A fixed-dose combination (FDC) of Gabapentin, an anticonvulsant and analgesic, and Nortriptyline, a tricyclic antidepressant (TCA). This combination is primarily used for the management of neuropathic pain, including diabetic neuropathy and post-herpetic neuralgia, by targeting multiple pain pathways. It is a rational pharmacotherapy for pain not adequately controlled by monotherapy.
Adult: Initially: One tablet (Gabapentin 100mg + Nortriptyline 10mg) at bedtime. Titrate gradually based on response and tolerability. Usual maintenance: 1 tablet in the morning and 1-2 tablets at bedtime. Maximum recommended daily dose of this FDC: Gabapentin 900mg + Nortriptyline 90mg (i.e., 9 tablets), but often limited by side effects.
Note: Take with or without food. Swallow whole with a glass of water. The bedtime dose helps mitigate daytime sedation and improves sleep. Do not crush or chew. Avoid abrupt discontinuation; taper over at least 1 week to prevent withdrawal (nortriptyline) or seizure risk (gabapentin).
The combination provides synergistic analgesia for neuropathic pain via complementary mechanisms. Gabapentin binds to the α2δ-1 subunit of voltage-gated calcium channels in the central nervous system, reducing the release of excitatory neurotransmitters (glutamate, substance P). Nortriptyline primarily inhibits the reuptake of norepinephrine (and to a lesser extent, serotonin) at presynaptic neurons, enhancing descending inhibitory pain pathways in the brainstem and spinal cord. It also exhibits sodium channel blockade and NMDA receptor antagonism at higher doses.
Pregnancy: Gabapentin: Pregnancy Category C (US FDA). Limited human data; use only if benefit justifies risk. Nortriptyline: Pregnancy Category D (Australian categorization) / Not recommended. Associated with neonatal withdrawal symptoms, jitteriness, and respiratory distress. Consult obstetrician and psychiatrist.
Driving: May impair alertness, motor coordination, and reaction time. Advise patients not to drive or operate heavy machinery until they know how the medication affects them, especially during initiation and dose escalation.
| Monoamine Oxidase Inhibitors (Phenelzine, Tranylcypromine) | Risk of hypertensive crisis, serotonin syndrome, hyperpyrexia. Contraindicated. | High |
| Other CNS Depressants (Alcohol, Opioids, Benzodiazepines) | Additive sedation, respiratory depression, impaired motor skills. | High |
| Anticholinergics (Atropine, Oxybutynin, TCAs) | Enhanced anticholinergic effects (dry mouth, urinary retention, constipation, confusion). | Moderate |
| CYP2D6 Inhibitors (Fluoxetine, Paroxetine, Quinidine) | Increased nortriptyline plasma levels, risk of toxicity. | Moderate |
| CYP2D6 Inducers (Rifampicin, Carbamazepine) | Decreased nortriptyline plasma levels, reduced efficacy. | Moderate |
| Antihypertensives | Nortriptyline may antagonize effects of guanethidine, clonidine. Potentiates orthostatic hypotension. | Moderate |
| Anticoagulants (Warfarin) | Nortriptyline may increase INR; monitor. | Low |
Same composition (Gabapentin (100mg) + Nortriptyline (10mg)), different brands: