Fervex for adults with raspberry flavor

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT FERVEX FOR ADULTS WITH RASPBERRY FLAVOUR (FERVEX FOR ADULTS RASPBERRY)

Composition:

Active substances: paracetamol, ascorbic acid, pheniramine maleate;

1 sachet contains: paracetamol 500 mg, ascorbic acid 200 mg, pheniramine maleate 25 mg;

Excipients: sucrose, anhydrous citric acid, sodium saccharin, raspberry flavour containing maltodextrin, potassium sorbate (E 202), sodium benzoate (E 211), propylene glycol (E 1520), potassium, sunset yellow FCF (E 110), amaranth red AC (E 129), brilliant blue FCF (E 133), starch sodium octenyl succinate (E 1450), sodium chloride and/or sodium sulphate, ethyl acetate, isoamyl acetate, acetic acid, benzyl alcohol, triacetin, vanillin, p-hydroxybenzylacetone.

Pharmaceutical form. Granular powder for oral solution.

Main physicochemical properties: granular powder from light pink to light beige in colour.

Pharmacotherapeutic group.

Other analgesics and antipyretics. Anilides. Paracetamol, combinations without psychotropic agents.

ATC code N02BE51.

Pharmacological properties.

Pharmacodynamics.

Pharmacological effects due to the components of the drug:

• pheniramine maleate – an H1-histamine receptor blocker, provides desensitizing action manifested as a reduction in inflammatory response of the upper respiratory tract mucous membranes (improves nasal breathing, reduces rhinorrhea, sneezing, and lacrimation);
• paracetamol exerts antipyretic and analgesic effects, which alleviate pain and fever (headache, myalgia);
• ascorbic acid compensates for the body's need for vitamin C.

Pharmacokinetics.

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract after oral administration. Maximum plasma concentration of paracetamol is reached within 30–60 minutes after ingestion. Paracetamol is rapidly distributed in all tissues. Concentrations in blood, saliva, and plasma are similar. Plasma protein binding is weak. Paracetamol is primarily metabolized in the liver to form conjugates with glucuronic acid and sulfates. A minor metabolic pathway, catalyzed by cytochrome P450, leads to the formation of a reactive intermediate metabolite (N-acetylbenzoquinone imine), which under normal conditions is rapidly detoxified by reduced glutathione and excreted in urine after conjugation with cysteine and mercapturic acid. However, in cases of severe overdose, the amount of this toxic metabolite increases.

Excretion occurs mainly via the kidneys, primarily as metabolites. Approximately 90% of the administered dose is excreted in urine within 24 hours, mainly as glucuronide conjugates (60–80%) and sulfate conjugates (20–30%).

About 5% of the administered dose is excreted unchanged. Elimination half-life is approximately 2 hours.

In cases of severe renal impairment (creatinine clearance less than 10 ml/min), excretion of paracetamol and its metabolites is slowed.

In elderly patients, the capacity for conjugation remains unchanged.

Pheniramine maleate is well absorbed from the gastrointestinal tract. It is primarily excreted by the kidneys. Plasma half-life is 60–90 minutes.

Ascorbic acid is well absorbed from the gastrointestinal tract. It is primarily excreted in urine.

Clinical characteristics.

Indications.

Common cold, rhinitis, rhinopharyngitis, and influenza-like conditions in adults and children aged 15 years and older, accompanied by:

• clear nasal discharge and lacrimation;
• sneezing;
• headache and/or fever.

Contraindications.

Hypersensitivity to the components of the drug or to other antihistamines; severe hepatic and/or renal dysfunction; congenital hyperbilirubinemia; glucose-6-phosphate dehydrogenase deficiency; alcoholism; blood disorders; severe anemia; leukopenia; severe arterial hypertension; unstable angina; severe cardiac conduction disorders; acute phase of myocardial infarction; severe atherosclerosis; decompensated heart failure; hyperthyroidism; acute urinary retention due to prostate hyperplasia; risk of urinary retention in urethral or prostate disorders; bladder neck obstruction; pyloroduodenal obstruction; active gastric or duodenal ulcer; closed-angle glaucoma; thrombosis; thrombophlebitis; diabetes mellitus; bronchial asthma; epilepsy; elderly age; fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase-isomaltase deficiency due to sucrose content.

