Patient adherence to generic gabapentin: A pragmatic study

Introduction

Gabapentin acts via voltage-sensitive calcium channels in cortical neurons resulting in increased levels and responses of γ-aminobutyric acid. It is indicated in two primary conditions: seizure control and neuropathic pain.^1–3 Similar to other countries, Neurontin® and generic gabapentin are available in clinical practice. Srinagarind Hospital is a University Hospital, Khon Kaen University, Thailand. Due to cheaper price, generic gabapentin is primarily used in all patients since August 2011. Neurontin® is eight times more expensive than generic gabapentin. Physicians, however, could prescribe original gabapentin if generic gabapentin was not effective.

The generic gabapentin should have comparable oral bioavailability with the original gabapentin. The Cmax and area under the curve of generic drug should also not differ more than 20% from the original product. ⁴ Data regarding the switch back rate of generic gabapentin to original gabapentin are limited. Currently, there is no clinical trial comparing the efficacy of original and generic gabapentin in Thailand. This study aimed to evaluate an adherence of generic gabapentin in clinical practice and show clinical features of patients who required original gabapentin.

Methods

The study was a retrospective longitudinal study. All consecutive adult patients aged >15 years who received gabapentin treatment at Srinagarind Hospital were included. The study period was from August 2011 to March 2013. Initially, all patients received generic gabapentin (Siam Pharmaceutical, Thailand). Physicians could switch to original gabapentin (Neurontin®, Pfizer, USA) if the patients did not improve after generic gabapentin treatment or if any adverse events occurred. The rate of original gabapentin switch treatment was calculated. Clinical features of all patients who required original gabapentin were also reviewed.

Data analysis

Descriptive statistics were used to identify numbers of patients who received generic gabapentin, numbers of patients who required switch therapy to original gabapentin, clinical characteristics of patients who required switch therapy to original gabapentin, and reasons for switch therapy to original gabapentin.

Results

During the study period, there were 5195 patients who initially received the generic gabapentin product. Of those, 310 patients (6.0%; 95% confidence interval of 5.3, 6.6%) required a switch therapy to the original gabapentin product. The median age of all patients who required original gabapentin switch therapy was 61 years (range 15–89 years). Approximately two-third of these patients was female (213 patients, 68.7%). The most common indication of gabapentin in the patients who had the need to switch therapy was neuropathic pain, in 266 patients (85.8%). Spondylosis was the most common diagnosis in 229 patients (73.8%), as shown in Table 1. The average duration of generic gabapentin treatment before switching to original gabapentin therapy was 107 ± 94 days (SD 94). The reason for switch therapy to original gabapentin was recorded in 22 patients (7.1%) due to ineffective treatment, while there were no data on reasons for switch therapy in the rest of the patients (288 patients, 92.9%). All patients who received original gabapentin therapy had improvement on pain control.

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Table 1.

Clinical features of patients who switched from generic to original gabapentin

Median age (range), years	61 (15–89)
Male gender, N (%)	97 (31.3)
Health insurance, N (%)
– Government insurance	260 (83.9)
– Social security insurance	11 (3.5)
– Universal coverage	28 (9)
– Self payment	4 (1.3)
– No data	3 (1)
Indication for gabapentin therapy – no. (%)
– Neuropathic pain	266 (85.8)
– Epilepsy	–
– Cancer pain	–
– Others	1 (0.3)
– N/A	43 (13.9)
Medical disease that contributed to gabapentin use – no. (%)
– Spondylosis	229 (73.8)
: C-Spondylosis	42
: L-Spondylosis	187
– Osteoarthritis	6 (1.9)
– Low back pain	4 (1.3)
– Epilepsy	–
– Malignancy	–
– Herniated nucleus pulposus	23 (7.4)
– Others	8 (2.6)
– Not available	40 (12.9)
Gabapentin use
– Duration of generic drug use (days)
Minimum	11
Maximum	412
Median	66
Mean	107
SD	94
– Dose of generic drug use
100 mg/d – no. (%)	4 (1.3)
200 mg/d – no. (%)	3 (1)
300 mg/d – no. (%)	90 (29)
600 mg/d – no. (%)	92 (29.7)
900 mg/d – no. (%)	111 (35.5)
1200 mg/d – no. (%)	3 (1)
1800 mg/d – no. (%)	1 (0.3)
2700 mg/d – no. (%)	1 (0.3)
N/A	5 (1.6)
– Duration of original drug use (days)
Minimum	3
Maximum	705
Median	225
Mean	227
SD	157
– Dose of original drug use
100 mg/d – no. (%)	–
200 mg/d – no. (%)	–
300 mg/d – no. (%)	110 (35.5)
600 mg/d – no. (%)	110 (35.5)
900 mg/d – no. (%)	73 (23.5)
1200 mg/d – no. (%)	8 (2.6)
1800 mg/d – no. (%)	4 (1.3)
2700 mg/d – no. (%)	1 (0.3)
Not available	4 (1.3)

Discussion

Generic medications may provide favorable outcomes, but this needs to be confirmed by clinical study. This study showed that most patients (4885 patients, 94.0%) adhered to generic gabapentin. The switch therapy to original gabapentin occurred in only 6.0% with unclear reasons in 92.9%.

The major advantage of generic medication is low cost. The long-term outcome to ensure the cost-effectiveness may need long-term follow-ups. Previous studies have shown that generic medication may be effective in diabetes and myasthenia gravis treatment.^5,6 In a study from Taiwan comparing original with the generic metformin product, the original metformin product lowered HbA1C level more than the generic metformin product. Patient adherence to the generic metformin product was more than 80%, but the adherence significantly lowered than the original metformin product. A pilot study of using pyrimine 60 or generic pyridostigmine (mestinon) for myasthenia gravis showed good responses in nine patients out of 13 patients (69.23%). In this study, generic gabapentin was effective in 4885 (94%) patients. In other words, generic gabapentin may be effective in neuropathic pain control with a good adherence rate.

The switched therapy to original gabapentin occurred in 6.0% of patients after using generic gabapentin for 107 days. The reason found in the medical records was no improvement after generic gabapentin treatment, while physicians did not mention reasons for switched therapy in the other 288 patients (92.9%); assuming that they also did not improve. An inadequate dose of gabapentin treatment may be a reason of inadequate treatment. The recommended dose for neuropathic pain is 1800–3600 mg/day. ⁷ Only two patients received the recommended adequate dose of generic gabapentin (Table 1).

Before the generic gabapentin implementation, the average cost for all gabapentin prescription was 501,952.03 baht/month (16,731.43 USD, 1 USD = 30 Baht). After the generic policy implementation in the hospital, the average cost for all gabapentin prescription lowered to 293,619.97 baht/month (9,787.33 USD). This policy saved 208,332.06 baht/month (6,944.40 USD) or 2,499,984 baht/year (83,332.80 USD). Note that the number is for only one University Hospital (approximately 1000 beds). If the policy would be implemented in all hospitals over Thailand, the government could save significant budget for the original gabapentin use. The generic gabapentin use may be appropriate for Thailand, ASEAN countries, or other developing countries.

Conclusion

Generic gabapentin therapy is effective as a pain controller in neuropathic pain with adherence rate of 94.0%. Generic gabapentin therapy may reduce cost and budget from the original gabapentin.