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

Is there a direct interaction between tesamorelin and gabapentin?

Tesamorelin is a synthetic analog of human growth hormone-releasing factor: the 44-amino-acid human sequence with a hexenoyl group on the N-terminal tyrosine, molecular weight about 5135.9 Da [1]. It binds and stimulates GRF receptors on pituitary somatotroph cells, so the pituitary releases more of the body's own growth hormone, which raises IGF-1 and IGFBP-3 [1]. Its approved use is reduction of excess abdominal fat in HIV-infected adults with lipodystrophy, and the label states it is not indicated for weight loss because its effect on weight is neutral [1]. Egrifta SV is given as 1.4 mg subcutaneously into the abdomen once daily, rotating sites and avoiding scar tissue, bruises and the navel [1]. Egrifta WR is a separate formulation at 1.28 mg once daily, and the two are not substitutable [4].

Gabapentin is a prescription anticonvulsant approved for postherpetic neuralgia in adults and as add-on treatment of partial-onset seizures in adults and children 3 years and older; neuropathic pain in people with HIV is not among the labeled uses [5]. A published review of newer antiepileptic drugs describes gabapentin as primarily renally excreted rather than metabolized by CYP450 enzymes, and classes it among agents essentially not associated with clinically significant pharmacokinetic interactions [2].

The Egrifta label names anticonvulsants. Does that cover gabapentin?

The drug interactions section of the Egrifta SV label covers two groups [1]. The first is drugs metabolized by cytochrome P450 enzymes. Because growth hormone may change CYP450-mediated clearance, the label lists corticosteroids, sex steroids, anticonvulsants and cyclosporine as examples and says to monitor patients who take them [1]. The second is glucocorticoids: growth hormone inhibits 11-beta-hydroxysteroid dehydrogenase type 1, an enzyme involved in converting cortisone to cortisol and prednisone to prednisolone, so people receiving glucocorticoid replacement for previously diagnosed hypoadrenalism may need higher maintenance or stress doses after starting Egrifta SV [1].

Gabapentin is an anticonvulsant by class, but it is primarily renally excreted rather than CYP450-metabolized [2]. Where the Egrifta label reports its own co-administration studies, the effects were small: simvastatin pharmacokinetics were not significantly changed, and ritonavir exposure fell by about 9% (AUC) and 11% (Cmax) [1].

What the Egrifta SV label asks you to monitor

IGF-1 first. Tesamorelin raises IGF-1, a growth factor, and the effects of prolonged elevation are unknown; the label says to monitor IGF-1 during therapy and to consider discontinuing if levels stay high (for example above 3 SDS), particularly when the reduction in visceral fat is not robust [1]. Among patients treated for 26 weeks, 47% had IGF-1 above 2 SDS and 36% above 3 SDS, with the rise seen as early as week 13; among those who stayed on treatment to 52 weeks, the figures were 34% and 23% [1].

Glucose second. Tesamorelin can cause glucose intolerance or diabetes: HbA1c of 6.5% or higher developed in 5% of tesamorelin-treated patients versus 1% on placebo by week 26, a hazard ratio of 3.3 (95% CI 1.4 to 9.6) [1]. The label directs that glucose status be evaluated before starting Egrifta SV and monitored periodically, and that patients with diabetes be monitored at regular intervals for potential development or worsening of retinopathy [1].

What the gabapentin information warns about

FDA warns that gabapentin may cause serious breathing difficulties in people taking opioid pain medicines or other drugs that depress the central nervous system, in people with conditions that reduce lung function such as COPD, and in older adults, and the agency required new respiratory depression warnings in the gabapentinoid labels [3]. FDA advised health care professionals to start at the lowest dose and monitor patients co-prescribed an opioid or a benzodiazepine, and listed symptoms to act on: confusion or disorientation, unusual dizziness, extreme sleepiness, slowed or shallow breathing, unresponsiveness and bluish skin [3].

The Egrifta SV warnings and precautions cover neoplasms, elevated IGF-1, fluid retention, glucose intolerance or diabetes, hypersensitivity reactions, injection-site reactions and increased mortality in acute critical illness [1].

Does gabapentin need a different dose with tesamorelin?

The tesamorelin label does not address gabapentin dosing [1]. What does change gabapentin dosing is kidney function: the gabapentin label sets lower maximum daily doses as creatinine clearance falls (for example 200 to 700 mg a day at a clearance above 15 to 29 mL/min).