Marcus

Approved Indications

• Peripheral Neuropathic Pain
• Diabetic Peripheral Neuropathy (DPN): Relief of pain associated with diabetic neuropathy.
• Post-Herpetic Neuralgia (PHN): Management of chronic pain following herpes zoster.

Clinically Accepted Off‑label Uses

• Neuropathic pain due to chemotherapy
• Fibromyalgia
• Central neuropathic pain: Emerging evidence supports use in spinal cord injury or multiple sclerosis.

Adults

• Initial dose: 5 mg orally twice daily (total 10 mg/day)
• Titration (after 1 week):
• Increase to 10 mg twice daily (20 mg/day) based on tolerability and response.
• Maximum dose: 15 mg twice daily (30 mg/day)

Elderly (≥65 years)

• Start at 5 mg once daily
• Increase to 5 mg twice daily (10 mg/day) as tolerated

Renal Impairment

• eGFR 30–59 mL/min/1.73 m²: 5 mg twice daily (max 10 mg/day)
• eGFR 15–29 mL/min/1.73 m²: 5 mg once daily
• eGFR <15 mL/min/1.73 m² or dialysis: Not recommended

Hepatic Impairment

• Mild-to-moderate: No adjustment
• Severe: Use with caution; data limited

Pediatrics (<18 years)

• Not approved; no established dosing

Mirogabalin is a selective ligand of the α₂δ subunit of voltage-gated calcium channels (VGCC), with high affinity for α₂δ-1 and moderate affinity for α₂δ-2. Binding reduces calcium influx into presynaptic nerve terminals, which suppresses release of excitatory neurotransmitters (e.g., glutamate, substance P, noradrenaline) in both peripheral and central nervous systems. This diminishes neuronal hyperexcitability and central sensitization, resulting in analgesia for neuropathic pain.

• Absorption: Rapid with Tmax ≈ 1 hour
• Bioavailability: ~85–90%
• Distribution: Low plasma protein binding (~25%)
• Metabolism: Primarily excreted unchanged; minor metabolism via glucuronidation
• Half-life: ~18 hours, allowing twice-daily dosing
• Excretion: ~60% in urine unchanged, remainder as metabolites; <10% fecal elimination

• Pregnancy: No FDA classification due to limited human data; animal studies show no major teratogenicity. Use only if benefits justify potential risks.
• Breastfeeding: Excreted in animal milk; human data lacking. Caution advised—decision to discontinue drug or breastfeeding should consider therapeutic need.

• Primary Class: Neuropathic pain analgesic
• Subclass: α₂δ ligand (related to gabapentinoids)

• Known hypersensitivity to mirogabalin or excipients
• Severe renal impairment without dose adjustment
• Use in pediatric patients (<18 years) not recommended

• CNS Depression: Monitor for somnolence, dizziness—especially if used with opioids or sedatives.
• Renal Function: Monitor regularly; adjust dosage in impairment.
• Weight Gain and Edema: Monitor in patients prone to fluid retention.
• Withdrawal Symptoms: Taper gradually—abrupt discontinuation may cause insomnia, headache, nausea, diarrhea.
• Abuse Potential: Though low, caution advised in patients with substance abuse history.
• Suicidal Ideation: Monitor mood changes; manage psychiatric comorbidities appropriately.

Common

• Dizziness
• Somnolence
• Headache
• Peripheral edema
• Weight gain
• Dry mouth
• Constipation

Less Common / Serious

• Blurred vision
• Confusion
• Gait disturbances
• Rare: Angioedema, hypersensitivity reactions, urinary retention

Typical Timing: CNS effects occur early (first few weeks); peripheral edema and weight gain may develop with prolonged use.

• CNS Depressants (e.g., benzodiazepines, opioids): Additive sedation—dose adjustment recommended.
• Diuretics: May increase edema risk; monitor fluid status.
• ACE-Inhibitors/ARBs: Edema and fluid retention more likely; monitor blood pressure and renal function.
• No significant interactions with food or CYP450 pathways.

• Japan (2023): Approved for DPN and PHN; real-world data supports safety and tolerability.
• Emerging Evidence (2022–2024): Clinical studies suggest efficacy in chemotherapy-induced neuropathy and fibromyalgia.
• Label Changes (2024): FDA safety recommendations updated to emphasize CNS effects, renal dosing adjustments, and gradual discontinuation.

• Temperature: Store at 20–25 °C (68–77 °F); excursions allowed between 15–30 °C
• Humidity & Light: Keep in original, tightly closed container; avoid excessive moisture
• Handling: Do not crush or chew extended-release tablets
• Reconstitution / Refrigeration: Not required