Pyridostigmine

 Risk Factor: C
 Class: AUTONOMICS / Parasympathomimetics (Cholinergics)

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Pyridostigmine is a quaternary ammonium compound with anticholinesterase activity used in the treatment of myasthenia gravis. The agent was not teratogenic in rats at doses up to 30 mg/kg/day, but maternal and fetal toxicity (reduced weight) were observed at the highest dose (1).

Although it is ionized at physiologic pH, the low molecular weight of pyridostigmine (about 261) allows the nonionized fraction to cross to the fetus. Pyridostigmine concentrations have been determined at birth in maternal plasma, cord blood, and amniotic fluid (2). Two women with long-term myasthenia gravis were treated throughout gestation with pyridostigmine, 360 mg and 420 mg per day, respectively. The latter woman was also treated with neostigmine (105 mg/day) and ambenonium (60 mg/day). In the first case, the maternal plasma, cord blood, and amniotic drug concentrations were 77, 65, and 290 ng/mL, respectively, and in the second, 53, 39, and 300 ng/mL, respectively. Thus, the cord blood:maternal plasma ratios were 0.84 and 0.74, respectively, whereas the amniotic fluid:maternal plasma ratios were 3.8 and 5.7 respectively (2).

Caution has been advised against the use in pregnancy of IV anticholinesterases because they may cause premature labor (3,4). This effect on the pregnant uterus increases near term.

A number of reports have described the apparent safe use of pyridostigmine during human gestation (2,3,4,5,6,7,8,9,10,11,12,13,14,15 and 16). However, a case report published in 2000 described microcephaly and central nervous system (CNS) injury in a newborn that was attributed to high-dose pyridostigmine (17). The infant's mother was a 24-year-old primigravida with a 14-year history of myasthenia gravis. She required high-dose pyridostigmine (15003000 mg/day) throughout gestation to control her diplopia and ptosis. In comparison, the average recommended daily dose is 600 mg, with daily doses up to 1500 mg required in severe cases (18). The mother denied smoking and the use of other drugs during pregnancy. At 36 weeks' gestation, an emergency cesarean section for fetal bradycardia was conducted, delivering a severely growth retarded (1880-g, <2nd percentile), hypotonic male infant with Apgar scores of 3 and 8 at 1 and 5 minutes, respectively. Shortly after birth, neonatal myasthenia gravis was diagnosed and two exchange transfusions were used to lower his acetylcholine receptor antibody titer and IV immunoglobulin was administered. The infant required immediate intubation because of poor respiratory effort and was continued on the respirator until age 3.5 months. Mild finger and wrist contractures and bilateral cryptorchidism were noted at birth, but he had no abnormal ocular findings (17). The head circumference was 33.5 cm at birth and 37 cm (<5th percentile) at 3 months of age. By about 5 months of age, a number of dysmorphic features were noted, including a broad nasal bridge with a prominent nose, slight downslanting palpebral fissures, high arched palate, short neck, broad chest, campylodactyly, and hammer toes (17). He continued to do poorly, requiring additional hospitalizations and mechanical ventilation. At 4.5 months, he was discharged home but readmitted 1 week later because of prolonged apnea and cyanosis. His weight (5.1 kg, 10th percentile) and head circumference (38 cm, <2nd percentile) were still retarded and he remained hypotonic. A cranial ultrasound, karyotyping, and TORCH titers (i.e., toxoplasmosis, other infections, rubella, cytomegalovirus, and herpes simplex) were normal or negative and there was no evidence of craniosynostosis. A brain magnetic resonance imaging scan at 5 months revealed apparent brachycephaly and mild ventriculomegaly. At 9 months of age, he still required nasal oxygen, tone was normal, and the joint contractures had resolved, but his reflexes were brisk and ankle clonus was evident. Because no other cause could be identified, the authors attributed the microcephaly and CNS injury to pyridostigmine (17).

Both antenatal and neonatal myasthenia gravis have been reported and either may result in perinatal death. Both forms of the disorder are caused by transplacental passage of antiacetylcholine receptor immunoglobulin G antibodies (11,19). The inhibited fetal skeletal muscle movement and development may result in pulmonary hypoplasia, arthrogryposis multiplex, and polyhydramnios (19).

Transient muscular weakness has been observed in about 20% of newborns of mothers with myasthenia gravis (11,19).

Breast Feeding Summary

Pyridostigmine is excreted into breast milk (15). Levels in two women receiving 120300 mg/day were 225 ng/mL, representing milk:plasma ratios of 0.361.13. Although pyridostigmine is an ionized quaternary ammonium compound, these values indicate that the nonionized fraction crosses easily into breast milk. The drug was not detected in the infants nor were any adverse effects noted. The authors estimated that the two infants were ingesting 0.1% or less of the maternal doses (15). The American Academy of Pediatrics considers pyridostigmine to be compatible with breast feeding (20).

