Usage
- This combination is primarily prescribed for the management of neuropathic pain (nerve pain) associated with conditions such as diabetic peripheral neuropathy, postherpetic neuralgia (shingles pain), spinal cord injury, fibromyalgia, and chronic low back pain. It can also be used for other types of neuropathic pain where the combination is deemed appropriate by the physician.
- Pharmacological Classification: Pregabalin is an anticonvulsant and Nortriptyline is a tricyclic antidepressant (TCA).
- Mechanism of Action: Pregabalin works by binding to calcium channels on nerve cells, reducing the release of neurotransmitters associated with pain signals. Nortriptyline increases the levels of serotonin and norepinephrine, neurotransmitters that play a role in mood regulation and pain perception. The combination targets pain through distinct but complementary mechanisms.
Alternate Names
- No widely recognized alternate names for the combination itself exist. However, the individual components may have other names in specific regions or in veterinary practice.
- Brand Names: The combination is marketed under various brand names like Nuring NT, Pregalin NT, and Pregabid NT. Other brand names may also exist.
How It Works
- Pharmacodynamics: Pregabalin reduces neuronal excitability by modulating calcium channels. Nortriptyline inhibits the reuptake of serotonin and norepinephrine, increasing their synaptic concentrations. These combined effects reduce pain signaling and improve mood.
- Pharmacokinetics:
- Pregabalin: Rapidly absorbed after oral administration, with high bioavailability (≥90%). Peak plasma concentration reached within 1.5 hours. Steady state achieved in 24-48 hours. Primarily excreted unchanged in the urine.
- Nortriptyline: Well-absorbed orally, but undergoes significant first-pass metabolism. Metabolized in the liver (primarily by CYP2D6) to active metabolites. Eliminated through renal and biliary routes.
- Mode of Action: Pregabalin binds to the alpha2-delta subunit of voltage-gated calcium channels, reducing calcium influx into nerve terminals and decreasing the release of neurotransmitters like glutamate, noradrenaline, and substance P. Nortriptyline inhibits the presynaptic reuptake of serotonin and norepinephrine, leading to enhanced neurotransmission.
- Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Pregabalin binds to the alpha2-delta subunit of voltage-gated calcium channels. Nortriptyline inhibits the reuptake transporters for serotonin and norepinephrine.
- Elimination Pathways: Pregabalin is primarily eliminated unchanged through renal excretion. Nortriptyline undergoes hepatic metabolism via CYP enzymes (mainly CYP2D6) and is eliminated via both renal and hepatic routes.
Dosage
Standard Dosage
Adults:
- The dosage is individualized and based on the patient’s response and tolerability. A common starting dose is Pregabalin 75 mg + Nortriptyline 10 mg twice daily. The dose can be titrated upwards as needed.
- The maximum dose for Pregabalin is generally 600 mg/day, while for Nortriptyline, it’s typically up to 150 mg/day, though lower doses are often used in the combination.
Children:
- Safety and efficacy have not been established in children. Use is generally not recommended.
Special Cases:
- Elderly Patients: Start with a low dose and titrate cautiously, monitoring closely for adverse effects.
- Patients with Renal Impairment: Pregabalin dose reduction is necessary. Nortriptyline dose adjustment may be required depending on the degree of impairment.
- Patients with Hepatic Dysfunction: Caution is advised, and dose adjustment for both drugs may be necessary.
- Patients with Comorbid Conditions: Individualized dosing is required, considering the specific comorbid conditions.
Clinical Use Cases
The primary use is for chronic neuropathic pain. The combination is generally not used in acute settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose adjustments are based on patient-specific factors like age, renal/hepatic function, and comorbidities. Therapeutic drug monitoring may be helpful, especially for Nortriptyline.
Side Effects
Common Side Effects
Dizziness, drowsiness, dry mouth, constipation, blurred vision, weight gain, peripheral edema, nausea, headache, and fatigue.
Rare but Serious Side Effects
Allergic reactions (angioedema, anaphylaxis), suicidal ideation, mood changes, cardiac arrhythmias, Stevens-Johnson syndrome, blood dyscrasias.
Long-Term Effects
Weight gain, cognitive impairment, sexual dysfunction, and dependence (with Pregabalin).
