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Experimental models indicate that frequent administration of heme induces chronic hepatic inflammation and a consequent induction of HO-1 that eventually triggers ALAS1 resulting in reoccurrence of disease.[106] Furthermore, significant issues such as frequent replacement of the venous access to prevent thromboembolic disease, risk of liver fibrosis, hepatic iron overload, and development of therapeutic tolerance to heme infusions have all been documented.[107,108] Heme arginate (Normosang ® ) is a compound of heme and arginine that has been used in treatment of acute porphyrias for nearly four decades in Europe

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Extension-phase data speaks to this directly