Reladorm (Tablets) Instructions for Use

Marketing Authorization Holder

Tarchomin Pharmaceutical Works Polfa, S.A. (Poland)

ATC Code

N05CB02 (Barbiturates in combination with other drugs)

Active Substances

Diazepam (Rec.INN registered by WHO)

Cyclobarbital (Rec.INN registered by WHO)

Dosage Form

Reladorm

Tablets 10 mg+100 mg: 10, 2750, 5000, or 7000 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – non-cell contour packs (1) – cardboard packs.
10 pcs. – blister contour packs (1) – cardboard packs.
2750 pcs. – polypropylene jars.
7000 pcs. – polypropylene jars.
5000 pcs. – polypropylene jars.
10 pcs. – blisters (1) – cardboard packs.

Clinical-Pharmacological Group

Hypnotic and sedative drug

Pharmacotherapeutic Group

Hypnotic agent

Pharmacological Action

A combined medicinal product that exerts sedative, hypnotic, anxiolytic, anticonvulsant, and central muscle relaxant effects.

Diazepam is a 1,4-benzodiazepine derivative. It acts on many structures of the central nervous system (CNS), primarily on the limbic system and hypothalamus, i.e., structures associated with the regulation of emotional activity. Like all benzodiazepines, it enhances the inhibitory effect of GABA-ergic neurons in the area of the cerebral cortex, hippocampus, cerebellum, brainstem, and other CNS structures. The result of this is a decrease in the activity of various groups of neurons: noradrenergic, cholinergic, dopaminergic, and serotonergic. The existence of specific benzodiazepine binding sites, which are protein structures of the cell membrane associated with the complex consisting of the GABA-A receptor and the chloride channel, has been established. The action of diazepam involves modulating the “sensitivity” of the GABA-ergic receptor, leading to an increase in the affinity of this receptor for gamma-aminobutyric acid (GABA), which is an endogenous inhibitory neurotransmitter. The consequence of activating the benzodiazepine receptor or GABA-A is an increase in the influx of chloride ions into the neuron through the chloride channel. This leads to hyperpolarization of the cell membrane, resulting in inhibition of neuronal activity (i.e., a decrease in neurotransmitter release). Clinically, Diazepam has anxiolytic, anticonvulsant, sedative, and moderately pronounced hypnotic effects; it reduces skeletal muscle tone.

Cyclobarbital is a hypnotic medicinal product, a derivative of barbituric acid, with an intermediate duration of action. It exerts a depressant effect mainly on the CNS, especially on the subcortical area (thalamus, hypothalamus, brainstem reticular formation, limbic system, some autonomic centers) and on the cerebral cortex. Barbiturates, used in small doses, have sedative and antiemetic effects; in high doses, they have hypnotic and antiepileptic effects; they have the ability to cause amnesia. The mechanism of action of barbituric acid derivatives is largely associated with the receptor complex, which includes the chloride channel, the GABA-A receptor, and the benzodiazepine receptor. This action, unlike 1,4-benzodiazepine derivatives, is nonspecific (receptors are absent). Barbiturates act directly on the chloride channel, acting independently of gamma-aminobutyric acid (GABA), even in cases where the ion channel is maximally activated by GABA.

Pharmacokinetics

Diazepam

Diazepam is well absorbed from the gastrointestinal tract; bioavailability is about 98%. After oral administration of 20 mg of diazepam, C_max in plasma is reached within 50-90 minutes and is 500 ng/ml. The binding of diazepam to plasma proteins is 94-99%. It penetrates the blood-brain barrier, the placental barrier, and is excreted in breast milk. It shows high affinity for adipose tissue. It is metabolized in the liver to form two active metabolites – N-desmethyldiazepam and N-methyloxazepam, which are then converted to oxazepam, which, in turn, is conjugated with glucuronic acid. T_1/2 is about 24-48 hours and may be prolonged in newborns, elderly patients, and patients with impaired liver and kidney function. Diazepam is excreted mainly by the kidneys as metabolites or unchanged (about 25%).

Cyclobarbital

It belongs to the group of barbiturates with an intermediate duration of action. After oral administration, Cyclobarbital is rapidly absorbed from the gastrointestinal tract. At a dose of 300 mg, C_max in plasma is reached within 20-180 minutes. Cyclobarbital is highly bound to blood proteins. It easily penetrates into tissues and biological fluids of the body, through the placental barrier, and is excreted in breast milk. Cyclobarbital is metabolized in the liver with the participation of microsomal enzymes to ketocyclobarbital. Hydroxylation of cyclobarbital results in the formation of more hydrophilic inactive metabolites. Cyclobarbital is a strong inducer of microsomal enzymes responsible for the metabolism of many drugs, including itself (autoinducer). A consequence of this is a decrease and shortening of the duration of action of simultaneously used drugs undergoing biotransformation involving isoenzymes of the cytochrome P450 system. T_1/2 is about 6 hours. Cyclobarbital is almost completely excreted by the kidneys as metabolites.

Indications

Insomnia; difficulty falling asleep; short-term sleep; irritability.

ICD codes

Dosage Regimen

Administer the dosage individually, strictly tailored to the patient’s clinical presentation and response.

For the management of insomnia and sleep initiation difficulties, take one tablet orally approximately 30 to 60 minutes before bedtime.

Ensure a minimum of 7-8 hours of uninterrupted sleep after administration to mitigate the risk of anterograde amnesia and daytime sedation.

Initiate therapy at the lowest effective dose for the shortest possible duration to minimize risks of tolerance, dependence, and withdrawal.

Closely monitor patients with a history of substance abuse or endogenous depression; prescribe limited quantities due to the elevated risk of dependence and intentional overdose.

Avoid abrupt discontinuation after prolonged use; implement a gradual dose reduction under medical supervision to prevent withdrawal syndrome.

This combination is contraindicated in patients with severe hepatic or renal impairment, myasthenia gravis, respiratory insufficiency, glaucoma, and in children, the elderly over 65, and during pregnancy or lactation.

Adverse Reactions

From the nervous system: headache and dizziness, tremor, myasthenia, ataxia, confusion, amnesia, muscle tremor and convulsions.

From the organ of vision: blurred vision, diplopia.

From the digestive system: gastrointestinal disorders, impaired liver function.

From the hematopoietic system: leukopenia, agranulocytosis.

Other: allergic reactions, drowsiness, habituation, drug dependence.

Contraindications

Hepatic and renal failure; glaucoma; myasthenia; suicidal tendency; hypercapnia; pregnancy; lactation period; porphyria; elderly age (over 65 years); childhood; hypersensitivity to the components of the combination.

With caution

History of drug, narcotic, or alcohol dependence.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Contraindicated in hepatic failure.

Use in Renal Impairment

Contraindicated in renal failure.

Pediatric Use

Contraindication — childhood.

Geriatric Use

Contraindication — elderly age (over 65 years).

Special Precautions

A thorough analysis of existing disorders should precede the decision to treat insomnia; other possible causes of insomnia (somatogenic, psychogenic, bad habits) must be excluded.

Must be used under strict medical supervision.

The use of the medicinal product may lead to the development of mental and physical drug dependence. The risk of developing drug dependence increases with the dose and duration of treatment and is higher in patients with a history of dependence on other medicinal products, as well as in patients with alcohol dependence. In case of drug dependence development, abrupt discontinuation of the drug may lead to withdrawal syndrome. Characteristic manifestations of withdrawal syndrome are: headache, muscle pain, psychomotor agitation and emotional tension, motor restlessness, confusion and disorientation, increased irritability, insomnia. In severe cases, the following may occur: loss of the sense of reality of the surroundings (derealization), personality disorders (depersonalization), increased sensitivity to touch (tactile hyperesthesia), increased sensitivity to auditory and visual stimuli (acoustic and light hyperesthesia), sensation of “pins and needles” and numbness of the extremities, hallucinations, or seizures.

This combination may cause anterograde amnesia. It is recommended to take it one hour before bedtime and to ensure conditions for continuous 7-8 hours of sleep.

It is not recommended to use the medicinal product in patients with psychoses.

Should be used with great caution in patients with symptoms of endogenous depression. These patients may experience suicidal thoughts. Due to the possibility of intentional overdose, it should be prescribed in lower doses.

During prolonged therapy, periodic studies of the morphological composition of peripheral blood and liver function tests are indicated.

During treatment and for 3 days after its completion, no alcoholic beverages should be consumed.

Effect on the ability to drive vehicles and operate machinery

During treatment and for 3 days after its completion, it is forbidden to drive vehicles and engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Enhances the sedative effect of antipsychotics, sedatives, general anesthetics, antidepressants, narcotic analgesics.

Microsomal oxidation inhibitors prolong the T_1/2 of diazepam.

Impairs the metabolism of phenytoin.

Incompatible with ethanol, anticoagulants, corticosteroids, doxycycline, griseofulvin, oral contraceptives.

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.