Dimedrol-darnitsa

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DIMEDROL-DARNITSA (DIMEDROL-DARNITSA)

Composition:

active substance: diphenhydramine;

1 ml of solution contains diphenhydramine hydrochloride 10 mg;

excipient: water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear colorless liquid.

Pharmacotherapeutic group. Antihistamines for systemic use. Aminoalkyl ether derivatives. Diphenhydramine. ATC code R06AA02.

Pharmacological properties.

Pharmacodynamics.

A first-generation H1-histamine receptor blocker that counteracts the effects of histamine mediated through this type of receptor. The action on the central nervous system (CNS) is due to blockade of brain H3-histamine receptors and inhibition of central cholinergic structures. It has pronounced antihistamine activity, reducing or preventing histamine-induced spasms of smooth muscles, increased capillary permeability, tissue edema, itching, and hyperemia. It produces a local anesthetic effect (after oral administration, transient numbness of oral mucosa may occur), blocks ganglionic cholinoreceptors (lowers blood pressure (BP) and affects the CNS), and exerts sedative, hypnotic, anti-Parkinson’s, and antiemetic effects. Antagonism with histamine is manifested predominantly in local vascular reactions during inflammation and allergy, rather than in systemic reactions, such as reduction in arterial pressure. However, after parenteral administration in patients with circulating blood volume deficiency, a decrease in BP and worsening of existing hypotension may occur due to ganglion-blocking action. In individuals with localized brain damage or epilepsy, it may activate (even at low doses) epileptic discharges on the electroencephalogram (EEG) and may provoke epileptic seizures. It is more effective against bronchospasm induced by histamine liberators (e.g., tubocurarine, morphine) and less effective against bronchospasm of allergic origin. Sedative and hypnotic effects are more pronounced with repeated administration.

Pharmacokinetics.

Plasma protein binding is 98–99%. The majority is metabolized in the liver, while a smaller portion is excreted unchanged in urine within 24 hours. The elimination half-life (T1/2) is 1–4 hours. It distributes well throughout the body and crosses the blood-brain barrier.

It is mainly metabolized in the liver via hydroxylation and conjugation into glucuronides; metabolites are eliminated in urine. It passes into breast milk and may cause a sedative effect in nursing infants. Maximum activity develops within 1 hour; duration of action is 4 to 6 hours.

Clinical characteristics.

Indications.

Anaphylactic shock, urticaria, hay fever (pollinosis), serum sickness, hemorrhagic vasculitis (capillarotoxicosis), polymorphic exudative erythema, Quincke's edema (angioedema), pruritic dermatoses, pruritus, allergic conjunctivitis and other allergic eye diseases, allergic reactions associated with the use of medicinal products, chorea, Ménière’s disease; postoperative vomiting.

Contraindications.

Hypersensitivity to the drug. Acute bronchial asthma attack, pheochromocytoma, epilepsy, congenital long QT syndrome or prolonged use of drugs that may prolong the QT interval and/or induce torsade de pointes, closed-angle glaucoma, benign prostatic hyperplasia, stenosing peptic ulcer of the stomach or duodenum, pyloroduodenal obstruction, bladder neck obstruction, bradycardia, cardiac arrhythmias, family history of sudden cardiac death, significant electrolyte imbalance (hypokalemia, hypomagnesemia). Porphyria.

Interaction with other medicinal products and other forms of interaction.

Diphenhydramine potentiates the effects of anesthetics, hypnotics, sedatives, narcotic analgesics, and local anesthetics. When used concomitantly with tricyclic antidepressants, enhanced cholinergic blockade and CNS depression may occur. There is a potential risk of seizures when used with analeptics. Concurrent use of monoamine oxidase inhibitors (MAOIs) and diphenhydramine may lead to increased blood pressure, as well as affect the central nervous and respiratory systems. The drug should be used with caution during MAOI therapy and for at least 2 weeks after discontinuation of MAOIs.

Concomitant use of medicinal products that prolong the QT interval on ECG (such as class Ia and III antiarrhythmics) should be avoided.

Since diphenhydramine exerts some antimuscarinic effects, the action of other anticholinergic drugs (e.g., atropine, tricyclic antidepressants) may be enhanced. Therefore, medical advice should be sought before taking diphenhydramine with such medicinal products.

Concomitant use of diphenhydramine with antihypertensive agents may increase fatigue. The drug enhances the effects of ethanol and reduces the efficacy of apomorphine when used as an emetic in poisoning. It should not be prescribed together with medicinal products containing diphenhydramine, including those intended for topical use.

Diphenhydramine is an inhibitor of the cytochrome P450 isoenzyme CYP2D6. Therefore, there is a potential for interaction with drugs primarily metabolized by CYP2D6, such as metoprolol and venlafaxine. Diphenhydramine should not be used in patients receiving any of these medicinal products.

Special precautions for use.

Subcutaneous administration is not recommended. Since diphenhydramine has atropine-like effects, it should be used with caution in patients with recent history of respiratory diseases (including bronchial asthma and bronchitis), increased intraocular pressure, hyperthyroidism, cardiovascular disorders, and arterial hypotension. It may worsen the course of obstructive lung diseases, severe cardiovascular disorders, ileus, and conditions with biliary tract obstruction. Diphenhydramine may cause drowsiness and may also induce excitation, hallucinations, and seizures, particularly in cases of overdose.

Concomitant use of other antihistamines, including topical antihistamines, as well as cough and cold remedies, should be avoided.

Use with caution in patients aged 60 years and older due to increased risk of dizziness, sedation, and arterial hypotension.

Use of diphenhydramine has been associated with QT interval prolongation on electrocardiogram. During post-marketing surveillance, cases of QT interval prolongation and torsade de pointes, related to overdose, have been reported.

