Tablets for motion sickness and nausea

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ANTI-DIZZINESS AND ANTI-NAUSEA TABLETS

Composition:

Active ingredient: dimenhydrinate;

1 tablet contains 50 mg of dimenhydrinate;

Excipients: microcrystalline cellulose, sodium croscarmellose, monohydrate lactose, magnesium stearate, colourant Yellow Sunset FCF (E 110).

Pharmaceutical form. Tablets.

Main physicochemical properties: orange-coloured, round, flat tablets. One side of the tablet bears the imprint «APO 50» or has no imprint, the other side has two cross-scored lines.

Pharmacotherapeutic group. Agents used in vestibular disorders. ATC code N07CA.

Pharmacological properties.

Pharmacodynamics.

Dramamine (dimenhydrinate) is a chlortheophylline salt of the well-known antihistamine diphenhydramine, which blocks H1-receptors and contains approximately 55% diphenhydramine and 45% 8-chlorotheophylline. The pharmacological activity of dimenhydrinate is due to diphenhydramine, which suppresses the central nervous system (CNS), and possesses anticholinergic, antiemetic, antihistaminic, and local anesthetic activities.

Anticholinergic effect: inhibition of vestibular stimulation in vertigo (Meniere's syndrome, motion sickness, sea and air sickness). Dimenhydrinate suppresses labyrinthine stimulation for up to 3 hours after administration.

Antiemetic effect: suppression of the vomiting reflex. The exact mechanism is not fully established. Dimenhydrinate inhibits the vomiting reflex induced by apomorphine, but is ineffective against vomiting caused by emetogenic chemotherapy. With prolonged use, the antiemetic effect may diminish.

Antihistaminic effect: pronounced sedative effect due to central M-cholinergic blockade. The CNS depressant effect persists for several days during continued administration of dimenhydrinate.

Pharmacokinetics.

After oral administration, dimenhydrinate is well absorbed from the gastrointestinal tract. Antiemetic effects begin approximately 30 minutes after intake, with a duration of action of 3–6 hours. It is widely distributed throughout the body, including the central nervous system. Plasma protein binding is 78%.

The active component of dimenhydrinate, diphenhydramine, is metabolized in the liver and is excreted primarily as metabolites within 24 hours. A minimal amount of unchanged substance is excreted in urine.

The elimination half-life is approximately 3.5 hours.

Clinical characteristics.

Indications.

• Prevention and relief of nausea and vomiting associated with motion sickness (sea or air travel), radiation therapy, medications (excluding agents used for chemotherapy in oncological diseases), and postoperatively.
• Symptomatic treatment of Ménière’s disease and other vestibular disorders.

Contraindications.

Hypersensitivity to dimenhydrinate and to other antihistamines of similar structure, or to any of the excipients contained in the formulation.

Closed-angle glaucoma, increased intracranial pressure, pheochromocytoma, porphyria, prostatic hyperplasia with urinary retention, epilepsy, eclampsia, acute asthma attack, severe hepatic impairment, severe renal impairment (creatinine clearance ≤ 25 mmol/min).

Interaction with other medicinal products and other forms of interactions.

Concomitant use of alcohol with dimenhydrinate should be avoided, as it may alter and enhance the effect of dimenhydrinate.

Diphenhydramine may enhance the anticholinergic effects of other medicinal products (e.g., atropine, antiparkinsonian agents, tricyclic antidepressants) and the central nervous system (CNS) depressant effects of agents such as barbiturates, hypnotics, sedatives, tranquilizers, antidepressants, morphine (analgesics, antitussives, medications used in substitution therapy), benzodiazepines, neuroleptics, centrally acting antihypertensives, baclofen, and thalidomide.

The drug may enhance the CNS depressant effects of antiepileptic medicinal products.

Concomitant use with monoamine oxidase inhibitors (MAOIs) may potentiate the anticholinergic effects of diphenhydramine; in individual cases, paralytic ileus (sometimes life-threatening), urinary retention, increased intraocular pressure have been reported; hypotension, CNS sedation, and respiratory depression are also possible.

The medicinal product enhances the effect of diazepam and exerts an action opposite to that of amphetamines and their derivatives. Administration of dimenhydrinate reduces the efficacy of corticosteroids and oral anticoagulants.

Concomitant use with bismuth-containing products, analgesics, psychotropic agents, and scopolamine may cause visual disturbances.

Particular caution is required when prescribing the medicinal product to patients receiving drugs that prolong the QT interval (Class I and II antiarrhythmics, certain antibiotics such as erythromycin, antimalarials, antihistamines, neuroleptic agents), or drugs that cause hypokalemia (e.g., certain specific diuretics).

Dimenhydrinate may mask the adverse effects of ototoxic agents, such as aminoglycosides.

Dimenhydrinate therapy should be discontinued at least three days before performing allergy testing, as its use may lead to false-negative results.

Special precautions for use

The drug should be prescribed with particular caution to patients suffering from liver or kidney diseases, hyperthyroidism, bradycardia, arterial hypertension, chronic respiratory disorders, bronchial asthma, hypokalemia, hypomagnesemia, pylorospasm, pyloroduodenal obstruction, gastric ulcer, intestinal obstruction, as well as those with congenital long QT syndrome or other clinically significant cardiac disorders (cardiovascular diseases, circulatory disorders, arrhythmias), and to patients concurrently taking other medicinal products that may prolong the QT interval or cause hypokalemia.

