Vicks antigrip complex

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT Vicks AntiGripComplex (Vicks AntiGripComplex)

Composition:

Active substances: paracetamol, guaifenesin, phenylephrine hydrochloride;

1 sachet contains paracetamol 500 mg, guaifenesin 200 mg, phenylephrine hydrochloride 10 mg;

Excipients: sucrose, anhydrous citric acid, tartaric acid, sodium cyclamate, sodium citrate, aspartame (E 951), acesulfame potassium, lemon flavor 8476 (contains butylated hydroxyanisole (E 320)), lemon juice flavor, menthol flavor, quinoline yellow (E 104).

Pharmaceutical form. Oral soluble powder.

Main physicochemical properties: almost white free-flowing powder, without large lumps or foreign particles. Has a characteristic citrus/menthol odor.

Pharmacotherapeutic group. Analgesics and antipyretics. Anilides. Paracetamol combinations without psychotropic agents. ATC code N02BE51.

Pharmacological properties.

Pharmacodynamics.

Paracetamol exerts analgesic and antipyretic effects, which are believed to occur primarily through inhibition of prostaglandin synthesis in the central nervous system.

Guaifenesin is an expectorant. It acts by increasing the volume and reducing the viscosity of secretions in the trachea and bronchi, thereby facilitating the expulsion of mucus during coughing.

Phenylephrine hydrochloride is a sympathomimetic agent that primarily stimulates α-adrenergic receptors. It acts as a decongestant by causing vasoconstriction, thereby reducing swelling, including swelling of the nasal mucosa and paranasal sinuses.

The active substances do not cause sedative effects.

Pharmacokinetics.

Paracetamol is rapidly and almost completely absorbed in the gastrointestinal tract, crosses the placental barrier, and a small amount passes into breast milk. Approximately 95% of acetaminophen is metabolized in the liver via sulfation, glucuronidation, and oxidation by the cytochrome P450 system. The elimination half-life ranges from 1 to 3 hours. Duration of action is 3–4 hours. It is excreted by the kidneys, mostly as metabolites, with 3% excreted unchanged.

Guaifenesin is rapidly absorbed in the gastrointestinal tract and metabolized to ß-(2-methoxy-phenoxy) lactic acid—an inactive metabolite—which is excreted in urine. The elimination half-life of guaifenesin is short—approximately 1 hour.

Phenylephrine hydrochloride is irregularly absorbed in the gastrointestinal tract and undergoes presystemic metabolism by monoamine oxidase in the intestinal wall and liver. Thus, orally administered phenylephrine has reduced bioavailability.

It is excreted in urine almost entirely as a sulfate conjugate. The plasma elimination half-life is 2–3 hours.

Clinical characteristics.

Indications.

Treatment of cold and flu symptoms (productive cough with difficult expectoration of sputum, headache, body aches and malaise, sore throat, nasal congestion, and elevated body temperature).

Contraindications.

Hypersensitivity to paracetamol, guaifenesin, phenylephrine hydrochloride, or any other component of the medicinal product. Severe cardiovascular disorders, arterial hypertension, diabetes mellitus, closed-angle glaucoma, hyperthyroidism, urinary retention due to benign prostatic hyperplasia, pheochromocytoma.

Porphyria, hepatic dysfunction, acute hepatitis, pancreatitis, severe renal impairment. Alcoholism.

Concomitant use with monoamine oxidase inhibitors (MAOIs) (or within two weeks after discontinuation of such therapy), tricyclic antidepressants, paracetamol-containing products, β-blockers, and other vasodilators or sympathomimetics.

Congenital hyperbilirubinemia (including Gilbert’s syndrome), glucose-6-phosphate dehydrogenase deficiency, rare hereditary fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency, blood disorders, severe hemolytic anemia, leukopenia.

Phenylketonuria.

Children under 12 years of age.

Interaction with other medicinal products and other forms of interaction.

Prolonged regular use of paracetamol may enhance the anticoagulant effect of warfarin and other coumarins, increasing the risk of bleeding; occasional use does not cause such an effect.

Prior to administration, medical advice should be sought if the patient is taking warfarin or similar anticoagulant agents.

Paracetamol hepatotoxicity may be enhanced by excessive alcohol consumption.

Metoclopramide or domperidone may increase the absorption rate of paracetamol, whereas cholestyramine may reduce it. Pharmacological interactions between paracetamol and other drugs have been reported. These interactions are unlikely to be clinically significant when recommended doses are used.

Barbiturates reduce the antipyretic effect of paracetamol.

