Orvis^® Flu (Powder) Instructions for Use

Marketing Authorization Holder

Evalar, CJSC (Russia)

Contact Information

Evalar, CJSC (Russia)

ATC Code

N02BE51 (Paracetamol in combination with other drugs, excluding psycholeptics)

Active Substances

Ascorbic acid (Rec.INN registered by WHO)

Paracetamol (Rec.INN registered by WHO)

Pheniramine (Rec.INN registered by WHO)

Dosage Forms

	Orvis® Flu	Powder for preparation of oral solution with lemon and ginger flavor 500 mg+25 mg+200 mg/pack: pack 4.95 g 10 pcs.
		Powder for preparation of oral solution with lemon flavor 500 mg+25 mg+200 mg/pack: pack 4.95 g 10 pcs.

Dosage Form, Packaging, and Composition

Powder for preparation of oral solution with lemon and ginger flavor granulated, from light pink with a yellowish tint to light brown in color with a characteristic smell of lemon and ginger; inclusions of white, gray and brown color are allowed; the presence of lumps that crumble with light pressure from a glass rod is allowed. The solution is light yellow in color with a pinkish or brownish tint, cloudy, with a characteristic smell of lemon and ginger; the presence of undissolved particles from yellowish to brown in color is allowed.

Excipients : maltodextrin, aspartame – 24.75 mg, sodium citrate (including sodium – 58.07 mg), citric acid, powdered lemon concentrate [lemon juice, maltodextrin, citric acid], dry ginger root extract [ginger root extract, starch, maltodextrin, colloidal silicon dioxide], lemon flavor [flavor composition, natural aromatic component, maltodextrin, gum arabic].

4.95 g – sachets made of combined material (10) – cardboard packs.

Powder for preparation of oral solution with lemon flavor granulated, from white to white with a pinkish or brownish tint in color with a characteristic smell of lemon; inclusions of brown color are allowed; the presence of lumps that crumble with light pressure from a glass rod is allowed. The solution is from colorless to pinkish or brownish in color with a characteristic smell of lemon; the presence of opalescence is allowed.

Excipients : maltodextrin, aspartame – 24.75 mg, sodium citrate (including sodium – 58.07 mg), citric acid, lemon flavor [flavor composition, natural aromatic component, maltodextrin, gum arabic].

4.95 g – sachets made of combined material (10) – cardboard packs.

Clinical-Pharmacological Group

Drug for symptomatic therapy of acute respiratory diseases

Pharmacotherapeutic Group

Remedy for the relief of symptoms of acute respiratory infections and the "common cold" (non-narcotic analgesic agent + H₁-histamine receptor blocker + vitamin)

Pharmacological Action

A combined preparation containing Paracetamol, pheniramine and ascorbic acid.

Paracetamol is a non-narcotic analgesic, blocks COX and inhibits the synthesis of prostaglandins, mainly in the CNS, acting on the centers of pain and thermoregulation; has analgesic and antipyretic effects.

Pheniramine is a blocker of histamine H₁-receptors, reduces rhinorrhea and lacrimation, eliminates spasmodic phenomena, swelling and hyperemia of the mucous membrane of the nasal cavity, nasopharynx and paranasal sinuses.

Ascorbic acid is involved in the regulation of redox processes, carbohydrate metabolism, blood clotting, tissue regeneration, and the synthesis of steroid hormones; reduces vascular permeability, reduces the need for vitamins B₁, B₂, A, E, folic acid, pantothenic acid. Improves the tolerability of paracetamol and prolongs its action (associated with the prolongation of T_1/2).

Pharmacokinetics

Absorption and Distribution

Paracetamol

After oral administration, it is rapidly absorbed from the gastrointestinal tract. C_max of the drug in blood plasma is reached within 10-60 minutes after administration. It is rapidly distributed throughout the body tissues, penetrates the blood-brain barrier. Binding to plasma proteins is insignificant and has no therapeutic significance, but increases with increasing dose.

Pheniramine

Well absorbed from the gastrointestinal tract.

Ascorbic acid

Well absorbed from the gastrointestinal tract. The time to reach maximum therapeutic concentration (TC_max) after oral administration is 4 hours.

Metabolism

Paracetamol

Metabolism occurs in the liver, 80% of the administered dose enters into conjugation reactions with glucuronic acid and sulfates to form inactive metabolites; 17% undergoes hydroxylation to form 8 active metabolites, which conjugate with glutathione to form already inactive metabolites. One of the hydroxylated intermediate metabolites exhibits hepatotoxic effects. This metabolite is neutralized by conjugation with glutathione, however, it can accumulate and in case of paracetamol overdose (150 mg of paracetamol/kg or 10 g of paracetamol orally) cause necrosis of hepatocytes.

