Download MODAFINIL for excessive sleepiness

Gwent Shared Care Protocol
MODAFINIL (Provigil®)
for the treatment of excessive sleepiness with narcolepsy
Protocol No. 23
General guidance
PLEASE CHECK http://www.gpmtc.wales.nhs.uk
FOR THE LATEST VERSION OF THIS PROTOCOL
The ABHB Medicines and Therapeutics Committee have endorsed this protocol. It outlines the
shared care arrangements for patients initiated on modafinil for daytime sleepiness associated
with narcolepsy only.
This protocol should be read in conjunction with the:
 Summary of Product Characteristics (SmPC) available at:
http://www.medicines.org.uk/EMC/medicine/11337/SPC/Provigil+100+mg+Tablets%2c+Pr
ovigil+200+mg+Tablets/
 The Shared Care Agreement Form (see Page 5)
1. Licensed
indication
The treatment of excessive sleepiness (in adults) associated with narcolepsy with or without
cataplexy.
Excessive sleepiness is defined as difficulty maintaining wakefulness and an increased likelihood
of falling asleep in inappropriate situations.
2. Therapeutic use
& Background
information
Excessive sleepiness is defined as difficulty maintaining wakefulness and an increased likelihood
of falling asleep in inappropriate situations.
Modafinil should be used only in patients who have had a complete evaluation of their excessive
sleepiness, and in whom a diagnosis of narcolepsy, has been made in accordance with ICSD
diagnostic criteria. Such an evaluation usually consists, in addition to the patient's history, sleep
measurements testing (for example an Epworth Sleepiness Scale score1 of 11 or more) in a
laboratory setting and exclusion of other possible causes of the observed hypersomnia.
The precise mechanism(s) through which modafinil promotes wakefulness is unknown.
In November 2010 the EMA’s CHMP concluded that the benefits of modafinil continued to
outweigh their risks only in the treatment of narcolepsy. The CHMP also concluded that
modafinil should no longer be used to treat:
 Obstructive sleep apnoea; (including in patients with excessive sleepiness despite
correctly using a Continuous Positive Airway Pressure machine)
 Shift work sleep disorder;
 Idiopathic hypersomnia.
3. Contraindications
&
Cautions
Modafinil is contraindicated in those with
1. Hypersensitivity to the active substance or to any of the excipients.
2. Uncontrolled moderate to severe hypertension
3. cardiac arrhythmias
Special Warnings/Precautions
 Patients with major anxiety should only receive treatment with modafinil in a specialist unit.
 Sexually active women of child-bearing potential should be established on a contraceptive
programme before taking modafinil. Since the effectiveness of oral contraceptives may be
reduced with modafinil, alternative/concomitant methods of contraception are
recommended (and for 2 months after discontinuation). For women not wishing to use
either a barrier method or non-medicated IUD, alternatives are; increasing the dose of
oestrogen in a combined pill, injections of some progestogens or a medicated IUD such as
Mirena.2
 It is recommended that modafinil tablets not be used in patients with a history of left
1
http://www.britishsnoring.co.uk/sleep_apnoea/epworth_sleepiness_scale.php
http://www.narcolepsy.org.uk/NewsEvents/Modafinilcontraceptives.aspx
This Shared Care Protocol should be read in conjunction with the appropriate Summary of Product Characteristics
Status: APPROVED
Issue Date: July 2012
Approved by: ABHB MTC
Page 1 of 5
Review Date: July 2015
2

ventricular hypertrophy or cor pulmonale. Modafinil should not be used in patients with
mitral valve prolapse who have experienced the mitral valve prolapse syndrome when
previously receiving CNS stimulants. This syndrome may present with ischaemic ECG
changes, chest pain or arrhythmia.
Patients should be advised that modafinil is not a replacement for sleep and good sleep
hygiene should be maintained. Steps to ensure good sleep hygiene may include a review of
caffeine intake.
Serious skin reactions
Stevens Johnson Syndrome, erythema multiforme, and toxic epidermal necrolysis have been
reported in association with modafinil.3 These conditions usually occurred within the first 5
weeks of treatment, although there have been isolated cases after more than 3 months’
treatment. In clinical trials, the risk of rash resulting in discontinuation of modafinil treatment
was higher in children than adults (0·8% vs no cases). Modafinil is not authorised for use in
children.
Psychiatric symptoms
Suicidal ideation, hallucinations, delusion, aggression, psychosis, and mania have been reported
in association with modafinil. These reactions have occurred mainly, but not exclusively, in
patients with a history of psychosis, depression, or mania.
Advice for healthcare professionals:
• Modafinil should be discontinued at the first sign of rash and not restarted
• Modafinil should be discontinued in patients who experience any psychiatric symptoms and
not restarted
• Modafinil should be used with caution in patients with a history of psychosis, depression, or
mania
• Modafinil should be used with caution in patients with a history of alcohol, drug, or illicit
substance abuse
In the USA modafinil is increasingly being diverted for nonmedical use by healthy individuals in
the expectation that it will improve cognitive performance.