Anticonvulsant drugs (including phenytoin, barbiturates, carbamazepine), which stimulate hepatic microsomal enzyme activity, may enhance the hepatotoxic effects of paracetamol due to increased conversion of paracetamol into hepatotoxic metabolites. Concomitant use of paracetamol with hepatotoxic agents increases the risk of hepatic toxicity.

Simultaneous use of high-dose paracetamol with isoniazid increases the risk of hepatotoxic syndrome.

Paracetamol reduces the efficacy of diuretics.

Paracetamol may reduce the bioavailability of lamotrigine, decreasing its efficacy through induction of hepatic metabolism.

Salicylates / acetylsalicylic acid may prolong the elimination of paracetamol from the body.

Concomitant therapy with paracetamol and NSAIDs (non-steroidal anti-inflammatory drugs) increases the risk of renal dysfunction.

Probenecid inhibits the conjugation of paracetamol with glucuronic acid, thereby reducing paracetamol clearance by almost half. When probenecid is used concomitantly, the dose of paracetamol should be reduced.

Concomitant use of paracetamol and AZT (zidovudine) increases the risk of neutropenia. Therefore, simultaneous use of paracetamol and AZT should be performed under medical supervision.

There is a hypertensive interaction between sympathomimetic amines, such as phenylephrine, and monoamine oxidase inhibitors. Phenylephrine may reduce the effectiveness of β-blocking agents and antihypertensive drugs. Phenylephrine increases the likelihood of arrhythmias in patients taking digitalis glycosides. There is a possibility that digitalis preparations may sensitize the myocardium to the effects of sympathomimetic agents. Conditions requiring the use of these drugs are contraindications for this medicinal product.

Phenylephrine may enhance the effects of other sympathomimetic amines (decongestants) on the cardiovascular system (particularly vasoconstrictive effects).

Concomitant use with halogenated anesthetics, such as chloroform, cyclopropane, halothane, enflurane, or isoflurane, may cause or exacerbate ventricular arrhythmias.

The medicinal product may affect laboratory test results for blood glucose and uric acid levels.

Guaifenesin enhances the effects of sedatives and muscle relaxants.

Phenylephrine hydrochloride should not be used with α-blockers, other antihypertensive agents, phenothiazine derivatives (e.g., promethazine), guanethidine, methyldopa, glucocorticosteroids, tricyclic antidepressants; appetite-affecting drugs, amphetamine-like psychostimulants, ergot alkaloids; other agents stimulating the central nervous system, theophylline. It should not be used concomitantly with other vasoconstrictive agents (regardless of the route of administration). Concurrent intake of phenylephrine and other sympathomimetics may lead to additive stimulation of the central nervous system to an extremely high level, resulting in nervousness, irritability, and insomnia. Seizure episodes are also possible.

Phenylephrine may cause hypertensive crisis or arrhythmias when used concomitantly with other adrenergic agents or MAO inhibitors, may cause severe arterial hypertension when combined with indomethacin and bromocriptine. Concurrent use of phenylephrine with β-blockers may lead to arterial hypertension and excessive bradycardia with possible heart block. Caution is advised when used with thyroid hormones and drugs affecting cardiac conduction (cardiac glycosides, antiarrhythmic agents).

When used concomitantly with drugs that promote potassium excretion, such as certain diuretics like furosemide, hypokalemia may be intensified and arterial sensitivity to vasopressor agents may be reduced.

Significant elevation of blood pressure may occur with intravenous administration of ergot alkaloids. Concurrent use of phenylephrine and ergot alkaloids increases the risk of ergotism. Alkaloids of Rauwolfia reduce the therapeutic effect of phenylephrine. Atropine sulfate blocks the reflex bradycardia caused by phenylephrine and increases the vasopressor response to phenylephrine.

Caution is advised when paracetamol is used concomitantly with flucloxacillin, as co-administration has been associated with metabolic acidosis with a high anion gap due to pyroglutamic acidosis, particularly in patients with risk factors (see section "Special precautions for use").

Special precautions for use.

Prolonged use of the medicinal product is not recommended.

If headache becomes persistent, medical advice should be sought.

Patients taking analgesics daily for mild forms of arthritis should consult a physician.

Due to the risk of overdose, the product must not be used concomitantly with other cold remedies, decongestants, or paracetamol-containing products. Prior to initiating treatment, ensure that medications containing sympathomimetics are not being administered simultaneously via multiple routes (i.e., orally and locally—nasal, ear, or eye preparations).

