Lekadol hot max
UkraineTable of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LEKADOL HOT MAX (LEKADOL HOT MAX)
Composition:
Active substances: paracetamol, phenylephrine hydrochloride;
1 sachet contains 1000 mg of paracetamol and 12.2 mg of phenylephrine hydrochloride, equivalent to 10.0 mg of phenylephrine;
Excipients: sucrose, ascorbic acid, anhydrous citric acid, sodium citrate, aspartame (E 951), sodium saccharin, colloidal anhydrous silicon dioxide, lemon flavoring "MN", code 143 (natural lemon oil, code 5243; natural lemon oil, code 5051; maltodextrin; mannitol (E 421); gluconolactone; acacia (gum arabic), sorbitol (E 420), colloidal anhydrous silicon dioxide); lemon flavoring "OS", code 134 (natural powdered lemon flavor, code 5090P; natural/ nature-identical liquid lime flavor, code 5151; natural lemon oil, code 5050; maltodextrin; mannitol (E 421); gluconolactone; acacia (gum arabic), sorbitol (E 420), alpha-tocopherol (E 307)).
Pharmaceutical form. Oral powder for solution.
Main physicochemical properties: free-flowing white powder, free of lumps and foreign particles.
Pharmacotherapeutic group. Analgesics, other analgesics and antipyretics.
ATC code N02B E51.
Pharmacological Properties.
Pharmacodynamics.
Paracetamol
In vivo, paracetamol exhibits both analgesic and antipyretic activity, primarily mediated through inhibition of cyclooxygenase (COX) in the central nervous system. Although this mechanism is identical to that of nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol does not demonstrate significant anti-inflammatory effects, nor does it suppress the formation of thromboxanes involved in blood coagulation. Additional pathways, such as serotonergic pain-modulating pathways, may also contribute to the antinociceptive effect of paracetamol.
Phenylephrine
Phenylephrine is a potent alpha1-adrenergic receptor agonist. Its action on peripheral alpha1-receptors causes vasoconstriction, reducing nasal mucosal swelling. When administered intravenously (i.v.), phenylephrine increases total peripheral vascular resistance, systolic and diastolic blood pressure, while heart rate decreases due to reflex bradycardia. Hemodynamic changes induced by i.v. phenylephrine may vary depending on age and baseline blood pressure. In young individuals with normal blood pressure, greater reductions in heart rate and systolic blood pressure are observed compared to young individuals with hypertension or elderly individuals with normal blood pressure, whereas in elderly individuals with hypertension, reflex bradycardia is less pronounced and the increase in systolic blood pressure is most marked.
No cases of sustained cardiovascular effects have been reported following oral administration of the drug at the recommended dose of 10–12.2 mg four times daily. Oral doses of 40–60 mg are required to produce clinically significant cardiovascular effects, such as increased diastolic blood pressure and reflex slowing of heart rate.
A hypertensive interaction exists between sympathomimetic amines, such as phenylephrine, and monoamine oxidase inhibitors (MAOIs). Phenylephrine may reduce the effectiveness of beta-blocking agents and antihypertensive drugs.
Pharmacokinetics.
Paracetamol
Absorption/Distribution
The absolute bioavailability of paracetamol following oral administration is 75–90%, and it is likely subject to first-pass metabolism. Depending on the dosage form, Tmax is usually reached within 15–20 minutes. However, the extent of absorption is independent of the dosage form.
Elimination
The elimination half-life is approximately 2–2.5 hours.
Metabolism
The main metabolites are glucuronide and sulfate conjugates (>80%), which are excreted in urine. Small amounts (<10%) of paracetamol are oxidized in the liver by cytochrome P4502E1 (CYP2E1). This reaction produces a highly reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which is responsible for the characteristic centrilobular hepatotoxicity observed after paracetamol overdose.
Phenylephrine
Absorption/Distribution
During intravenous infusion, peak concentrations of free 3H-phenylephrine are reached at the end of the infusion, after which plasma concentration declines biphasically, decreasing by 80% within the first 15 minutes, followed by a slower decline with a mean elimination half-life of 2 hours. Following oral administration, phenylephrine is absorbed in the gastrointestinal tract, with peak plasma concentrations achieved within 45–75 minutes.
Elimination
After a brief initial phase of rapid elimination, the mean elimination half-life is 2.5 hours. At steady state, the volume of distribution is 340 L, indicating distribution into certain tissue compartments. Renal clearance constitutes only a fraction of total plasma clearance.
Metabolism
Due to extensive first-pass metabolism, the overall bioavailability of phenylephrine is approximately 38%, of which only 1% is the active, unconjugated parent compound.
Phenylephrine retains its activity as a decongestant following oral administration, reaching the vascular bed of the nasal mucosa via systemic circulation. When used orally as a nasal decongestant, phenylephrine is typically administered at 4–6 hour intervals.