The drug should be prescribed with caution to elderly patients, as they are more prone to orthostatic hypotension, obesity, chronic constipation (risk of developing paralytic ileus), benign prostatic hyperplasia, Parkinson's disease, and often take sedatives. These patients should receive the lowest recommended adult dose, as they are more sensitive to the anticholinergic effects of the drug.

The drug contains lactose.

If you have been diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicinal product.

Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

The drug contains the dye sunset yellow FCF (E 110), which may cause allergic reactions.

Use during pregnancy or breastfeeding

The drug is contraindicated during pregnancy. Dimenhydrinate passes into breast milk in small amounts; therefore, breastfeeding should be discontinued during treatment.

Ability to affect reaction speed when driving or operating machinery

The drug may cause drowsiness, impaired coordination, dizziness, and prolonged reaction time. Therefore, patients should refrain from driving vehicles or operating machinery with a high risk of injury during treatment.

Dosage and Administration

Take orally, regardless of food intake. The tablet can be taken with a small amount of water.

Prevention and relief of nausea and vomiting associated with motion sickness (sea or air sickness), radiation therapy, medications, or after surgery

For prevention of sea or air sickness, the recommended dose should be taken at least 30 minutes before boarding a vehicle (airplane or ship).

Adults and children aged 12 years and older:

The recommended dose is 50 mg (1 tablet) taken 30–60 minutes before travel. This dose may be repeated as needed every 4–6 hours with doses of 50–100 mg.

The maximum daily dose must not exceed 400 mg.

Children aged 6–12 years:

The recommended dose is 25–50 mg (1/2–1 tablet), which may be repeated as needed every 6–8 hours. The maximum daily dose must not exceed 150 mg.

Children aged 2–6 years:

The recommended dose is 25 mg (1/2 tablet), which may be repeated as needed every 6–8 hours. The maximum daily dose must not exceed 75 mg.

The maximum daily dose in pediatric practice must not exceed 5 mg/kg.

Elderly patients should be started on an initial dose of 25 mg (1/2 tablet).

For Menière’s disease and other vestibular disorders

Adults: 50–100 mg (1–2 tablets) every 4–6 hours as needed, without exceeding the maximum daily dose of 400 mg.

Use with caution in patients with renal and/or hepatic impairment.

In hepatic impairment, the dose should be reduced by half.

In renal impairment, the usual dose is recommended.

Children

The efficacy and safety of the medicinal product in children under 2 years of age have not been established. The drug may be used in children aged 2 years and older.

Overdose

Symptoms: Initial symptoms of overdose appear 0.5–2 hours after ingestion of a toxic dose (25 mg/kg body weight), predominantly as headache, dizziness, fatigue, and drowsiness.

After some time, additional symptoms develop: itching, skin vasoconstriction, pupil dilation with slowed pupillary reflex, cycloplegia, nystagmus, decreased muscle strength, diminished tendon reflexes, and urinary retention. Heart rate increases significantly, and blood pressure may rise or fall.

Symptoms of central nervous system (CNS) depression (slurred speech, disorientation in time and space, ataxia, coma) or CNS excitation (seizures, psychosis with hallucinations) may also occur, progressively worsening.

Treatment: gastric lavage, administration of enterosorbents, symptomatic therapy.

Adverse reactions.

Nervous system disorders: dizziness, headache, drowsiness, excitement, insomnia, depressed state, fatigue, increased reaction time, muscle weakness, impaired motor coordination, tremor, anxiety, difficulty concentrating and memory impairment, seizures, hallucinations.

Eye disorders: glaucoma, visual disturbances, increased intraocular pressure, possible blurred vision, diplopia.

Ear and labyrinth disorders: tinnitus.

Cardiovascular disorders: palpitations, tachycardia, arrhythmia, angina attacks, arterial hypotension, including orthostatic.

Gastrointestinal disorders: stomach pain, diarrhea, constipation, dry mouth, nausea, vomiting, increased or decreased appetite, weight gain.

Skin and subcutaneous tissue disorders: allergic reactions, photosensitivity, exfoliative dermatitis, rash, urticaria.

Lymphatic system and blood-forming system disorders: hemolytic anemia.

Immune system disorders: angioneurotic edema, anaphylactic shock (rare).

Renal and urinary disorders: urinary disturbances (urinary retention due to anticholinergic effect), difficulty in urination.

Hepatobiliary disorders: liver function abnormalities, cholestatic jaundice.

Respiratory disorders: nasal congestion, increased bronchial secretion viscosity.

Other: arthralgia, decreased sweating, dryness of mucous membranes.

Prolonged use of dimenhydrinate may lead to drug dependence.

Shelf life. 5 years.

Storage conditions.

Store in a place inaccessible to children, at a temperature not exceeding 30 °C.

Packaging. 25 or 10 tablets in a blister; 1 blister per cardboard package.

Availability. Over-the-counter.

Manufacturer. Pharmascience Inc.

Manufacturer's address and location of business activity.

6111 Royalmount Avenue, Suite 100, Montreal, Quebec H4P 2T4, Canada.

6111 Royalmount Avenue, 100, Montreal, Quebec H4P 2T4, Canada.