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

Is there a known interaction between liraglutide and rivaroxaban?

The Saxenda and Victoza interaction sections do not name rivaroxaban [1][2]. They address delayed gastric emptying of oral medicines and, for Victoza, hypoglycemia with insulin or a sulfonylurea [1][2].

Liraglutide is a peptide with 97% amino acid sequence homology to human GLP-1. It is metabolized like a large protein, without a specific organ of elimination, and intact liraglutide is not found in urine or feces. Its plasma half-life is about 13 hours after subcutaneous injection, which supports once-daily dosing [1].

Rivaroxaban is an oral direct factor Xa inhibitor that targets free and clot-bound factor Xa and factor Xa in the prothrombinase complex [3]. It is a CYP3A4 and P-glycoprotein substrate [4]. In 12 healthy volunteers, two weeks of St John's wort, which induces both, lowered rivaroxaban AUC to 0.76 of the pre-induction value (90% CI 0.70 to 0.82), Cmax to 0.86, and factor Xa inhibition to 0.80 [5]. A separate 12-volunteer study found rivaroxaban AUC and Cmax about 25% lower after St John's wort and concluded the combination should be avoided [4]. A 2014 pharmacokinetic review states that rivaroxaban has multiple elimination pathways and no clinically relevant interactions with most commonly prescribed medications [3].

What the liraglutide labels say about oral medicines

The Saxenda label states that liraglutide causes a delay of gastric emptying and so has the potential to affect the absorption of oral medicines taken at the same time. It also states that in clinical pharmacology trials liraglutide did not affect the absorption of the tested oral medicines to any clinically relevant degree, and says to monitor for potential consequences of delayed absorption [1]. The Victoza label carries both statements and adds that caution should be exercised when oral medicines are given with it [2]. FDA-approved generic liraglutide exists, with generic applications referencing either Saxenda or Victoza [6].

The human numbers in the Saxenda label come from an oral contraceptive study using 0.03 mg ethinylestradiol and 0.15 mg levonorgestrel. Liraglutide lowered the peak concentration of ethinylestradiol by 12% and of levonorgestrel by 13%, left ethinylestradiol AUC unchanged, raised levonorgestrel AUC by 18%, and delayed time to peak by 1.5 hours [1].

Rivaroxaban absorption and food

Rivaroxaban is absorbed rapidly, with maximum plasma concentrations reached 2 to 4 hours after tablet intake. Oral bioavailability is high, 80% to 100%, for the 10 mg tablet irrespective of food intake and for the 15 mg and 20 mg tablets when taken with food. Variability in its pharmacokinetic parameters is moderate, with a coefficient of variation of 30% to 40%. Terminal half-life is 5 to 9 hours in healthy young subjects and 11 to 13 hours in elderly subjects [3].

Dehydration and kidney function

The Saxenda label lists acute kidney injury due to volume depletion under its warnings and says to monitor renal function in patients reporting reactions that could lead to volume depletion [1]. The Victoza label carries the same warning and notes that most reported cases occurred in patients who had gastrointestinal reactions leading to dehydration, such as nausea, vomiting or diarrhea [2]. In the Saxenda adult trials (3,384 patients on Saxenda versus 1,941 on placebo), nausea occurred in 39.3% versus 13.8% and vomiting in 15.7% versus 3.9% [1]. With Victoza, nausea was reported by 18% at 1.2 mg and 20% at 1.8 mg versus 5% on placebo [2].

Which liraglutide products this covers

Saxenda is the weight-management product, given at 3 mg daily once titration is complete. Victoza is the type 2 diabetes product, given at up to 1.8 mg daily. Both are once-daily subcutaneous injections [1][2].

The bottom line

Nothing in the Saxenda or Victoza labels says liraglutide and rivaroxaban cannot be used together, and nothing in them says the pair is free of effect [1][2]. The only absorption signal the liraglutide labels raise is delayed gastric emptying, which did not change absorption of the tested oral medicines to a clinically relevant degree [1][2].