The product is recommended for use only when all symptoms are present (pain and/or fever, nasal congestion, and chesty cough).

Do not take with alcohol. The risk of hepatotoxicity is increased in patients with alcoholic liver disease or in those who abuse alcohol.

Patients with persistent or chronic cough (caused by smoking, asthma, chronic bronchitis, or emphysema) should consult a physician regarding the possibility of using this medicinal product.

The product should be used with caution in the following cases: renal impairment; myasthenia gravis; in combination with cough suppressants (containing guaifenesin). Since the medicinal product contains paracetamol, it should be used with caution in patients taking hepatotoxic medicinal products, digitalis preparations, methyldopa, or other antihypertensive agents; in chronically undernourished patients (low glutathione levels); in patients with Raynaud's phenomenon, granulocytopenia, severe hemolytic anemia, or acute gastrointestinal disorders.

Use with caution in patients with benign prostatic hyperplasia (due to the possibility of urinary retention).

Sucrose

The medicinal product contains sucrose. Patients with rare hereditary fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase-isomaltase deficiency should not take this product.

Sodium

The medicinal product contains 157 mg of sodium per 1 dose. This should be taken into account by patients on a sodium-controlled diet.

Aspartame

The medicinal product contains aspartame (E 951)—a source of phenylalanine. It may be harmful to people with phenylketonuria.

Cases of high anion gap metabolic acidosis (HAGMA) due to 5-oxoprolinuria (pyroglutamic acidosis) have been reported in patients with severe conditions such as severe renal failure, sepsis, malnutrition, or other causes of glutathione deficiency (e.g., chronic alcoholism), who were treated with paracetamol at therapeutic doses for prolonged periods or with a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol is recommended, along with careful monitoring. Measurement of urinary 5-oxoproline levels may be useful in identifying pyroglutamic acidosis as the underlying cause of HAGMA in patients with multiple risk factors.

Use during pregnancy or breastfeeding.

The use of this medicinal product is not recommended during pregnancy or breastfeeding due to insufficient data on its safety.

Ability to affect reaction speed when driving or operating machinery.

The medicinal product has a minor influence on reaction speed, which should be taken into account when driving or operating machinery.

Dosage and Administration.

For oral use.

Dissolve the contents of 1 sachet in a standard cup (250 ml) of hot, but not boiling water. Take while warm.

Adults, elderly and children aged 12 years and older: 1 sachet.

Repeat if necessary every 4–6 hours, but no more than four doses (4 sachets) per day; the interval between doses should be at least 4 hours. Do not exceed the recommended doses, especially in patients with increased blood coagulation.

The duration of treatment should be determined by a physician. Do not use the drug for longer than 3 days without consulting a doctor. If symptoms do not resolve, consult a physician.

Children.

Contraindicated in children under 12 years of age. For children aged 12 years and older, use under medical supervision.

Overdose.

Paracetamol.

In case of overdose, symptoms caused by paracetamol will be most prominent. The risk of overdose is higher in elderly patients, children, patients with liver disease, chronic alcoholism, and chronic malnutrition.

If a patient has taken a dose exceeding the recommended amount, immediate medical attention is required due to the risk of liver damage, which may lead to fatal outcomes.

Liver damage may occur in adults who have ingested 10 g or more of paracetamol, and in children who have ingested more than 150 mg/kg body weight. Liver damage may also result from ingestion of 5 g or more of paracetamol if the patient is undergoing long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort, or other drugs that induce liver enzymes; regularly consumes alcohol; or has suspected glutathione depletion, such as in malnutrition, cystic fibrosis, HIV infection, fasting, or cachexia.

Symptoms.

Symptoms of paracetamol overdose within the first 24 hours include pallor, nausea, vomiting, anorexia, and abdominal pain. Liver damage may develop 12–72 hours after ingestion. Glucose metabolism disturbances 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, indicated by flank pain, hematuria, and proteinuria, may develop even in the absence of severe liver damage. Cases of cardiac arrhythmias and pancreatitis have been reported.

With prolonged use of the drug in high doses, blood disorders may include aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia. Central nervous system effects may include dizziness, psychomotor agitation, and disorientation. Urinary system effects may include nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis).

Treatment.

In cases of paracetamol overdose, patients must be immediately hospitalized for emergency medical care, regardless of the absence of severe early symptoms. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or risk of organ damage.

