A fixed-dose combination (FDC) of Gabapentin, a gamma-aminobutyric acid (GABA) analogue anticonvulsant, and Nortriptyline, a tricyclic antidepressant (TCA). This combination is primarily used for the management of neuropathic pain, particularly diabetic peripheral neuropathy and postherpetic neuralgia, by targeting multiple pain pathways. It is a rational pharmacotherapy for pain unresponsive to monotherapy.
Adult: Usually 1 tablet (Gabapentin 400mg + Nortriptyline 10mg) at bedtime. Initiation: Often started with gabapentin monotherapy, then nortriptyline added, but FDC can be initiated in patients already stabilized on lower doses. Titration: Based on response and tolerability. Maximum: Typically 1 tablet TDS (Gabapentin 1200mg + Nortriptyline 30mg/day). Nortriptyline dose rarely exceeds 50-75mg/day for pain.
Note: Take with or without food. For better tolerability, the bedtime dose is crucial. Swallow whole with a full glass of water. Do not crush or chew. If a dose is missed, take it as soon as remembered unless it's close to the next dose. Do not double the dose.
The combination provides synergistic analgesia for neuropathic pain via complementary mechanisms. Gabapentin binds to the alpha-2-delta 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 nerve terminals, enhancing descending inhibitory pain pathways in the spinal cord. It also exhibits sodium channel blockade, NMDA receptor antagonism, and anticholinergic, antihistaminic, and alpha-1 adrenergic blocking activity.
Pregnancy: Gabapentin: Pregnancy Category C (US FDA). Data in humans is limited; potential risk. Use only if benefit justifies risk. Nortriptyline: Pregnancy Category D (US FDA). Evidence of risk. Associated with neonatal withdrawal symptoms (jitteriness, seizures, respiratory distress). Not recommended in pregnancy unless absolutely necessary. Consult obstetrician and neurologist/psychiatrist.
Driving: ADVISE NOT TO DRIVE or operate heavy machinery, especially during initial treatment and dose escalation. Causes dizziness, drowsiness, and blurred vision.
| Monoamine Oxidase Inhibitors (MAOIs) - Phenelzine, Selegiline | Risk of hypertensive crisis, serotonin syndrome, hyperpyrexia, seizures. | Contraindicated |
| Other CNS Depressants - Alcohol, Opioids, Benzodiazepines (Alprazolam), Barbiturates | Additive CNS depression, respiratory depression, sedation, impaired motor skills. | Major |
| Anticholinergics - Atropine, Oxybutynin, Tricyclics, Antipsychotics | Additive anticholinergic effects: urinary retention, constipation, blurred vision, cognitive impairment. | Major |
| CYP2D6 Inhibitors - Fluoxetine, Paroxetine, Quinidine | Increased nortriptyline plasma levels, risk of toxicity. | Major |
| CYP2D6 Inducers - Rifampicin | Decreased nortriptyline plasma levels, reduced efficacy. | Moderate |
| Antihypertensives (especially Alpha-blockers like Prazosin) | Enhanced hypotensive effect, risk of severe orthostasis. | Moderate |
| Anticoagulants (Warfarin) | Nortriptyline may alter anticoagulant response; monitor INR. | Moderate |
| Antacids (Aluminum, Magnesium hydroxide) | Reduce gabapentin absorption by up to 20%. Administer gabapentin at least 2 hours after antacid. | Moderate |
Same composition (Gabapentin (400mg) + Nortriptyline (10mg)), different brands: