Fervex for adults without sugar

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FERVEX FOR ADULTS SUGAR FREE

Composition:

Active ingredients: paracetamol, ascorbic acid (vitamin C), pheniramine maleate;

1 sachet contains: paracetamol 500 mg, ascorbic acid (vitamin C) 200 mg, pheniramine maleate 25 mg;

Excipients: mannitol (E 421), anhydrous citric acid, povidone, anhydrous trimagnesium dicitrate, aspartame (E 951), lemon flavor: flavoring ingredients (approximately 5.5%): alpha-pinene, beta-pinene, sabinene, myrcene, limonene, gamma-terpinene, para-cymene, linalool, neral, geranial, geranyl acetate, geraniol; non-flavoring ingredients (approximately 94.5%): triacetin (E 1518), modified starch (E 1450), acacia plant gum (E 414), ethanol.

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: white or almost white granular powder.

Pharmacotherapeutic group.
Analgesics and antipyretics. ATC code: N02BE51.

Pharmacological properties.

Pharmacodynamics.

Pharmacological effects due to the components of the drug:

• Pheniramine maleate – an H1-histamine receptor blocker, provides a desensitizing effect manifested by reduction of inflammatory reactions in the mucous membranes of the upper respiratory tract (improvement of nasal breathing, reduction of rhinorrhea, sneezing, and lacrimation);
• Paracetamol exerts antipyretic and analgesic effects, which alleviate pain and fever (headache, myalgia);
• Ascorbic acid meets the body's requirements 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 administration. Paracetamol is rapidly distributed into all tissues. Concentrations in blood, saliva, and plasma are similar. Plasma protein binding is weak. Paracetamol is primarily metabolized in the liver by conjugation with glucuronic acid and sulfates. A minor metabolic pathway, catalyzed by cytochrome P450, leads to the formation of a reactive intermediate (N-acetylbenzoquinoneimine), 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 primarily via the kidneys. 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. The elimination half-life is approximately 2 hours.

Pheniramine maleate is well absorbed from the gastrointestinal tract. It is excreted primarily via the kidneys. Ascorbic acid is well absorbed from the gastrointestinal tract and is excreted mainly in the urine.

Clinical characteristics.

Indications.

Symptomatic treatment of colds, allergic rhinitis, influenza, rhinopharyngitis manifested by chills, headache, runny nose, sneezing, and lacrimation.

Contraindications.

Hypersensitivity to the components of the drug or to other antihistamines; severe impairment of liver and/or kidney function; phenylketonuria; congenital hyperbilirubinemia; glucose-6-phosphate dehydrogenase deficiency; alcoholism; blood disorders; severe anemia; leukopenia; severe arterial hypertension; unstable angina pectoris; severe cardiac conduction disorders; acute phase of myocardial infarction; severe atherosclerosis; decompensated heart failure; hyperthyroidism; acute urinary retention due to prostate hyperplasia; bladder neck obstruction; pyloroduodenal obstruction; gastric or duodenal ulcer in the acute phase; closed-angle glaucoma; thrombosis; thrombophlebitis; severe forms of diabetes mellitus; epilepsy; elderly age. Do not use with monoamine oxidase inhibitors (MAOIs) or within two weeks after discontinuation of MAOIs. Contraindicated in patients taking tricyclic antidepressants or beta-blockers. Contraindicated in urolithiasis if ascorbic acid is administered in doses exceeding 1 g per day.

Special precautions.

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

Use with caution in patients with diabetes mellitus.

Alcohol enhances the sedative effect of pheniramine maleate and the hepatotoxicity of paracetamol.

Ascorbic acid may alter laboratory test results (blood glucose, bilirubin, transaminase activity).

Risk of primarily psychological dependence may occur when recommended doses are exceeded or with prolonged treatment.

To prevent overdose, check and exclude all medications containing paracetamol.

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

Precautionary measures.

Consumption of alcoholic beverages or use of sedatives (especially barbiturates) increases the sedative effect of pheniramine maleate; therefore, these substances should be avoided during treatment.

