A fixed-dose combination (FDC) of Pregabalin, a gabapentinoid anticonvulsant and neuropathic pain agent, and Nortriptyline, a tricyclic antidepressant (TCA). This combination is primarily used for the management of neuropathic pain conditions, particularly diabetic peripheral neuropathy (DPN) and post-herpetic neuralgia (PHN), where monotherapy is insufficient. It offers synergistic action by modulating both calcium channels and monoamine reuptake.
Adult: Usually 1 capsule (Pregabalin 75mg + Nortriptyline 10mg) once or twice daily, preferably at bedtime to minimize daytime sedation. Initiate with once daily at bedtime. Dose can be titrated based on response and tolerability, typically after 3-7 days. Maximum recommended dose is 2 capsules per day (Pregabalin 150mg + Nortriptyline 20mg).
Note: Administer orally with or without food. Taking with food may reduce dizziness and drowsiness. Swallow whole with a glass of water. Do not crush or chew. Evening administration is preferred to capitalize on sedative effects for improving sleep. Avoid abrupt discontinuation; taper over at least one week to prevent withdrawal symptoms (especially for pregabalin).
The combination provides a dual mechanism for neuropathic pain relief. Pregabalin binds to the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system, reducing the release of excitatory neurotransmitters (glutamate, noradrenaline, substance P). Nortriptyline primarily inhibits the reuptake of norepinephrine and, to a lesser extent, serotonin at presynaptic neurons, increasing their concentration in the synaptic cleft. It also exhibits sodium channel blockade, NMDA receptor antagonism, and anticholinergic activity, contributing to its analgesic and side effect profile.
Pregnancy: Pregabalin: Category C (US FDA). Limited human data; animal studies show teratogenicity. Use only if benefit outweighs risk. Nortriptyline: Category D (Australian categorization) / Category C (US FDA). Potential risks include neonatal withdrawal symptoms. Avoid during pregnancy unless absolutely necessary. Consult specialist.
Driving: ADVISE NOT TO DRIVE. The combination causes dizziness, drowsiness, blurred vision, and impaired motor coordination, especially during initiation and dose escalation. Patients should not operate machinery or drive until they know how the medication affects them.
| Monoamine Oxidase Inhibitors (MAOIs) - Phenelzine, Selegiline | Risk of hypertensive crisis, serotonin syndrome, hyperpyrexia, death. | Contraindicated |
| Other CNS Depressants (Alcohol, Benzodiazepines, Opioids) | Additive CNS depression, severe sedation, respiratory depression, impaired motor skills. | Major |
| CYP2D6 Inhibitors (Fluoxetine, Paroxetine, Quinidine) | Increased nortriptyline plasma levels, leading to toxicity. | Major |
| Anticholinergics (Atropine, Oxybutynin, TCAs) | Enhanced anticholinergic effects (dry mouth, constipation, urinary retention, confusion). | Moderate |
| Antihypertensives | Potentiation of hypotensive effect, especially postural hypotension. | Moderate |
| Tramadol | Increased risk of seizures and serotonin syndrome. | Moderate |
| Warfarin | Nortriptyline may alter anticoagulant response; monitor INR. | Moderate |
Same composition (Pregabalin (75mg) + Nortriptyline (10mg)), different brands: