Duonika^® (Tablets) Instructions for Use

Marketing Authorization Holder

Valenta Pharm, JSC (Russia)

ATC Code

R06AA59 (Doxylamine in combination with other drugs)

Active Substances

Doxylamine (Rec.INN registered by WHO)

Pyridoxine (Rec.INN registered by WHO)

Dosage Form

Duonika®

Enteric-soluble film-coated tablets 10 mg+10 mg

Dosage Form, Packaging, and Composition

Enteric-soluble film-coated tablets

10 pcs. – blister packs (6 pcs.) – cardboard packs (60 pcs.) – By prescription
15 pcs. – blister packs (4 pcs.) – cardboard packs (60 pcs.) – By prescription

Pharmacotherapeutic Group

Systemic antihistamines; alkylamine esters

Pharmacological Action

Doxylamine is a histamine H₁-receptor blocker from the ethanolamine group that crosses the blood-brain barrier. It has hypnotic, sedative, antihistamine, and m-cholinolytic action.

Pyridoxine (vitamin B₆) and its metabolites are involved in metabolism and are necessary for the normal functioning of the central and peripheral nervous systems.

The combined use of doxylamine and pyridoxine provides relief from nausea and vomiting.

It relieves nausea and vomiting during pregnancy.

Pharmacokinetics

Doxylamine and Pyridoxine are absorbed from the gastrointestinal tract, mainly in the jejunum. The C_max of doxylamine and pyridoxine in blood plasma is observed 7.5 and 5.5 hours after administration of this agent, respectively. Food intake slows down the absorption of both doxylamine and pyridoxine. This is associated with a lower C_max of doxylamine, while the extent of absorption does not change. Pyridoxine binds well to blood plasma proteins, primarily albumin. Its main active metabolite, pyridoxal-5′-phosphate, accounts for at least 60% of the circulating concentration in the blood. Doxylamine is biotransformed in the liver by N-dealkylation to the main metabolites: N-desmethyl Doxylamine and N,N-didesmethyl Doxylamine. Pyridoxine is a prodrug that is metabolized primarily in the liver. During the biotransformation of pyridoxine, primary and secondary metabolites are formed, along with reverse conversion to Pyridoxine. The main, but inactive, metabolite of pyridoxine is 4-pyridoxic acid. Pyridoxine is more effectively taken up by hepatocytes in its phosphorylated form. The rate of phosphorylation of pyridoxine is much greater than that of dephosphorylation. The active metabolites of pyridoxine include, primarily, pyridoxal-5′-phosphate. The main metabolites of doxylamine, N-desmethyl Doxylamine and N,N-didesmethyl Doxylamine, are excreted by the kidneys. The T_1/2 of doxylamine and pyridoxine is 12.5 and 0.5 hours, respectively.

Indications

For women over 18 years of age for the treatment of nausea and vomiting during pregnancy.

ICD codes

Dosage Regimen

Orally.

The dosing regimen in any trimester of pregnancy is selected individually, depending on the time of onset, duration, severity, and frequency of symptoms.

As the pregnancy progresses, the woman should be consulted about the need for further use of this agent.

A gradual dose reduction is recommended when discontinuing this agent to prevent the possibility of sudden recurrence of nausea and vomiting symptoms.

Adverse Reactions

Nervous system disorders frequency unknown – drowsiness, dizziness, headache.

Gastrointestinal disorders frequency unknown – heartburn, stomach irritation, loose stools, constipation, flatulence, nausea, dysgeusia.

Immune system disorders frequency unknown – hypersensitivity.

Metabolism and nutrition disorders frequency unknown – hyperglycemia, hypokalemia.

Psychiatric disorders frequency unknown – anxiety, attention deficit/hyperactivity disorder, depression, disorientation, intolerance, insomnia, mood swings, nightmares.

General disorders and administration site conditions frequency unknown – weakness, fatigue, lethargy, loss of strength.

Contraindications

Hypersensitivity to doxylamine, pyridoxine, or any of the excipients included in the used drug; hypersensitivity to other antihistamines; bronchial asthma; closed-angle glaucoma; stenosing peptic ulcer of the stomach and duodenum; obstruction of the bladder neck; use of MAO inhibitors, including linezolid and methylthioninium chloride (methylene blue); children and adolescents under 18 years of age; breastfeeding period.

Use in Pregnancy and Lactation

The drug is intended for use by pregnant women. Based on adequate and well-controlled studies, the combination of doxylamine and pyridoxine can be used throughout the entire period of pregnancy.

Contraindicated for use during breastfeeding.

Use in Hepatic Impairment

Due to the possible increase in the half-life of doxylamine, a dose adjustment downward is recommended.

Use in Renal Impairment

Due to the possible increase in the half-life of doxylamine, a dose adjustment downward is recommended.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

For patients over 65 years of age, due to possible dizziness and drowsiness, as well as due to the possible increase in the half-life of doxylamine, a dose adjustment to reduce the frequency of administration of this agent is recommended.

Special Precautions

Like all hypnotic or sedative drugs, Doxylamine may exacerbate sleep apnea syndrome by increasing the number and duration of apnea attacks.

Possible abuse of first-generation histamine H₁-receptor blockers, including Doxylamine, can lead to physical and psychological dependence, which has been reported with the intentional intake of higher doses of doxylamine than recommended.

Effect on ability to drive vehicles and operate machinery

This agent may cause drowsiness due to the anticholinergic properties of doxylamine.

Women taking the drug should refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Use is contraindicated in women taking MAO inhibitors, which prolong and enhance the anticholinergic effect of antihistamines.

Concomitant use of this combination with drugs that depress the central nervous system (barbiturates, hypnotics, narcotic analgesics, antitussives, tranquilizers, and sedatives) is not recommended. Doxylamine may enhance the CNS depressant effect of such drugs.

When used concomitantly with drugs that have m-cholinolytic action (atropine, imipramine antidepressants, most histamine H₁-receptor blockers with atropine-like action, anticholinergic antiparkinsonian drugs, antispasmodic drugs with atropine-like action, disopyramide, phenothiazine neuroleptics, clozapine), the risk of such side effects as urinary retention, constipation, dry mouth, and others increases.

When taken with food, a decrease in absorption from the gastrointestinal tract is possible.

Ethanol enhances the sedative effect of most histamine H₁-receptor blockers, including doxylamine, so simultaneous use of this agent with alcoholic beverages and medications containing ethanol should be avoided.

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.