Does gabapentin (Neurontin) cause edema?

From the Guidelines

Gabapentin can cause edema, particularly in the lower extremities, as a common adverse effect. This is supported by a recent study published in the Mayo Clinic Proceedings in 2023 1, which notes that edema of the lower extremities is frequently reported in patients taking gabapentin. The study highlights that this side effect may counteract the benefits of topical medications, emphasizing the need for careful consideration and monitoring in patients prescribed gabapentin. Some key points to consider when prescribing gabapentin include:

• The medication is relatively safe, with sedation being the most common adverse effect, but edema is also a significant concern
• Edema may develop gradually, typically within the first few weeks of treatment
• Patients with pre-existing conditions, such as heart, kidney, or liver disease, may be at higher risk for gabapentin-induced edema
• Management of edema may involve reducing the dose, switching to an alternative medication, or adding a mild diuretic, and patients should consult their healthcare provider if they experience bothersome edema while taking gabapentin.

From the FDA Drug Label

The most common adverse reactions associated with the use of gabapentin in adults, not seen at an equivalent frequency among placebo-treated patients, were dizziness, somnolence, and peripheral edema Table 3 lists adverse reactions that occurred in at least 1% of gabapentin-treated patients with postherpetic neuralgia participating in placebo-controlled trials and that were numerically more frequent in the gabapentin group than in the placebo group. Metabolic and Nutritional Disorders Peripheral edema 8 2 TABLE 4 Adverse Reactions in Pooled Placebo-Controlled Add-On Trials In Epilepsy Patients >12 years of age Body System/ Adverse Event GabapentinaN=543 % Placeboa N=378 % Body As A Whole Peripheral Edema 2 1

Gabapentin can cause edema. The drug label reports that peripheral edema occurred in 8% of patients with postherpetic neuralgia and 2% of patients with epilepsy, which is more frequent than in the placebo group 2. Key points include:

• Peripheral edema is listed as a common adverse reaction in the drug label.
• The incidence of peripheral edema varies by condition, with 8% of patients with postherpetic neuralgia and 2% of patients with epilepsy experiencing this side effect.
• These rates are higher than those reported in the placebo group.

From the Research

Gabapentin and Edema

• Gabapentin, also known as Neurontin, has been associated with peripheral edema as a potential side effect 3, 4, 5, 6, 7.
• The incidence of pedal edema with gabapentin use is approximately 7 to 7.5% in elderly patients receiving doses above 1200 mg/day 5.
• However, lower doses of gabapentin can also cause this adverse effect, as illustrated by a case report of a young male patient who developed bilateral lower extremity edema while taking 300mg of gabapentin twice daily 5.
• The development of edema may lead to a potentially harmful prescribing cascade, where individuals are subsequently prescribed diuretics and exposed to diuretic-induced adverse events 6.
• Gabapentinoids, including gabapentin, can cause concentration-dependent peripheral edema of early onset, with a primary mechanism of non-cardiogenic peripheral edema being vasodilatory edema secondary to altered myogenic tone 7.

Risk Factors and Onset

• The median time to onset of non-cardiogenic edema and acute heart failure associated with gabapentinoids is 23 days and 17 days, respectively 7.
• Cardiogenic and non-cardiogenic peripheral edema often occur frequently after a dose escalation, and the course is rapidly favorable after discontinuation of gabapentinoid 7.
• The female-to-male ratio of patients experiencing gabapentinoid-induced peripheral edema or heart failure is 4:1, with a median age of 77 years 7.

Clinical Implications

• Gabapentin should be administered with care, not only in patients with advanced cardiac pathology but also in all patients, due to the potential side effects of peripheral edema and acute heart failure 3.
• Increased awareness of the prescribing cascade associated with gabapentinoids is required to reduce the unnecessary use of diuretics and the exposure of patients to additional adverse drug events 6.