Lekadol hot
UkraineTable of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LEKADOL HOT (LEKADOL HOT)
Composition:
Active substances: paracetamol, phenylephrine hydrochloride;
1 sachet contains 500 mg of paracetamol and 12.2 mg of phenylephrine hydrochloride, equivalent to 10.0 mg of phenylephrine;
Excipients: sucrose, ascorbic acid, citric acid anhydrous, 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/identical to natural 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. Powder for oral solution.
Main physicochemical properties: free-flowing white powder, free of large 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, which is primarily achieved through inhibition of cyclooxygenase (COX) in the central nervous system. Although this mechanism is similar to that of nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol does not demonstrate significant anti-inflammatory effects and does not suppress the formation of thromboxanes involved in blood coagulation. Additional pathways may also contribute to the antinociceptive effect of paracetamol, such as serotonergic pathways that reduce pain.
Phenylephrine
Phenylephrine is a potent alpha1-adrenergic receptor agonist. Its action on peripheral alpha1-receptors causes vasoconstriction, reducing swelling and congestion of the nasal mucosa. When administered intravenously, phenylephrine increases total peripheral vascular resistance, systolic arterial pressure (SAP), and diastolic arterial pressure (DAP), while heart rate decreases due to reflex bradycardia. Hemodynamic changes caused by intravenous phenylephrine may vary depending on age and baseline arterial pressure. In young individuals with normal blood pressure, a greater reduction in heart rate and a decrease in SAP are observed compared to young individuals with arterial hypertension and elderly individuals with normal blood pressure, whereas in elderly individuals with arterial hypertension, reflex bradycardia is less pronounced and the increase in SAP is most marked.
No cases of sustained cardiovascular effects have been reported following oral administration 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 DAP 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-blockers and antihypertensive drugs.
Pharmacokinetics.
Paracetamol
Absorption/Distribution
The absolute bioavailability of paracetamol following oral administration is 75–90% and is likely subject to first-pass metabolism. Depending on the dosage form, the time to reach maximum concentration (Tmax) is usually 15–20 minutes. However, the extent of absorption does not depend on the dosage form.
Elimination
The elimination half-life is approximately 2–2.5 hours.
Metabolism
The primary metabolites are glucuronide and sulfate conjugates (>80%), which are excreted in urine. A small amount (<10%) of paracetamol is oxidized in the liver by cytochrome P4502E1 (CYP2E1). This reaction produces a highly reactive metabolite, N-acetyl-β-benzoquinone imine (NAPQI), which is responsible for the characteristic centrilobular hepatotoxicity observed after paracetamol overdose.
Phenylephrine
Absorption/Distribution
During intravenous infusion, the maximum concentration (Cmax) of free 3H-phenylephrine is reached at the end of the infusion, after which plasma concentration decreases biphasically, with an 80% reduction within the first 15 minutes, followed by a slower decline with a mean elimination half-life of 2 hours. After oral administration, phenylephrine is absorbed in the gastrointestinal tract, and peak plasma concentration (Cmax) is achieved within 45–75 minutes.
Elimination
Following a short 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 nasal 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.
- Closed-angle glaucoma.
- Hyperthyroidism.
- Use in patients receiving treatment with tricyclic antidepressants.
- Use in patients taking monoamine oxidase inhibitors (MAOIs), or within 2 weeks after discontinuation of such therapy.
- 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 administered concomitantly with anticholinergic agents (e.g., glycopyrronium, propantheline), and increased when administered with metoclopramide or domperidone. Absorption may also be reduced when administered concomitantly with cholestyramine. Isoniazid reduces paracetamol clearance, potentially enhancing its effect and/or toxicity due to inhibition of its hepatic metabolism. Regular long-term use of paracetamol may potentiate the anticoagulant effect of warfarin or other coumarin derivatives, and increase the risk of bleeding; this effect is not pronounced with occasional paracetamol use.
Probenecid reduces paracetamol clearance by inhibiting glucuronide conjugation.
Regular use of paracetamol may reduce zidovudine metabolism (increasing the risk of neutropenia).
Paracetamol may prolong the elimination 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 such as phenelzine, isocarboxazid, nialamide, tranylcypromine, moclobemide, antiparkinsonian agents such as selegiline, and other drugs such as furazolidone.
MAO inhibitors (including moclobemide): hypertensive interactions 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 debrezoquine, 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 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 within 2 weeks after discontinuation of MAOI therapy.
Special precautions for use
The medicinal product should be used with caution in patients with:
- Raynaud's disease;
- diabetes;
- moderate or severe renal impairment;
- hepatic dysfunction: mild or moderate hepatocellular insufficiency (including Gilbert’s syndrome) and when used concomitantly with medicinal products that impair liver function;
- haemolytic anaemia;
- dehydration;
- chronic malnutrition;
- glutathione depletion due to poor nutrition;
- phaeochromocytoma.
This medicinal product must not be used concurrently with medicinal products containing paracetamol. Use in higher than recommended doses may lead to severe liver damage. In case of overdose, immediate medical advice should be sought, even if the patient feels well, due to the risk of delayed serious liver injury. Clinical signs of liver dysfunction usually appear within 2 days after taking the medicinal product. An antidote should be administered as soon as possible. See also section "Overdose".
Alcoholic beverages should be avoided during treatment, since ethanol taken concomitantly with paracetamol may cause liver damage.
Patients should not use other sympathomimetic agents simultaneously, including other nasal or ocular antihistamine preparations.
