Dramina^® (Tablets) Instructions for Use

Marketing Authorization Holder

Jadran-Galenski Laboratorij, D.D. (Croatia)

Contact Information

JADRAN-GALENSKI LABORATORIJ D.D. (Croatia)

ATC Code

R06AA11 (Dimenhydrinate)

Active Substance

Dimenhydrinate (Rec.INN registered by WHO)

Dosage Form

Dramina®

Tablets 50 mg: 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Tablets are white, round, smooth, flat-cylindrical, with a bevel and a score on one side.

Excipients: ludipress [lactose monohydrate, povidone K30, crospovidone], microcrystalline cellulose, magnesium stearate.

5 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (1) – cardboard packs.

Clinical-Pharmacological Group

Histamine H₁-receptor blocker used for motion sickness

Pharmacotherapeutic Group

Systemic antihistamines; H1-histamine receptor blocker

Pharmacological Action

The main mechanism of action of dimenhydrinate is the suppression of acetylcholine synthesis.

Dimenhydrinate is the chlorotheophylline salt of diphenhydramine, consisting of 55% diphenhydramine and 45% 8-chlorotheophylline. For this reason, the active substance of dimenhydrinate is diphenhydramine, which has a depressant effect on the CNS (penetrates the blood-brain barrier well), as well as anticholinergic, antiemetic, antihistamine (histamine H₁-receptor blocker), and local anesthetic effects (blocks sodium ion flow). It is assumed that the anticholinergic action of dimenhydrinate causes suppression of vestibular stimulation (in small doses it acts on the otoliths, and in large doses on the semicircular canals), which occurs during motion sickness or dizziness. Dimenhydrinate inhibits labyrinthine stimulation within 3 hours of administration. The inhibition occurs due to the antimuscarinic action of dimenhydrinate.

Pharmacokinetics

Absorption and Distribution

Dimenhydrinate is well absorbed from the gastrointestinal tract after oral administration. The antiemetic effect occurs 15-30 minutes after administration. The effect lasts for 3-6 hours. About 78% of the drug is bound to plasma proteins. It penetrates the placental and blood-brain barrier well and is excreted in milk.

Metabolism and Excretion

It undergoes intensive first-pass metabolism in the liver, mainly via the CYP2D6 enzyme system. The T_1/2 of dimenhydrinate is about 3.5 hours. It is excreted in the urine as a metabolite and unchanged.

Indications

The drug is intended for use from 3 years of age

• Motion sickness (seasickness, carsickness, and airsickness);
• Prevention and treatment of symptoms of vestibular and labyrinthine disorders (dizziness, nausea, vomiting), except for symptoms caused by anticancer therapy;
• Ménière’s disease.

ICD codes

Dosage Regimen

Take orally. Tablets are best taken after meals to minimize stomach irritation and should be taken with sufficient fluid (e.g., water).

The drug should be used for the shortest period necessary to reduce symptoms.

Adults

For the prevention of motion sickness, take 1-2 tablets 30 minutes before travel.

Motion sickness (seasickness, carsickness, airsickness) – 1-2 tablets 2-3 times/day.

Prevention and treatment of symptoms of vestibular and labyrinthine disorders (dizziness, nausea, vomiting), except for symptoms caused by anticancer therapy – 1-2 tablets 2-3 times/day.

Ménière’s disease – 1-2 tablets 2-3 times/day.

The maximum daily dose for adults should not exceed 350 mg (7 tablets).

The duration of drug use and the possibility of repeating the course of treatment is determined by the doctor.

Special patient groups

Elderly patients

For the treatment of elderly patients, the minimum recommended adult dose of the drug should be used, because patients in this group have increased sensitivity to the anticholinergic effect of the drug.

Children

For the prevention of motion sickness, the drug should be taken 30 minutes before travel.

Children over 12 years

Motion sickness (seasickness, carsickness, airsickness) – 1-2 tablets 2-3 times/day.

Prevention and treatment of symptoms of vestibular and labyrinthine disorders (dizziness, nausea, vomiting), except for symptoms caused by anticancer therapy – 1-2 tablets 2-3 times/day.

Ménière’s disease – 1-2 tablets 2-3 times/day .

