Accidental fampridine toxicity from a compounding pharmacy

Compounding pharmacies; a disruptive force or a danger to our safety? #MSBlog #MSResearch

When you buy slow-release fampridine you are paying for innovation; innovation costs money.  #MSBlog #MSResearch

"In response to a question yesterday about cheaper versions of Fampridine. The case below illustrates the dangers of using a compounding pharmacy to cut costs. The pharmacy made a mistake and gave the patient 10X the prescribed dose. As you can see the side effects of too much fampridine or 4-aminopyridine can be life threatening. Although this patient had a spinal cord injury the lessons are the same for MSers. In fact I have been told by a Canadian colleagues of a similar overdose in a patient of his with MS. Please be careful."

"The other thing about Fampridine is that it is slow release formulation. Being slow release is critical to its mode of action and safety. The slow-release formulation prevents peak blood levels that you see when you take the standard formulation. The peak drug levels are what causes the side effects; in particular seizures. The following figure below demonstrates to you the so called pharmacokinetic* profile of immediate- and prolonged-release fampridine formulations. You can see the levels on immediate release (red) peak at over 50ng/mL and fall very quickly. The slow-release (black) have a delayed peak, which is around 20ng/mL and fall slower. What you are paying for when you buy Fampridine is the R&D that has gone into developing this slow-release preparation and the costs of doing the clinical trials and showing that the drug is relatively safe and effective. Based on this I would not recommend using other formulations of fampridine. This is why it is illegal to prescribe alternative formulations in Europe if there is licensed formulation available. I am aware that this financial implications of this policy, but we have to trust our politicians when they make these sorts of rules."

* pharmacokinetic = may be simply defined as what the body does to a drug. Pharmacokinetic properties of drugs may be affected by elements such as the site of administration and the dose of administered drug. These may affect the absorption rate. Pharmacokinetics is often studied in conjunction with pharmacodynamics, i.e. the study of a drug's pharmacological effect on the body.

Schwam E. Severe accidental overdose of 4-aminopyridine due to a compounding pharmacy error. J Emerg Med. 2011 Jul;41(1):51-4. 

BACKGROUND: 4-Aminopyridine (4-AP) is a potassium channel-blocking drug used to ameliorate symptoms of multiple sclerosis and spinal cord injury by facilitating neural impulse conduction. It is not Food and Drug Administration (FDA) approved, but information about it is disseminated via the Internet, and it is currently available from compounding pharmacies with a physician's prescription. Dose-related toxicity is frequent and includes dizziness, insomnia, paresthesia, asthenia, headache, tremor, delirium, choreoathetosis, and seizures.

OBJECTIVES: To report a case of life-threatening accidental overdose of 4-AP resulting from a pharmacy error.

CASE REPORT: A 42-year-old man with a history of C3 spinal cord injury with residual left-sided weakness and anesthesia, taking 4-AP, presented to the Emergency Department with the sudden onset of abdominal pain, vertigo, anxiety, profuse diaphoresis, hypersalivation, hypertension, bradycardia, agitation, and choreoathetosis, followed by status epilepticus. Toxicity due to 4-AP was suspected and the patient was treated symptomatically. He recovered with permanent short-term memory loss after a prolonged and complicated hospital course. Analysis of the pills, which had been prescribed for him by a physician and specially compounded by a pharmacist, showed that they contained approximately 10 times the dose indicated on the label, a dose that reliably produces severe toxicity.

CONCLUSION: Emergency physicians should be familiar with the signs of 4-AP toxicity. Additionally, they should be aware that 4-AP and other non-FDA-approved medications may be available to patients from compounding pharmacies, and that quality control of made-to-order drug compounding may not be up to the standard that is expected with mass-produced pharmaceuticals.

CoI: multiple

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