Dormikern 25Mg 14 Film-coated Tablets

Dormikern (25 Mg 14 Coated Tablets)

Doxylamine, hydrogen succinate

ACTION AND MECHANISM

- [ANTIALLERGIC], [HISTAMINERGIC ANTAGONIST (H-1)]. Doxylamine is a derivative of ethanolamine, which competitively, reversibly and nonspecifically blocks H1 receptors, reducing the systemic effects of histamine. It leads to vasoconstriction and decreased vascular permeability, reducing redness and edema associated with allergy. Partially mitigates symptoms associated with allergic processes such as eye redness or nasal congestion. It also produces a slight bronchodilator effect and a decrease in dermal itching.

- [HYPNOTIC]. Doxylamine is able to cross the blood-brain barrier, and act on central H1 receptors, leading to sedation. It seems that the sedative effect may also be due to antagonism of muscarinic and serotonergic receptors. Doxylamine has sedative effects superior to those of other ethanolamines.

- [MUSCARINIC CHOLINERGIC ANTAGONIST (M)], [ANTIEMETIC]. Doxylamine is a nonspecific antagonist capable of also blocking other receptors such as central or peripheral muscarinic receptors. Its anticholinergic effects appear to be less potent than those of other ethanolamines. The blockade of the central H1 and cholinergic receptors could exert an antiemetic effect, although it has not been fully clarified.

PHARMACOKINETICS

- Absorption: Doxylamine is well absorbed from the intestine, but undergoes an intense hepatic first-pass effect that reduces bioavailability. After administration of a 25 mg dose, the Cmax of 100 ng / ml is reached within 2-3 hours. The sedative effects begin after 30 minutes and are maximum after 1-3 hours. Their duration is 6-8 hours.

- Metabolism: Although not adequately studied, doxylamine appears to be rapidly and almost completely metabolized in the liver.

- Elimination: Doxylamine and its metabolites are eliminated with urine. Its elimination half-life is 10 hours.

INDICATIONS

- Symptomatic treatment of [INSOMNIA], particularly when there is difficulty falling asleep, there are frequent interruptions during it or an early morning awakening.

POSOLOGY

- Adults: 25 mg / 24 h. If daytime drowsiness occurs, it is recommended to reduce the dose to 12.5 mg or advance the intake to ensure that at least 8 hours elapse before waking up.

Maximum dose: 25 mg / 24 h.

- Children and adolescents <18 years: The safety and efficacy have not been evaluated so it should not be used.

- Elderly: they are more prone to suffer from other pathologies that may recommend a dose reduction. In the event of unwanted adverse effects, the dose will be 12.5 mg / 24 h.

Duration of treatment : it should be as short as possible. In general, it can range from a few days to a week. It should not be administered for a period exceeding 7 days without consulting a doctor.

DOSAGE IN KIDNEY INSUFFICIENCY

Accumulation of doxylamine and its metabolites is possible.

- Moderate renal failure (CLcr 30-60 ml / min) or severe (CLcr <30 ml / min): reduce the dose to 12.5 mg / 24 h or control the time interval between taking the medicine and the time of awakening . In the case of interval control, doxylamine intake should be advanced to avoid morning drowsiness, taking into account the degree of functional disability of the patient and the pharmacokinetic properties of the drug.

DOSAGE IN LIVER INSUFFICIENCY

Since it is metabolized mainly in the liver, the dose should be reduced to the degree of functional disability of the liver. It is advisable to reduce the dose to 12.5 mg / 24 h.

RULES FOR CORRECT ADMINISTRATION

It will be administered half an hour before bedtime, to exert its effects, with a sufficient amount of liquid (preferably water). It should not be taken with alcoholic beverages.

Administration with food : can be taken with or without food.

CONTRAINDICATIONS

- Hypersensitivity to any component of the drug. There may be cross reactions with other antihistamines, so it is not recommended to use any H1 antihistamine in patients who have presented hypersensitivity to any compound in the group.

- [ASTHMA CRISIS]. For some authors, doxylamine could worsen asthma, so its use in an acute attack is not recommended.

- [PORFIRIA]. H1 antihistamines have been associated with the appearance of porphyric outbreaks and are therefore not considered safe in these patients.

PRECAUTIONS

- [RENAL INSUFFICIENCY]. In patients with renal insufficiency, an accumulation of metabolites may occur. Since these metabolites could be active, it is recommended to prolong the administration periods in patients with moderate or severe renal insufficiency (CLcr less than 60 ml / minute).

