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Best Care for Everyone
GABAPENTIN – SAFE PRESCRIBING – DOES THE DOSE FIT?
4PROVIDE CLEAR DOSING AND TITRATION INSTRUCTIONS WHEN INITIATING GABAPENTIN
4DOSE AS PER RENAL FUNCTION
4DO NOT STOP ABRUPTLY IF USED FOR EPILEPSY
4USE WITH CAUTION IN PEOPLE AT RISK OF FALLS AND WARN ABOUT SEDATION
4INVESTIGATE SERIOUS ADVERSE EFFECTS
Gabapentin is an anticonvulsant that is used for certain types
of epilepsy in patients who have not achieved adequate control
with standard anti-epileptic drugs (AEDs). Gabapentin does
not require serum level monitoring and does not alter the
serum concentration of other AEDs.1
In some patients, gabapentin can also relieve neuropathic
pain (e.g. diabetic peripheral neuropathy), and skin conditions
associated with pain such as post-herpetic neuralgia.
Gabapentin is funded where tricyclic antidepressants
are either ineffective or not tolerated.2 Amitriptyline and
gabapentin can be used in combination if the patient has an
inadequate response to either drug at the maximum tolerated
dose.
Gabapentin is also useful for post-operative analgesia3 and for
migraine prophylaxis (unapproved indication).
The effective dose range for epilepsy is usually 900 to 1800mg
per day;1 however, some patients may require the maximum
dose of 1200mg three times daily (3600mg per day).4
PROVIDE CLEAR DOSING AND TITRATION
INSTRUCTIONS WHEN INITIATING GABAPENTIN
Note: Antacids can reduce the efficacy of gabapentin when
taken at the same time.9 Inform patients to take antacids at
least 2 hours before or after taking gabapentin.4
Gabapentin has a short half-life and has to be dosed three to
four times daily. To reduce troublesome adverse effects that
can occur upon initiation (e.g. somnolence, dizziness
and ataxia), start with an evening dose, and then gradually
up-titrate the dose as tolerated. Some patients may take up
to 4 weeks to achieve the optimal dose, requiring one week
at each dose level.
Slow dose titration of gabapentin5
For neuropathic pain, it is important to test the benefit of
gabapentin at each dose level, before progressing to higher
doses. Benefit may not necessarily be enhanced with higher
doses.6 The optimal dose varies widely between patients from
100mg at night up to 1200mg three times per day, depending
on patient age and other medical conditions. Consider other
agents after 4 to 6 weeks if gabapentin does not provide
adequate relief,7 or if side effects become unacceptable.
The efficacy of gabapentin for neuropathic pain has been
scrutinised over recent years.6 The Cochrane Collaboration
has concluded that gabapentin provides substantial pain relief
in about a third of people who take it for neuropathic pain.8
DOSE AS PER RENAL FUNCTION
Dose adjustments are necessary for patients with poor renal
function because gabapentin is cleared renally. Refer to the
following table for maximum dosing recommendations.1,4
Gabapentin dosing recommendations1
Renal function
(eGFR mL/min/1.73m2)
Total daily dose (mg/day)*
Time
Dose
Greater than 80
900-3600
Day 1-3
300mg at night
50-79
600-1800
Day 4-7
300mg twice daily
30-49
300-900
Week 2
300mg three times daily
15-29
150#-600
Week 3
600mg three times daily
Less than 15
150#-300
Slower titration (e.g. in 100mg increments) is especially
beneficial for the elderly or for patients with renal impairment
or multiple medical problems.1
*To be administered as a three times daily regimen
# To be administered as 300mg on alternate days
Note: Dose adjustments are not required for patients with
impaired hepatic function.1
➥ continued
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Best Care for Everyone
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GABAPENTIN
DO NOT STOP ABRUPTLY IF USED FOR
EPILEPSY
Abrupt withdrawal of anticonvulsants may precipitate a
seizure; if gabapentin is to be discontinued, this should
be done gradually over at least a week.1 Other adverse
events that have been observed following the abrupt
discontinuation of gabapentin include anxiety, insomnia,
nausea and sweating.1
Due to the short half-life of gabapentin, in order to minimise
the risk of breakthrough seizures, ensure the patient
understands that they should not allow more than 12 hours
to elapse between regular doses.1
Note: Gabapentin may worsen or exacerbate absence
and myoclonic seizures and should not be given to these
patients, or to patients with mixed seizure disorders that
involve absence seizures.1,4
USE WITH CAUTION IN PEOPLE AT RISK OF
FALLS AND WARN ABOUT SEDATION
The most frequent side effects associated with gabapentin
are somnolence and dizziness.1 For this reason, elderly
patients (and their caregivers) must be informed that these
effects can increase the risk of falls.6
Patients should be advised not to drive or operate dangerous
machinery until it is known whether gabapentin affects
their ability to do so safely.1 The degree of drowsiness and
sedation will depend on the individual. Patients should be
warned about these risks when prescribing.