Interaction with other medicinal products and other forms of interaction.

Unrecommended combinations.

Due to the presence of pheniramine, ethanol enhances the sedative effect of H1-blockers; therefore, driving or operating machinery should be avoided. Consumption of alcoholic beverages and use of medicinal products containing ethanol should be avoided during treatment.

Combinations requiring caution.

Due to the presence of pheniramine, other sedatives may cause central nervous system depression, including: morphine derivatives (analgesics, antitussives, and substitution therapy), neuroleptics, barbiturates, benzodiazepines; anxiolytics other than benzodiazepines (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, medicinal products with anticholinergic (atropine-like) effects—such as imipramine antidepressants, most anticholinergic H1-blockers, anticholinergics, antiparkinsonian agents, atropine-like spasmolytics, disopyramide, phenothiazine neuroleptics, and clozapine—may add undesirable anticholinergic effects such as urinary retention, constipation, and dry mouth.

The absorption rate of paracetamol may be increased when used concomitantly with metoclopramide and domperidone, and decreased when used with cholestyramine. The anticoagulant effect of warfarin and other coumarins, with an increased risk of bleeding, may be enhanced by long-term concomitant use of paracetamol. Occasional use has no significant effect.

Barbiturates reduce the antipyretic effect of paracetamol.

Anticonvulsants (including phenytoin, barbiturates, carbamazepine), which stimulate hepatic microsomal enzyme activity, may enhance the hepatotoxic effect of paracetamol due to increased conversion of the drug into hepatotoxic metabolites. Concurrent use of paracetamol with isoniazid increases the risk of hepatotoxic syndrome. Paracetamol reduces the effectiveness of diuretics.

Ascorbic acid enhances intestinal absorption of iron, increases blood levels of ethinylestradiol, penicillins, and tetracyclines; decreases blood levels of antipsychotic drugs and phenothiazine derivatives. Glucocorticoids reduce body stores of ascorbic acid. Concurrent intake of ascorbic acid and deferoxamine increases tissue iron toxicity, especially in cardiac muscle, which may lead to circulatory decompensation. It 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.

Caution is advised when using paracetamol concomitantly with flucloxacillin, as co-administration has been associated with metabolic acidosis with a high anion gap, particularly in patients at risk ("Special considerations for use").

Special precautions for use

If the patient has liver or kidney disease, consult a physician before using the medication. Consult a physician before use if the patient is taking warfarin or similar anticoagulant agents. It should be noted that patients with alcohol-induced necrotic liver damage have an increased risk of hepatotoxic effects of paracetamol; the drug may affect laboratory test results for blood glucose and uric acid levels. In patients with severe infections such as sepsis, which are associated with reduced glutathione levels, the use of paracetamol increases the risk of metabolic acidosis. Symptoms of metabolic acidosis include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. Seek immediate medical attention if these symptoms occur.

Do not exceed the recommended doses. If symptoms persist, consult a physician.

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 medication late in the day. Due to the stimulating effect of ascorbic acid on corticosteroid hormone production, kidney function and arterial blood pressure should be monitored when high doses are used.

Use the medication cautiously in patients 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, potentially leading to paradoxical vitamin deficiency 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 involving 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). Fecal occult blood testing may yield false-negative results.

Caution is advised when using paracetamol concomitantly with flucloxacillin due to an increased risk of developing high anion gap metabolic acidosis, particularly in patients with severe renal insufficiency, sepsis, malnutrition, and other conditions associated with glutathione deficiency (e.g., chronic alcoholism), as well as those taking maximum daily doses of paracetamol. Close monitoring is recommended, including measurement of urinary 5-oxoproline levels.

This medicinal product contains a small amount of ethanol (alcohol), less than 100 mg per dose.

Use during pregnancy or breastfeeding

Since the effects of the medication on pregnancy or breastfeeding have not been sufficiently studied, it should not be used during these periods.

