ACTION AND MECHANISM

- [ANTIALLERGIC], [HISTAMINERGIC ANTAGONIST (H-1)]. 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.- [HYPNOTIC]. Diphenhydramine is able to cross the blood-brain barrier and act on central H1 receptors, resulting in sedation. It appears that the sedative effect may also be due to the antagonism of muscarinic and serotonergic receptors.- [MUSCARINIC CHOLINERGIC ANTAGONIST (M)], [ANTIEMETIC]. Diphenhydramine is a nonspecific antagonist capable of blocking other receptors, such as central or peripheral muscarinic receptors. Blockade of central H1 and cholinergic receptors could exert an antiemetic effect, although this is not fully understood.

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

- This medicine will be administered with food.
- 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 diphenhydramine 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 diphenhydramine 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

Diphenhydramine 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 five times the human therapeutic dose have not shown any adverse fetal effects. Diphenhydramine crosses the placenta. There is conflicting data regarding the effects of diphenhydramine on pregnancy, although there are no adequate and well-controlled human studies to date. Articles have been published in which first-trimester diphenhydramine administration was associated with cleft palate, but this has not been confirmed in other studies. Diphenhydramine has occasionally been used to treat hyperemesis gravidarum. However, its use is only recommended in the absence of safer therapeutic alternatives.

PHARMACOKINETICS

Oral administration:- Absorption: Diphenhydramine is well absorbed from the intestine, but undergoes an intense first-pass effect in the liver, which reduces bioavailability to 40-60%. After administration of a dose, it appears in plasma within 15 minutes and its Cmax is reached after 1-4 hours. Its effects last 6-8 hours.- Distribution: Diphenhydramine is widely distributed throughout the body, crossing the blood-brain and placental barriers. It is also excreted in milk. The degree of plasma protein binding is 98-99%. After oral administration of a 50 mg dose, Vd values ​​of 3.3-6.8 L/kg are obtained.- Metabolism: It is rapidly and almost completely metabolized in the liver, mainly producing diphenylmethoxyacetic acid and, to a lesser extent, N-demethylated derivatives. The different metabolites are subsequently conjugated with glycine and glutamine.- Elimination: The metabolites are eliminated in the urine, with only 1% appearing unchanged. Its elimination half-life is 2.4-9.3 hours. Cl values ​​are between 600-1300 ml/minute.Pharmacokinetics in special situations:- Race: In Asian individuals it appears to present a lower binding to plasma proteins and a higher Vd (480 l).- Renal failure: In cases of moderate or severe renal failure (CLcr less than 60 ml/minute, retention of metabolites could occur.- Liver failure: An increase in the elimination half-life has been observed in these patients, depending on the degree of liver function.

INDICATIONS

- [INSOMNIA]. Short-term treatment of insomnia, particularly when there is difficulty falling asleep.

INTERACTIONS

Diphenhydramine may mask symptoms induced by ototoxic drugs by reducing vertigo or dizziness. It may also potentiate the photosensitizing effects of other active ingredients, leading to photosensitivity reactions. Drug interactions have also been reported with the following active ingredients: - Ethyl alcohol. The combined administration of alcohol and diphenhydramine may potentiate 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 diphenhydramine with other anticholinergic drugs may potentiate the anticholinergic effects; therefore, it is recommended to avoid the combination. - Sedatives (opioid analgesics, barbiturates, benzodiazepines, antipsychotics). The combined administration of diphenhydramine with a sedative drug may potentiate the hypnotic action. Extreme caution is recommended.

LACTATION

Diphenhydramine 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

Diphenhydramine is not recommended in children under six years of age, especially newborns and infants, because they may be more susceptible to anticholinergic adverse effects, which include paradoxical excitation of the central nervous system and seizures. The efficacy of diphenhydramine as a sedative in children under 12 years of age has not been evaluated. Because hyperexcitability is more common in these patients, its use is not recommended. Although there are no clinical trials evaluating the efficacy and safety of antihistamines in children 12-18 years of age, they have traditionally been used for the treatment of insomnia and allergies. Extreme vigilance is recommended in these patients.