Do not use concomitantly with monoamine oxidase inhibitors (MAOIs) and within 2 weeks after discontinuation of MAOIs. The drug is contraindicated in patients taking tricyclic antidepressants or β-blockers. Contraindicated in urolithiasis if ascorbic acid intake exceeds 1 g per day.

Do not use in children under 15 years of age.

Interaction with other medicinal products and other forms of interaction.

Unfavorable combinations.

During treatment, avoid consumption of alcoholic beverages and use of medicinal products containing ethanol, as ethanol enhances the sedative effect of H1-blockers (pheniramine). Therefore, patients should refrain from driving or operating machinery.

Combinations requiring caution.

Due to the presence of pheniramine, concomitant use with other sedative agents may lead to central nervous system depression, particularly with: morphine derivatives (analgesics, antitussives, and substitution therapy), neuroleptics, barbiturates, benzodiazepines, non-benzodiazepine anxiolytics (e.g., meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H1-blockers, centrally-acting antihypertensives, baclofen, and thalidomide.

Due to the presence of pheniramine, concomitant use with drugs exhibiting anticholinergic (atropine-like) effects, such as imipramine-type antidepressants, most anticholinergic H1-blockers, anticholinergics, antiparkinsonian agents, atropine-like spasmolytics, disopyramide, phenothiazine neuroleptics, and clozapine, may increase the risk of undesirable anticholinergic effects such as urinary retention, constipation, and dry mouth.

Combinations to be used with caution.

Concomitant use with oral anticoagulants may enhance their effect, increasing the risk of bleeding, particularly when paracetamol is taken at maximum doses (4 g/day) for at least 4 days. Regular monitoring of INR (International Normalized Ratio) is recommended. The dose of oral anticoagulant may need adjustment during and after paracetamol treatment.

Paracetamol may interfere with blood glucose measurement by the glucose oxidase-peroxidase method, leading to falsely elevated glucose concentrations.

Paracetamol may interfere with blood urea measurement by the phosphotungstic acid method.

The absorption rate of paracetamol may be increased when used concomitantly with metoclopramide and domperidone, and decreased with cholestyramine. Barbiturates reduce the antipyretic effect of paracetamol.

Anticonvulsant drugs (including phenytoin, barbiturates, carbamazepine), which stimulate hepatic microsomal enzyme activity, may enhance the hepatotoxic effect of paracetamol by increasing its conversion into hepatotoxic metabolites. Concomitant use of paracetamol with isoniazid increases the risk of hepatotoxic syndrome. Paracetamol reduces the efficacy of diuretics.

Paracetamol should be used with caution when administered 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").

Do not use concomitantly with alcohol.

Ascorbic acid enhances intestinal absorption of iron, increases levels of ethinylestradiol, penicillins, and tetracyclines; and decreases blood levels of antipsychotic drugs and phenothiazine derivatives. Glucocorticoids reduce body stores of ascorbic acid. Concurrent use of ascorbic acid and deferoxamine increases tissue iron toxicity, particularly in cardiac muscle, potentially leading to circulatory decompensation. Ascorbic acid should be administered only 2 hours after deferoxamine injection. High doses of ascorbic acid reduce the effectiveness of tricyclic antidepressants. Absorption of ascorbic acid is reduced when taken concomitantly with oral contraceptives, fruit or vegetable juices, or alkaline drinks.

Special precautions.

In case of high body temperature or prolonged fever persisting for 5 days during treatment with the drug, or if signs of superinfection appear, consult a physician to determine the appropriateness of continuing therapy.

Ascorbic acid may alter the results of laboratory tests (blood glucose, bilirubin, transaminase activity).

Consult a physician regarding the possibility of using the drug in patients with impaired kidney or liver function. Consult a physician before using the drug if the patient is taking warfarin or similar agents with anticoagulant effects.

In patients with alcoholic liver disease, the risk of hepatotoxic effects of paracetamol is increased. The drug may affect laboratory test results for blood uric acid levels.

Do not exceed the recommended doses.

Do not take the drug with other products containing paracetamol.

If symptoms do not resolve or if headache becomes persistent, consult a physician.

The risk of primarily psychological dependence may occur when exceeding recommended doses or during prolonged treatment.

For adults with body weight over 50 kg, the total daily dose of paracetamol should not exceed 4 g.

