Ankzilera^® (Capsules) Instructions for Use

Marketing Authorization Holder

Nizhpharm JSC (Russia)

Manufactured By

Inpharmasci (France)

Contact Information

NIZHPHARM group of companies (Russia)

ATC Code

N05BX03 (Etifoxine)

Active Substance

Etifoxine (Rec.INN registered by WHO)

Dosage Form

Ankzilera®

Capsules 50 mg: 24 or 60 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin, with an opaque white body and an opaque blue cap; capsule contents – an almost white powder.

Excipients: fumaric acid, lactose monohydrate, stearic acid.

Composition of the capsule cap: Patent Blue V (E131), Azorubine (E122), Titanium Dioxide (E171), Water, Gelatin.
Composition of the capsule body: Titanium Dioxide (E171), Water, Gelatin.

12 pcs. – blisters (2) – cardboard packs.
15 pcs. – blisters (4) – cardboard packs.

Clinical-Pharmacological Group

Anxiolytic (tranquilizer)

Pharmacotherapeutic Group

Psycholeptics; anxiolytics; other anxiolytics

Pharmacological Action

Etifoxine hydrochloride belongs to the benzoxazine derivatives and has an anxiolytic effect, with a lesser sedative effect. It does not cause addiction or withdrawal syndrome.

In in vitro and in vivo studies in rats and mice, it has been shown that the anxiolytic activity of etifoxine is due to its dual mechanism of action (direct and indirect) on GABA-A receptors, improving GABAergic neurotransmission.

When directly affecting the GABA-A receptor through allosteric modulation, Etifoxine binds predominantly to the β₂– or β₃-subunits of the receptor; studies have shown that Etifoxine binds to the GABA-A receptor at sites different from the benzodiazepine binding site.

The indirect action is provided by increasing the synthesis of neurosteroids (via activation of the mitochondrial translocator protein), such as allopregnanolone, which is also a positive allosteric modulator of the GABA-A receptor.

Pharmacokinetics

Absorption

Rapidly absorbed from the gastrointestinal tract. Time to reach C_max in blood – 2-3 hours.

Metabolism

Rapidly metabolized in the liver to form several metabolites. One of the metabolites (diethylethifoxine) is active and its T_1/2 is about 20 hours.

Penetrates the placental barrier.

Excretion

T_1/2 – about 6 hours. Excreted mainly in the urine as metabolites, and also unchanged in small amounts. Also excreted in bile.

Indications

Adults aged 18 years and over

• Treatment of anxiety and related psychosomatic disorders.

ICD codes

Dosage Regimen

Orally, with a small amount of water.

The dose of the drug is determined by the doctor, individually, depending on the patient’s condition.

Usually prescribed as 1 caps. 3 times/day or 2 caps. 2 times/day (150-200 mg/day). Duration of treatment – from several days to 4-6 weeks, depending on the patient’s condition.

If a dose is missed, the dose should not be doubled at the next intake.

Children

Contraindicated in children under 18 years of age.

Adverse Reactions

Classification of adverse reactions by organ systems is presented with the frequency of their occurrence: very common (≥1/10), common (≥1/100 but <1/10), uncommon (≥1/1000 but <1/100), rare (≥1/10000 but <1/1000), very rare (<1/10000), frequency unknown (cannot be estimated from available data).

Nervous system disorders rare – slight drowsiness, appearing in the first days of administration and usually disappearing on its own during treatment.

Gastrointestinal disorders very rare – lymphocytic colitis.

Skin and subcutaneous tissue disorders: rare – skin reactions: maculopapular rash, erythema multiforme, pruritus, facial edema; very rare – allergic reactions (urticaria, angioedema); severe skin reactions (DRESS syndrome, Stevens-Johnson syndrome, generalized exfoliative dermatitis); frequency unknown – anaphylactic shock, leukocytoclastic vasculitis.

Hepatobiliary disorders: very rare – hepatitis, cytolytic hepatitis.

Reproductive system and breast disorders very rare – metrorrhagia in women taking oral contraceptives.