4. Typical dosage
regimen (adults)
Initially 200mg daily, either in 2 divided doses morning and at noon or as a single dose in the
morning, dose adjusted according to response to 200–400mg daily in 2 divided doses or as a
single dose. Doses greater than 400mg daily are not be covered by this protocol and will be
specialist prescribed.
ELDERLY initiate at 100mg daily.
Initiation and dose adjustment will be the responsibility of the Specialist Centre.
Duration of treatment: Treatment should be continued only when it is considered to be having a
worthwhile effect in terms of maintaining wakefulness.
5. Drug
interactions
Check BNF Appendix
1 before coprescribing any
other drug.
6. Adverse drug
reactions
Ciclosporin
Oestrogens
Phenytoin
modafinil reduces plasma concentration of ciclosporin
modafinil accelerates metabolism of oestrogens (reduced contraceptive
effect – see Section 3 above
modafinil possibly increases plasma concentration of phenytoin
Adverse event (reported frequency)
Headache
(Very common affecting approximately 21% of patients)
Tachycardia and/or palpitations (Common ≥1/100 to
<1/10)
3
Management
Usually mild or moderate, dose
dependent and disappears within a few
days – discuss with specialist if persists
Discontinue in patients who develop
arrhythmia and do not restart until the
The FDA reported that it had received 6 cases of severe cutaneous adverse effects associated with modafinil from its initial
marketing in Dec. 98 to Jan. 07; of these, 5 required hospitalisation.
This Shared Care Protocol should be read in conjunction with the appropriate Summary of Product Characteristics
Status: APPROVED
Issue Date: July 2012
Approved by: ABHB MTC
Page 2 of 5
Review Date: July 2015
Adverse drug
reactions continued
All serious adverse
events should be
reported to
MHRA/CHM using
the Yellow Card.
Gastrointestinal (Common ≥1/100 to <1/10)
including abdominal pain, nausea, dry mouth, diarrhoea,
dyspepsia, constipation, decreased appetite,
Various (all common ≥1/100 to <1/10):
 Abnormal LFTs (dose related increases in ALP & GGT)
 Dizziness, somnolence, paraesthesia, blurred vision
 Vasodilatation, chest pain
 Asthenia
 Nervousness, insomnia, anxiety, depression, abnormal
thinking, confusion.
Serious skin reactions (Unknown frequency)
including erythema multiforme, Stevens-Johnson
Syndrome, Toxic Epidermal Necrolysis, and Drug Rash with
Eosinophilia and Systemic Symptoms (DRESS).
Psychiatric symptoms (Unknown frequency)
including psychosis, mania, delusions or hallucinations and
suicidal ideation.
condition has been adequately
evaluated and treated
Discuss with specialist if severe or
persistent
Discuss with specialist if substantial or
persistent
Discontinue at the first sign of rash and
do not restart
Discontinue in patients who experience
any psychiatric symptoms and do not
restart
7. Baseline
investigations
To be undertaken by specialist
1. Physical examination
2. FBC, U&Es, creatinine, eGFR measurement, LFTs, & TFTs
3. ECG – Patients with abnormal findings should receive further specialist evaluation and
treatment before modafinil treatment is considered
8. Ongoing
Monitoring
Specialist:
To re-evaluate the long-term use for the individual patients on a six-monthly basis (yearly once
stable). This will include assessment of any development of de novo or exacerbation of preexisting psychiatric disorders – particularly the appearance or worsening of suicide-related
behaviour.
LFTs at 2, 6 and 12 months after initiation and yearly thereafter.
Primary care:
BP and heart rate should be monitored every 6 months in patients receiving modafinil.
Ongoing and regular review of physical health and well being.
9. Pharmaceutical
aspects
10. Specialist centre
contact
information
N/A
11. Criteria for
shared care
Prescribing responsibility will only be transferred when:
 Treatment is for a specified indication.
 Treatment has been initiated and established by the Specialist Centre.
 The patient’s initial reaction to and progress on the drug is satisfactory.
 The patient’s general physical, mental and social circumstances are such that he/she would
benefit from shared care arrangements.
12. Responsibilities
of initiating
consultant
 To undertake sleep measurements testing and excluding other possible causes of the
hypersomnia, to diagnose narcolepsy.
 To provide a patient information leaflet indicating the risks and benefits associated with
modafinil.
 To advise the patient on potential side effects and the action to be taken should they occur
(particularly skin reactions and psychiatric symptoms).
If stopping the medication or needing advice please contact:
Dr Melissa Hack (Consultant Physician Royal Gwent Hospital)
Dr Meirion Llewellyn (Consultant Physician Royal Gwent Hospital)
Dr Ken Dawson (Consultant Neurologist Nevill Hall Hospital)
01633 238201
01633 238459
01873 732739
This Shared Care Protocol should be read in conjunction with the appropriate Summary of Product Characteristics
Status: APPROVED
Issue Date: July 2012
Approved by: ABHB MTC
Page 3 of 5
Review Date: July 2015
Responsibilities of
initiating consultant
continued
13. Responsibilities
of Primary Care
 To confirm the patient’s understanding and consent to treatment.
