Usage
- Flupirtine is prescribed for acute and chronic pain, particularly musculoskeletal pain. It was also used for pain following trauma or orthopedic surgery and injuries, tension headaches, dysmenorrhea, and cancer pain. Note that as of 2018, it is only indicated for acute pain and limited to a maximum of two weeks of treatment due to the risk of liver toxicity.
- Pharmacological classification: Non-opioid analgesic, neuronal potassium channel opener.
- Mechanism of action: Flupirtine activates voltage-gated potassium channels, specifically the Kv7 family. This leads to neuronal hyperpolarization, reducing neuronal excitability and attenuating pain signal transmission. It also acts as a functional NMDA receptor antagonist.
Alternate Names
- Katadolon
- Flupirtin Maleat
- Brand names: Katadolon, Trancopal, Metanor
How It Works
- Pharmacodynamics: Flupirtine’s primary effect is analgesia achieved through the opening of Kv7 potassium channels and indirect NMDA receptor antagonism. It has also shown muscle relaxant properties due to inhibition of mono- and polysynaptic reflexes.
- Pharmacokinetics:
- Absorption: Flupirtine is rapidly and almost completely absorbed after oral administration, with bioavailability of about 90% and rectal bioavailability about 70%. Peak plasma concentrations are reached within 1.6 to 2 hours after oral administration. Steady state is reached after approximately 2 days.
- Metabolism: Flupirtine is extensively metabolized in the liver, primarily via oxidative degradation and acetylation. Major metabolites include p-fluorohippuric acid, an acetylated metabolite, and a mercapturic acid metabolite.
- Elimination: Flupirtine and its metabolites are eliminated primarily through renal excretion (about 72%) and to a lesser extent in feces (about 18%). The elimination half-life is approximately 6.5 hours in healthy adults, but it may be prolonged in elderly patients and those with renal impairment.
- Mode of Action: Flupirtine binds to and activates Kv7 potassium channels, leading to an efflux of potassium ions and hyperpolarization of neuronal membranes. This reduces neuronal excitability and inhibits pain signal transmission. Its NMDA receptor antagonism further contributes to the analgesic effect.
- Receptor binding, enzyme inhibition, or neurotransmitter modulation: Kv7 potassium channel opener, functional NMDA receptor antagonist.
- Elimination pathways: Primarily renal excretion; some hepatic metabolism and fecal excretion.
Dosage
Standard Dosage
Adults:
- For acute pain: 100 mg every 4-6 hours, not exceeding 600mg per day. Treatment duration should not exceed two weeks.
Children:
- Not generally recommended for children under 18 years of age.
Special Cases:
- Elderly Patients: Initiate with a lower dose (e.g., 50 mg) and titrate cautiously.
- Patients with Renal Impairment: Dose adjustment is needed. Start with the lowest effective dose.
- Patients with Hepatic Dysfunction: Contraindicated in patients with liver disease.
- Patients with Comorbid Conditions: Use with caution in patients with myasthenia gravis or chronic alcoholism.
Clinical Use Cases
- Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use, Emergency Situations: Flupirtine injection (100mg solution) is indicated for short term management of acute post operative pain.
Dosage Adjustments
Dose adjustments are necessary for elderly patients and those with renal impairment. Liver function tests should be monitored during treatment, especially with prolonged use.
Side Effects
Common Side Effects
- Dizziness, drowsiness, fatigue, nausea, dry mouth, itching, bloating, elevated liver enzymes.
Rare but Serious Side Effects
- Liver injury (including liver failure), allergic reactions.
Long-Term Effects
- Potential for liver toxicity with prolonged use.
Adverse Drug Reactions (ADR)
- Hepatotoxicity, severe allergic reactions, drug-induced liver injury.
Contraindications
- Liver disease (including hepatic encephalopathy, cholestasis, and primary biliary cirrhosis), myasthenia gravis, chronic alcoholism, hypersensitivity to flupirtine.
Drug Interactions
- CYP450 interactions: Carbamazepine (inducer) may decrease flupirtine levels.
- Other interactions: Increased risk of bleeding with warfarin; increased risk of hepatotoxicity with paracetamol; increased sedation with alcohol, benzodiazepines, and other sedatives.
Pregnancy and Breastfeeding
- Contraindicated during pregnancy and breastfeeding due to potential fetal risks and lack of safety data.
Drug Profile Summary
- Mechanism of Action: Kv7 potassium channel opener, NMDA receptor antagonist.
- Side Effects: Dizziness, drowsiness, fatigue, nausea, liver toxicity.
- Contraindications: Liver disease, myasthenia gravis, chronic alcoholism.
- Drug Interactions: Carbamazepine, warfarin, paracetamol, alcohol, sedatives.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 100 mg every 4-6 hours as needed for acute pain (maximum 2 weeks of treatment). Dose reduction in elderly and renal impairment.
- Monitoring Parameters: Liver function tests.
Popular Combinations
- Limited data available, as its use has been restricted and eventually withdrawn.
Precautions
- Monitor liver function tests regularly during therapy.
- Use with caution in elderly patients and those with renal impairment.
- Avoid concurrent use with hepatotoxic drugs.
- May cause drowsiness, affecting ability to drive or operate machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Flupirtine?
A: The recommended dosage for acute pain in adults is 100 mg every 4-6 hours, not to exceed 600 mg/day. Treatment should be limited to a maximum of 2 weeks.
Q2: What are the most serious side effects of Flupirtine?
A: The most serious side effect is liver toxicity, which can lead to liver failure. Regular monitoring of liver function tests is essential.
Q3: In which patients is Flupirtine contraindicated?
A: Flupirtine is contraindicated in patients with pre-existing liver disease, myasthenia gravis, and chronic alcoholism.
Q4: Can Flupirtine be used during pregnancy or breastfeeding?
A: No, Flupirtine is contraindicated during pregnancy and breastfeeding due to potential risks to the fetus or neonate.
Q5: How does Flupirtine work to relieve pain?
A: Flupirtine activates Kv7 potassium channels and indirectly antagonizes NMDA receptors, leading to neuronal hyperpolarization and reduced pain signal transmission.
Q6: What are the common side effects of Flupirtine?
A: Common side effects include dizziness, drowsiness, nausea, dry mouth, itching, and elevated liver enzymes.
Q7: Does Flupirtine interact with other medications?
A: Yes, clinically significant interactions can occur with carbamazepine, warfarin, paracetamol, alcohol, and sedatives.
Q8: Why is the use of Flupirtine restricted to acute pain?
A: Due to the risk of liver injury associated with long-term use, flupirtine is now restricted to treating acute pain for a maximum of 2 weeks.
Q9: Are there any specific monitoring requirements during Flupirtine therapy?
A: Yes, regular monitoring of liver function tests (LFTs) is crucial due to the potential for hepatotoxicity.
Q10: What should patients be advised regarding lifestyle while taking Flupirtine?
A: Patients should be advised that Flupirtine may cause drowsiness and should therefore avoid driving or operating heavy machinery until they know how it affects them. Alcohol should be avoided, as it can exacerbate the sedative effects.