Alcohol can further increase the drowsiness associated
with gabapentin, but to varying degrees depending on the
individual.4 Although alcohol does not affect the efficacy of
gabapentin, it can increase the seizure risk in patients with
epilepsy. Most people with epilepsy can have one or two
units of alcohol without increasing the chances of having a
seizure.4
Note: Gabapentin has been reported to enhance the
analgesic effects of morphine. This combination can actually
benefit patients in the post-operative setting because lower
doses of morphine may be sufficient. Morphine can also
increase the bioavailability of gabapentin, so if patients
are maintained on gabapentin (e.g. for epilepsy) and
require morphine, observe them closely for drowsiness.
Dose reductions of gabapentin and/or morphine may be
necessary.1
INVESTIGATE SERIOUS ADVERSE EFFECTS
Rash
Patients taking AEDs, including gabapentin, are at risk
of drug rash with eosinophilia and systemic symptoms
(DRESS) syndrome. This is a rare, but potentially lifethreatening condition. Patients should be advised to
inform their doctor immediately if they notice any signs of
hypersensitivity such as fever, lymphadenopathy or rash.
Gabapentin should be discontinued if hypersensitivity is
confirmed.1
Suicidality
As with other AEDs, gabapentin may increase the risk
of suicidal thoughts or behaviour. Patients should be
monitored for the emergence or worsening of depression,
suicidal thoughts, or unusual changes in mood or behaviour.
These may occur as early as one week after starting
treatment and continue for the duration of treatment.
Patients, caregivers and families should be advised to be
alert to these symptoms and report them to the prescriber if
they occur.1
Note: Other side-effects associated with gabapentin include
abnormal liver function tests, taste disturbance, headache
and weight gain.
➥ continued
Best Care for Everyone
GABAPENTIN
ACKNOWLEDGEMENTS
We wish to thank Michal Kluger, Pain Specialist, Waitemata Pain Services
and and Claire McGuinniety, Pharmacist, Waitemata DHB for their valuable
contribution to this bulletin.
REFERENCES
1. Arrow Pharmaceuticals (NZ) Limited. Arrow- Gabapentin capsules
datasheet. 17-05-12. http://www.medsafe.govt.nz/profs/datasheet/a/
arrowgabapentincap.pdf (Accessed 21-04-13)
2. Pharmaceutical Management Agency, New Zealand (PHARMAC) Special
Authority form Gabapentin SA1071 May 2013 http://www.pharmac.govt.
nz/2013/05/01/SA1071.pdf (Accessed 29-4-13)
3. Straube S, Derry S, Moore RA, Wiffen PJ, McQuay HJ. Single dose oral
gabapentin for established acute postoperative pain in adults. Cochrane
Database of Systematic Reviews 2010, Issue 5. Art. No.: CD008183.
DOI: 10.1002/14651858.CD008183.pub2. http://onlinelibrary.wiley.com/
doi/10.1002/14651858.CD008183.pub2/pdf (Accessed 19-04-13)
4. The New Zealand Formulary, Gabapentin. http://www.nzf.org.nz/nzf_2629.
html?searchterm=gabapentin (Accessed 21-04-13)
5. Kluger M. Pain specialists website, gabapentin (updated 10-04-11)
http://pain-specialists.com/index.php?option=com_content&view=article&
id=120:gabapentin&catid=66:gabapentin&Itemid=11 (Accessed 08-05-13)
6. Best Practice Advisory Centre. New evidence shows less benefit of
gabapentin for neuropathic pain. Best Practice Journal 2010;28:54-5
http://www.bpac.org.nz/magazine/2010/june/snippets.asp#gabapentin
(Accessed 19—4-13)
7. Ritchie ED, Cameron F. Pain management guidelines book. National
Health Service Tayside 2010. http://school.tayside-anaesthesia.net/
resources/4/pain%20guidelines%202010.pdf (Accessed 08-05-13)
8. Moore RA, Wiffen PJ, Derry S, McQuay HJ. Gabapentin for chronic
neuropathic pain and fibromyalgia in adults. Cochrane Database
of Systematic Reviews 2011, Issue 3. Art. No.: CD007938. DOI:
10.1002/14651858.CD007938.pub2. http://onlinelibrary.wiley.com/
doi/10.1002/14651858.CD007938.pub2/pdf (Accessed 19-04-13)
9. Yagi T, Naito T, Mino YU et al. Impact of concomitant antacid
administration on gabapentin plasma exposure and oral bioavailability
in healthy adult subjects. Drug Metabolism and Pharmacokinetics
2012;27(2):248-54 http://www.ncbi.nlm.nih.gov/pubmed/22240839
(Accessed 22-04-13)
For further information on other high-risk medicines visit our website at: www.saferx.co.nz
No: 0182-01-109, Issued: July 2013, Review: July 2015
DISCLAIMER: This information is provided to assist primary care health professionals with the use of prescribed medicines. Users of this information must always consider current
best practice and use their clinical judgement with each patient. This information is not a substitute for individual clinical decision making. Issued by the Quality Use of Medicines Team
at Waitemata District Health Board, email: [email protected]
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