Sermorelin and Rivaroxaban Interaction: What Patients and Clinicians Need to Know

Is there a known interaction between sermorelin and rivaroxaban?

Rivaroxaban's labeled interaction risk runs two ways: drugs that change how much rivaroxaban circulates, mainly through CYP3A4 and P-glycoprotein, and drugs that impair hemostasis and add to bleeding risk [2]. No study has measured sermorelin against either route. There is also no current sermorelin label to check, because the last FDA-approved sermorelin product was withdrawn in 2009 [3][4].

What the Xarelto label says about interacting drugs

Rivaroxaban is cleared by CYP3A4/5 and CYP2J2 metabolism and by P-glycoprotein and BCRP transport [2]. The label says to avoid combined P-glycoprotein and strong CYP3A inhibitors such as ketoconazole and ritonavir, and combined P-glycoprotein and strong CYP3A inducers such as rifampin, carbamazepine, phenytoin and St John's wort, which lower rivaroxaban exposure and may increase thromboembolic events [2]. Clarithromycin is also a combined P-gp and strong CYP3A inhibitor, but the label says no precautions are needed with it [2].

For the herbal inducer, in 12 healthy volunteers, two weeks of a hyperforin-containing St John's wort extract lowered the rivaroxaban 20 mg AUC ratio to 0.76 (90% CI 0.70 to 0.82), the Cmax ratio to 0.86, and the factor Xa inhibition ratio to 0.80 [5]. That study tested St John's wort, not sermorelin.

The label also warns that aspirin, P2Y12 inhibitors, other antithrombotics, fibrinolytics, NSAIDs, SSRIs and SNRIs raise bleeding risk, and that Xarelto can cause serious and fatal bleeding [2]. It is contraindicated in active pathological bleeding and in severe hypersensitivity to the drug [2].

What sermorelin is, and where it fits

Sermorelin is the shortest synthetic peptide with the full biological activity of GHRH [1]. It acts on the pituitary to trigger growth hormone release; in healthy men given an intravenous dose, the peptide was eliminated quickly while growth hormone stayed elevated for about 3 hours [6]. Geref, the only approved sermorelin, was approved for pediatric idiopathic growth hormone deficiency and for a pituitary diagnostic test [3]. The manufacturer discontinued it in 2008, FDA withdrew both approvals effective June 18, 2009, and FDA later determined it was not withdrawn for safety or effectiveness reasons [3]. Sermorelin sold today is compounded, and compounded drugs are not FDA-approved [4]. Because no sermorelin product is currently FDA-approved, there is no current approved dose. HealthRX.com offers sermorelin by prescription.

What the label says about monitoring

The Xarelto label says monitoring the anticoagulant effect with PT, INR, aPTT or anti-factor Xa tests is not recommended, and that protamine sulfate and vitamin K are not expected to affect its activity [2].