10.3 Neuromuscular disorders – Somerset Prescribing Formulary

Related guidance:

Therapeutic Area	Formulary Choices	Cost for 28 (unless otherwise stated)	Rationale for decision / comments
Neuroprotective drugs	Riluzole
	as Emylif®	50mg orodispersible film: £168.00 (56)	NHS Somerset classify as an Amber 2 drug for amyotrophic lateral sclerosis form of motor neurone disease. Adult: 50 mg twice daily. Riluzole is not recommended for use in patients with impaired renal function. Riluzole should be prescribed with care in patients with a history of abnormal liver function, or in patients with slightly elevated serum transaminases up to 3 times the upper limit of the normal range, bilirubin and/or gamma-glutamyl transferase levels. Baseline elevations of several liver function tests (especially elevated bilirubin) should preclude the use of riluzole. Because of the risk of hepatitis, serum transaminases should be measured before and during therapy with riluzole. ALT should be measured every month during the first 3 months of treatment, every 3 months during the remainder of the first year, and periodically thereafter. ALT levels should be measured more frequently in patients who develop elevated ALT levels. Riluzole should be discontinued if the ALT levels increase to 5 times the upper limit of the normal range. Patients should be warned to report any febrile illness to their physicians. The report of a febrile illness should prompt physicians to check white blood cell counts and to discontinue riluzole in case of neutropenia. Cases of interstitial lung disease have been reported in patients treated with riluzole, some of them were severe. If respiratory symptoms develop such as dry cough and/or dyspnoea, chest radiography should be performed, and in case of findings suggestive of interstitial lung disease (e.g. bilateral diffuse lung opacities), riluzole should be discontinued immediately. Riluzole is contraindicated in patients who are pregnant or breast-feeding.
	as Teglutik®	25mg/5ml oral suspension sugar free: £100.00 (300ml)
		50mg tablet: £300.23 (56)
Drugs for neuromuscular disorders	NHS Somerset classify Nusinersen as a Red drug (specialist prescribing only) as per Traffic light guidance.
	NHS Somerset classify Risdiplam as a Red drug (specialist prescribing only) as per Traffic light guidance.
Anticholinesterases	Pyridostigmine	60mg tablet: £17.37 (200)	NHS Somerset classify as an Amber 2 drug for Myasthenia gravis Adult: 30–120mg, doses to be given at suitable intervals throughout day; usual dose 0.3–1.2g daily in divided doses, it is inadvisable to exceed a total daily dose of 450mg in order to avoid acetylcholine receptor down-regulation; patients requiring doses exceeding 450mg daily will usually require input from a specialised neuromuscular service. Immunosuppressant therapy is usually considered if the dose of pyridostigmine exceeds 360mg daily.
Anticholinesterases	Pyridostigmine	12mg/1ml oral solution sugar free: £90.00 (150ml)
Cannabinoids	Dronabinol/Cannabidiol as Sativex®	2.7mg/2.5mg dose oromucosal spray: £300.00 (270)	NHS Somerset classify as an Amber 2 drug for symptom improvement in adult patients with moderate to severe spasticity due to multiple sclerosis who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity related symptoms during an initial trial of therapy only after initiation by specialist. The number of sprays should be increased each day as per table in SPC. The afternoon/evening dose should be taken at any time between 4 pm and bedtime. When the morning dose is introduced, it should be taken at any time between waking and midday. The patient may continue to gradually increase the dose by 1 spray per day, up to a maximum of 12 sprays per day, until they achieve optimum symptom relief. There should be at least a 15 minute gap between sprays. Following the titration period, patients are advised to maintain the optimum dose achieved. The median dose in clinical trials for patients with multiple sclerosis is eight sprays per day. Once the optimum dose has been achieved, patients may spread the doses throughout the day according to individual response and tolerability. Re-titration upwards or downwards may be appropriate if there are any changes in the severity of the patient's condition, changes in their concomitant medication or if troublesome adverse reactions develop. Doses of greater than 12 sprays per day are not recommended. The patient's response to Sativex should be reviewed after four weeks of treatment. If a clinically significant improvement in spasticity related symptoms is not seen during this initial trial of therapy, then treatment should be stopped. In the clinical trials this was defined as at least a 20% improvement in spasticity related symptoms on a 0-10 patient reported numeric rating scale. The value of long term treatment should be re-evaluated periodically. Administration to patients with moderate or severe hepatic impairment is not advised. Effects of Sativex may be exaggerated or prolonged in patients with impaired renal function. Men and women of child bearing potential should take reliable contraceptive precautions for the duration of therapy and for three months after discontinuation of therapy. Patients on hormonal contraceptives should be advised to use an additional alternative, non-hormonal/reliable barrier method of birth control during Sativex therapy. Sativex is contraindicated during breast-feeding. Sativex may produce undesirable effects such as dizziness and somnolence which may impair judgement and performance of skilled tasks. Patients should not drive, operate machinery or engage in any hazardous activity if they are experiencing any significant CNS effects such as dizziness or somnolence. Patients should be aware that Sativex has been known to cause a few cases of loss of consciousness. This medicine can impair cognitive function and can affect a patient's ability to drive safely.
Muscle relaxants, centrally acting	Baclofen	10mg tablet: £1.45 (84)	NHS Somerset classify as an Amber 2 drug for chronic severe spasticity resulting from disorders such as multiple sclerosis or traumatic partial section of spinal cord. Adult: initially 5 mg 3 times a day, gradually increased; maintenance up to 60 mg daily in divided doses, review treatment if no benefit within 6 weeks of achieving maximum dose; maximum 100 mg per day. Manufacturer advises use with caution in hepatic impairment. Use with caution in renal impairment. Only use if potential benefit outweighs risk if eGFR less than 15 mL/minute/1.73 m2.
	Baclofen	5mg/5ml oral solution sugar free: £2.75 (300ml)
	NHS Somerset classify intrathecal Baclofen as a Red drug (specialist prescribing only) as per Traffic light guidance.
	Tizanidine	2mg tablet: £7.12 (120)	NHS Somerset classify as an Amber 2 drug for spasticity associated with multiple sclerosis. Adult: initially 2 mg daily, then increased in steps of 2 mg daily in divided doses, increased at intervals of at least 3–4 days and adjust according to response; usual dose up to 24 mg daily in 3–4 divided doses; maximum 36 mg per day. Tizanidine should be used with caution in patients with renal insufficiency (creatinine clearance < 25 mL/min). Tizanidine is contraindicated in patients with severe hepatic impairment. Since hepatic dysfunction has been reported in association with tizanidine, but rarely at daily doses up to 12 mg, it is recommended that liver function tests should be monitored monthly for the first four months in patients receiving doses of 12 mg and higher and in patients who develop clinical symptoms suggestive of hepatic dysfunction, such as unexplained nausea, anorexia or tiredness. Treatment with tizanidine should be discontinued if serum levels of serum glutamic-pyruvic transaminase and/or serum glutamic-oxaloacetic transaminase are persistently above three times the upper limit of the normal range. Tizanidine should be discontinued in patients with symptoms compatible with hepatitis or where jaundice occurs. The safety of tizanidine in pregnancy or breast feeding has not been established and should not be used in pregnancy or breast feeding unless the benefit clearly outweighs the risk.
Muscle relaxants, directly acting	Dantrolene	25mg capsule: £16.87 (100)	NHS Somerset classify as an Amber 2 drug for muscle cramps in motor neurone disease. Adult: initially 25 mg daily, then increased to up to 100 mg 4 times a day, dose increased at weekly intervals.
Muscle relaxants, directly acting	Dantrolene	100mg capsule: £43.07 (100)