FDA's advice on_acetaminophen_(paracetamol)_associated serious skin reactions

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FDA advises healthcare professionals and patients about serious skin reactions induced by Paracetamol.

FDA advises healthcare professionals and patients about serious skin reactions induced by Paracetamol.

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  • 1. FDA’s advice on Acetaminophen (Paracetamol) associated Serious skin reactions P. Naina Mohamed Pharmacologist
  • 2. Introduction  FDA notified healthcare professionals and patients that acetaminophen has been associated with a risk of rare but serious skin reactions.  Paracetamol is a common active ingredient to treat pain and reduce fever.  It is included in many prescription and over-the-counter (OTC) products.  The skin reactions induced by Paracetamol includes Stevens- Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP) which can be fatal.  These reactions can occur with first-time use of acetaminophen or at any time while it is being taken.  Other drugs used to treat fever and pain/body aches (e.g., NSAIDS, such as ibuprofen and naproxen) also carry the risk of causing serious skin reactions, which is already described in the warnings section of their drug labels.
  • 3. Introduction  The symptoms of Skin reactions induced by Paracetamol include rash, blisters and, in the worst case, widespread damage to the surface of skin.  Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are the two most serious skin reactions linked in rare cases to acetaminophen. They usually require hospitalization and can cause death.  Problems usually begin with flu-like symptoms followed by rash, blistering and extensive damage to the surfaces of the skin. Recovery can take weeks or months, and possible complications include scarring, changes in skin pigmentation, blindness and damage to internal organs.  Acute generalized exanthematous pustulosis (AGEP), usually resolves within two weeks of stopping the medication that caused the problem.  A serious skin reaction can occur at any time, even if you've taken acetaminophen previously without a problem. There is currently no way of predicting who might be at higher risk.  Patients should stop taking the product immediately when they develop a rash or other skin reaction and seek medical attention right away.  If patients ever had a skin reaction when taking acetaminophen, they should not take the drug again and discuss alternate pain relievers/fever reducers with the health care professional.
  • 4. Mechanism of development of Fever Infectious or Aseptic stimuli Leukocytes Endogenous pyrogens (Pyrogenic cytokines, such as interleukin- 1b (IL-1b), tumor necrosis factor (TNF), and interleukin-6 (IL-6)) Elevation of prostaglandin E (PGE) in the cerebrospinal fluid Elevated PGE acts on the Preoptic area of the anterior hypothalamus (POAH) Alter the firing rate of neurons that control thermoregulation in the hypothalamus Increase in the hypothalamic set point of body temperature Enhanced release of thyroid hormones, glucocorticoids, and catecholamines Cutaneous vasoconstriction, shivering, and nonshivering thermogenesis Reduction of heat loss and increased heat gain Fever
  • 5. Mechanism of action of Paracetamol Paracetamol (Acetaminophen) Penetrates the blood-brain barrier Blocks Cycloxygenase (COX3) in brain Blocks the formation and release of prostaglandins (PGE) in the central nervous system Inhibit the action of endogenous pyrogens on the heat-regulating centers in the brain Antipyretic effect
  • 6. Mechanism of action of Paracetamol (Other Mechanisms) Antipyretics Diminished leukocyte-endothelial cell interactions, Reduced pyrogenic cytokine production, Enhanced expression of anti-inflammatory molecules, Boosting the activity of endogenous antipyretic messengers Suppress tissue inflammation
  • 7. Hypersensitivity reactions Paracetamol Inhibits cyclooxygenase (COX)-3 & COX 1 Reduced formation of PGE2 Decreased inhibition of 5- Lipoxygenase enzyme Increased prodution of Cysteinyl Leukotrienes from Arachidonic acid Hypersensitivity reactions
  • 8. Hypersensitivity reactions (Other Mechanism) Paracetamol IgE mediated immune mechanisms Hypersensitivity reactions
  • 9. Conclusion  Health care professionals should be aware of this rare risk of paracetamol induced serious skin reactions.  Any patient who develops a skin rash or reaction while using paracetamol or any other pain reliever/fever reducer should stop the drug and seek medical attention right away.  Anyone who has experienced a serious skin reaction with paracetamol should not take the drug again and should contact their health care professional to discuss alternative pain relievers/fever reducers.  FDA will require that a warning be added to the labels of prescription drug products containing paracetamol to address the risk of serious skin reactions.  FDA will also request that manufacturers add a warning about serious skin reactions to the product labels of OTC paracetamol drug products marketed under a new drug application and will encourage manufacturers of drug products marketed under the OTC monograph do the same.
  • 10. References  http://www.fda.gov/Safety/MedWatch/SafetyInformation/ SafetyAlertsforHumanMedicalProducts/ucm363519.htm? source=govdelivery  http://www.fda.gov/ForConsumers/ConsumerUpdates/uc m363010.htm?source=govdelivery  http://www.ncbi.nlm.nih.gov/pubmed/22555261  http://www.scai.cl/sites/default/files/Bibliografia%20Suge rida%20Hipersensibilidad%20a%20paracetamol.pdf  http://www.aacijournal.com/content/3/1/24  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1113161/  http://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%2 0Documents/Practice%20and%20Parameters/drug- allergy-updated-practice-param.pdf