Egrifta (Tesamorelin) and Warfarin Interaction: What Patients and Clinicians Need to Know

What the Egrifta labels say about drugs cleared by CYP450

Tesamorelin is a growth hormone-releasing factor analog. It stimulates the pituitary to release the body's own growth hormone, which raises IGF-1 [1]. Its drug interactions section is short. It reports one pharmacokinetic study, with simvastatin, then a general statement:

"Published data indicate that GH may modulate cytochrome P450 (CYP450) mediated antipyrine clearance. These data suggest that GH may alter the clearance of compounds known to be metabolized by CYP450 liver enzymes (e.g., corticosteroids, sex steroids, anticonvulsants, and cyclosporine). Monitor patients for potential interactions when administering EGRIFTA SV in combination with other drugs known to be metabolized by CYP450 liver enzymes." [1][2]

Warfarin is not among the examples given, and no warfarin study appears in that section [1][2]. Warfarin is metabolized by CYP450 enzymes [3], so it falls within the category of drugs that monitoring statement covers.

How the warfarin label describes enzyme effects

The warfarin label describes how warfarin itself is cleared: the more potent S-enantiomer, 2 to 5 times the activity of R-warfarin, is metabolized by CYP2C9, while R-warfarin is metabolized by CYP1A2 and CYP3A4 [3]. The label states that inducers of CYP2C9, 1A2 or 3A4 have the potential to decrease warfarin's effect and lower INR by reducing warfarin exposure, and that inhibitors can do the reverse [3]. The Egrifta labels do not classify tesamorelin as an inducer or inhibitor of these enzymes [1][2].

The measured numbers are small

In healthy subjects, co-administration with tesamorelin changed simvastatin exposure (AUC) by about -8% and simvastatin acid by about -15%; ritonavir AUC fell about 9% and its peak concentration about 11% [1]. The label describes this as no significant impact [1]. Neither study involved warfarin or measured INR.

What the warfarin label says to watch

The boxed warning is bleeding risk: warfarin can cause major or fatal bleeding, and regular INR monitoring is required in all treated patients [3]. Bleeding is more likely in the first month. Risk factors the label names include INR above 4.0, age 65 or older, highly variable INRs, prior gastrointestinal bleeding, hypertension, cerebrovascular disease, anemia, malignancy, trauma, renal impairment, certain genetic factors, certain other drugs and long duration of therapy [3]. Keeping the INR in the therapeutic range does not remove the risk of bleeding [3].

The label's targets are INR 2.5 (range 2.0 to 3.0) for venous thromboembolism and for non-valvular atrial fibrillation, and 3.0 (range 2.5 to 3.5) for tilting disk and bileaflet mechanical valves in the mitral position [3]. The label says to obtain INR every 1 to 4 weeks once stable, and to monitor more frequently when starting or stopping other drugs, including botanicals, or when changing their doses [3].

Are the two drugs contraindicated together?

No. Tesamorelin's contraindications are disruption of the hypothalamic-pituitary axis, active malignancy, known hypersensitivity to tesamorelin or its excipients, and pregnancy [1][2]. Warfarin's contraindications include pregnancy except in women with mechanical heart valves at high thromboembolic risk, hemorrhagic tendencies or blood dyscrasias, recent or planned CNS or eye surgery, active bleeding conditions, and several procedure-related settings [3]. Neither label lists the other drug [1][3].

The specific interaction the Egrifta label explains: glucocorticoids

Besides the general CYP450 statement, the Egrifta labels explain one specific interaction by mechanism, with glucocorticoid replacement. GH inhibits 11-beta-hydroxysteroid dehydrogenase type 1, the enzyme required to convert cortisone to its active metabolite cortisol. Patients receiving glucocorticoid replacement for previously diagnosed hypoadrenalism may therefore need higher maintenance or stress doses after starting tesamorelin; cortisone acetate and prednisone are affected more than other steroids [1][2]. That mechanism concerns cortisone and prednisone, not warfarin.