Muscle Injury After Intramuscular Administration of Diclofenac: A Case Report Supported by Magnetic Resonance Imaging

Abstract

Intramuscular injection of diclofenac is still frequently practiced, although there is ample evidence that the risk of local tissue intolerability is highly underestimated. The aim of this study was to evaluate local toxicity in a patient using magnetic resonance imaging. A patient who gave written informed consent received a medically indicated intramuscular administration of diclofenac 75 mg/2 mL. Simultaneously with magnetic resonance imaging of the depot, a clinical–chemical evaluation and quantification of diclofenac in plasma was performed. A manifold enhancement of the T2-weighted magnetic resonance signal was observed in a muscle area of approximately 60 mL volume, with maximum signal intensity 30 min after injection, the time of maximum diclofenac plasma exposure. Plasma creatine kinase activity was elevated approximately sixfold within 8 h and normalized within 1 week, whereas the magnetic resonance enhancement disappeared within 5 weeks. Interestingly, the patient did not complain about any clinical symptoms at the injection site. Asymptomatic tissue injury after intramuscular injection of diclofenac, caused by intramuscular dosing, can be reliably evaluated by magnetic resonance imaging and should be applied early during the development of parenteral dosage forms. Clinical Trials Registration Number: BB130/16 (Ethics Committee of the University Medicine Greifswald).

Multiparametric magnetic resonance imaging to characterize cabotegravir long‐acting formulation depot kinetics in healthy adult volunteers

“…Noninvasive imaging approaches to assess LA drug distribution in humans for durations of weeks to months have been sparingly applied, because detection techniques to directly assess drug substance are not readily available 29–33 . Computed tomography has been used to assess LA injectable depot location variability between gluteal muscle and SC adipose fat and, in doing so, has been used to determine the association between BMI and IM misinjections 28,34 .…”

“…Our findings of cabotegravir LA drug being distributed along IM fascial planes is consistent with previous clinical observations and with our previous preclinical MRI study findings, which were confirmed using imaging mass spectroscopy showing cabotegravir LA drug colocated within interfacial planes of muscles. 12,31,33 When examining which key imaging endpoints (e.g., volume, surface area, T2-weighted, ADC) were key markers associated with drug absorption and PK exposure, the drug depot surface area assessed within 2 hours of administration was highly correlated with early plasma cabotegravir PK, C max and with partial AUC 0-4wk . This is unsurprising because insoluble drug particle dissolution rates are directly related to specific surface area of the drug particle, 36,37 and dissolution studies showing surface area of insoluble drugs used as LA injectables correlated well with in vivo drug exposure.…”

The Surgical Treatment of Tissue Necrosis due to Diclofenac Sodium Injection (Nicolau Syndrome)

“…NSAIDs, such as diclofenac sodium, may cause cytotoxic effects by altering local pH levels and activating the preapoptotic pathways. Therefore, even a proper injection inside the musculature may cause local destruction (6,17,18). On the other hand, the necrosis mimics a perforasome as its demarcation line passes over the injection area.…”

COMPARATIVE DICLOFENAC DETECTION FOR CHRONIC TOXICITY LEVELS USING WATER SOLUBLE Zn-METALLOPORPHYRIN, GOLD NANOPARTICLES AND THEIR HYBRID

“…Diclofenac, 2-[ (2,6-dichlorophenyl)-amino]-benzeneacetic acid, is a synthetic nonsteroidal anti-inflammatory analgesic drug [10], pharmaceutically formulated as different salts, usually as potassium and sodium. The drug is used to treat rheumatoid arthritis, osteoarthritis [22,16], musculoskeletal injuries [38], ankle sprain injuries [28,29] and is administered as post-surgery analgesic in human and veterinary medicine [23]. Many patients taking diclofenac for arthritis also need additional drugs for other chronic health problems such as hypertension [40].…”