Miro Tablets

(Mirogabalin)

COMPOSITION

DESCRIPTIONS

Miro contains Mirogabalin, it is thought to exert an analgesic effect by suppressing calcium current in the nervous system and also involved in the activation effect of the descending pain-suppressing system on the noradrenaline pathway.

INDICATIONS:

Miro is indicated for the treatment of Neuropathic pain (PNP) including Diabetic peripheral neuropathic pain (DPNP) and Postherpetic neuralgia (PHN).

DOSAGE AND ADMINISTRATION:

In general, for adults, the initial dose of 5mg of Mirogabalin is orally administered twice daily, then the dose is gradually increased by 5mg at intervals of 1 week or longer, and 15mg of Mirogabalin is orally administered twice daily. The dose may be adjusted axccording to the patient’s agge and symptoms in the range of 10mg to 15mg, and administered twice daily.

CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY

Mechanism of Action

Mirogabalin, it is thought to exert an analgesic effect by suppressing calcium current through binding to the  a2 & subunit,which play an auxiliary role in the function of voltage- gated calcium channels in the nervous system. Furthermore, it has been suggested that the analgesic effect of Mirogabalin is also involved in the avtivation effect of the descending pain-supperssing system on the noradrenalin pathway.

PHARMACOKINETICS    

Blood concentration: Plasma concentration

Single dose

When a single oral dose of 2.5, 5, 10 and 15mg of Mirogabalin (each dose of 6 patients ) was orally administered to healthy adults, C_max was reached 1 hour after administration and t_1/2 was 2.96 to 3.37 hours. C_max and AUC_inf increased in proportion to the dose. Plasma Mirogabalin concentration transition after a single oral administration

Repeated administration

When 10 and 15mg ( each dose of 6 patients ) of Mirogabalin was orally administered twice daily for 7 days to healthy adults, it reached a steady state by the 3^rd day of administration, and t_1/2 on the 7^th day of administration increased in proportion to the dose. Plasma Mirogabalin concentration transition during repeated oral administration (7^th day of administration).

Absorption

Effect of diet

A single oral dose of 15mg of Mirogabalin to 30 healthy adults resulted in C_max of 230 and 188_ng/ml

on an empty stomach and after meals, T_max of 1.00 and 1.50 hours, and AUC_last of 884 and 833ng. hr/ml, respectively. Postprandial administration reduced C_max by about 18% and T_max by 0.5 hours, but decreased AUC_inf by about 6%

Distribution

Volume of distribution

The apparent terminal phase volume of distribution (Vz/F) after a single oral dose of 2.5, 5, 10 and 15mg of Mirogabalin to 6 healthy adults ranged from 78.01 to 87.97L.

Blood cell transfer rate

In experiments with 14C.labeled substances, Mirogabalin was transferred to erythrocytes and the ratio of whole blood concentration to human plasma concentration was 0.85 to 0.87 (in vitro).

Metabolism

after a single oral dose of 2.5, 5, 10 and 15mg of 14C-labeled adult males (6 patients), about 97% of the administered radioactivity was recovered in the urine, and about 76% of them were unchanged. The urinary metabolites other than the unchanged form were lactams, and 0.6%of the dose was recovered. In addition, N –glucuronic acid conjugated metabolized by UGT were also detected.

Excretion

The CL / F of 6 healthy adults after a single oral dose of 2.5, 5, 10 and 15mg of Mirogabalin was 16.50-18.24 L / hr. At this time, the urinary excretion rate of the unchanged drug was 63.2 to 71.5%, and the renal clearance was 10.4 12.4 L / hr. When a single oral dose of 14C labelled 2.5, 5, 10 and 15mg was given to healthy adult males (6 patients), the cumulative excretion rate of radioactivity reached 98% or more by 168 hours after administration, and about 97% of the administered radioactivity was excreted in the uring and about 1% was excreted in the feces (foreigner data).