- [LIVER FAILURE]. Doxylamine is extensively metabolized by hepatic metabolism. In the event of liver failure, 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], [GRAVE MYASTENIA], stenosing [PEPTIC ULCER] or [INTESTINAL OBSTRUCTION]. Due to the anticholinergic effects of doxylamine, these conditions could worsen, so it is recommended to exercise extreme caution and suspend treatment in case of worsening.

- Caution is also advised in [HYPOPOTASEMIA] or other electrolyte abnormalities.

- Patients with [QT INTERVAL PROLONGATION] ([HEART ARRITHMIA]) should be treated with caution, since, although this effect has not been observed with doxylamine, other antihistamines may cause a prolongation of this interval.

- Diseases of the lower respiratory tree, such as [ASTHMA], [PULMONARY EMPHYSEMA] or [CHRONIC OBSTRUCTIVE PULMONARY DISEASE]. According to some authors, doxylamine could 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 asthmatic 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, and therefore could lower the seizure threshold.

- [APENDICITIS]. Due to its antiemetic effects, it could interfere with the diagnosis of appendicitis. It is recommended to previously rule out the presence of appendicitis in patients with vomiting of unknown origin.

- Ototoxicity. Doxylamine can exert a beneficial effect in case of vertigos, tinnitus and dizziness, therefore it could mask the ototoxicity induced by ototoxic drugs such as parenteral aminoglycosides, carboplatin, cisplatin, chloroquine and erythromycin among others.

- Photosensitivity. Doxylamine could lead to photosensitivity phenomena, so it is recommended not to sunbathe during treatment, and protect yourself with sunscreen.

- Alcohol intake should be avoided during treatment.

- Extreme temperatures. H1 antihistamines may aggravate exhaustion-dehydration syndrome and heat stroke due to decreased sweating caused by their anticholinergic effects. Those patients being treated with these drugs are recommended to avoid exposure to very high temperatures, especially in the case of young children, the elderly or people with serious chronic diseases. It is also advisable to follow adequate hygienic-dietary measures, such as adequate aeration and hydration.

ADVICE TO THE PATIENT

- This medicine will be administered half an hour before bedtime. If daytime drowsiness occurs, it is recommended to reduce the dose or advance the dose to ensure that at least 8 hours elapse before waking up.

- Treatments longer than a week are not recommended. If after this time, the insomnia continues or worsens, it is recommended to consult with the doctor.

- It can cause drowsiness, so it is recommended to exercise caution when driving, and not to combine it with drugs or other sedative substances such as alcohol.

- Patients on sedative drugs are not advised to self-medicate with doxylamine products without consulting a physician.

- It is advisable not to sunbathe during the treatment.

- Any chronic pathology that the patient presents should be notified to the doctor before starting treatment.

- Exposure to extreme temperatures should be avoided during the use of this medicine, keeping in a cool environment, hydrating properly.

SPECIAL WARNINGS

- Doxylamine could mask the ototoxic effects of some drugs, so it is recommended to periodically evaluate acoustic functionality 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 in the event of a heat wave, and especially if the patient is a small child, an elderly person or a person with a serious illness.

- Due to the antiallergic effects of this medicine, it could give false negatives in dermal tests of hypersensitivity to antigenic extracts. It is recommended to suspend the administration of this medicine at least 72 hours before the test.

INTERACTIONS

Doxylamine may mask ototoxic drug-induced symptoms by reducing vertigo or dizziness. Similarly, it could enhance the photosensitizing effects of other active ingredients that give rise to photosensitivity reactions. In addition, drug interactions have been described with the following active ingredients:

- Ethyl alcohol. The joint administration of alcohol and doxylamine could enhance the sedative effects of both substances. It is recommended to avoid alcohol consumption during treatment.

- Anticholinergics (antiparkinsonians, tricyclic antidepressants, MAOIs, neuroleptics). The administration of doxylamine together with other anticholinergic drugs could potentiate the anticholinergic effects, so it is recommended to avoid the association.

- Sedatives (opioid analgesics, barbiturates, benzodiazepines, antipsychotics). Co-administration of doxylamine with a sedative drug could enhance the hypnotic action. It is recommended to extreme precautions.

PREGNANCY

Safety in animals : In studies with rats at doses 125 times higher than human ones, no risk to the fetus has been evidenced. However, when dosing 125-375 times the maximum doses in humans, the appearance of skeletal abnormalities, characterized by undulation of the ribs, and diaphragmatic hernias have been observed.

Human safety: Doxylamine crosses the placenta. There is great controversy about the teratogenic effects of doxylamine. This drug has been used frequently for the prevention of gestational nausea and vomiting. Epidemiological studies have not shown adverse effects on the fetus, although in some the administration of doxylamine during the first trimester of pregnancy was associated with cases of cleft palate. However, it has not been possible to establish a causal relationship with doxylamine and these effects have not been observed in other studies. However, due to the lack of adequate and well-controlled studies in humans, it cannot be ruled out that it is weakly teratogenic. This medicine should therefore be used in pregnant women with caution, and only if the benefits outweigh the possible risks.