Each sachet contains 1.8 g of sucrose. This should be taken into account in diabetic patients.
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.
Contains aspartame (E 951), a phenylalanine derivative. May be harmful for patients with phenylketonuria.
Caution should be exercised in asthmatic patients sensitive to acetylsalicylic acid, as mild-intensity bronchospasm (cross-reaction) has been reported during paracetamol use.
Use during pregnancy or breastfeeding
Pregnancy
Paracetamol
Epidemiological studies in pregnancy have not shown adverse effects associated with paracetamol used at recommended doses.
Phenylephrine
There are only limited data available on the use of phenylephrine during pregnancy. Vasoconstriction of the uterine vessels and impaired 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 potential association between fetal developmental abnormalities and phenylephrine exposure in the first trimester, use of the product should be avoided during pregnancy.
Furthermore, since phenylephrine may reduce placental perfusion, the product should not be used in patients with a history of pre-eclampsia.
Period of breastfeeding
Paracetamol
Paracetamol is excreted in breast milk, but in quantities 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 be transferred to the infant. Until further information becomes available, phenylephrine should be avoided during breastfeeding.
Therefore, this product is not recommended during pregnancy and breastfeeding.
Reproductive function
Preclinical data for paracetamol do not indicate a 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 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 (125 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, the medication 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 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 can be fatal.
Overdose of paracetamol following a single ingestion in adults or children may cause hepatocellular necrosis, which can 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, along with decreased prothrombin levels, may appear within 12–48 hours after ingestion.
Liver damage is possible 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 at therapeutic 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:
- chronic 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 deficiency, e.g., due to malnutrition, cystic fibrosis, HIV infection, fasting, or cachexia.
Symptoms
Symptoms of paracetamol overdose appearing within the first 24 hours: nausea, vomiting, anorexia, pallor, and abdominal pain. Liver damage may manifest 12–48 hours after ingestion. Glucose metabolism disturbances and metabolic acidosis may occur. In severe poisoning, liver 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 injury. Cardiac arrhythmias and pancreatitis have also been reported.
Prolonged use of paracetamol in high doses may lead to hypokalemia.
Treatment
Prompt treatment is crucial in managing paracetamol overdose. Despite the absence of significant early symptoms, patients should be urgently referred to a hospital for immediate medical care. Symptoms such as nausea or vomiting may be mild and do not necessarily reflect the severity of overdose or 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 at least 4 hours after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be initiated within 24 hours of paracetamol ingestion, but maximum protective effect is achieved within 8 hours. The efficacy of the antidote declines sharply after this period. If required, intravenous N-acetylcysteine should be administered according to the established dosing regimen. If vomiting is not an issue, oral methionine may be a suitable alternative, particularly in remote settings outside hospital care.
Phenylephrine
Severe phenylephrine overdose may result in hemodynamic changes and cardiovascular collapse, accompanied by respiratory depression, seizures, and arrhythmias. However, a smaller amount of a combined paracetamol and phenylephrine hydrochloride product is required to cause hepatotoxicity related to 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 in individuals with pre-existing narrow-angle glaucoma), tachycardia, palpitations, allergic reactions (e.g., rash, urticaria, allergic dermatitis), dysuria, and urinary retention (most likely in patients with bladder outflow obstruction, such as those with 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 produce 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.
Adverse Reactions
The following frequency categories were used to classify adverse reactions: 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
Uncommon: blood disorders, including thrombocyte disorders, agranulocytosis, leukopenia, thrombocytopenia, hemolytic anemia, pancytopenia.
Frequency not known: neutropenia.
Immune system disorders
Uncommon: allergic reactions or hypersensitivity reactions, including skin rashes, urticaria, anaphylaxis, and bronchospasm.
Gastrointestinal disorders
Rare: acute pancreatitis.
Hepatobiliary disorders
Uncommon: liver function abnormalities (elevated liver transaminase levels), liver failure, hepatic necrosis, jaundice.
Skin and subcutaneous tissue disorders
Uncommon: hypersensitivity, including skin rashes and urticaria, pruritus, increased sweating, purpura, angioneurotic edema.
Renal and urinary disorders
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, and other serious skin reactions have been reported very rarely.
Cases of multi-form erythema, laryngeal edema, anaphylactic shock, anemia, liver function abnormalities and hepatitis, kidney function abnormalities (severe kidney dysfunction, hematuria, anuria), gastrointestinal disorders, and vertigo have been reported with a frequency categorized as "frequency not known."
Serious skin reactions have been reported very rarely.
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
Uncommon: allergic reactions or hypersensitivity reactions, including skin rashes, urticaria, anaphylaxis, and bronchospasm.
Nervous system disorders
Uncommon: insomnia, nervousness, tremor, anxiety, restlessness, confusion, irritability, dizziness, and headache may occur.
Cardiac disorders
Uncommon: tachycardia, palpitations.
Vascular disorders
Uncommon: 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.
Storage conditions. No special temperature storage conditions required. Store in the original packaging. Keep out of reach of children.
Packaging. 10 or 20 sachets per cardboard box.
Prescription status. Over-the-counter (without prescription).
Manufacturer.
- Solutas Pharma GmbH
- HERMES Arzneimittel GmbH
Manufacturer's address and location of operations.
- Otto-von-Guericke-Allee 1, 39179 Barleben, Germany
- Schwingstraße 1a, 9400 Wolfsberg, Austria