Reporting of Suspected Adverse Reactions

It is important to report suspected adverse reactions after registration of a medicinal product in order to ensure continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are encouraged to report any suspected adverse drug reactions through the national adverse reaction reporting system of the member states of the Eurasian Economic Union.

Contraindications

• Hypersensitivity to etifoxine or to any of the excipients included in the drug;
• Shock states (depression of the central nervous system of any etiology);
• Severe hepatic and/or renal impairment;
• Myasthenia gravis;
• Patients with severe forms of hepatitis or hepatic cytolysis during previous treatment with etifoxine;
• Patients who have experienced serious skin reactions during previous treatment with etifoxine, such as drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), Stevens-Johnson syndrome (SJS) or generalized exfoliative dermatitis;
• Children under 18 years of age.

Use in Pregnancy and Lactation

Do not use the drug during pregnancy and breastfeeding.

Use in Hepatic Impairment

The use of the drug in severe hepatic impairment is contraindicated.

Use in Renal Impairment

The use of the drug in severe renal impairment is contraindicated.

Pediatric Use

Contraindicated for use in children under 18 years of age.

Special Precautions

Severe skin reactions

Very rarely, severe skin reactions have been observed with the use of etifoxine, including skin rash combined with eosinophilia and manifestations of DRESS syndrome, Stevens-Johnson syndrome and generalized exfoliative dermatitis.

The onset of skin reactions with etifoxine use was noted from several days to 1 month, depending on the manifestations of the reaction.

According to post-marketing surveillance data, after discontinuation of etifoxine, the outcome of most skin reactions is generally favorable. No fatalities associated with skin reactions have been observed with etifoxine use.

Patients should be informed about the risks of developing skin reactions, as well as the need for careful monitoring for such manifestations. If a toxic skin reaction to Etifoxine is detected, the drug should be discontinued and under no circumstances resumed.

Severe liver reactions

In the post-marketing period, very rare cases of cytolytic hepatitis have been observed with the use of etifoxine.

According to post-marketing surveillance data, the time to onset of liver reactions after etifoxine use ranges from 2 weeks to 1 month from the start of treatment.

Due to the risk of liver reactions, caution is required when using etifoxine in elderly patients, in case of previous viral hepatitis, as well as in the presence of other special conditions identified in the patient, in the opinion of the attending physician.

Liver disorders may be asymptomatic and are detected only by laboratory testing. Patients at risk of liver dysfunction should have liver enzyme activity monitored before starting treatment with etifoxine and one month after the end of treatment.

If toxic liver function disorders are detected, the drug should be discontinued immediately and under no circumstances resumed.

Lymphocytic colitis

In the post-marketing period of etifoxine use, isolated cases of lymphocytic colitis have been noted.

If watery diarrhea occurs in patients receiving Etifoxine, the drug should be discontinued immediately and under no circumstances resumed. The patient must be examined.

Metrorrhagia

In the post-marketing period of etifoxine use, there have been cases of metrorrhagia in women receiving oral contraceptives.

Mutual potentiation of action

Etifoxine hydrochloride preparations should be taken with particular caution with drugs that depress the central nervous system, due to the risk of possible mutual potentiation of their action (see section “Drug Interactions”).

Excipients

The drug contains lactose monohydrate. Patients with rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this drug.

The drug contains the dye Azorubine (E122). Azorubine may cause allergic reactions.

Effect on ability to drive vehicles and operate machinery

Due to the risk of drowsiness, driving and activities requiring increased attention, such as operating machinery, should be avoided during treatment.

Overdose

Symptoms lethargy, excessive drowsiness.

Treatment if necessary, symptomatic therapy is carried out. There is no specific antidote.

Drug Interactions

Potentiates the effect of drugs that depress the central nervous system, such as: opioid analgesics, barbiturates, hypnotics, benzodiazepines, histamine H₁-receptor blockers, antipsychotics, antidepressants with sedative effect, centrally acting antihypertensive agents, baclofen, thalidomide.

Enhances the effect of ethanol.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

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.