Treatment should be discontinued and immediate medical attention sought if patients develop signs or symptoms that may be associated with cardiac arrhythmia. Patients should be advised to immediately report any cardiac symptoms.

Use with caution in patients with hepatic or renal impairment.

Patients with moderate to severe hepatic or renal insufficiency may require dose reduction.

During treatment with this medicinal product, exposure to UV radiation and alcohol consumption should be avoided. Patients should inform their physician about using this medicinal product, as its antiemetic effect may complicate the diagnosis of appendicitis and recognition of symptoms of overdose with other medicinal products.

The duration of diphenhydramine use should be as short as possible. Tolerance and/or dependence may develop with prolonged use.

Signs or symptoms indicating potential abuse should be monitored.

Use during pregnancy or breastfeeding.

Diphenhydramine is contraindicated during pregnancy due to lack of adequate data on safety and efficacy.

If use of the medicinal product is necessary, breastfeeding should be discontinued.

Ability to affect reaction speed when driving or operating machinery.

Due to its sedative and hypnotic effects, patients should refrain from potentially hazardous activities requiring heightened attention and rapid psychomotor reactions while being treated with this medicinal product.

Method of Administration and Dosage.

The medicinal product should be administered to adults intramuscularly and intravenously by drip infusion.

The drug must not be administered subcutaneously due to its irritant effect.

For intramuscular administration, the single dose is 10–50 mg (1–5 mL); the maximum single dose is 50 mg (5 mL), the maximum daily dose is 150 mg (15 mL). For intravenous administration, the drug should be infused slowly in a dose of 20–50 mg (2–5 mL) of dimedrol in 100 mL of 0.9% sodium chloride solution. The duration of treatment depends on the therapeutic effect achieved and the patient's tolerance to the drug.

Children.

The drug must not be used in pediatric practice.

Overdose.

Symptoms: dry mouth, respiratory depression, persistent mydriasis, facial flushing, central nervous system (CNS) depression or excitation, depression, confusion, hyperkinesia, seizures, delirium, tachycardia, arrhythmia, fever, tremor, dystonic reactions, and ECG changes. Overdose with high doses of dimedrol may lead to rhabdomyolysis, delirium, toxic psychosis, coma, and cardiovascular collapse.

Treatment: symptomatic and supportive therapy with careful monitoring of respiratory function and arterial pressure. Epinephrine and analeptics must not be used. Intravenous drip infusion of plasma substitutes and oxygen therapy. Physostigmine (0.02–0.06 mg/kg body weight administered intravenously) may be used as an antidote in cases of diphenhydramine hydrochloride overdose, repeated several times if anticholinergic symptoms worsen. In cases of physostigmine overdose, atropine administration is recommended. In the event of seizures or symptoms of CNS excitation, diazepam should be administered parenterally.

Adverse Reactions

All adverse reactions are listed by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), frequency not known (cannot be estimated from the available data).

Eye disorders: very rare – increased intraocular pressure; frequency not known – dry eyes, visual disturbances, diplopia, pupil dilation.

Ear and labyrinth disorders: frequency not known – acute labyrinthitis, tinnitus, disturbances in movement coordination.

Respiratory, thoracic and mediastinal disorders: frequency not known – dryness of nasal and pharyngeal mucosa, nasal congestion, bronchial secretion thickening, chest tightness, dyspnea, shortness of breath.

Gastrointestinal disorders: common – dry mouth; frequency not known – transient numbness of oral mucosa, anorexia, nausea, epigastric pain, vomiting, diarrhea, constipation.

Renal and urinary disorders: frequency not known – frequent and/or difficult urination, urinary retention.

Nervous system disorders: common – general weakness, fatigue, sedation, decreased attention, reduced psychomotor reaction speed, dizziness, somnolence; very rare – seizures; frequency not known – headache, movement coordination disturbances, restlessness, increased excitability, fear of fatal outcome, irritability, nervousness, insomnia, euphoria, confusion, tremor, neuritis, paresthesia, dyskinesia. In patients with localized brain lesions or epilepsy, seizure discharges on EEG may be activated (even with low doses of dimenhydrinate), and the medicinal product may provoke an epileptic seizure. Elderly patients are more prone to confusion and paradoxical excitation (e.g., increased energy, restlessness, nervousness).

Cardiac disorders: frequency not known – arterial hypotension, palpitations, tachycardia, arrhythmia, extrasystoles, cyanosis of skin and mucous membranes.

Blood and lymphatic system disorders: rare – thrombocytopenia; frequency not known – agranulocytosis, hemolytic anemia, hemolytic jaundice.

Immune system disorders: frequency not known – hypersensitivity reactions, including anaphylactic shock and angioneurotic edema.

Skin and subcutaneous tissue disorders: very rare – contact dermatitis; frequency not known – hyperemia, pruritus, polymorphic rashes, urticaria.

Musculoskeletal and connective tissue disorders: frequency not known – muscle twitching.

Reproductive system and breast disorders: frequency not known – increased frequency of menstruation, early menstruation.

General disorders and administration site conditions: frequency not known – increased sweating, chills, fever, hyperthermic syndrome, photosensitization, local necrosis following subcutaneous or intradermal injection.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after medicine authorization is an important procedure. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national reporting system.

Shelf life. 4 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze.

Keep out of reach of children.

Incompatibilities.

Do not mix with other medicinal products in the same container. Use only the recommended solvent.

Packaging.

1 ml in a vial; 5 vials in a blister pack; 2 blister packs in a carton.

Prescription status. Prescription only.

Manufacturer. JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's address and location of business activity.

13, Boryspylska Street, Kyiv, 02093, Ukraine.