Enoxaparin sodium/methylprednisolone/remdesivir

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

In a case report, three patients [two women and one man; ages not stated] were described, who developed urticaria, itching maculo-papular rash or fixed erythema during treatment with remdesivir, enoxaparin sodium or off-label methylprednisolone [dosages and routes not stated].

Case 1: This report describes a woman, who developed urticaria during off-label treatment with methylprednisolone for COVID-19 infection: The woman was diagnosed with COVID-19 infection. She started receiving paracetamol for fever. In addition, she was prescribed with unspecified low molecular weight heparin for prophylaxis of thrombotic events. Few days later, she reported feeling of shortness of breath; thus, she was prescribed off-label methylprednisolone. After 4 days of methylprednisolone therapy, her symptoms improved, but she reported acute onset of urticaria, with itching hives on the belly and the back. Therefore, treatment with methylprednisolone was changed to off-label prednisone, and unspecified antihistamine therapy was started. After a couple days of unspecified antihistamine therapy, she reported complete resolution of urticaria, which eventually relapsed after a couple of days. This time urticaria affected all over the trunk, arms and legs. At this time, her treatment did not change and longer unspecified antihistamine therapy was prescribed, which was enough to treat the acute presentation of urticaria without another relapse. After a total of 12 days since the beginning of the therapy, she became afebrile and regained the sense of taste. After 3 weeks, COVID-19 swab became negative. The unspecified antihistamine therapy was suspended after a total of 2 consecutive weeks, with no further episodes of urticaria.

Case 2: This report describes a man, who developed itching maculo-papular rash during treatment with remdesivir for COVID-19-related bilateral interstitial pneumonia: The man was admitted for COVID-19-related bilateral interstitial pneumonia, with moderate acute respiratory distress syndrome, which was initially treated with high-flow nasal oxygen therapy. Upon admission, he started receiving off-label treatment with dexamethasone 6 mg/day. In addition, he was prescribed with unspecified low molecular weight heparin for prophylaxis of thrombotic events. However, his condition persisted. Thus, treatment with remdesivir was started. One hour after the administration of the first dose of remdesivir, he developed an itching maculo-papular rash under the neck, which further expanded on the upper trunk. Thus, treatment with remdesivir was discontinued and antihistamine therapy with chlorphenamine was started. The rash did not expand further, and disappeared in the subsequent days.

Case 3: This report describes a woman, who developed fixed erythema during treatment with enoxaparin sodium for prophylaxis of thrombotic events: The woman was admitted for COVID-19-related bilateral interstitial pneumonia with severe respiratory failure, initially treated with high-flow nasal oxygen therapy and then with continuous positive airway pressure. Upon admission, she started receiving off-label treatment with azithromycin, lopinavir/ritonavir and tocilizumab for COVID-19-related bilateral interstitial pneumonia. In addition, she was prescribed with enoxaparin sodium for prophylaxis of thrombotic events. During day 35 of admission, she developed a fixed erythema on the trunk and the limbs; thus, treatment with lopinavir/ritonavir and tocilizumab was suspended. The fixed erythema was attributed to enoxaparin sodium; hence, treatment with enoxaparin sodium was changed to fondaparinux sodium. A brief course of methylprednisolone for fixed erythema was completed, with subsequent resolution of the rash in the course of a few days.