CONTRAINDICATIONS

hypersensitivity to the active substance or to any of the excipients.

WARNINGS AND PRECAUTIONS

– Patients with renal dysfunction: When administering to patients with renal dysfunction, adjust the dose and dosing interval with reference to the creatinine clearance values shown in the following table.  Start with a low dose and increase if tolerable and inadequate.

		Degree of renal dysfunction (CLcr: ml / min)
		Mild (90>CLcr≥ 60)	Moderate (60> CLcr ≥30)	Severe (including hemodialysis patient) (30> CLcr)
Daily dose		10-30mg	5-15mg	2.5-7.5mg
Initial dose		Twice a day 1 time 5mg	2.5mg once twice a day	Once a day 2.5mg
Effective dose	Minimum dose	10 mg once twice a day	1 time 5mg twice a day	Once a day 1 time 5mg
	Recommended dose	1 time 15mg twice a day	7.5mg once twice a day	Once a day 7.5mg

●Since dizziness, somenolence, loss of consciousness, etc. may occur, patients taking this drug should be carefuol not to engage in dangerous machine operations such as driving a car.

●Be careful of obesity as it may cause weight gain and if signs of obesity appear, take appropriate measures such as diet and exercise therapy. In particular, weight gain may be observed with increased dose or long-term administration, so body weight should be measured regularly.

●Since the treatment of neuropathic pain with this drug is not a causative therapy but a symptomatic treatment, diagnosis and treatment of the disease that causes the pain should be performed at the same time, and this drug should not be administered indiscriminately.

●Sudden discontinuation of this drug may cause withdrawal symptoms such as insomnia, nausea, diarrhea, and loss of appetite.

Therefore, when discontinuing administration, the dose should be reduced gradually.

●Eye disorders such as amblyopia, visual abnormalities, blurred vision and diplopia may occur.

Children

No data is available for children.

Elderly

Carefully administer the drug by adjusting the dose and interval with reference to the creatinine

clearance rate. Renal function is often impaired. There is a risk of falling and fractures due to dizziness, somnolence, loss of consciousness, etc.

Pregnancy

Administer to pregnant or potentially pregnant women only if the therapeutic benefit outweighs the risks.

Breast-feeding

Consider continuing or discontinuing breastfeeding, taking into account the therapeutic benefit and benefits of breastfeeding.

SIDE EFFECTS

The following are the side effects as described below:

Dizziness, somnolence, unconsciousness, liver dysfunction, headache, tremor, hypoesthesia, memory impairment, amnesia, articulation disorder, hallucinations, delirium, blurred vision, increased eosinophil count, orthostatic hypotension, hypertension, constipation, abdominal distension, dry mouth, gastritis, vomiting, increased appetite, loss of appetite, epigastric pain, gastroesophageal reflux disease.

DRUG INTERACTIONS

Probencid

The action of this drugmay be enhanced.

It is considered that blood concentration of this drug increases due to the inhibitory action of probenecid of OAT1, OAT3 and UGT.

Cimitedine

The action of this drug may be enhanced.

It is considered that the blood concentration of this drug increases due to the inhibitory action of cimetidine on MATE1 and MATE2-K.

Alcohol (drinking )

may increase attention and loss of equilibrium function. It is thought that they mutually enhance the central nervous system depressant effect.

OVERDOSE

Symptoms

For patients with fibromyalgia, overdose cases of up to 60mg daily have been reported. Symptoms of overdose were euphoria, dysarthria, headache, dysphagia, arthritis, joint swelling, and asthenia.

Treatment

15.3% of this drug is removed by hemodialysis.

INSTRUCTIONS

Store below 30°C. Protect from heat, light and moisture. Keep out of the reach of children.

PRESENTATION

Miro Tablets 2.5mg are available in pack size of 10’s.

Miro Tablets 5mg are available in pack size of 10’s.

Miro Tablets  10mg are available in pack size of 10’s.  

Miro Tablets 15mg are available in pack size of 10’s.