ACTION AND MECHANISM

- [ANTIALLERGIC], [HISTAMINERGIC ANTAGONIST (H-1)]. Dimenhydrinate is an equimolar complex of diphenhydramine and a theophylline derivative, 7-chlorotheophylline. Diphenhydramine is an ethanolamine derivative that competitively, reversibly, and nonspecifically blocks H1 receptors, decreasing the systemic effects of histamine. It causes vasoconstriction and decreased vascular permeability, reducing the redness and edema associated with allergies. It partially mitigates symptoms associated with allergic processes such as eye redness or nasal congestion. It also produces a mild bronchodilator effect and a reduction in skin itching. Dimenhydrinate is a nonspecific H1 antagonist, so it is capable of antagonizing other receptors such as central and peripheral cholinergic receptors. By crossing the blood-brain barrier and blocking H1 and muscarinic receptors, it will cause sedation, but milder than ethanolamines.- [MUSCARINIC CHOLINERGIC ANTAGONIST (M)], antiemetic. Dimenhydrinate is a non-specific antagonist capable of also blocking other receptors such as central or peripheral muscarinic receptors. Blocking central H1 and cholinergic receptors could have an antiemetic effect, although this is not fully understood. It has been shown that this drug is capable of inhibiting vestibular stimulation, initially inhibiting stimuli formed in the otolic system, and at higher doses, in the semicircular canals. After continued use, tolerance to the antiemetic effects has been observed.

SPECIAL WARNINGS

- Dimenhydrinate may mask the ototoxic effects of some drugs, so it is recommended to periodically evaluate acoustic function in patients treated with these drugs.
- Before using this medicine in patients with vomiting of unknown origin, it is recommended to rule out the presence of appendicitis.
- It is recommended to monitor the patient's hydration during a heat wave, especially if the patient is a young child, an elderly person, or someone with a serious illness.
- Due to the anti-allergic effects of this medication, it may cause false negative results in skin hypersensitivity tests to antigenic extracts. It is recommended that you discontinue taking this medication at least 72 hours before the test.

SENIORS

Elderly patients are more sensitive to the adverse effects of antihistamines, such as dizziness, sedation, confusion, hypotension, and hyperexcitability, as well as to anticholinergic effects (dry mouth, urinary retention, precipitation of glaucoma). Antihistamines can be used in patients over 65 years of age, but extreme caution should be exercised. If side effects persist or are severe, discontinuation of treatment is advisable.

PATIENT ADVICE

- Administer when symptoms appear, along with food, to reduce gastric discomfort. For sensitive individuals, it may be administered 1-2 hours before travel.
- The dose may be repeated during the trip, provided that the intervals between doses are respected and the maximum recommended dose is not exceeded.
- It can cause drowsiness, so it is recommended to be cautious when driving and not to combine it with medications or other sedative substances such as alcohol.
- Patients receiving sedative drugs are not advised to self-medicate with dimenhydrinate products without consulting a physician.
- It is advisable not to sunbathe during treatment.
- The doctor must be notified of any chronic pathology the patient has before starting treatment.
- Exposure to extreme temperatures should be avoided while using this medication, by staying in a cool environment and staying adequately hydrated.

CONTRAINDICATIONS

- Hypersensitivity to any component of the medication. Cross-reactions with other antihistamines may occur, so the use of any H1 antihistamine is not recommended in patients who have previously experienced hypersensitivity to any compound in this group.- [ASTHMA ATTACK]. Some authors believe that dimenhydrinate may worsen asthma, so its use is not recommended in an acute attack.- [PORPHYRIA]. H1 antihistamines have been associated with the onset of porphyric attacks, so they are not considered safe in these patients.

EFFECTS ON DRIVING

Dimenhydrinate may substantially impair the ability to drive and/or operate machinery. Patients should avoid operating hazardous machinery, including automobiles, until they are reasonably certain that drug treatment does not adversely affect them.

PREGNANCY

FDA Category B. Studies in rats and rabbits using doses 20-25 times the human dose have shown no evidence of fetal harm. Adequate and well-controlled studies have not been conducted in humans. However, dimenhydrinate has been used for hyperemesis gravidarum without significant adverse effects. However, there are reports of a possible association between administration during the last two weeks of pregnancy and the development of retrolental fibroplasia in premature infants. Although the possibility of fetal harm appears remote, this drug should only be used when the benefits outweigh the potential risks.

PHARMACOKINETICS

Oral administration:- Absorption: Dimenhydrinate is well absorbed from the intestine, but undergoes a strong first-pass effect in the liver. After administration of a dose, the effects appear within 15-30 minutes, and last for 3-6 hours. The Tmax is 2 hours.- Distribution: Dimenhydrinate is widely distributed throughout the body, crossing the blood-brain and placental barriers. It is also excreted in small amounts in milk.- Metabolism: It is rapidly and almost completely metabolized in the liver.- Elimination: The metabolites are eliminated in the urine.

