Acute treatments

Sumatriptan

• Tablet 50mg, 100mg (£0.20 = per 100mg tablet)
• Solution for injection 6mg/0.5ml syringe (£56.60 = pack 2 generic pre-filled syringes)
• Solution for injection 3mg/0.5ml syringe (£39.50 = pack 2 pre-filled syringes) (see note 2 below)
• Nasal spray 10mg/0.1ml actuation, 20mg/0.1ml actuation (£42.47 = 20mg pack 6 unit doses)

Indications

• Treatment of acute migraine
• Cluster headache

Dose

• Oral: migraine. Dose: 50mg (some patients may require 100mg); the dose may be repeated after at least 2 hours if migraine recurs; maximum 300mg in 24 hours
• Subcutaneous 6mg injection: cluster headache or migraine. Dose: a single 6mg injection; the dose may be repeated once after at least 1 hour if headache recurs; maximum 12mg in 24 hours
• Subcutaneous 3mg injection: migraine if sumatriptan 6mg injection is effective, but not tolerated. Dose: a single 3mg injection; the dose may be repeated once after at least 1 hour if headache recurs; maximum 6mg in 24 hours (see note 2 below)
• Intranasally: cluster headache (unlicensed) or migraine. Dose: 10–20mg into one nostril; the dose may be repeated once after at least 2 hours if headache recurs. Maximum in 24 hours: two 10mg doses or two 20mg doses.

Notes

1. Sumatriptan nasal spray is licensed for use in children aged 12 to 18 years of age.
2. Sumatriptan 3mg subcutaneous injection is included in the formulary for the treatment of migraine only. There is very limited evidence comparing sumatriptan 3mg and 6mg subcutaneous injection. If sumatriptan 6mg subcutaneous injection is effective but not tolerated, consider reducing the dose to the 3mg injection. If a patient consistently uses more doses of sumatriptan 3mg injection than the 6mg injection, prescribing of the 3mg injection should be reconsidered.
3. All prescriptions for sumatriptan should be written generically.

Frovatriptan

• Tablet 2.5mg (£3.21 = per tablet)

Indications

• Treatment of acute migraine

Dose

• 2.5mg as soon as possible after onset repeated after 2 hours if migraine recurs (patient not responding should not take second dose for same attack); maximum 5mg in 24 hours

Notes

1. Frovatriptan has a long elimination half-life and may be of benefit for patients who experience recurrence of headache.

Rizatriptan

• Tablet 5mg, 10mg (£2.37 = per 10mg tablet)
• Orodispersible tablets sugar free 10mg (£1.83 = per tablet)

Indications

• Treatment of acute migraine

Dose

• 10mg as soon as possible after onset repeated after 2 hours if migraine recurs (patient not responding should not take second dose for same attack); maximum 20mg in 24 hours

Notes

1. Orodispersible or wafer formulations obviate the need for water but do not get absorbed in the mouth.
2. The plasma concentration of rizatriptan is increased by propranolol. For patients taking propranolol the maximum dose of rizatriptan is 5mg.

Rimegepant

• Oral lyophilisate sugar free 75mg (£25.80 = pack of 2; £103.20 = pack of 8)

• Acute treatment of migraine in line with NICE TA919 (see note 9)
  • 75mg once daily if required. Maximum dose 75mg/day (see note 1)
• Prophylaxis of episodic migraine in line with NICE TA906 (specialist input) (see notes 2 and 8)
  • 75mg every other day
• Hepatic impairment: No dose adjustment in mild or moderate hepatic impairment. Avoid in severe hepatic impairment.
• Renal impairment: No dose adjustment in mild, moderate or severe renal impairment. Caution during frequent use in severe renal impairment. Avoid in end-stage renal impairment (CrCL<15ml/min).