Clinical characteristics.
Indications.
Symptomatic treatment of cold and influenza: pain, sore throat, headache, nasal congestion, and elevated body temperature.
Contraindications.
- Hypersensitivity to the active substances or to any other component of the medicinal product.
- Severe cardiovascular disorders.
- Arterial hypertension.
- Glaucoma.
- Hyperthyroidism.
- Use in patients receiving treatment with tricyclic antidepressants.
- Use in patients currently receiving treatment with MAO inhibitors, or within 2 weeks after discontinuation of such treatment.
- Severe hepatic impairment.
- Acute hepatitis.
- Alcoholism.
- Concomitant use of other sympathomimetic antihistamines.
- Prostatic hypertrophy.
Interaction with other medicinal products and other forms of interaction.
Paracetamol
Medicinal products that induce hepatic microsomal enzymes, such as alcohol, barbiturates, anticonvulsants (e.g., phenytoin, phenobarbital, methylphenobarbital, primidone), rifampicin, MAO inhibitors, and tricyclic antidepressants, may increase the hepatotoxicity of paracetamol, especially following overdose.
The rate of paracetamol absorption may be reduced when used concomitantly with anticholinergic agents (e.g., glycopyrronium, propantheline), and increased when used concomitantly with metoclopramide or domperidone. Absorption may also be reduced when used concomitantly with cholestyramine. Isoniazid reduces the clearance of paracetamol, potentially enhancing its effect and/or toxicity by inhibiting its hepatic metabolism. With regular, long-term use of paracetamol, the anticoagulant effect of warfarin or other coumarin derivatives may be enhanced, increasing the risk of bleeding; this effect is not pronounced with occasional use of paracetamol.
Probenecid reduces paracetamol clearance by inhibiting glucuronide conjugation.
Regular use of paracetam0ol may reduce the metabolism of zidovudine (increasing the risk of neutropenia).
Paracetamol may prolong the half-life of chloramphenicol.
Phenylephrine
Phenylephrine may interact with other sympathomimetics, vasodilators, alpha- and beta-blockers, and other antihypertensive agents (including guanethidine).
The vasoconstrictive effect of phenylephrine may be enhanced when used concomitantly with digoxin, MAO inhibitors, tricyclic antidepressants (e.g., amitriptyline, amoxapine, clomipramine, desipramine, doxepin), tetracyclic antidepressants (e.g., maprotiline), antidepressants (e.g., phenelzine, isocarboxazid, nialamide, tranylcypromine, moclobemide), Parkinson’s disease medications (e.g., selegiline), and other agents such as furazolidone.
MAO inhibitors (including moclobemide): a hypertensive interaction may occur between sympathomimetic amines such as phenylephrine and MAO inhibitors.
Sympathomimetic amines: concomitant use of phenylephrine with other sympathomimetic amines may increase the risk of cardiovascular adverse effects.
Beta-blockers and other antihypertensive agents (including debrisoquin, guanethidine, reserpine, methyldopa): phenylephrine may reduce the effectiveness of beta-blockers and antihypertensive agents. The risk of hypertension and other cardiovascular adverse effects may be increased.
Tricyclic antidepressants (e.g., amitriptyline): may increase the risk of cardiovascular adverse effects when used with phenylephrine.
Digoxin and cardiac glycosides: concomitant use of phenylephrine may increase the risk of arrhythmias or myocardial infarction.
The medicinal product is contraindicated in patients currently receiving MAO inhibitors or who have received them within 2 weeks after discontinuation of MAO inhibitor therapy.
Special precautions for use.
This medicinal product should be used with caution in patients with:
- Raynaud's disease;
- diabetes;
- moderate or severe renal impairment;
- hepatic function disorders: mild or moderate hepatocellular insufficiency (including Gilbert's syndrome), severe hepatic insufficiency (Child-Pugh score < 9), severe hepatitis, and concomitant use of medicinal products that impair liver function;
- hemolytic anemia;
- dehydration;
- alcohol dependence;
- chronic malnutrition;
- glutathione depletion due to nutritional deficiencies;
- prostate hyperplasia;
- pheochromocytoma;
- closed-angle glaucoma.
This medicinal product must not be used concurrently with medicinal products containing paracetamol. Use in doses higher than recommended may lead to severe liver damage. In case of overdose, immediate medical advice must be sought, even if the patient feels well, due to the risk of delayed severe liver injury. Clinical signs of liver dysfunction usually appear within 2 days after ingestion. An antidote should be administered as soon as possible. See also section "Overdose".
Alcoholic beverages should be avoided during treatment, as ethanol taken concomitantly with paracetamol may cause liver damage.
Patients should not use other sympathomimetic agents simultaneously, including other nasal or ophthalmic antihistamines.