References

1. Levine BS, Parker RM. Reproductive and developmental toxicity studies of pyridostigmine bromide in rats. Toxicology 1991;69:291300.
2. Lefvert AK, Osterman PO. Newborn infants to myasthenic mothers: a clinical study and an investigation of acetylcholine receptor antibodies in 17 children. Neurology 1983;33:1338.
3. Foldes FF, McNall PG. Myasthenia gravis: a guide for anesthesiologists. Anesthesiology 1962;23:83772.
4. McNall PG, Jafarnia MR. Management of myasthenia gravis in the obstetric patient. Am J Obstet Gynecol 1965;92:51825.
5. Plauche WC. Myasthenia gravis in pregnancy. Am J Obstet Gynecol 1964;88:4049.
6. Chambers DC, Hall JE, Boyce J. Myasthenia gravis and pregnancy. Obstet Gynecol 1967;29:597603.
7. Hay DM. Myasthenia gravis and pregnancy. J Obstet Gynaecol Br Commonw 1969;76:3239.
8. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977:34556.
9. Blackhall MI, Buckley GA, Roberts DV, Roberts JB, Thomas BH, Wilson A. Drug-induced neonatal myasthenia. J Obstet Gynaecol Br Commonw 1969;76:15762.
10. Rolbin SH, Levinson G, Shnider SM, Wright RG. Anesthetic considerations for myasthenia gravis and pregnancy. Anesth Analg (Cleve) 1978;57:4417.
11. Plauche WC. Myasthenia gravis in pregnancy: An update. Am J Obstet Gynecol 1979;135:6917.
12. Eden RD, Gall SA. Myasthenia gravis and pregnancy: A reappraisal of thymectomy. Obstet Gynecol 1983;62:32833.
13. Cohen BA, London RS, Goldstein PJ. Myasthenia gravis and preeclampsia. Obstet Gynecol 1976;48(Suppl):35S7S.
14. Catanzarite VA, McHargue AM, Sandberg EC, Dyson DC. Respiratory arrest during therapy for premature labor in a patient with myasthenia gravis. Obstet Gynecol 1984;64:81922.
15. Hardell LI, Lindstrom B, Lonnerholm G, Osterman PO. Pyridostigmine in human breast milk. Br J Clin Pharmacol 1982;14:5657.
16. Carr SR, Gilchrist JM, Abuelo DN, Clark D. Treatment of antenatal myasthenia gravis. Obstet Gynecol 1991;78:4859.
17. Niesen CE, Shah NS. Pyridostigmine-induced microcephaly. Neurology 2000;54:18734.
18. Product information. Mestinon. ICN Pharmaceuticals, 2000.
19. Gilchrist JM. Muscle disease in the pregnant woman. Adv Neurol 1994;64:193208.
20. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.
    
    

Questions and Answers

A 41 years old woman with myasthenia gravis is taking pyridostigmine and prednisone?, A 41 years old woman with myasthenia gravis is taking pyridostigmine and prednisone. she is complaining of increased fatigue and weakness and has difficulty breathing. what concerns should you have? might the client's difficulty breathing be related to her fatigue and weakness? could these manifstations be related to myasthenia gravis or its treatment?

i've worked with people with myathenia gravis, although my specialty involves the respiratory system, and myasthenia gravis is a neuromuscular disorder -- you'd probably think what does it have to do with respiration.

the muscle weakness and fatigue the person feels are the symptoms of myasthenia gravis -- which is basically weakness of muscles all over, and since our breathing is controlled not only by our diaphragmatic muscles, but other muslces in the chest as well -- when the muscles gets weak, so is the breathing.

so to answer your question, yes, the breathing problem is related to the disease itself.

How can I find out if my medications will be available in Japan?, I take two medications Mestinon (Pyridostigmine Bromide) and Prednisone. How can I find out if these two are available in Japan? And is it possible to get my meds shipped to me, in Japan, or is that illegal?

The site below will ship to Japan.

http://www.internationalpharmacy.com/en/...

You will have to pay a LOT more money if you do it this way unless you are being relocated as an expat and your company will continue your US-based health care coverage. Japanese health care will not.

Mestinon is available but is clased as a controlled substance. You'll need a Japanese doctor to presribe it and get a new prescription every 30 days.

http://www.tokyokasei.co.jp/catalog/P133...

Prednisone is also available:
http://www.tokyokasei.co.jp/catalog/P127...

my mother has myasthenia gravis, the meds are blowing her up. pyridostigmine 60mg&prednisone 10mg. help?, she's very depressed, because she's not able to drop the xtra weight. Please help her. They tried lowering her meds but her illness became worse.

Unfortunately, there is no magic answer, the steroid, prednisone, is making her blow up, and if she does not take it, she will eventually die. What she can do: nothing. What you can do for her: BE SUPPORTIVE, encouraging and make sure she does not cheat herself by not take the steroid. Good Luck