INDICATIONS

- [MOTION SICKNESS]. Prevention and treatment of [NAUSEA], [VOMITING], and [VERTIGO] associated with travel.

INTERACTIONS

Dimenhydrinate may mask symptoms induced by ototoxic drugs by reducing vertigo or dizziness. Similarly, it may enhance the photosensitizing effects of other active ingredients that lead to photosensitivity reactions. Drug interactions have also been reported with the following active ingredients: - Ethyl alcohol. The combined administration of alcohol and dimenhydrinate may enhance the sedative effects of both substances. It is recommended to avoid alcohol consumption during treatment. - Anticholinergics (antiparkinsonian drugs, tricyclic antidepressants, MAOIs, neuroleptics). The administration of dimenhydrinate with other anticholinergic drugs may enhance the anticholinergic effects; therefore, it is recommended to avoid the combination. - Sedatives (opioid analgesics, barbiturates, benzodiazepines, antipsychotics). The combined administration of dimenhydrinate with a sedative drug may enhance the hypnotic action. Extreme caution is recommended.

LACTATION

Dimenhydrinate may inhibit lactation due to its anticholinergic effects. It is also excreted in breast milk in small amounts, although it is unknown whether these could have effects on the nursing infant. However, children are more sensitive to anticholinergic reactions and may more frequently experience paradoxical hyperexcitability reactions. It is recommended to discontinue breastfeeding or avoid administration of this medication.

CHILDREN

Dimenhydrinate is not recommended in children under two years of age, especially newborns and infants, because they may be more susceptible to anticholinergic adverse effects. Cases of paradoxical reactions with hyperexcitability have been reported in children over two years of age, especially at high doses, so its use is recommended with caution.

RULES FOR CORRECT ADMINISTRATION

Administer with food, water or milk to reduce gastric discomfort.

POSOLOGY

- Children 7-12 years: 2-4 packs (25-50 mg)/6-8 h. Maximum dose 12 packs (150 mg)/24 h.
- Children 2-6 years: 1-2 packs (12.5-25 mg)/6-8 h. Maximum dose 6 packs (75 mg)/24 h.
- Children under 2 years of age: Safety and efficacy have not been evaluated.
Administer at least 30 minutes before travel, and preferably 1-2 hours before.

PRECAUTIONS

- [RENAL FAILURE]. Safety and efficacy have not been evaluated in patients with renal impairment, but dimenhydrinate metabolites are eliminated in the urine, so accumulation of these metabolites may occur. Since these metabolites may be active, it may be necessary to extend administration periods in patients with renal impairment, especially in moderate or severe cases (CLcr less than 60 ml/minute). - [LIVER FAILURE]. Dimenhydrinate is extensively metabolized by the liver. In cases of liver impairment, an increase in plasma concentration may occur, with the consequent risk of adverse effects. A dosage adjustment may be necessary in these patients depending on the degree of liver function.- Patients suffering from [GLAUCOMA], [PROSTATIC HYPERPLASIA] or [URINARY BLADDER OBSTRUCTION], [ARTERIAL HYPERTENSION], [CARDIAC ARRHYTHMIA], [MYASTHENIA GRAVIS], stenosing [PEPTIC ULCER] or [INTESTINAL OBSTRUCTION]. Due to the anticholinergic effects of dimenhydrinate, these conditions may worsen; therefore, extreme caution is recommended and treatment should be discontinued if worsening occurs.- Lower respiratory tract diseases such as [ASTHMA], [PULMONARY EMPHYSEMA] or [CHRONIC OBSTRUCTIVE PULMONARY DISEASE]. According to some authors, H1 antihistamines may decrease the volume of bronchial secretions, increasing their viscosity, due to their anticholinergic effects, which could aggravate these conditions. However, there is not much clinical evidence, despite which, extreme caution is recommended in these patients. As a general rule, their use is not recommended in patients with asthma attacks (See Contraindications).- [EPILEPSY]. Caution should be exercised in epileptic patients, since antihistamines have occasionally been associated with paradoxical hyperexcitability reactions, even at therapeutic doses, which could lower the seizure threshold.- [APPENDICITIS]. Due to their antiemetic effects, they may interfere with the diagnosis of appendicitis. It is recommended to rule out the presence of appendicitis beforehand in patients with vomiting of unknown origin.- Ototoxicity. Dimenhydrinate may have a beneficial effect in cases of vertigo, tinnitus, and dizziness, and may therefore mask ototoxicity induced by ototoxic drugs such as parenteral aminoglycosides, carboplatin, cisplatin, chloroquine, and erythromycin, among others. - Photosensitivity. Dimenhydrinate may cause photosensitivity, so it is recommended to avoid sunbathing during treatment and to protect yourself with sunscreen. - Extreme temperatures. H1 antihistamines may aggravate heat exhaustion syndrome and heat stroke due to the decrease in sweating caused by their anticholinergic effects. Patients receiving these medications are advised to avoid exposure to very high temperatures, especially young children, the elderly, or people with serious chronic illnesses. It is also advisable to follow appropriate hygienic and dietary measures, such as adequate ventilation and hydration.