One sachet contains 3.9 g of sucrose. This should be taken into account by patients with diabetes mellitus.
The medicinal product contains sucrose and sorbitol (E 420). Patients with rare hereditary conditions such as fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency should not take this product.
The medicinal product contains aspartame (E 951), a phenylalanine derivative, which may be harmful to patients with phenylketonuria.
Caution is advised in patients with asthma sensitive to acetylsalicylic acid, as mild bronchospasm has been reported during paracetamol use (cross-reactivity).
Use during pregnancy or breastfeeding.
Pregnancy
Paracetamol
Epidemiological studies on pregnancy have not shown adverse effects from paracetamol used at the recommended dose.
Phenylephrine
There are only limited data on the use of phenylephrine during pregnancy. Vasoconstriction of the uterine vessels and reduced uterine blood flow associated with phenylephrine use may lead to fetal hypoxia.
The safety of this medicinal product during pregnancy and lactation has not been established. However, due to the possible association of fetal developmental disorders with phenylephrine exposure in the first trimester, use of the product during pregnancy should be avoided.
Furthermore, since phenylephrine may reduce placental perfusion, the product should not be used in patients with a history of pre-eclampsia.
Breastfeeding period
Paracetamol
Paracetamol is excreted in breast milk, but in amounts that are not clinically significant. Available published data do not justify recommending discontinuation of breastfeeding during paracetamol therapy.
Phenylephrine
There is insufficient information regarding the excretion of phenylephrine in breast milk and the amount of the drug that may pass into the infant's body. Until additional information becomes available, use of phenylephrine should be avoided during breastfeeding.
Therefore, this product is not recommended for use during pregnancy and breastfeeding.
Reproductive function
Results from preclinical studies of paracetamol do not indicate any risk to male or female reproductive function at clinically relevant doses. The effect of phenylephrine on male or female reproductive function has not been studied.
Ability to affect reaction speed when driving vehicles or operating machinery.
The product has no effect or negligible effect on the ability to drive a vehicle or operate machinery.
Method of Administration and Dosage
Method of Administration
Orally, after dissolving in water.
Dissolve the contents of 1 sachet in a standard cup (250 ml) of hot, but not boiling, water. Take while warm. Due to the presence of ascorbic acid in the formulation, consumption of alkaline mineral water after administration is not recommended.
Adults
1 sachet per dose. If necessary, administration may be repeated every 4–6 hours.
Children aged 16 years and older
1 sachet per dose. If necessary, administration may be repeated every 6 hours.
Elderly patients
No special dose adjustment is required.
Hepatic impairment
Patients with impaired liver function or Gilbert’s syndrome should reduce the dose or increase the interval between doses.
Renal impairment
In cases of severe renal impairment (creatinine clearance less than 10 ml/min), the dosing interval should be at least 8 hours.
The maximum daily dose is 4 sachets.
The treatment course should not exceed 3–5 days.
If symptoms do not begin to improve within 3 days of treatment, or if the patient’s condition worsens, medical advice must be sought.
Children
For use in children aged 16 years and older. Not recommended for children under 16 years of age, except when prescribed by a physician.
Overdose
Paracetamol
There is a risk of poisoning, particularly in elderly patients, young children, patients with liver disease, chronic alcoholism, or chronic malnutrition. In these cases, overdose may be fatal.
Overdose of paracetamol following a single ingestion in adults or children causes hepatocellular necrosis, which may lead to complete and irreversible liver damage, resulting in hepatic failure, metabolic acidosis, and encephalopathy, potentially progressing to coma and death. Concurrently, elevated levels of liver transaminases (AST, ALT), lactate dehydrogenase, and bilirubin occur alongside decreased prothrombin levels, which may appear 12–48 hours after ingestion.
Liver damage may occur in adults who have ingested a paracetamol dose exceeding the recommended amount (a single dose of 10 g or more of paracetamol). A single dose of 5 g or more of paracetamol may lead to liver injury if the patient has risk factors (see below).
Liver damage may occur in adults who have ingested a paracetamol dose exceeding the recommended amount. It is believed that an excess of a toxic metabolite (normally detoxified by glutathione when paracetamol is taken at usual doses) irreversibly binds to liver tissue.
Some patients may have an increased risk of liver injury due to the toxic effects of paracetamol.
Risk factors include:
- prolonged use of carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John’s wort, or other drugs that induce liver enzymes, or
- regular consumption of excessive amounts of alcohol, or
- glutathione system deficiency, e.g., malnutrition, cystic fibrosis, HIV infection, fasting, cachexia.
Symptoms
Symptoms of paracetamol overdose appearing within the first 24 hours include nausea, vomiting, anorexia, pallor, and abdominal pain. Liver damage may manifest 12–48 hours after ingestion. Disturbances in glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, hemorrhage, hypoglycemia, cerebral edema, and death. Acute renal failure with acute tubular necrosis may present with severe lumbar pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have also been reported.