LACTATION

Doxylamine could inhibit lactation due to its anticholinergic effects. It is unknown whether doxylamine is excreted in human milk, but other antihistamines do. Because children are more sensitive to anticholinergic reactions, and may more frequently present paradoxical hyperexcitability reactions, it is recommended to stop breastfeeding or avoid the administration of this drug.

KIDS

The efficacy and safety of doxylamine as a sedative in children under 18 years of age have not been evaluated. Since anticholinergic symptoms and hyperexcitability are more common in these patients, its use is not recommended.

SENIORS

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

EFFECTS ON DRIVING

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

ADVERSE REACTIONS

The side effects of doxylamine are usually mild and transient, being more frequent during the first days of treatment. Like other ethanolamines, doxylamine mainly causes drowsiness and anticholinergic phenomena, but there is great interindividual variability with respect to the frequency and intensity of symptoms, affecting mainly young children and the elderly. The most common adverse reactions are:

- Digestive. [NAUSEA], [VOMITING], [CONSTIPATION], [DIARRHEA], [EPIGASTRIC PAIN], [ANOREXIA], [DRY MOUTH].

- Neurological / psychological. [Drowsiness] is common, especially at the beginning of treatment, and usually subsides after 2-3 days. [DISORIENTATION], [ATAXIA], [MYASTENIA], [VERTIGO], [ASTENIA], [HEADACHE] may also appear. Exceptionally, cases of paradoxical [EXCITABILITY] have been observed, especially in young children. This hyperexcitability occurs with [INSOMNIA], [NERVIOSISM], [SHREAM], [IRRITABILITY], [EUPHORIA], [DELUSION], palpitations and even [SEIZURES].

- Cardiovascular. On specific occasions, and usually in the event of an overdose, [TACHYCARDIA], [PALPITATIONS] and others [CARDIAC ARRHYTHMIA] such as [EXTRASISTOLE] or [CARDIAC BLOCK] can occur. These effects could be due to anticholinergic activity. [HYPOTENSION] or [ARTERIAL HYPERTENSION] have occasionally been described.

- Respiratory. Sometimes there can be an increase in the viscosity of bronchial secretions, which can make breathing difficult.

- Genitourinary. [URINARY RETENTION] and [SEXUAL IMPOTENCE] may appear due to cholinergic blockade.

- Hematological. [HEMOLYTIC ANEMIA], [AGRANULOCYTOSIS], [LEUCOPENIA], [THROMBOCYTOSIS] or [PANCYTOPENIA] have rarely been described.

- Eyepieces. Due to anticholinergic activity a [GLAUCOMA] and [VISION DISORDERS] such as [BLURRED VISION] or [DIPLOPIA] could occur. [TINNITUS] may also occur.

- Allergic / dermatological. [HYPERSENSITIVITY REACTIONS] may occur after systemic administration of antihistamines, although less frequently than if applied topically. [PHOTOSENSITIVITY REACTIONS] may also appear after intense exposure to sunlight, with [DERMATITIS], [PRURITO], [EXANTEMATIC ERUPTIONS] and [ERYTHEMA].

OVERDOSE

Symptoms: Symptoms usually appear after 30 minutes to 2 hours, and are usually variable, presenting greater severity in children and over 65 years. Moderate nervous depression, 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 described. A fever higher than 41.8 ºC may also appear.

In the most severe cases, especially in children, symptoms may worsen, with hypotension, seizures, respiratory depression, loss of consciousness, coma, and death. However, doxylamine poisoning is rarely life-threatening, and recovery is complete within 24-48 hours.

Treatment: The treatment will consist of the usual measures designed to favor the elimination of the drug. If less than 3 hours have elapsed 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, a stomach lavage and activated charcoal can be administered. Saline laxatives such as magnesium sulfate can be used.

The symptoms of poisoning can be eliminated with the following drugs.

- Central anticholinergic effects. Intravenous physostigmine.

- Seizures. Slow intravenous infusion of diazepam at a dose of 0.1 mg / kg, in those patients who do not respond to physostigmine.

- Hypotension. Administer norepinephrine, phenylephrine, or dopamine, avoiding the administration of epinephrine, which can worsen hypotension.

- Ventricular arrhythmias. Propranolol.

If necessary, intubation and assisted breathing may be used. The use of analeptics is not recommended as they could induce the appearance of seizures.

Dormikern Leaflet 25Mg 14 Coated Tablets