Activated charcoal should be considered if an excessive dose of paracetamol was ingested within the past hour. Plasma paracetamol concentration should be measured 4 hours or later after ingestion (earlier concentrations are unreliable). Administration of SH-group donors and glutathione synthesis precursors (such as methionine, N-acetylcysteine) intravenously is recommended, with doses determined based on paracetamol blood concentration and time elapsed since ingestion. N-acetylcysteine treatment may be administered up to 48 hours after paracetamol ingestion, but maximum protective effect is achieved when administered within 8 hours after ingestion. The efficacy of the antidote decreases sharply after this time. Intravenous N-acetylcysteine should be administered according to established dosage regimens. In the absence of vomiting, oral methionine may be used as an appropriate alternative in remote areas outside hospital settings.

Phenylephrine hydrochloride.

Overdose may intensify adverse reactions, especially with prolonged use. Signs of severe phenylephrine overdose include: irritability, excitation, tremor, sleep disturbances, restlessness, anxiety, nervousness, headache, seizures, palpitations, paresthesia, inappropriate behavior, psychosis with hallucinations, confusion, weakness, anorexia, nausea, vomiting, oliguria, urinary retention, painful or difficult urination, facial flushing, cold sensation in extremities, hyperpyrexia, chest pain and discomfort, dyspnea, non-cardiogenic pulmonary edema, elevated arterial blood pressure with associated reflex bradycardia and arrhythmia, pallor, piloerection, increased sweating, hyperglycemia, hypokalemia, peripheral vasoconstriction, reduced blood flow to vital organs, potentially leading to impaired renal perfusion, metabolic acidosis, and increased cardiac workload due to elevated systemic vascular resistance. Severe overdose symptoms include severe peripheral and visceral vasoconstriction leading to cardiovascular collapse. Severe vascular constriction complications are more likely in patients with hypovolemia and severe bradycardia.

Treatment includes early gastric lavage, as well as symptomatic and supportive measures.

Guaifenesin.

Overdose with small or moderate doses may cause dizziness and gastrointestinal disturbances. Very high doses may cause symptoms such as excitation, confusion, and respiratory depression.

Side effects.

Immune system disorders: anaphylaxis; hypersensitivity reactions, including angioedema.

Skin and subcutaneous tissue disorders: hypersensitivity reactions, including skin rash, pruritus, and urticaria; erythema multiforme. Very rare cases of severe skin reactions (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome) have been reported.

Blood and lymphatic system disorders: anemia, sulfhemoglobinemia, and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia. With prolonged use at doses exceeding therapeutic levels, aplastic anemia, pancytopenia, and thrombocytopenia (which may lead to nosebleeds and/or bleeding gums, bruising, or hemorrhage), leukopenia, neutropenia, and agranulocytosis have been observed.

Nervous system disorders (usually occurring with high-dose intake): rarely dizziness, headache, psychomotor agitation, disorientation, disturbances of consciousness, insomnia, restlessness, nervousness, tremor, irritability, anxiety.

Eye disorders: mydriasis, photophobia, acute angle-closure glaucoma.

Cardiovascular system disorders: tachycardia, bradycardia, chest pain, dyspnea, increased blood pressure, palpitations, arrhythmia.

Gastrointestinal disorders: gastrointestinal discomfort, nausea, vomiting, diarrhea, loss of appetite, epigastric pain, acute pancreatitis.

Metabolism and nutrition disorders: metabolic acidosis with high anion gap (frequency unknown (cannot be estimated from available data)). Cases of metabolic acidosis with high anion gap as a result of pyroglutamic acidosis have been observed in patients with risk factors taking paracetamol (see section "Special precautions for use"). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients.

Hepatobiliary disorders: liver function abnormalities, increased serum liver enzyme activity, usually without development of jaundice, hepatonecrosis (a dose-dependent effect).

Renal and urinary disorders: urinary retention or difficulty in urination (in case of prostate enlargement), renal colic, dysuria, sterile pyuria. Rare reports of bladder or kidney stones have occurred in patients who have taken large amounts of guaifenesin over a prolonged period. Isolated cases of interstitial nephritis have been reported following long-term use of high-dose paracetamol.

Endocrine system disorders: hypoglycemia, up to hypoglycemic coma.

Respiratory system disorders: dyspnea, bronchospasm in patients sensitive to acetylsalicylic acid and other NSAIDs.

Shelf life. 3 years.

Storage conditions. Store out of reach of children at a temperature not exceeding 25 °C.

Packaging. 5 or 10 sachets per box.

Prescription status. Over-the-counter.

Manufacturer. Raftern Laboratories Limited.

Manufacturer's address and place of business.
Exeter Road, Raftern, Braunton, EX33 2DL, United Kingdom.