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

Precautionary measures.

Consumption of alcohol or use of sedatives (especially barbiturates) increases the sedative effect of pheniramine maleate; therefore, avoid using these substances during treatment.

Each sachet contains 7.6 g of sucrose. This should be taken into account in patients with diabetes mellitus. The drug should not be used in patients with hereditary fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase/isomaltase deficiency (rare inherited disorders).

Each sachet contains less than 1 mmol (23 mg) of sodium, indicating that the drug is essentially "sodium-free."

Each sachet contains 1.2 mg of benzyl alcohol, which may cause allergic reactions.

Each sachet contains traces of sodium benzoate (E211).

This medicinal product contains the colorants sunset yellow FCF (E 110) and amaranth (E 129), which may cause allergic reactions.

Very rare cases of serious skin reactions have been reported. Patients should be informed about the possibility of early signs of these serious skin reactions, such as rash or other signs of hypersensitivity. If such signs occur, the drug should be discontinued.

Use with particular caution in patients with iron metabolism disorders (hemochromatosis, hemosiderosis, thalassemia).

Since ascorbic acid has a mild stimulating effect, it is not recommended to take this drug late in the day. Due to the stimulating effect of ascorbic acid on corticosteroid hormone production when used in high doses, kidney function and blood pressure should be monitored.

The drug should be used cautiously in conditions with increased blood coagulability.

Use with particular caution in patients with a history of nephrolithiasis (risk of hyperoxaluria and oxalate precipitation in the urinary tract after high-dose ascorbic acid intake).

Prolonged use of high doses of ascorbic acid may accelerate its own metabolism, leading to paradoxical hypovitaminosis after discontinuation of treatment. Do not exceed the recommended dose.

Do not use simultaneously with other products containing vitamin C.

Absorption of ascorbic acid may be impaired in conditions with intestinal motility disorders, enteritis, or achylia (suppressed gastric secretion).

It should be noted that high-dose vitamin C intake may alter certain laboratory test parameters (uric acid, creatinine, inorganic phosphates). The test for occult blood in stool may yield a false-negative result.

The medicinal product contains sunset yellow FCF (E 110), which may cause allergic reactions.

Use during pregnancy or breastfeeding.

Since the effect of the drug on pregnancy or breastfeeding has not been sufficiently studied, it should not be used during these periods.

Ability to affect reaction speed when driving or operating machinery.

There may be a significant effect on reaction speed when driving or operating machinery. The drug may cause drowsiness, especially at the beginning of treatment. Therefore, avoid driving or operating machinery during treatment.

Concomitant use of the drug with alcoholic beverages, medicinal products containing ethanol, or other sedatives increases these risks.

Method of Administration and Dosage

Administer as an oral solution.

The contents of the sachet should be taken after dissolving in a sufficient amount of hot or cold water.

Dosage.

This medicinal product is intended only for use in adults and children aged 15 years and older.

The dose is 1 sachet 2 or 3 times daily.

An interval of 4 hours should always be maintained between doses.

For treatment of influenza-like conditions, it is recommended to take this medication with hot water in the evening.

Duration of treatment.

The maximum duration of treatment is 5 days.

In patients with severe renal impairment (creatinine clearance below 10 mL/min), the dosing interval should be at least 8 hours.

Children.

Do not administer to children under 15 years of age.

Overdose.

Related to ascorbic acid.

Ascorbic acid is well tolerated. It is a water-soluble vitamin, and any excess is excreted in urine. However, prolonged use of high doses of vitamin C may suppress the function of the islet apparatus of the pancreas, requiring monitoring of pancreatic status. Overdose may lead to changes in renal excretion of ascorbic and uric acids during urine acidification, with a risk of precipitation of oxalate calculi. High-dose ascorbic acid administration may cause vomiting, nausea, or diarrhea, which resolve after discontinuation of ascorbic acid intake.

Related to pheniramine.

Pheniramine overdose may cause convulsions (especially in children), impaired consciousness, and coma.

Atropine-like symptoms occur in pheniramine overdose: mydriasis, photophobia, dryness of skin and mucous membranes, hyperthermia, and intestinal atony. Central nervous system depression leads to impaired respiratory and cardiovascular function (bradycardia, arterial hypotension, collapse).

Related to paracetamol.