Children from 7 to 12 years

Motion sickness (seasickness, carsickness, airsickness) – 1/2 – 1 tablet 2-3 times/day.

Prevention and treatment of symptoms of vestibular and labyrinthine disorders (dizziness, nausea, vomiting), except for symptoms caused by anticancer therapy – 1/2 – 1 tablet 2-3 times/day.

Ménière’s disease – 1/2 – 1 tablet 2-3 times/day.

Children from 3 to 6 years

Motion sickness (seasickness, carsickness, airsickness) – 1/4-1/2 tablet 2-3 times/day.

Prevention and treatment of symptoms of vestibular and labyrinthine disorders (dizziness, nausea, vomiting), except for symptoms caused by anticancer therapy – 1/4-1/2 tablet 2-3 times/day.

Ménière’s disease – 1/2 – 1 tablet 2-3 times/day.

The maximum daily dose for children aged 3 to 6 years should not exceed 75 mg (1.5 tablets).

Adverse Reactions

The adverse events presented below are listed according to the affected organs and organ systems and frequency of occurrence. Frequency is defined as follows: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), frequency unknown (frequency cannot be estimated from the available data).

Blood and lymphatic system disorders: very rare – hemolytic anemia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia or pancytopenia.

Immune system disorders: rare – anaphylactic shock.

Psychiatric disorders: common – mood changes, agitation, anxiety; uncommon – insomnia.

Nervous system disorders: common – drowsiness; uncommon – dizziness, impaired concentration and memory (especially in elderly patients), tremor, impaired coordination, confusion, hallucinations; rare – headache, sleep disorder, dizziness, orthostatic hypotension; very rare – paradoxical CNS stimulation (especially in children); unknown frequency – convulsions.

Eye disorders: rare – glaucoma, visual disturbances (mydriasis, blurred vision, diplopia).

Ear and labyrinth disorders: rare – tinnitus.

Cardiac disorders: rare – palpitations, tachycardia and hypotension.

Respiratory, thoracic and mediastinal disorders: common – nasal congestion; unknown frequency – increased viscosity of bronchial secretion.

Gastrointestinal disorders: common – dry mouth, constipation, diarrhea, nausea, abdominal pain.

Hepatobiliary disorders: unknown frequency – deviation from the norm of biochemical parameters of liver functional state (cholestatic jaundice).

Skin and subcutaneous tissue disorders: rare – rash, erythema; unknown frequency – allergic skin reactions, photosensitivity.

Musculoskeletal and connective tissue disorders: very common – muscle weakness.

Renal and urinary disorders: common – urination disorder (urinary retention due to anticholinergic effect).

Reproductive system and breast disorders: unknown frequency – decreased breast milk secretion.

General disorders and administration site conditions: rare – edema (angioedema).

Contraindications

• Hypersensitivity to dimenhydrinate or any of the excipients included in the drug;
• Hypersensitivity to antihistamine drugs;
• Acute attacks of bronchial asthma;
• Closed-angle glaucoma;
• Pheochromocytoma;
• Porphyria;
• Convulsions (epilepsy, eclampsia);
• Prostatic hyperplasia;
• Galactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose monohydrate);
• Pregnancy (I and III trimester);
• Breastfeeding period;
• Children under 3 years of age.

With caution: severe impairment of liver/kidney function due to the risk of accumulation; chronic respiratory diseases, bronchial asthma; elderly patients with a higher tendency to develop orthostatic hypotension, obesity and sedation, chronic constipation (risk of paralytic ileus) or potential prostatic hypertrophy; pyloric stenosis; pyloroduodenal obstruction; cardiac rhythm disorders, bradycardia; congenital long QT interval or other clinically significant cardiovascular disorders (CHD, circulatory disorders, arrhythmia); Parkinson’s disease (especially in the elderly).

Use in Pregnancy and Lactation

Pregnancy

There are no data on the use of dimenhydrinate in pregnant women, as studies in this category of patients have not been conducted.

It is not recommended to use Dimenhydrinate during pregnancy unless its potential benefit to the mother outweighs the potential risk to the fetus. Dramina^® tablets should not be used in the III trimester of pregnancy, as they may stimulate premature uterine contractions.

