Rankvilon^® (Tablets) Instructions for Use

Marketing Authorization Holder

Valenta Pharm, JSC (Russia)

Contact Information

VALENTA PHARM JSC (Russia)

ATC Code

N05BX (Other anxiolytics)

Dosage Form

Rankvilon®

Tablets 1 mg: 60 pcs.

Dosage Form, Packaging, and Composition

Tablets white or almost white, round, flat-cylindrical, with a bevel.

Excipients: lactose monohydrate, microcrystalline cellulose, magnesium stearate, croscarmellose sodium.

15 pcs. – blister packs (4) – cardboard packs.
20 pcs. – blister packs (3) – cardboard packs.

Clinical-Pharmacological Group

Anxiolytic (tranquilizer)

Pharmacotherapeutic Group

Psycholeptics; anxiolytics; other anxiolytics

Pharmacological Action

Mechanism of action

Rankvilon^® is an anxiolytic of peptide nature. It is a low-affinity blocker of cholecystokinin type 1 receptors (CCK1), which is associated with the anxiolytic effect of the drug.

Pharmacodynamic effects

The action of the drug Rankvilon^® is manifested in the reduction or elimination of the mental, somatic, and vegetative components of anxiety and fear, as well as irritability, and anxiety-induced disturbances of night sleep and cognitive functions. It does not have a muscle relaxant effect, does not possess narcogenic potential, and with the use of the drug Rankvilon^®, drug dependence is not formed and a withdrawal syndrome does not develop.

Clinical efficacy and safety

Two double-blind, randomized, placebo-controlled, multicenter clinical studies of the drug Rankvilon^® involved 168 (study RAN-02-01-2020) and 220 (study RAN-03-03-2022) adult patients with anxiety disorders against the background of neurasthenia and adjustment disorders. In the phase III study RAN-4 03-03-2022, the use of the drug at a dose of 6 mg/day statistically significantly led to a reduction in the severity of anxiety on the HARS scale, the severity of the condition on the CGI-i and CGI-s scales, as well as the total asthenia score on the MFI-20 scale after 2 and after 4 weeks from the start of therapy compared to placebo. In the Rankvilon^® group, the proportion of patients with a significant reduction in anxiety level on the HARS scale (a reduction of 50% or more from the baseline value – the primary endpoint) after 4 weeks was 70.0%, and in the placebo group – 24.8%. Statistically significant differences from placebo in the frequency of adverse events, including those related to the study therapy, were absent in the conducted studies. No serious adverse events or cases of adverse events leading to premature discontinuation of patients from the studies were identified.

Preclinical safety data

In studies using a pharmacogenetic approach in inbred animals with different levels of emotional reactivity, a pronounced anxiolytic effect of the active substance of the drug was established in animals with a “passive” type of response to emotional stress exposure, in the absence of the effect of the active substance of the drug on the behavior of animals with an “active” reaction to stress.

Experimental studies have shown that the active substance of the drug Rankvilon^® relieves anxiety reactions induced by withdrawal of ethanol and benzodiazepine tranquilizers, does not affect ECG parameters and the functioning of the respiratory center in animals.

According to the results of toxicological studies, the active substance of the drug Rankvilon^® corresponds to toxicity class 5 according to the international system of classification and labeling of chemicals GHS (Globally Harmonized System) – practically non-toxic substances. Experimental studies have shown that the active substance of the drug Rankvilon^® does not possess genotoxic properties, does not exhibit mutagenic and potential carcinogenic activity, immunotoxic effects, does not have local irritant effects, does not have embryo-, fetotoxic or teratogenic effects, and does not affect reproductive function.

Pharmacokinetics

Absorption

After oral administration, the drug is rapidly absorbed into the systemic circulation. Food intake has little effect on the absorption of the drug in terms of such pharmacokinetic parameters as C_max value and the time to reach it (T_max). The mean C_max after a single dose of 3 mg of the drug on an empty stomach and after a meal (M±SD) are 7.3±3.7 ng/ml and 8.5±4.8 ng/ml, respectively. T_max after a single dose of 3 mg of the drug on an empty stomach and after a meal are 1 h and 1.5 h, respectively. An increase in AUC_0-t by 1.3 times was noted after a single dose of 3 mg of the drug after a meal compared to taking the drug on an empty stomach. AUC_0-t on an empty stomach and after a meal is 17.5±8.6 ng×h/ml and 22.0±13.0 ng×h/ml, respectively.