Notes

1. Maximum daily dose is one 75mg lyophilisate. Rimegepant is licensed for both acute treatment and prophylaxis of migraine (see above). Patients should not take an additional 75mg lyophilisate for acute treatment of migraine on the same day as receiving rimegepant for prophylaxis of migraine.
2. For prophylaxis of migraine:
   1. Treatment with rimegepant may be started in primary care on the advice of a specialist.
   2. In addition, initiation of rimegepant by GPs who are confident to do this without specialist input is accepted. Refer to guidance on the prophylaxis of migraine for patient groups requiring specialist input and additional information on treatment review.
3. Interactions: Rimegepant is metabolised by CYP3A4. Concomitant administration with strong CYP3A4 inhibitors, or moderate or strong CYP3A4 inducers is not recommended. Rimegepant is also associated with additional drug interactions. Refer to the BNF or rimegepant SmPC for advice on drug interactions.
4. Cardiovascular disease: Clinicians should be aware that the following patients were excluded from the phase 3 trials of rimegepant:
   1. Current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischaemic heart disease, coronary artery vasospasm, and cerebral ischaemia.
   2. Patients with myocardial infarction, acute coronary syndrome, percutaneous coronary intervention, cardiac surgery, stroke or TIA during the 6 months prior to being enrolled in the trial.
   3. Uncontrolled hypertension. Patients with stable hypertension 3 months prior to being enrolled were eligible to participate in the trial.
   4. History or current evidence of arrhythmia and some ECG changes (e.g. left bundle branch block).
5. Pregnancy and breastfeeding: There are limited data from the use of rimegepant in pregnant women and in breastfeeding. Refer to the rimegepant SmPC for further information.
6. The lyophilisate should be placed on the tongue or under the tongue. It can be taken without liquid.
7. The annual cost per patient for prophylaxis of migraine is £2,368.
8. NICE TA906: Rimegepant is recommended as an option for preventing episodic migraine in adults who have at least 4 and fewer than 15 migraine attacks per month (July 2023), only if at least 3 preventative treatments have not worked:
   1. Stop rimegepant after 12 weeks of treatment if the frequency of migraine attacks does not reduce by at least 50%.
   2. If people with the condition and their clinicians consider rimegepant to be 1 of a range of suitable treatments, after discussing the advantages and disadvantages of all the options, use the least expensive. Take account of administration costs, dosage, price per dose and commercial arrangements.
9. NICE TA919: Rimegepant is recommended as an option for the acute treatment of migraine with or without aura in adults (Oct 2023), only if for previous migraines:
   1. at least 2 triptans were tried and they did not work well enough or
   2. triptans were contraindicated or not tolerated, and non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol were tried but did not work well enough.

Prophylaxis of migraine

Drugs used for prophylaxis of migraine not listed below:

• Botulinum Toxin Type A (Botox) (see 4.9.3 Drugs used in essential tremor, chorea, tics, and related disorders)

Pizotifen

• Tablet 500microgram, 1.5mg (£1.77 = 1.5mg x 28 tablets)

Indications

• Prevention of vascular headache including classical migraine, common migraine, and cluster headache

Dose

• Initially 500micrograms at night increased gradually to usual dose of 1.5mg at night or in 3 divided doses; may be further increased up to maximum daily dose 4.5mg (but rarely necessary), maximum single dose 3mg

Notes

1. The evidence for the use of pizotifen is limited and weight gain and sedation are often unacceptable side effects of this drug, it has now been superseded.

Atogepant

• Tablets 10mg, 60mg (28 = £182.16)

Indications and dose:

• Prophylaxis of migraine in line with NICE TA973
  • 60mg once daily
  • Reduce dose to 10mg once daily with concomitant use of specific medicines (see note 2)
• Renal impairment: 10mg once daily in severe renal impairment (CrCL<30ml/min). No dose adjustment in mild or moderate renal impairment
• Hepatic impairment: No dose adjustment in mild or moderate hepatic impairment. Avoid in severe hepatic impairment

Notes

1. Treatment initiation:
   1. Treatment with atogepant may be started in primary care on the advice of a specialist.
   2. In addition, initiation of atogepant by GPs who are confident to do this without specialist input is accepted. Refer to guidance on the prophylaxis of migraine for patient groups requiring specialist input and additional information on treatment review.
2. Interactions: Atogepant is metabolised by CYP3A4 and eliminated via the OATP pathway. Reduce daily dose of atogepant to 10mg once daily with concomitant administration of a strong CYP3A4 or OATP inhibitors. Refer to the BNF or atogepant SmPC for advice on drug interactions.
3. Cardiovascular disease: Clinicians should be aware that the following patients were excluded from the phase 3 trials of atogepant:
   1. Clinically significant ischaemic heart disease (e.g., unstable angina pectoris).
   2. Clinically significant cardiac rhythm or conduction abnormalities (e.g., atrial fibrillation, second- or third-degree heart block) or risk factors for Torsade de Pointes.
   3. Myocardial infarction, transient ischemic attack, or stroke within 6 months prior to enrolment in the trial.
   4. Heart failure (NYHA class III or IV).
   5. Hypertension (sitting systolic BP > 160mmHg or sitting diastolic BP > 100mmHg).
4. Avoid in pregnancy and in breastfeeding. Refer to the SmPC for further information.
5. The annual cost per patient for prophylaxis of migraine is £2,368.
6. NICE TA973 (May 2024): Atogepant is recommended as an option for preventing migraine in adults who have at least 4 migraine days per month, only if at least 3 preventive medicines have failed
   1. Stop atogepant after 12 weeks if the frequency of migraines does not reduce by:
      1. at least 50% in episodic migraine (defined as fewer than 15 headache days per month)
      2. at least 30% in chronic migraine (defined as 15 or more headache days per month, with at least 8 of those having features of migraine).
   2. If people with the condition and their healthcare professional consider atogepant to be 1 of a range of suitable treatments, after discussing the advantages and disadvantages of all the options, use the least expensive. Take account of administration costs, dosage, price per dose and commercial arrangements.

