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

Do finasteride and gabapentin interact?

Finasteride's prescribing information states that no drug interactions of clinical importance have been identified with finasteride, and that it does not appear to affect the cytochrome P450 enzyme system [1]. Compounds tested in people include antipyrine, digoxin, propranolol, theophylline and warfarin, with no clinically meaningful interactions found [1].

Finasteride itself is extensively metabolized in the liver, mainly by CYP3A4, into two metabolites that carry no more than 20% of its activity; about 39% of a dose appears in urine as metabolites and 57% in feces [1].

Gabapentin is handled differently. It is not appreciably metabolized and does not inhibit the hepatic enzymes that clear other drugs, and it is excreted renally with an elimination half-life of about 6 hours [2]. Its absorption is saturable, so bioavailability falls as the dose rises: roughly 60% at 900 mg a day and about 33% at 3,600 mg a day [2].

What the labels record about using them together

The finasteride label does not describe a study of finasteride with gabapentin. What exists is finasteride's trial experience with nearby drug classes.

The Propecia label states that although specific interaction studies were not performed, finasteride 1 mg or more was used in clinical studies with anticonvulsants, benzodiazepines, alpha-blockers, ACE inhibitors, beta blockers, calcium-channel blockers, cardiac nitrates, diuretics, NSAIDs, H2 antagonists and quinolone anti-infectives without evidence of clinically significant adverse interactions [1]. Gabapentin is not named in that list. The Proscar label for finasteride 5 mg carries a similar statement [5].

Propecia is the finasteride 1 mg tablet, indicated for male pattern hair loss in men only, taken once daily with or without food [6][1]. Proscar is the 5 mg tablet, indicated for symptomatic benign prostatic hyperplasia in men with an enlarged prostate [7].

Where the real interaction risk sits: gabapentin and CNS depressants

FDA's December 19, 2019 safety communication warned that serious breathing difficulties can occur in people taking gabapentin who have respiratory risk factors: opioid pain medicines or other drugs that depress the central nervous system, lung conditions such as COPD, and older age [3]. FDA required new respiratory depression warnings in the gabapentinoid labels and told health professionals to start 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 [3].

The symptoms FDA lists are confusion or disorientation, unusual dizziness or lightheadedness, extreme sleepiness or lethargy, slowed or shallow breathing, unresponsiveness, and bluish-colored skin, especially on the lips, fingers and toes; the agency advises seeking medical attention immediately for these [3].

The clearest data on the opioid combination come from Ontario. In a nested case-control study among opioid users, 1,256 people who died of opioid-related causes were compared with 4,619 matched controls; gabapentin had been prescribed in the previous 120 days in 12.3% of cases versus 6.8% of controls, an adjusted odds ratio of 1.49 (95% CI 1.18 to 1.88), and 1.58 (1.09 to 2.27) at gabapentin doses of 1,800 mg a day or more [8]. That is observational data and cannot establish cause [8].

Finasteride is not an opioid or a benzodiazepine. It is a competitive inhibitor of type II 5-alpha-reductase, the enzyme that converts testosterone to DHT, and it has no affinity for the androgen receptor [1]. Propecia's Warnings and Precautions section covers pregnancy exposure, PSA interpretation, high-grade prostate cancer and pediatric use, while its postmarketing section lists depression, suicidal ideation and behavior, and sexual dysfunction that continued after stopping [1][4].

Finasteride's psychiatric labeling, in its actual form

On May 31, 2022, FDA sent a safety labeling change order citing new information on suicidal ideation and behavior, additional sexual dysfunction, and psychoneurocognitive events; supplement S-030, approved August 1, 2022, changed the Propecia postmarketing wording to 'depression, suicidal ideation and behavior' [4]. The current Proscar label lists 'depression' and 'suicidal ideation' [5]. These entries are voluntary reports from a population of uncertain size, and the labels state that a causal relationship cannot reliably be established [4]. Neither Propecia nor Proscar carries a boxed warning [1][5].

Larger cohort studies, mostly in older men with BPH, give a mixed picture. In Ontario, 93,197 men aged 66 or older who started a 5-alpha reductase inhibitor were compared with matched unexposed men: suicide hazard ratio 0.88 (95% CI 0.53 to 1.45), self-harm 1.88 (1.34 to 2.64) in the first 18 months only, and depression 1.94 (1.73 to 2.16) in the first 18 months and 1.22 (1.08 to 1.37) afterward [9]. A Swedish register study of 2,236,876 men, in which finasteride starters had a median age of 73, found a finasteride depression hazard ratio of 1.61 (1.48 to 1.75) that stayed constant over time, with no suicide association (1.22, 0.99 to 1.49) [10].

Does kidney function change the picture?

Kidney function bears mainly on gabapentin. Gabapentin is eliminated unchanged by the kidneys, so kidney function affects its clearance [2]. Finasteride takes a different route: extensive liver metabolism, mainly by CYP3A4, with metabolites leaving in urine and feces [1].

Proscar is indicated for symptomatic BPH in men with an enlarged prostate [7], while gabapentin is FDA-approved for postherpetic neuralgia (nerve pain after shingles) and as add-on therapy for partial seizures [3]. FDA's 2019 communication treats older age itself as a respiratory risk factor for gabapentin [3].