There is a risk of toxicity in elderly individuals and particularly in young children (therapeutic overdoses and accidental poisonings occur quite frequently). Paracetamol overdose can be fatal. Symptoms within the first 24 hours include pallor, nausea, vomiting, anorexia, and abdominal pain.

Liver damage may become evident 12–48 hours after overdose. Glucose metabolism disturbances and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to hemorrhage and hypoglycemia. Acute renal failure with acute tubular necrosis may manifest as severe lumbar pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have also been reported.

Overdose of more than 10 g of paracetamol in adults and 150 mg/kg body weight in children in a single dose causes hepatic cytolysis, which may lead to complete and irreversible necrosis, resulting in hepatocellular failure, metabolic acidosis, and encephalopathy, potentially progressing to coma and death.

Elevated levels of liver transaminases, lactate dehydrogenase, and bilirubin, along with increased prothrombin time, may appear 12–48 hours after ingestion.

In patients with risk factors (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort, or other drugs inducing liver enzymes; chronic excessive ethanol consumption; glutathione deficiency states such as malnutrition, cystic fibrosis, HIV infection, starvation, cachexia), ingestion of 5 g or more of paracetamol may lead to liver damage. Long-term use of the drug in high doses may result in aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia. High-dose intake may cause CNS effects such as dizziness, psychomotor agitation, and disorientation; urinary system effects include nephrotoxicity (renal colic, interstitial nephritis, capillary necrosis).

Emergency measures.

• Immediate hospitalization;
• determination of initial plasma paracetamol concentration;
• immediate removal of the ingested drug by gastric lavage;
• standard overdose treatment includes administration of the antidote N-acetylcysteine, either intravenously or orally. The antidote should be administered as early as possible, preferably within 10 hours of overdose;
• symptomatic therapy.

Side effects

Blood and lymphatic system disorders: anemia, sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia; thrombosis, hyperprothrombinemia, erythrocytopenia, thrombocytopenia, neutrophilic leukocytosis, agranulocytosis, purpura, leukopenia, neutropenia, bruising or bleeding.

Immune system disorders: anaphylaxis, anaphylactic shock, hypersensitivity skin reactions including pruritus, skin and mucous membrane rashes (usually erythematous, urticaria, purpura), angioneurotic edema, erythema multiforme (including Stevens–Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome).

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

Gastrointestinal disorders: dry mouth, nausea, heartburn, vomiting, constipation, epigastric pain, diarrhea, liver function disturbances, increased liver enzyme activity (usually without jaundice), hepatonecrosis (dose-dependent effect).

Endocrine system disorders: hypoglycemia up to hypoglycemic coma.

Nervous system disorders: rarely – headache, dizziness, sleep disturbances, insomnia, sedation or drowsiness, confusion, hallucinations, nervousness, impaired motor coordination, tremor; in individual cases – coma, seizures, dyskinesia, behavioral changes, increased excitability; disturbances of balance and memory, inattention, dizziness, especially in elderly patients. Anticholinergic effects, e.g. dry mucous membranes, constipation, accommodation disorders, mydriasis, palpitations, risk of urinary retention. Orthostatic hypotension.

Cardiovascular system disorders: in isolated cases – tachycardia, myocardial dystrophy (dose-dependent effect with prolonged use), orthostatic hypotension.

Metabolism and nutrition disorders: disturbances in zinc and copper metabolism.

Renal and urinary system disorders: urinary retention and difficulty in urination, aseptic pyuria.

Skin disorders: eczema.

Eye disorders: dry eyes, mydriasis, accommodation disorders.

With prolonged use in high doses: damage to the glomerular apparatus of the kidneys, crystalluria, formation of urate, cystine and/or oxalate concretions in the kidneys and urinary tract; damage to the islet apparatus of the pancreas (hyperglycemia, glucosuria) and impaired glycogen synthesis up to the development of diabetes mellitus.

Side effects related to ascorbic acid: when used in doses exceeding 1 g per day – irritation of the gastrointestinal mucosa, renal failure, arterial hypertension.

Metabolism and nutrition disorders: metabolic acidosis with high anion gap with frequency "unknown" (cannot be estimated from available data).

Description of selected side effects

Metabolic acidosis with high anion gap

Cases of metabolic acid游戏副本