Prolonged use of high-dose paracetamol may lead to hypokalemia.
Treatment
Immediate treatment is crucial in cases of paracetamol overdose. Despite the absence of significant early symptoms, patients should be urgently referred to hospital for immediate medical care. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Treatment should follow established guidelines.
Activated charcoal should be administered if overdose occurred within 1 hour. Plasma paracetamol concentration should be measured 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine is possible within 24 hours after paracetamol ingestion; however, maximum protective effect is achieved within 8 hours after ingestion. The efficacy of the antidote decreases sharply after this time. If necessary, N-acetylcysteine should be administered intravenously according to the established dosing regimen. In cases where the patient is located far from a hospital, oral methionine may be used as an alternative to N-acetylcysteine, provided vomiting is not a problem for the patient.
Phenylephrine
Features of severe phenylephrine overdose include hemodynamic changes and cardiovascular collapse with respiratory depression, seizures, and arrhythmias. However, a smaller amount of the combined product containing paracetamol and phenylephrine hydrochloride is required to cause liver toxicity associated with paracetamol than to cause serious toxicity related to phenylephrine. Treatment includes symptomatic and supportive measures. Hypertensive effects can be managed with intravenous alpha-blocking agents.
Symptoms
Phenylephrine overdose may cause: nervousness, headache, dizziness, insomnia, elevated blood pressure, nausea, vomiting, reflex bradycardia, mydriasis, acute angle-closure glaucoma (most likely to occur in individuals with closed-angle glaucoma), tachycardia, palpitations, allergic reactions (e.g., rash, urticaria, allergic dermatitis), dysuria, and urinary retention (most likely in patients with urinary outflow obstruction, e.g., benign prostatic hyperplasia).
Additional symptoms may include arterial hypertension and, possibly, reflex bradycardia. In severe cases, confusion, seizures, and arrhythmias may occur. However, the amount required to cause serious phenylephrine toxicity is greater than that needed to cause paracetamol-related liver toxicity.
Treatment
Treatment should be clinically appropriate. Severe arterial hypertension may require treatment with alpha-blocking agents such as phentolamine.
Side effects
The following frequency categories were used to assess side effects: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), frequency not known (cannot be estimated from available data).
Paracetamol
Blood and lymphatic system disorders
Rare: blood disorders, including thrombocytopenia, agranulocytosis, leukopenia, thrombocytopenia, hemolytic anemia, pancytopenia.
Frequency not known: neutropenia.
Immune system disorders
Rare: allergic or hypersensitivity reactions, including skin rash, urticaria, anaphylaxis, and bronchospasm.
Gastrointestinal disorders
Very rare: acute pancreatitis.
Hepatobiliary disorders
Rare: liver function abnormalities (elevated liver transaminase levels), liver failure, hepatic necrosis, jaundice.
Skin and subcutaneous tissue disorders
Rare: hypersensitivity reactions, including skin rash and urticaria, pruritus, increased sweating, purpura, angioneurotic edema.
Renal and urinary disorders
Very rare: interstitial nephritis after prolonged use of high doses of paracetamol; sterile pyuria (cloudy urine).
Frequency not known: urinary retention (especially in men).
Cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, anemia, liver function disorders and hepatitis, kidney function disorders (severe renal impairment, hematuria, enuresis), gastrointestinal disorders, and vertigo have been reported with a frequency categorized as "frequency not known".
Very rare cases of serious skin reactions have been reported.
Children
The frequency, type, and severity of adverse reactions in children aged 16 years and older are expected to be no different from those in adults.
Phenylephrine
Immune system disorders
Rare: allergic or hypersensitivity reactions, including skin rash, urticaria, anaphylaxis, and bronchospasm.
Nervous system disorders
Rare: insomnia, nervousness, tremor, anxiety, restlessness, confusion, irritability, dizziness, and headache may occur.
Cardiac disorders
Rare: tachycardia, palpitations.
Vascular disorders
Rare: arterial hypertension.
Gastrointestinal disorders
Common: anorexia, nausea, vomiting.
Frequency not known: abdominal discomfort.
Children
The frequency, type, and severity of adverse reactions in children aged 16 years and older are expected to be no different from those in adults.
Shelf life. 2 years. Diluted solution in hot water: 1 hour.
Storage conditions. No special temperature storage conditions required. Store in the original packaging. Keep out of reach of children.
Packaging. 10 sachets per cardboard box.
Pharmaceutical classification. Over-the-counter (OTC).
Manufacturer.
- Saliutas Pharma GmbH
- HERMES Pharma Ges.m.b.H.
Manufacturer's address and place of business.
- Otto-von-Guericke-Allee 1, 39179 Barleben, Germany
- Schimmingstraße 1a, 9400 Wolfsberg, Austria