Distribution

The active substance of the drug penetrates into all body fluids and may accumulate in tissues. The apparent V_d of the active substance after oral administration in doses from 1 mg to 15 mg averages 2.5 L/kg. According to preclinical studies, the active substance penetrates the BBB and has a relatively high tropism for brain tissues.

Metabolism

In experimental studies on metabolism in vitro when incubating the active substance with human liver microsomes, relatively high microsomal stability was established.

Excretion

T_1/2 of the drug from blood plasma after taking 3 mg is (M±SD) 1.8±0.902 h and 1.3±0.6 h for administration on an empty stomach and after a meal, respectively.

Linearity

According to clinical studies, in the dose range of 1-15 mg, the pharmacokinetics are linear.

Indications

For adults from 18 years

• Anxiety disorders in neurasthenia and adjustment disorder.

ICD codes

Dosage Regimen

Orally, during or after meals, approximately at the same time. The recommended time interval between doses is 4-6 hours.

Adults: 2 tablets 3 times/day. The maximum daily dose is 6 mg.

The recommended course of application is 28 days.

Study of the drug in elderly patients has not been conducted.

Study of the drug in patients with impaired renal function has not been conducted.

Study of the drug in patients with impaired hepatic function has not been conducted.

Safety and efficacy in children aged 0 to 18 years have not been established. Data are not available. The drug Rankvilon^® is contraindicated for use in children under 18 years of age.

Adverse Reactions

Determination of the frequency of adverse reactions is carried out in accordance with the following criteria: very common (≥1/10), common (from ≥1/100 to <1/10), uncommon (from ≥1/1000 to <1/100), rare (from ≥1/10000 to <1/1000), very rare (<1/10000), frequency unknown (cannot be estimated from the available data).

In clinical studies of the drug, the following adverse reactions were registered.

Psychiatric disorders frequency unknown – irritability, dreaminess, affective lability, insomnia, sleep initiation disorder, sleep disorder, sleep disturbances, somnolence, daytime sleepiness.

Nervous system disorders frequency unknown – headache, dizziness, somnolence, tremor, dysgeusia, attention disturbance.

Eye disorders frequency unknown – reversible visual acuity deterioration.

Gastrointestinal disorders frequency unknown – nausea, diarrhea.

Musculoskeletal and connective tissue disorders frequency unknown – arthralgia.

Renal and urinary disorders frequency unknown – proteinuria.

General disorders frequency unknown – asthenia.

Contraindications

• Hypersensitivity to amide N-(6-phenylhexanoyl)glycyl-L-tryptophan or to any of the excipients included in the drug.

Use in Pregnancy and Lactation

Pregnancy

Data on the use of the drug Rankvilon^® in pregnant women are not available. The use of the drug during pregnancy is contraindicated. If pregnancy occurs, the drug should be discontinued.

Breastfeeding

It is unknown whether Rankvilon^® penetrates into breast milk. The use of the drug during breastfeeding is contraindicated. If it is necessary to take the drug during lactation, breastfeeding should be discontinued for the duration of treatment.

Fertility

Data on the effect of the drug on human fertility are not available.

Use in Hepatic Impairment

Study of the drug in patients with impaired hepatic function has not been conducted.

Use in Renal Impairment

Study of the drug in patients with impaired renal function has not been conducted.

Pediatric Use

Safety and efficacy in children aged 0 to 18 years have not been established. Data are not available. The drug Rankvilon^® is contraindicated for use in children under 18 years of age.

Geriatric Use

Study of the drug in elderly patients has not been conducted.

Special Precautions

Excipients

Sodium. The drug Rankvilon^® contains less than 1 mmol (23 mg) of sodium per one tablet, that is, it is essentially sodium-free.

Lactose. The drug Rankvilon^® contains lactose. Patients with rare hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take the drug Rankvilon^®.

Effect on ability to drive vehicles and operate machinery

It has not been studied, however, considering the mechanism of action and the profile of possible adverse reactions, it can be assumed that the drug has a moderate effect on the ability to drive vehicles and operate machinery. Patients should be warned about the possibility of adverse reactions that affect these abilities (see section “Adverse Reactions”). During the treatment period, it is necessary to refrain from driving vehicles and operating machinery.

Overdose

No cases of drug overdose have been reported.

Treatment in case of overdose is symptomatic therapy.

Drug Interactions

Interaction studies have not been conducted.

Storage Conditions

The drug should be stored at a temperature not exceeding 25°C.

Shelf Life

Shelf life – 2 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.