Rimegepant

• Oral lyophilisate sugar free 75mg (£25.80 = pack of 2; £103.20 = pack of 8)

Indications:

• Prophylaxis of episodic migraine in line with NICE TA906 (refer to entry under acute treatment above for TA criteria and additional supporting information)

Eptinezumab

• Solution for infusion vials 100mg/1ml

Notes

1. NICE TA871: Eptinezumab (Vyepti) is recommended as an option for preventing migraine in adults (March 2023), only if:
   1. they have 4 or more migraine days a month
   2. at least 3 preventive drug treatments have failed and
   3. the company provides it according to the commercial arrangement.
2. Stop eptinezumab after 12 weeks of treatment if:
   1. in episodic migraine (less than 15 headache days a month) the frequency does not reduce by at least 50%
   2. in chronic migraine (15 headache days a month or more with at least 8 of those having features of migraine) the frequency does not reduce by at least 30%.
3. The preferred option in Devon for the treatment of patients with chronic migraine who have failed on at least 3 preventative drug treatments is Botulinum Toxin Type A (Botox) (see 4.9.3 Drugs used in essential tremor, chorea, tics, and related disorders).

Erenumab

• Solution for injection pre-filled pens 70mg/1ml, 140mg/1ml

Notes

1. NICE TA682: Erenumab (Aimovig) is recommended as an option for preventing migraine in adults (March 2021), only if:
   1. they have 4 or more migraine days a month
   2. at least 3 preventive drug treatments have failed
   3. the 140mg dose of erenumab is used and
   4. the company provides it according to the commercial arrangement.
2. Stop erenumab after 12 weeks of treatment if:
   1. in episodic migraine (less than 15 headache days a month) the frequency does not reduce by at least 50%
   2. in chronic migraine (15 headache days a month or more with at least 8 of those having features of migraine) the frequency does not reduce by at least 30%.
3. The preferred option in Devon for the treatment of patients with chronic migraine who have failed on at least 3 preventative drug treatments is Botulinum Toxin Type A (Botox) (see 4.9.3 Drugs used in essential tremor, chorea, tics, and related disorders).

Fremanezumab

• Solution for injection pre-filled pens 225mg/1.5ml

Notes

1. NICE TA764: Fremanezumab (Ajovy) is recommended as an option for preventing migraine in adults (February 2022), only if:
   1. they have 4 or more migraine days a month
   2. at least 3 preventive drug treatments have failed and
   3. the company provides it according to the commercial arrangement.
2. Stop fremanezumab after 12 weeks of treatment if:
   1. in episodic migraine (fewer than 15 headache days a month), the frequency does not reduce by at least 50%
   2. in chronic migraine (15 headache days a month or more with at least 8 of those having features of migraine), the frequency does not reduce by at least 30%.
3. The preferred option in Devon for the treatment of patients with chronic migraine who have failed on at least 3 preventative drug treatments is Botulinum Toxin Type A (Botox) (see 4.9.3 Drugs used in essential tremor, chorea, tics, and related disorders).

Galcanezumab

• Solution for injection pre-filled pens 120mg/1ml

Notes

1. NICE TA659: Galcanezumab (Emgality) is recommended as an option for preventing migraine in adults (November 2020), only if:
   1. they have 4 or more migraine days a month
   2. at least 3 preventive drug treatments have failed and
   3. the company provides it according to the commercial arrangement.
2. Stop galcanezumab after 12 weeks of treatment if:
   1. in episodic migraine (less than 15 headache days a month) the frequency does not reduce by at least 50%
   2. in chronic migraine (15 headache days a month or more with at least 8 of those having features of migraine) the frequency does not reduce by at least 30%.
3. The preferred option in Devon for the treatment of patients with chronic migraine who have failed on at least 3 preventative drug treatments is Botulinum Toxin Type A (Botox) (see 4.9.3 Drugs used in essential tremor, chorea, tics, and related disorders).

Non-steroidal anti-inflammatory drugs

Aspirin and metoclopramide

• Oral powder sachets sugar free, aspirin 900mg plus metoclopramide 10mg

Indications

• Acute migraine

Dose

• One sachet in water at onset of attack, repeated after 2 hours if necessary (maximum 3 sachets in 24 hours)

Notes

1. Antimigraine preparations containing metoclopramide are not suitable for patients under the age of 20 years.

Other preparations

Dihydergotamine

• Injection 1mg/1ml (unlicensed preparation)

Flunarizine

• Capsules 5mg (unlicensed preparation)

Methysergide

• Tablets 1mg (unlicensed preparation)

Other treatments

gammaCore

(non-invasive vagus nerve stimulator)

• Starter kit (93 days)
• Refill kit (31 days or 93 days)

Indications:

• Cluster headache

Notes:

1. To be prescribed by a headache specialist only.
2. gammaCore is included in the formulary only for use in line with NICE MTG46 and the NHS England MedTech Funding Mandate Policy 2021/22, that is, as a treatment option for cluster headache in the following circumstances:
   1. the first 3 month period of gammaCore use is offered by the company free of charge and
   2. treatment with gammaCore should only continue for people whose symptoms reduce in the first 3 months.