Flugesic^® (Capsules) Instructions for Use

Marketing Authorization Holder

Lupin, Ltd. (India)

ATC Code

N02BG07 (Flupirtine)

Active Substance

Flupirtine (Rec.INN registered by WHO)

Dosage Form

Flugesic®

Capsules 100 mg: 10, 30 or 50 pcs.

Dosage Form, Packaging, and Composition

Capsules are hard gelatin, size No. 2, with a white body and a white cap; the capsule contents are an almost white powder.

Excipients: calcium hydrogen phosphate dihydrate – 219.05 mg, copovidone – 1 mg, colloidal silicon dioxide – 1.7 mg, magnesium stearate – 3.25 mg.

Composition of the capsule shell No. 2: body: gelatin – up to 100%, titanium dioxide (E 171) – 2.1118%, cap: gelatin – up to 100%, titanium dioxide (E 171) – 2.1118%.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (5) – cardboard packs.

Clinical-Pharmacological Group

Non-opioid centrally acting analgesic

Pharmacotherapeutic Group

Non-narcotic analgesic agent

Pharmacological Action

A centrally acting analgesic. It is a selective activator of neuronal potassium channels. It does not belong to opioids and does not cause dependence or addiction.

It has analgesic, muscle relaxant, and neuroprotective effects, based on indirect antagonism to NMDA receptors, activation of descending pain modulation mechanisms, and GABAergic processes.

At therapeutic concentrations, Flupirtine does not bind to α₁-, α₂-adrenergic receptors, serotonin 5HT₁-, 5HT₂ receptors, dopamine, benzodiazepine, opioid, central m- and n-cholinergic receptors.

The antispastic effect on muscles is associated with the blockade of excitation transmission to motor neurons and interneurons, leading to the relief of muscle tension. This effect of flupirtine is manifested in many chronic diseases accompanied by painful muscle spasms (musculoskeletal pain in the neck and back, arthropathies, tension headaches, fibromyalgia).

Due to its neuroprotective properties, it protects nerve structures from the toxic effects of high concentrations of intracellular calcium ions, which is associated with the ability of flupirtine to block neuronal ionic calcium channels and reduce the intracellular flow of calcium ions.

Pharmacokinetics

After oral administration, it is almost completely (up to 90%) and rapidly absorbed from the gastrointestinal tract.

It is metabolized in the liver (up to 75% of the administered dose) to form the active metabolite M1 (2-amino-3-acetamido-6-[4-fluoro]-benzylaminopyridine). Metabolite M1 is formed as a result of hydrolysis of the urethane structure (phase 1 reaction) and subsequent acetylation (phase 2 reaction). This metabolite provides an average of 25% of the analgesic activity of flupirtine. Another metabolite (M2 – biologically inactive) is formed as a result of the oxidation reaction (Phase I) of p-fluorobenzyl followed by conjugation (Phase 2) of p-fluorobenzoic acid with glycine.

T_1/2 is about 7 hours (10 hours for the parent substance and metabolite M1), which is sufficient to provide an analgesic effect. The concentration of the active substance in the blood plasma is proportional to the dose.

It is excreted mainly by the kidneys (69%): 27% is excreted unchanged, 28% as metabolite M1 (acetyl-metabolite), 12% as metabolite M2 (para-fluorohippuric acid) and the remaining third consists of several metabolites with an unidentified structure. A small part of the dose is excreted from the body with bile and feces.

In patients over 65 years of age, compared with young patients, there is an increase in T_1/2 (up to 14 hours after a single dose and up to 18.6 hours after administration for 12 days) and C_max in plasma is correspondingly 2-2.5 times higher.

Indications

Acute and chronic pain syndrome in the following diseases and conditions: muscle spasm, malignant neoplasms, primary dysmenorrhea, headache, post-traumatic pain, pain during trauma/orthopedic surgeries and interventions.

ICD codes

Dosage Regimen

Determine the dose individually based on pain severity and patient response.

For adults, administer one 100 mg capsule 3 to 4 times daily.

The maximum single dose is one capsule (100 mg).

The maximum daily dose is 400 mg (four capsules).

Take capsules with a sufficient amount of liquid, with or without food.

For chronic pain, initiate therapy with the lowest effective dose.

For acute pain, use the shortest duration necessary for symptom control.

Adjust the regimen for patients over 65 years of age; use a lower initial dose and extend the dosing interval.

Adjust the regimen for patients with impaired liver function; reduce dose and frequency.

Adjust the regimen for patients with impaired renal function; reduce dose and frequency.

Do not exceed the recommended maximum daily dose.

Discontinue treatment if pain persists or liver function abnormalities occur.

Adverse Reactions

From the central nervous system often weakness at the beginning of treatment; depression, sleep disorders, sweating, anxiety, nervousness, tremor, headache are possible; rarely – confusion, visual disturbances.

From the digestive system dizziness, heartburn, nausea, vomiting, constipation or diarrhea, flatulence, abdominal pain, dry mouth, loss of appetite are possible; in some cases – increased activity of liver transaminases, hepatitis (acute or chronic, occurring with or without jaundice, with or without elements of cholestasis).

Allergic reactions rarely – increased body temperature, urticaria and itching.

Contraindications

Hepatic insufficiency with signs of encephalopathy, cholestasis, severe myasthenia, chronic alcoholism, pregnancy, children and adolescents under 18 years of age, hypersensitivity to flupirtine.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy.

If it is necessary to use during lactation, the issue of stopping breastfeeding for the duration of treatment should be decided, since it has been shown that a small amount of flupirtine is excreted in breast milk.

Use in Hepatic Impairment

Contraindicated in hepatic insufficiency with signs of encephalopathy. Use with caution in case of impaired liver function – it is necessary to adjust the dosage regimen.

Use in Renal Impairment

Use with caution in case of impaired renal function – it is necessary to adjust the dosage regimen.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Use with caution in patients over 65 years of age.

Special Precautions

Use with caution in case of impaired liver and/or kidney function, in patients over 65 years of age. Patients in these groups require dosage regimen adjustment.

Side effects mainly depend on the dose. In many cases, they disappear on their own as therapy continues or after the end of treatment.

When treating with flupirtine, false-positive results of the test with diagnostic strips for bilirubin, urobilinogen and protein in the urine are possible. A similar reaction is possible during the quantitative determination of bilirubin levels in blood plasma.

When used in high doses, in some cases, urine may turn green, which is not a clinical sign of any pathology.

In patients with impaired liver or kidney function, the activity of liver enzymes and the content of creatinine in the urine should be monitored.

With the simultaneous use of flupirtine with drugs that are also metabolized in the liver, regular monitoring of liver enzyme activity is required.

Combined use of flupirtine and medicinal products containing paracetamol and carbamazepine should be avoided.

Influence on the ability to drive vehicles and operate machinery

Considering that Flupirtine may impair attention and slow down the body’s reactions, it is recommended to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions during treatment with the drug.

Drug Interactions

Flupirtine enhances the effect of sedatives, muscle relaxants, and ethanol.

The possibility of displacement of flupirtine from protein binding by other simultaneously taken drugs should be taken into account. However, it has been shown that Flupirtine is capable of displacing warfarin and diazepam from protein binding; when taken simultaneously with these drugs, this may lead to an increase in their activity.

With simultaneous use of flupirtine and coumarin derivatives, an enhancement of the anticoagulant effect is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.