 To initiate modafinil and make any dosage adjustments.
 Once the patient has reached a stable dose of modafinil, to send the Shared Care Agreement
Form (copy below) to the GP.
 To monitor modafinil in accordance with Section 8 of this Protocol.
 To re-evaluate the long-term use for the individual patients in accordance with Section 8 –
the long-term efficacy of modafinil has not been evaluated (> 9 weeks).
 To ensure Primary Care receive adequate and timely information on the specialist patient
reviews (wherever undertaken).
 To inform the GP if the patient fails to attend an appointment and clearly indicate that the
patient is receiving modafinil.
 To discontinue modafinil if it is unsuitable for the patient for reasons of efficacy (based on
an appropriate method of assessment) or tolerability.
 To return the Shared Care Agreement Form (below) to the requesting consultant within one
week of receipt.
 Once the patient is on stable dose, to issue ongoing prescriptions for modafinil as per
dosage schedule recommended by the specialist.
 Ongoing physical health monitoring and management (including BP and heart rate) subject
to ongoing specialist review (as above).
 To attend hospital and GP clinic appointments.
14. Responsibilities
of patients/carer  Failure to attend will result in medication being reviewed and possibly stopped on specialist
advice.
 To report adverse effects to their specialist or GP (particularly skin reactions and psychiatric
symptoms).
15. Responsibilities
of all prescribers
Any suspected serious adverse reaction to an established drug should be reported to MHRA
via the “Yellow Card scheme.” http://yellowcard.mhra.gov.uk/
16. Responsibilities
of pharmacists
 Whenever practicable, to reaffirm with the patient/carer the importance of reporting any
unexplained side-effects (particularly skin reactions and psychiatric symptoms).
BNF Section 4.4 CNS stimulants
17. Supporting
documentation /
Summary of Product Characteristics:
information
http://www.medicines.org.uk/EMC/medicine/11337/SPC/Provigil+100+mg+Tablets%2c+
Provigil+200+mg+Tablets/
Patient Information Leaflet:
http://www.medicines.org.uk/EMC/medicine/2599/PIL/Provigil+100+mg+Tablets%2c+P
rovigil+200+mg+Tablets/
The association of modafinil with serious rash and psychiatric symptoms was highlighted in the
March 2008 issue of the MHRA’s Drug Safety Update:
http://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON014099
Indications restricted:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Modafinil/h
uman_referral_000236.jsp&murl=menus/regulations/regulations.jsp&mid=WC0b01ac0580024e
9a
18. GP request letter Shared Care Agreement Form – Attached below
This Shared Care Protocol should be read in conjunction with the appropriate Summary of Product Characteristics
Status: APPROVED
Issue Date: July 2012
Approved by: ABHB MTC
Page 4 of 5
Review Date: July 2015
Shared Care Agreement Form
CONSULTANT REQUEST
To: Dr.
Your patient:
NHS No. (10digit):
was seen on:
with a diagnosis of:
I recommend that the following drug is initiated:
This drug has been accepted as suitable for shared care by the ABHB MTC. I agree to the responsibilities set out in
the protocol SCP No. 23 (copy attached). This should be read in conjunction with the definition of shared care at:
http://www.wales.nhs.uk/sites3/Documents/371/Doc%202%20Defining%20shared%20care.pdf
I am requesting your agreement to sharing the care of this patient. The preliminary tests set out in the protocol
have been carried out. I am currently prescribing the stabilising treatment.
I would like you to undertake treatment from:
The initial treatment will be:
The baseline tests are:
If you undertake treatment I will reassess the patient in ____ weeks. You will be sent a written summary within 14
days. I will accept referral for reassessment at your request.
The medical staff of the department are available at all times to give you advice.
Consultant Name:
Signature:
Department:
Hospital:
Date:
Contact Telephone Nos:
GP RESPONSE (Please circle the appropriate number below detailing your response)
1. I am willing to undertake shared care as set out in SCP No. 22 for this patient.
2. I would like further information. Please contact me on: _______________________
3. I am unable to undertake shared care for this patient because: (Please state)
_________________________________________________________________________________
G.P. Signature _________________________________________
Date _________
Practice Address/Stamp ________________________________________________
PLEASE RETURN WHOLE COMPLETED FORM OR A COPY TO THE REQUESTING CONSULTANT WITHIN 1 WEEK
BY FAXING TO 01633 243250
This Shared Care Protocol should be read in conjunction with the appropriate Summary of Product Characteristics
Status: APPROVED
Issue Date: July 2012
Approved by: ABHB MTC
Page 5 of 5
Review Date: July 2015