF and sodium oxybate summary of product characteristics. Sodium oxybate is licensed in adults for the treatment of narcolepsy with cataplexy. ⁱ Lower cost estimate is based on the exact cost for the volume required (270 ml) for a 30‑day supply at a dose of 4.5 g daily. However sodium oxybate is a special container with a pack size of 180 ml, therefore the pack cannot be split. In practice the prescribed quantity would need to be a multiple of 180 ml, taking into account that sodium oxybate is a schedule 2 controlled drug and the quantity prescribed should be enough meet the person's clinical needs for no more than 30 days (Drug Tariff, February 2017; NICE guideline on Controlled drugs: safe use and management).

Current or estimated usage

The company anticipate that pitolisant will be used initially for people with narcolepsy who either cannot tolerate current treatments or have not responded to these. They estimate that there are approximately 30,000 people in the UK with narcolepsy, about 5,000 of who receive medicines to treat this. Of these, they estimate that about 50% of people who are currently being treated may have issues with their existing medicines and may be eligible for treatment with pitolisant; equating to 2,500 people over a 5‑year period (source: Lincoln Medical Ltd, October 2016).

Likely place in therapy

Pitolisant is the first of a new class of medicine, a histamine H3‑receptor antagonist/inverse agonist, licensed to treat narcolepsy. The European Public Assessment Report (EPAR) concluded that there is sufficient evidence supporting pitolisant efficacy in the treatment of narcolepsy with or without cataplexy in adults and the safety profile is acceptable in this condition, although further long-term safety data are required.

Pitolisant is an additional class of medicine that could be used to treat narcolepsy with or without cataplexy. Other medicines licensed for use in this rare condition include the central nervous system stimulants, modafinil and dexamfetamine, and the central nervous system depressant, sodium oxybate. The EPAR suggests that modafinil is the first-line treatment for excessive daytime sleepiness in people with narcolepsy, but its effect on cataplexy is less clear. However, modafinil and other stimulants can have serious cardiovascular and central nervous system side effects (including hypertension, tachycardia, anxiety and depression) and could lead to abuse disorders and weight loss. The summary of product characteristics (SPC) for modafinil states that while studies have demonstrated a low potential for dependence, the possibility of dependence with long-term use cannot be entirely excluded, and caution is needed in people with a history of alcohol, drug or illicit substance abuse. Further information to support the safe use of modafinil is available in a Drug Safety Update from 2011.

Sodium oxybate is used in particular to treat cataplexy, but it has abuse potential. The SPC for sodium oxybate states that there is no clear evidence of dependence at therapeutic doses, but this possibility cannot be excluded because of reports of dependence after illicit use at frequent repeated doses in excess of the therapeutic dose range. Sodium oxybate is a schedule 2 controlled drug with requirements around supply, possession, prescribing, and record keeping.

In the limited number of clinical trials that are available with pitolisant in narcolepsy, the most frequent adverse drug reactions reported were insomnia, headache, nausea, anxiety, irritability, dizziness, depression, tremor, sleep disorders, fatigue, vomiting, vertigo, dyspepsia, weight increase, and upper abdominal pain. No rebound effects were seen but the pitolisant SPC states that treatment discontinuation should be monitored.

The SPC states that long-term efficacy data are limited and the continued efficacy of pitolisant should be regularly evaluated. In the published trials, pitolisant 5 mg to 40 mg per day was superior to placebo for improvements in excessive daytime sleepiness, time awake in a darkened room and weekly cataplexy rate, but it was not established as non-inferior to modafinil 100 mg to 400 mg per day for improving excessive daytime sleepiness. In the unpublished pivotal trial pitolisant 5 mg to 20 mg per day was not superior to placebo for improving excessive daytime sleepiness.

In addition to effectiveness, safety and patient factors, local decision makers will need to take cost into account when considering the likely place in therapy of pitolisant. The 30‑day cost of pitolisant at a dose of 4.5 mg to 36 mg once daily is £310.00 to £620.00 (MIMS, February 2017, excluding VAT). The 30‑day cost of other medicines used for narcolepsy is £6.06 to £318.24 for stimulants such as modafinil, dexamfetamine or methylphenidate and £540.00 to £1,080.00 for sodium oxybate (Drug Tariff, February 2017, excluding VAT).