RULES FOR CORRECT ADMINISTRATION

Diphenhydramine should be administered half an hour before bedtime to allow it to take full effect.

POSOLOGY

- Adults, oral:

PRECAUTIONS

- [RENAL FAILURE]. Accumulation of metabolites may occur in patients with renal impairment. Because these metabolites may be active, it is recommended to prolong administration periods in patients with moderate or severe renal impairment (CLcr less than 60 ml/minute). The dosage will be determined by the glomerular filtration rate (See Dosage). - [LIVER FAILURE]. Diphenhydramine is extensively metabolized by the liver. In cases of liver impairment, an increase in plasma concentration may occur, with a 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 diphenhydramine, 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, diphenhydramine may decrease the volume of bronchial secretions, increasing their viscosity, due to its 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, its use is not recommended in patients with asthma attacks (See Contraindications). - [APPENDICITIS]. Due to its antiemetic effects, it 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. Diphenhydramine 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 REACTIONS]. Diphenhydramine may lead to photosensitivity phenomena, so it is recommended not to sunbathe during treatment and to protect yourself with sunscreen.- Extreme temperatures. H1 antihistamines may aggravate heat exhaustion-dehydration 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 RELATING TO EXCIPIENTS

- This medicine contains lactose. Patients with hereditary [LACTOSE INTOLERANCE] or galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

ADVERSE REACTIONS

The side effects of diphenhydramine are usually mild and transient, being more frequent during the first days of treatment. Like other ethanolamines, diphenhydramine 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. [DROWSINESS] is common, especially at the beginning of treatment, and usually decreases after 2-3 days. [DISORIENTATION], [PSYCHOMOTOR LECORDINATION], [MYASTHENIA], [VERTIGO], [ASTHENIA], [HEADACHE] may also occur. Exceptionally, cases of paradoxical [EXCITABILITY] have been observed, especially in young children. This hyperexcitability is accompanied by [INSOMNIA], [NERVOUSNESS], [TREMOR], [IRRITABILITY], [EUPHORIA], [DELIRIUM], palpitations and even [CONVULSIONS].- Cardiovascular. Occasionally, and normally 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 can 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 [BLURRED VISION] or [DIPLOPIA] may occur.- Allergic/dermatological. [HYPERSENSITIVITY REACTIONS] may appear after the systemic administration of antihistamines, although less frequently than with topical application. [PHOTOSENSITIVITY REACTIONS] may also occur after intense exposure to sunlight, with [DERMATITIS], [PRURITUS], [EXANTHEMATOUS ERUPTIONS] and [ERYTHEMA].

OVERDOSE

Symptoms: Symptoms usually appear within 30 minutes to 2 hours and are variable, being more severe in children and people 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. If less than 3 hours have passed since ingestion, emetics may be administered, taking the necessary precautions to avoid aspiration, especially in children and the elderly. Inducing vomiting is not recommended in comatose or unconscious individuals. If emesis is contraindicated, gastric lavage may be performed and activated charcoal administered. Saline laxatives such as magnesium sulfate may be used. Symptoms of poisoning may be relieved with the following drugs: - Central anticholinergic effects. Intravenous physostigmine. - Seizures. Slow intravenous infusion of diazepam at a dose of 0.1 mg/kg in patients who do not respond to physostigmine. - Hypotension. Administer norepinephrine, phenylephrine, or dopamine, avoiding the administration of epinephrine, which may worsen hypotension. - Ventricular arrhythmias. Propranolol. If necessary, intubation and assisted respiration may be used. The use of analeptics is not recommended, as they may induce seizures.

COMPOSITION

Diphenhydramine: 50 milligrams - hydrochloride
LACTOSE (EXCIPIENT): 255 MILLIGRAMS