PRECAUTIONS RELATED TO EXCIPIENTS

- Because it contains methyl parahydroxybenzoate, it may cause allergic reactions (possibly delayed).

ADVERSE REACTIONS

The side effects of dimenhydrinate are usually mild and transient, being more frequent during the first days of treatment. Like other ethanolamines, dimenhydrinate mainly causes drowsiness and anticholinergic phenomena, but there is great interindividual variability with respect to the frequency and intensity of the symptoms, affecting mainly young children and the elderly. The most common adverse reactions are: - Digestive. [NAUSEA], [VOMITING], [CONSTIPATION], [DIARRHEA], [EPIGASTRIC PAIN], [ANOREXIA], [DRY MOUTH]. These symptoms can be reduced by administering the antihistamine with meals. - Neurological/psychological. [DROWSY] is frequent (1-9%), especially at the beginning of treatment, and usually decreases after 2-3 days. [HEADACHE], [VERTIGO] and [DIZZINESS] have also been reported. Rarely, cases of paradoxical [EXCITABILITY] have been observed, especially in young children. This hyperexcitability is accompanied by [INSOMNIA], [NERVOUSNESS], [CONFUSION], [TREMOR], [IRRITABILITY], [EUPHORIA], [DELIRIUM], palpitations and even [CONVULSIONS]. - Cardiovascular. Occasionally, and usually in the case of an overdose, [TACHYCARDIA], [PALPITATIONS] and other [CARDIAC ARRHYTHMIA] such as [EXTRASYSTOLE] or [HEART BLOCK] may occur. These effects could be due to anticholinergic activity. Occasionally, [HYPOTENSION] or [ARTERIAL HYPERTENSION] have been described. - Respiratory. Occasionally, an increase in the viscosity of bronchial secretions may occur, which may make breathing difficult. - Genitourinary. [URINARY RETENTION] and [SEXUAL IMPOTENCE] may appear due to cholinergic blockade.- Hematological. [HEMOLYTIC ANEMIA], [AGRANULOCYTOSIS], [LEUKOPENIA], [THROMBOPENIA] or [PANCYTOPENIA] have been rarely described.- Ocular. Due to anticholinergic activity, [GLAUCOMA] and [VISION DISORDERS] such as [MYDRIASIS], [BLURRED VISION] or [DIPLOPIA] may occur.- Allergic/dermatological. [HYPERSENSITIVITY REACTIONS] may appear after the systemic administration of antihistamines, which may even cause [ANAPHYLAXIS]. [PHOTOSENSITIVITY REACTIONS] may also appear after intense exposure to sunlight, with [DERMATITIS], [PRURITUS], [EXANTHEMATOUS ERUPTIONS] and [ERYTHEMA].

OVERDOSE

Symptoms: Symptoms usually appear within 2 hours, although they can last up to 18 hours, and are usually variable, being more severe in children and those over 65 years of age. Moderate nervous breakdown with sedation and apnea, cardiovascular collapse, hyperexcitability with insomnia, hallucinations, tremors, or seizures, and anticholinergic symptoms such as dry mouth, blurred vision, and urinary retention have been reported. Fever above 41.8°C may also occur. In more severe cases, especially in children, symptoms may worsen, leading to hypotension, seizures, respiratory depression, loss of consciousness, coma, and death. Treatment: Treatment will consist of standard measures to promote drug elimination. The administration of emetics is usually ineffective. However, gastric lavage may be beneficial if less than 3 hours have passed since ingestion. The patient should be kept calm to minimize central nervous system stimulation. Seizures can be treated with diazepam in adults and phenobarbital in children at doses of 5-6 mg/kg. Hypotension can be treated with vasopressors, although epinephrine should be avoided as it can further decrease blood pressure. If necessary, intubation and assisted respiration may be necessary. The use of analeptics is not recommended as they may induce seizures.

COMPOSITION

DIMENHYDRINATE: 12.5 MILLIGRAMS
SODIUM SALTS (EXCIPIENT): 5.5 MILLIGRAMS
SORBITOL (E-420) (EXCIPIENT): 500 MILLIGRAMS
METHYL PARAHYDROXYBENZOATE (E-218) (EXC): 5 MILLIGRAMS - SODIUM (SALT)
PROPYL PARAHYDROXYBENZOATE (E-216) (EXC: 1.25 MILLIGRAMS - SODIUM (SALT)