Download QA248_4Pyridostigmine_neostigmine_FINAL

Medicines Q&As
Q&A 248.4
How do you convert an oral pyridostigmine or neostigmine dose to
a parenteral neostigmine dose?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Published: November 2015
Summary




There is no direct conversion of oral pyridostigmine to parenteral neostigmine.
60mg pyridostigmine oral is approximately equivalent to 500 micrograms neostigmine IV and 11.5 mg neostigmine IM or SC.
15mg neostigmine oral is equivalent to 1.0 - 1.5mg intramuscular or subcutaneous neostigmine
or 0.5mg (500micrograms) intravenous neostigmine.
Patients who have their oral dose of pyridostigmine converted to a parenteral dose of
neostigmine should be monitored closely to ensure that the neostigmine is adequately controlling
their symptoms of myasthenia gravis and not causing untoward side effects. Doses should be
adjusted accordingly.
Background
Pyridostigmine is a reversible inhibitor of the enzyme cholinesterase with actions similar to those of
neostigmine, but is slower in onset and has a longer duration of action.(1;2) Both pyridostigmine and
neostigmine are licensed for the treatment of myasthenia gravis: pyridostigmine is given orally whilst
neostigmine can be administered both orally and parenterally.(2-4) For the parenteral route,
neostigmine is licensed for the treatment of myasthenia gravis when given subcutaneous (SC) or
intramuscular (IM); the intravenous (IV) route is licensed for reversal of non-depolarising
neuromuscular blockade.(3)
The dose of pyridostigmine can vary from 30 - 120mg every 3-4 hours, with between 5-20 tablets
taken daily.(2) The total daily dose of parenteral neostigmine can vary between 5-20mg, with 1-2.5mg
given by IM or SC injection every 2-4 hours.(3) Oral neostigmine doses are usually 15 – 30mg at
regular intervals throughout the day, with up to 5-20 tablets taken daily.(4) Higher doses may be
needed in some patients. (2-4)
Patients with myasthenia gravis suffer with weak and easily fatigued muscles, including those of the
proximal limbs, extraocular muscles and the muscles of mastication, speech and facial expression. (5)
Dysphagia can occur: if the patient is unable to swallow but requires anticholinesterases, parenteral
neostigmine may be substituted for pyridostigmine, but how is the dose conversion carried out?
Answer
No formal guidelines or studies for switching between oral pyridostigmine to parenteral neostigmine
have been identified in the medical literature.