The use of dimenhydrinate in the I trimester of pregnancy is contraindicated.

Breastfeeding period

Dimenhydrinate is excreted in breast milk and may reduce its secretion. It is recommended to stop breastfeeding during treatment.

Fertility

There are no data on the effect of dimenhydrinate on fertility.

Use in Hepatic Impairment

Use with caution in severe liver dysfunction due to the risk of accumulation.

Use in Renal Impairment

Use with caution in severe renal dysfunction due to the risk of accumulation.

Pediatric Use

The drug is contraindicated in children under 3 years of age.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

With prolonged use, Dimenhydrinate may lead to a falsely positive high serum theophylline level.

During treatment with dimenhydrinate, the consumption of alcoholic beverages should be avoided.

Dimenhydrinate therapy should be discontinued several days before allergen testing, as it may lead to false-negative allergy tests.

The medicinal product contains lactose. Patients with rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

In extremely high air temperatures, there is a risk of heat stroke caused by the anticholinergic effect of dimenhydrinate. It is recommended to avoid exposure to very high temperatures.

Dimenhydrinate may cause photosensitization phenomena, it is recommended to refrain from visiting solariums and prolonged exposure of the skin to direct sunlight.

Effect on the ability to drive vehicles and mechanisms

Given the side effects, caution should be exercised when engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions (including driving).

Overdose

Symptoms

Symptoms of dimenhydrinate overdose (especially in children) are similar to those of atropine overdose and include dryness of the mouth, nose, and throat, facial flushing, slow or difficult breathing, weakness, dilated pupils, agitation, hallucinations, confusion, ataxia, intermittent clonic convulsions, coma, cardiorespiratory collapse and death.

Overdose symptoms may be delayed for up to 2 hours after administration of excessive doses of the drug, and death may occur within 18 hours. In adults, 500 mg or more of dimenhydrinate may cause particularly difficult speech, swallowing and symptoms of psychosis that are indistinguishable from psychosis caused by atropine overdose.

Treatment

Treatment is symptomatic and supportive. Administration of activated charcoal is recommended. Emetics are usually ineffective, but early gastric lavage (with endotracheal intubation to prevent aspiration of gastric contents) may be helpful in the absence of convulsions.

The patient should be kept in a quiet environment to minimize CNS stimulation. Convulsions can be treated with diazepam. To relieve severe symptoms of the anticholinergic syndrome, physostigmine (after a physostigmine test) can be administered intravenously. In case of severe respiratory depression, a respirator must be used.

Drug Interactions

The anticholinergic effect of dimenhydrinate (potential urinary retention, constipation and dry mouth) may be enhanced when used concomitantly with anticholinergic drugs (atropine, antiparkinsonian drugs, tricyclic antidepressants, etc.).

The use of MAO inhibitors enhances the sedative and anticholinergic effects of dimenhydrinate: paralytic ileus, urinary retention, increased intraocular pressure, decreased blood pressure and respiratory impairment may develop. Concomitant use of dimenhydrinate with MAO inhibitors should be avoided.

Morphine derivatives (analgesics, antitussives, synthetic morphine substitutes), benzodiazepines, barbiturates, anxiolytics, hypnotics, neuroleptics, antidepressants, central hypotensive agents, baclofen, thalidomide may enhance CNS depression.

Dimenhydrinate may mask

• Early signs of ototoxicity associated with the use of aminoglycoside antibiotics;
• Skin reaction to skin allergy tests.

Concomitant administration of dimenhydrinate and drugs that prolong the QT interval (some antibiotics, neuroleptics, class I antiarrhythmic agents and class III antimalarial agents) or cause hypokalemia (e.g., diuretics) should be avoided.

Concomitant use of antihypertensive agents and dimenhydrinate may lead to increased fatigue and enhancement of the antihypertensive effect.

Alcohol intake enhances the sedative effect of antihistamines acting on H₁-receptors, therefore alcoholic beverages and alcohol-containing medicines should not be consumed during treatment with dimenhydrinate.

Dimenhydrinate enhances the action of adrenaline, noradrenaline and other sympathomimetics.

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 – 5 years. Do not use after the expiration date printed on the package.

Dispensing Status

The drug is dispensed without a 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.