Ability to affect reaction speed when driving or operating machinery

The medication may cause drowsiness; therefore, patients should refrain from driving or operating machinery while taking this medication.

Dosage and Administration.

For oral use. Adults and children aged 15 years and older should take 1 sachet 2–3 times daily. The contents of the sachet should be dissolved in a glass of cold or warm water. For patients with symptoms of a cold, it is preferable to take the solution warm. The solution should be taken immediately after preparation. The interval between doses should be at least 4 hours. The maximum duration of treatment is 5 days.

For patients with severe renal impairment (creatinine clearance less than 10 mL/min), the interval between doses should be at least 8 hours.

Children.

Do not use in children under 15 years of age.

Overdose.

Related to ascorbic acid.

Ascorbic acid is well tolerated. It is a water-soluble vitamin, and excess amounts are excreted in urine. However, prolonged use of high doses of vitamin C may suppress the function of pancreatic islet cells, requiring monitoring of pancreatic status. Overdose may alter renal excretion of ascorbic and uric acids, particularly during urine acidification, increasing the risk of precipitation of oxalate calculi. High-dose ascorbic acid may cause vomiting, nausea, or diarrhea, which resolve after discontinuation.

Related to pheniramine.

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

Pheniramine overdose leads to anticholinergic-like symptoms: mydriasis, photophobia, dryness of skin and mucous membranes, hyperthermia, and intestinal atony. Central nervous system depression may result in respiratory and cardiovascular dysfunction (bradycardia, arterial hypotension, collapse).

Related to paracetamol.

There is a risk of toxicity in elderly individuals and especially in young children (therapeutic overdose and accidental poisoning occur relatively frequently).

Paracetamol overdose can be fatal.

Symptoms

Nausea, vomiting, anorexia, pallor, increased sweating, and abdominal pain, typically appearing within the first 24 hours.

Acute renal failure with acute tubular necrosis may present 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.

With prolonged use of the drug in high doses, hematological complications 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, capillary necrosis). Gastrointestinal effects may include hepatonecrosis.

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

Elevated levels of hepatic transaminases, lactate dehydrogenase, and bilirubin, along with increased prothrombin levels, may occur 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; alcohol abuse; glutathione deficiency (digestive disorders, cystic fibrosis, HIV infection, fasting, cachexia)), ingestion of 5 g or more of paracetamol may cause liver damage.

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 after overdose;
• methionine as symptomatic therapy.

Adverse reactions.

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

Immune system disorders: anaphylaxis, anaphylactic shock, hypersensitivity skin reactions including pruritus, skin and mucous membrane rashes (usually erythematous, urticarial), angioneurotic edema, multiform erythema (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 development of jaundice, hepatonecrosis (dose-dependent effect).

Endocrine system disorders: hypoglycemia up to hypoglycemic coma.

Nervous system disorders: rarely – headache, dizziness, sleep disturbances, insomnia, drowsiness, confusion, hallucinations, nervousness, tremor; in individual cases – coma, seizures, dyskinesia, behavioral changes, increased excitability; disturbances of balance and memory, inattention, especially in elderly patients.

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, renal colic.

Skin disorders: eczema.

Eye disorders: dry eyes, mydriasis, accommodation disturbances.

With prolonged use in high doses: glomerular apparatus damage in kidneys, crystalluria, formation of urate, cystine and/or oxalate calculi in 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.

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

Shelf life. 3 years.

Storage conditions.

No special storage conditions required.

Keep out of reach of children.

Packaging.

8 sachets in a cardboard box.

Dispensing category. Over-the-counter.

Manufacturer.

UPSA SAS, France / UPSA SAS, France.

Manufacturer's address and place of business.

979, avenue des Pyrenees, 47520 Le Passage, France / 979, avenue des Pyrenees, 47520 Le Passage, France;

or

304, avenue du Docteur Jean Bru, 47000 Agen, France / 304, avenue du Docteur Jean Bru, 47000 Agen, France.