Intravenous doses of pyridostigmine and of neostigmine are about one-thirtieth (1/30) of the
usual oral doses.(1;6)
An oral dose of 15mg neostigmine is equivalent to 1.0 to 1.5mg neostigmine given by IM or SC
injection, or 500 micrograms neostigmine given IV injection [15mg/30 = 0.5mg, or
500micrograms].(4)
The potency ratio of IV pyridostigmine to IV neostigmine has been estimated to be 4.35 to 1. So
an IV dose of 500micrograms neostigmine is approximately equivalent to 2000micrograms (2mg)
of IV pyridostigmine [4 x 500micrograms].(6;7)
The 2mg IV pyridostigmine dose is 1/30th of the oral dose.(1) So a 2mg IV pyridostigmine dose is
equivalent to a 60mg oral pyridostigmine dose. It therefore follows that a 60mg oral
pyridostigmine dose is equivalent to approximately 500 micrograms neostigmine IV and 1-1.5mg
neostigmine IM or SC.
Available through NICE Evidence Search at www.evidence.nhs.uk
1
Medicines Q&As
Calculations:
Drug
Route
Dose
Equivalent to:
Neostigmine
Oral
15mg
 500micrograms IV (1/30th of the oral dose)
 1mg to 1.5mg IM or SC
IV
2000
micrograms
(2mg)
Pyridostigmine
 Potency ratio of IV pyridostigmine to IV neostigmine is
approximately 4.35:1
 Therefore 500micrograms of IV neostigmine is approximately
equivalent to 500 x 4.35 = 2175 micrograms of IV pyridostigmine
 IV dose is approximately 1/30th of the oral dose.
 Therefore an IV dose of 2mg pyridostigmine is approximately
Pyridostigmine
Oral
60mg
equivalent to 30x2mg = 60mg.
 This is equivalent to 500micrograms neostigmine IV, or 1mg to
1.5mg IM or SC.
Patients who have their oral dose of pyridostigmine converted to a parenteral dose of neostigmine
should be monitored closely to ensure that the neostigmine is adequately controlling their symptoms
of myasthenia gravis and not causing untoward side effects. Doses should be adjusted accordingly.
Limitations
There are no formal studies which look at the direct conversion between oral pyridostigmine and
parenteral neostigmine.
References
(1) Pyridostigmine bromide. Latest modification 13/12/2013. Sweetman SC(ed), Martindale: The
Complete Drug Reference [online]. London: Pharmaceutical Press.
https://www.medicinescomplete.com/mc/. Accessed on 28/09/2015.
(2) Summary of Product Characteristics. Mestinon 60mg Tablets. Meda Pharmaceuticals. Date of
revision of the text: 23/06/2014. http://www.medicines.org.uk/emc/. Accessed on 28/09/2015.
(3) Summary of Product Characteristics. Neostigmine Methylsulfate Injection BP 2.5mg in 1ml.
Hameln Pharmaceuticals Ltd. Date of revision of the text:31/03/2015.
http://www.medicines.org.uk/emc/. Accessed on 28/09/2015.
(4) Summary of Product Characteristics. Neostigmine bromide tablets 15mg. Alliance
Pharmaceuticals. Date of revision of text: 15/01/2015. http://www.medicines.org.uk/emc/.
Accessed on 28/09/2015.
(5) Neurological disease: Disease of voluntary muscle. Myasthenia gravis. Kumar & Clark's
Clinical Medicine. Eighth edition. Kumar, P. and Clark, M. Edinburgh: Saunders Elsevier,
2012: 1151-1152.
(6) Dollery C. Pyridostigmine (bromide). In:Therapeutic Drugs (2nd edition). Churchill
Livingstone. Edinburgh., 1999: 289-291.
(7) Pyridostigmine: Comparative efficacy. Neostigmine, reverse of neuromuscular blockade.
Monograph last modified: 21/08/2015. In: DRUGDEX® System (electronic version). Truven
Health Analytics, Greenwood Village, Colorado, USA. Available at:
http://www.micromedexsolutions.com/ (cited: Sept 9th 2015).
Available through NICE Evidence Search at www.evidence.nhs.uk
2
Medicines Q&As
Quality Assurance
Prepared by
Cherry Chung (based on earlier work by Alexandra Denby), London Medicines Information Service
(Northwick Park Hospital)
Date Prepared
16th October 2015
Checked by
Varinder Rai, London Medicines Information Service (Northwick Park Hospital)
Date of check
9th November 2015
Search strategy
 Embase: (PYRIDOSTIGMINE/ad, do, dt, im, iv, po, pa, pk, sc) AND ((NEOSTIGMINE/ad, do, dt,
im, iv, po, pa, pk, sc ) OR (NEOSTIGMINE METHYL SULFATE/ad, do, dt, im, iv, pa, pk, sc
))[Limit to: Human and Publication Year 2014-2015]
 Embase: ((NEOSTIGMINE METHYL SULFATE/iv) OR (NEOSTIGMINE/iv)) AND (MYASTHENIA
GRAVIS/dt) [Limit to: Human and Publication Year 2014-2015]
 Medline: (PYRIDOSTIGMINE BROMIDE/AD, PK, TU) AND (NEOSTIGMINE/AD, PK, TU) [Limit
to: Publication Year 2014-2015 and Humans]
 PubMed: (("neostigmine/administration and dosage"[MeSH Terms] OR
"neostigmine/pharmacokinetics"[MeSH Terms]) OR "neostigmine/therapeutic use"[MeSH Terms])
AND (("pyridostigmine bromide/administration and dosage"[MeSH Terms] OR "pyridostigmine
bromide/pharmacokinetics"[MeSH Terms]) OR "pyridostigmine bromide/therapeutic use"[MeSH
Terms]) AND ("2014/01/01"[PDAT] : "2015/10/05"[PDAT])
 In-house database/ resources
 Manufacturers (S Yates, Medical Information Officer, Valeant Pharmaceuticals, 06/11/08; A
Slabbert, Medical Information Officer, Hameln pharmaceuticals ltd, 11/11/08)
Available through NICE Evidence Search at www.evidence.nhs.uk
3