E 63 Pill: Gabapentin 300mg — What It Is and Why Combining It with Opioids Is Dangerous

Gabapentin has become one of the most prescribed medications in the United States, with tens of millions of prescriptions written annually. The yellow capsule marked E 63 — manufactured by Aurobindo Pharma — is one of the most commonly dispensed versions of the drug. It was originally developed as an anti-epileptic agent, but its clinical use expanded dramatically into pain management, anxiety, and numerous off-label applications. Alongside this expansion has come a growing and serious public health concern: gabapentin's role in potentiating opioid overdose deaths.

Pill Identification

Aurobindo Pharma is one of the largest generic pharmaceutical manufacturers globally, headquartered in India with a major U.S. presence. Their "E" series imprints identify multiple products in their generic line. The E 63 capsule is a standard-size hard gelatin capsule in yellow, imprinted "E 63" on the capsule body. It contains gabapentin 300mg.

Gabapentin is sold under the brand name Neurontin (manufactured by Pfizer) and has been available as a generic since 2004. It is available in 100mg, 300mg, and 400mg capsule forms and 600mg and 800mg tablet forms. The 300mg capsule is the most commonly prescribed strength and a frequent starting point for therapy.

Pregabalin (brand name Lyrica) is a related drug — sometimes called gabapentin's "successor" — that works through a similar mechanism but is a Schedule V controlled substance federally. Gabapentin itself is not federally scheduled, though several states have independently placed it in Schedule V due to growing concerns about misuse and overdose contribution.

What Gabapentin Is Used For

Gabapentin was FDA-approved in 1993 as an adjunctive therapy for partial onset seizures in adults and children. It works by binding to a subunit of voltage-gated calcium channels in the central nervous system, which modulates the release of excitatory neurotransmitters. This mechanism reduces abnormal neuronal firing in epilepsy and also dampens pain signal transmission in certain nerve pain syndromes.

Approved indications include:

• Adjunctive therapy for partial-onset seizures (with and without secondary generalization)
• Post-herpetic neuralgia (nerve pain following shingles)

Off-label uses — for which gabapentin is commonly prescribed but not FDA-approved — include diabetic neuropathy, fibromyalgia, restless leg syndrome, alcohol withdrawal, anxiety disorders, and various other pain conditions. The extensive off-label prescribing of gabapentin has been a subject of significant scrutiny and litigation, particularly following revelations that Pfizer illegally promoted Neurontin for off-label uses before generics became available.

The Opioid Potentiation Risk: A Serious and Growing Danger

The mechanism behind gabapentin's opioid potentiation is not fully understood, but gabapentin's central nervous system depressant effects appear to compound opioid-induced respiratory depression. The respiratory system's sensitivity to opioids is already the primary mechanism of opioid overdose death, and adding gabapentin — even at prescribed amounts — can push this over a fatal threshold, particularly during sleep.

Research from Ontario, Canada examined over 100,000 opioid users and found that those who were co-prescribed gabapentin had substantially higher overdose mortality rates. Similar findings have emerged from U.S. data. The risk appears to be dose-dependent on both sides of the combination. Several U.S. states have responded by scheduling gabapentin as a controlled substance and requiring prescribers to check PDMPs when prescribing it.

Gabapentin has also been found in a significant percentage of drug-related overdose deaths — not always as a co-prescription but also as a substance obtained separately and combined with illicit opioids. This reflects gabapentin's appearance in the illicit drug market, where it is sometimes used to enhance the effects of street opioids including heroin and fentanyl — a practice that substantially increases overdose risk.

Other Safety Information

Beyond the opioid interaction, gabapentin has its own safety profile worth understanding. Common side effects include somnolence (sleepiness), dizziness, ataxia (coordination problems), and fatigue. These effects can be pronounced, particularly when starting treatment or increasing the amount, and can impair driving and work performance.

Abrupt discontinuation of gabapentin after prolonged use can precipitate withdrawal symptoms including anxiety, insomnia, nausea, pain, and in some cases seizures — even in patients who were not prescribed it for epilepsy. Gabapentin should be tapered rather than abruptly stopped under medical guidance.

Gabapentin can cause or worsen depression and has been associated with suicidal ideation. The FDA requires an anticonvulsant warning for all drugs in this class regarding the risk of suicidal thinking and behavior.

Frequently Asked Questions

Is gabapentin a controlled substance?

At the federal level, gabapentin is not classified as a controlled substance under the Controlled Substances Act. However, Michigan, Tennessee, Kentucky, Virginia, Wyoming, North Dakota, Alabama, Indiana, and other states have independently scheduled gabapentin at the state level. Prescribers and patients in those states face additional requirements. The regulatory landscape continues to evolve.

Why is gabapentin prescribed with opioids if the combination is risky?

Gabapentin and opioids are sometimes prescribed together for certain pain conditions — particularly neuropathic pain — because each addresses different pain pathways and the combination can improve pain control at lower amounts of each drug. However, this requires careful medical supervision, risk assessment, and monitoring. The elevated overdose risk must be explicitly weighed by the prescriber, and patients need to understand the risk, particularly around sleep and any other CNS depressants.

Can gabapentin be misused?

Yes. Gabapentin can produce a euphoric or calming effect in some individuals, particularly at higher amounts, which has led to its misuse. Its appearance in the illicit drug market — sometimes sold on the street — is a recognized public health concern. It is sometimes used to potentiate the effects of opioids or to self-manage opioid withdrawal, both of which carry significant risks.

What is the difference between gabapentin and pregabalin?

Pregabalin (Lyrica) works through the same calcium channel binding mechanism as gabapentin but is more potent, has more predictable absorption, and is FDA-approved for additional indications including fibromyalgia and generalized anxiety disorder. Pregabalin is a Schedule V controlled substance federally, reflecting its higher recognized abuse potential compared to gabapentin. Both drugs share the opioid potentiation risk.