Adverse Drug Reactions (ADR)
Angle-closure glaucoma (with Nortriptyline), neuroleptic malignant syndrome, serotonin syndrome (when combined with other serotonergic drugs).
Contraindications
Hypersensitivity to either component, recent myocardial infarction, severe liver disease, urinary retention (BPH), concomitant use of MAO inhibitors, uncontrolled angle-closure glaucoma, breastfeeding.
Drug Interactions
- CNS depressants (alcohol, benzodiazepines, opioids), antihypertensives, anticholinergics, CYP2D6 inhibitors or inducers (fluoxetine, paroxetine, quinidine), other serotonergic drugs (SSRIs, SNRIs, triptans), MAO inhibitors.
- Alcohol should be avoided.
- Consult drug interaction resources for specific interactions with other medications, OTC drugs, and supplements.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Pregabalin - Category C; Nortriptyline - Category C. Use only if the potential benefits outweigh the risks.
- Fetal Risks: Potential for congenital malformations and neonatal withdrawal symptoms.
- Breastfeeding: Both drugs are excreted in breast milk. Breastfeeding is generally not recommended.
Drug Profile Summary
- Mechanism of Action: Pregabalin: Calcium channel modulation; Nortriptyline: Serotonin and norepinephrine reuptake inhibition.
- Side Effects: Dizziness, drowsiness, dry mouth, constipation, blurred vision, weight gain. Serious side effects include allergic reactions, suicidal thoughts, and cardiac arrhythmias.
- Contraindications: Hypersensitivity, recent MI, severe liver disease, urinary retention, concomitant use of MAO inhibitors, breastfeeding.
- Drug Interactions: CNS depressants, antihypertensives, anticholinergics, CYP2D6 inhibitors/inducers, serotonergic drugs.
- Pregnancy & Breastfeeding: Category C; use with caution; breastfeeding not recommended.
- Dosage: Individualized based on patient response and tolerability; typical starting dose is Pregabalin 75mg + Nortriptyline 10mg BID.
- Monitoring Parameters: Pain scores, mood, vital signs, weight, adverse effects.
Popular Combinations
Often used as a standalone combination. Adding a topical analgesic or NSAID for localized pain relief may be considered.
Precautions
- Screen for allergies, cardiovascular disease, liver/kidney dysfunction, glaucoma, and suicidal ideation.
- Avoid alcohol.
- Caution in the elderly.
- Monitor for weight gain and mood changes.
- Driving restrictions may be necessary due to drowsiness and dizziness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Nortriptyline + Pregabalin?
A: The starting dose is usually Pregabalin 75 mg + Nortriptyline 10 mg twice daily, titrated as needed based on individual response and tolerability.
Q2: What are the most common side effects?
A: Dizziness, drowsiness, dry mouth, constipation, blurred vision, and weight gain.
Q3: Is this combination safe during pregnancy?
A: Both drugs are Pregnancy Category C. Use only if potential benefits outweigh the risks. Consult with a specialist.
Q4: Can patients breastfeed while taking this combination?
A: Breastfeeding is generally not recommended as both drugs are excreted in breast milk.
Q5: How should I manage a patient experiencing significant drowsiness?
A: Consider reducing the dose of one or both medications. Advise against driving or operating machinery. Explore alternative treatment options if drowsiness persists.
Q6: What are the signs of an allergic reaction to this combination?
A: Watch for rash, itching, hives, swelling of the face, lips, or tongue, difficulty breathing, and dizziness. Seek immediate medical attention if these occur.
Q7: Can this combination be used with other pain medications?
A: Use with other CNS depressants (like opioids or benzodiazepines) requires extreme caution due to additive effects. Consult drug interaction resources for potential interactions with other medications.
Q8: How long does it take for this combination to work?
A: It may take several weeks to achieve maximal pain relief. Individual responses vary.
Q9: What should I do if a patient develops suicidal thoughts while taking this combination?
A: Discontinue the medication and refer the patient for psychiatric evaluation immediately. Nortriptyline, in particular, carries a risk of increased suicidal thoughts, especially in young adults.
Q10: Are there any specific monitoring parameters for this combination?
A: Monitor pain levels, mood changes, vital signs, and weight. Be alert for adverse effects, particularly in elderly patients and those with renal or hepatic impairment. Periodically reassess the need for continued therapy.
