Joël Schlatter1, David Nguyen2, Michèle Zamy3, Sofiane Kabiche2, Jean-Eudes Fontan2, Salvatore Cisternino4,5. 1. Pharmacie, Hôpital Universitaire Necker - Enfants Malades, APHP, Paris, France. joel.schlatter@aphp.fr. 2. Pharmacie, Hôpital Jean Verdier, APHP, Hôpitaux Universitaires de Paris-Seine-Saint-Denis (HUPSSD), Bondy, France. 3. Pharmacovigilance, Hôpital Saint-Antoine, APHP, Hôpitaux Universitaires Est Parisien, Paris, France. 4. Pharmacie, Hôpital Universitaire Necker - Enfants Malades, APHP, Paris, France. 5. INSERM UMR-S 1144, Université Paris Descartes, Faculté de pharmacie, Paris, France.
Abstract
PURPOSE: Complications of the intrathecal route may cause potential toxicity related to the medical device and properties of the administered drug and/or excipient. A description of clinical and histological effects of polyethylene glycol and miripirium after Depo-Medrol injection, and the adverse reactions of particulate methylprednisolone acetate was conducted. The safety of the intrathecal route with excipients, label and off-label drugs is discussed. METHODS: A bibliographic search in Medline, Google, and Cochrane database from 1940 to June 2016 was performed. The keywords included 'intrathecal methylprednisolone acetate', 'miripirium', 'myristyl-gamma-picolinium', 'side effects', 'intrathecal Depo-Medrol', 'polyethylene glycol', and 'intrathecal devices' used individually or in combination. RESULTS: Adverse reactions have been reported with this intrathecal administration route such as arachnoiditis, bladder dysfunction, headache, meningitis. Some pharmaceutical excipients have been associated with specific toxicity issues and with allergic and anaphylaxis reactions. Additives of methylprednisolone acetate formulations such as polyethylene glycol and miripirium chloride can be neurotoxic when injected intrathecally. Polyethylene glycol-an antimicrobial agent widely used in pharmaceutical drugs-has been associated with cardiovascular, hepatic, respiratory, and CNS toxicity. CONCLUSIONS: Intrathecal methylprednisolone acetate (Depo-Medrol) therapy seems not fully safe due to reported adverse events. The use of other forms of corticosteroid therapy free from excipients should be emphasized such as soluble methylprednisolone sodium succinate.
PURPOSE: Complications of the intrathecal route may cause potential toxicity related to the medical device and properties of the administered drug and/or excipient. A description of clinical and histological effects of polyethylene glycol and miripirium after Depo-Medrol injection, and the adverse reactions of particulate methylprednisolone acetate was conducted. The safety of the intrathecal route with excipients, label and off-label drugs is discussed. METHODS: A bibliographic search in Medline, Google, and Cochrane database from 1940 to June 2016 was performed. The keywords included 'intrathecal methylprednisolone acetate', 'miripirium', 'myristyl-gamma-picolinium', 'side effects', 'intrathecal Depo-Medrol', 'polyethylene glycol', and 'intrathecal devices' used individually or in combination. RESULTS: Adverse reactions have been reported with this intrathecal administration route such as arachnoiditis, bladder dysfunction, headache, meningitis. Some pharmaceutical excipients have been associated with specific toxicity issues and with allergic and anaphylaxis reactions. Additives of methylprednisolone acetate formulations such as polyethylene glycol and miripirium chloride can be neurotoxic when injected intrathecally. Polyethylene glycol-an antimicrobial agent widely used in pharmaceutical drugs-has been associated with cardiovascular, hepatic, respiratory, and CNS toxicity. CONCLUSIONS: Intrathecal methylprednisolone acetate (Depo-Medrol) therapy seems not fully safe due to reported adverse events. The use of other forms of corticosteroid therapy free from excipients should be emphasized such as soluble methylprednisolone sodium succinate.
Entities:
Keywords:
Drug safety; Intrathecal injection; Methylprednisolone acetate; Off-label
Authors: Jeanette K Doorduijn; Gustaaf W van Imhoff; Bronno van der Holt; Harry C Schouten; Martijn R Schaafsma; Marius A MacKenzie; Joke W Baars; Marie José Kersten; Pieternella J Lugtenburg; Martin J van den Bent; Roelien H Enting; Fokje M Spoelstra; Philip Poortmans; Jacoline E C Bromberg Journal: Hematol Oncol Date: 2016-08-17 Impact factor: 5.271