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

Is there a known interaction between sermorelin and gabapentin?

Gabapentin is a prescription anticonvulsant first approved in 1993 and labeled for nerve pain after shingles in adults and as add-on treatment for partial-onset seizures [1]. Sermorelin acetate is a 29-amino-acid analogue of human growth hormone-releasing hormone. It acts on the pituitary to prompt release of the body's own growth hormone; it is not growth hormone itself [4].

No published study has given the two drugs to the same people, so there is no measured interaction to describe.

There is no current FDA-approved sermorelin product label to check. Geref, the only FDA-approved sermorelin, was discontinued by its manufacturer in 2008, and FDA withdrew both of its applications in 2009 [3]. Sermorelin sold in the US today is compounded, and compounded drugs are not reviewed by FDA for safety, effectiveness or quality before they are marketed [5].

FDA's 2019 communication names the combinations that concern regulators: opioid pain medicines, other central nervous system depressants, and benzodiazepines in particular [1].

Why a liver-enzyme interaction looks unlikely on gabapentin's side

Gabapentin is not appreciably metabolized in humans and does not inhibit the liver enzymes that break down other drugs. It is excreted renally, with an elimination half-life of approximately 6 hours [2]. On that basis, a liver-enzyme interaction coming from gabapentin looks unlikely [2].

Gabapentin absorption is saturable. Absolute bioavailability falls from 60% at 900 mg a day to 33% at 3600 mg a day, and peak plasma concentrations arrive 3 to 4 hours after an oral dose [2].

What FDA and the gabapentin label warn about

FDA's 2019 Drug Safety Communication warned that serious breathing difficulties can occur in people taking gabapentin who have respiratory risk factors: opioid pain medicines or other CNS depressants, lung conditions such as COPD, and older age. FDA required new respiratory depression warnings in the labels and told prescribers to start gabapentinoids at the lowest dose and monitor for respiratory depression and sedation when co-prescribing with an opioid or another CNS depressant such as a benzodiazepine [1].

FDA lists these symptoms as reasons to seek medical attention immediately: confusion or disorientation, unusual dizziness or lightheadedness, extreme sleepiness or lethargy, slowed, shallow or difficult breathing, unresponsiveness, and bluish-colored skin, especially on the lips, fingers and toes [1].

Sedation and dizziness are common with gabapentin even without a second drug. In an 8-week randomized trial of 165 adults with painful diabetic neuropathy, gabapentin titrated from 900 to 3600 mg a day was associated with more dizziness than placebo (24% versus 4.9%) and more somnolence (23% versus 6%) [6].

Opioid co-prescription has its own signal. An Ontario nested case-control study compared 1,256 people who died of opioid-related causes with 4,619 matched opioid users. Gabapentin had been prescribed in the prior 120 days in 12.3% of the deaths versus 6.8% of controls, and the adjusted odds ratio of opioid-related death with co-prescribed gabapentin was 1.49 (95% CI 1.18 to 1.88) [7]. That is observational data.

Why kidney function matters for gabapentin

Gabapentin leaves the body through the kidneys rather than through liver metabolism [2], so when kidney function is reduced the drug is cleared more slowly and stays in the body longer. FDA also lists older age among the respiratory risk factors for gabapentin [1].

Does sermorelin add sedation?

A 1-year, open-label, multicenter trial treated 110 previously untreated prepubertal children with growth hormone deficiency; 86 were evaluable for efficacy [8]. Height velocity rose from 4.1 cm per year at baseline to 8.0 cm per year at 6 months and 7.2 cm per year at 12 months, and 74% were good responders at 6 months. No adverse changes appeared in general biochemistry or hormone tests, fasting glucose did not change, IGF-I was not excessively raised, and sermorelin was well tolerated overall [8]. That trial reports no sedation result.

After an intravenous dose in healthy men, GHRH(1-29) was eliminated quickly, yet growth hormone levels stayed elevated for about 3 hours [9]. That is a hormone effect, not a measured effect on alertness.

What this means in practice

The gabapentin side is where the documented risk sits. In a neuropathic pain trial it caused dizziness and drowsiness more often than placebo [6], and FDA says it can cause serious breathing problems when combined with an opioid or another central nervous system depressant, especially in older adults and people with lung disease [1].