Ascorbic acid

Metabolized mainly in the liver.

Excretion

Paracetamol

It is excreted by the kidneys in the form of metabolites, mainly in the form of conjugates. Less than 5% of the administered dose is excreted unchanged. T_1/2 is from 1 to 3 hours.

Pheniramine

T_1/2 from blood plasma is from 1 to 1.5 hours. It is excreted from the body mainly through the kidneys.

Ascorbic acid

It is excreted by the kidneys, through the intestines, with sweat in unchanged form and in the form of metabolites.

Indications

For adults and children from 15 years of age

• For acute respiratory infections, acute respiratory viral infections (ARVI), nasopharyngitis (runny nose), influenza to relieve the following symptoms:
  • Elevated body temperature;
  • Chills;
  • Headache;
  • Nasal congestion;
  • Rhinorrhea;
  • Lacrimation;
  • Sneezing;
  • Pain in muscles and joints.

ICD codes

Dosage Regimen

Orally. Before use, dissolve the contents of one sachet in a glass (200 ml) of hot water (50-60°C (-76°F)). Add sugar if necessary. Take the solution freshly prepared, in accordance with the proposed dosage. The drug Orvis^® Flu can be taken at any time of the day, but the best effect is achieved by taking the drug before bedtime, at night.

Adults

1 sachet 2-3 times/day.

The maximum daily dose of paracetamol for body weight over 50 kg should not exceed 4 g/day (or 8 sachets of the drug); in children or patients with body weight of 40-50 kg, the maximum daily dose of paracetamol should not exceed 3 g/day, for body weight less than 40 kg – no more than 2 g/day.

The interval between doses of the drug should be at least 4 hours.

The drug should not be taken for more than 3 days as an antipyretic and for more than 5 days as an analgesic.

The maximum duration of treatment is 5 days.

If no relief of symptoms is observed within 5 days after starting the drug, elevated body temperature persists or after initial reduction it suddenly rises again, it is necessary to consult a doctor.

Special patient groups

In patients with impaired renal function (CrCl <10 ml/min), the interval between doses of the drug should be at least 8 hours.

In patients with chronic or decompensated liver diseases, in patients with hepatic insufficiency, chronic alcoholism, in debilitated patients and in dehydration, the daily dose of paracetamol should not exceed 3 g.

Children

The dosage regimen for children aged 15 to 18 years does not differ from the dosage regimen for adults.

The drug Orvis^® Flu is contraindicated for use in children from 0 to 15 years (see section "Contraindications"), because the safety and efficacy of the drug in children under 15 years of age have not been established. Data are not available.

Adverse Reactions

The drug is well tolerated at recommended doses. When using the drug, the following adverse reactions were noted (frequency unknown (cannot be estimated from available data))

From the blood and lymphatic system anemia, leukopenia, agranulocytosis, thrombocytopenia.

From the immune system: allergic reactions (erythema, skin rash, itching, angioedema, anaphylactic shock).

From the nervous system drowsiness, confusion, hallucinations, impaired concentration (more often in elderly patients), agitation, nervousness, insomnia, coordination dysfunction, tremor.

From the organ of vision accommodation disturbance.

From the heart palpitations.

From the vessels orthostatic hypotension, dizziness.

From the digestive system dry mouth, nausea, vomiting, abdominal pain, constipation.

From the kidneys and urinary tract urination disorder.

Contraindications

• Hypersensitivity to paracetamol, ascorbic acid, pheniramine or to any of the excipients that make up the drug
• Erosive and ulcerative lesions of the gastrointestinal tract (in the acute phase);
• Hepatic insufficiency;
• Closed-angle glaucoma;
• Urinary retention associated with prostate diseases and urination disorders;
• Portal hypertension;
• Alcoholism;
• Phenylketonuria;
• Deficiency of the enzyme glucose-6-phosphate dehydrogenase;
• Pregnancy;
• Breastfeeding period;
• Age under 15 years.

With caution

• Renal insufficiency (CrCl <10 ml/min);
• Congenital hyperbilirubinemias (Gilbert’s, Dubin-Johnson and Rotor syndromes);
• Viral hepatitis;
• Alcoholic hepatitis;
• Elderly age;
• Concomitant or within the previous 2 weeks use of MAO inhibitors, tricyclic antidepressants;
• Concomitant use of drugs that can negatively affect the liver;
• Bronchial asthma;
• Chronic bronchitis;
• Recurrent formation of urate stones in the kidneys.

Use in Pregnancy and Lactation

Pregnancy

Due to the lack of animal studies and clinical studies on the use of the combination of paracetamol, ascorbic acid and pheniramine during pregnancy, the use of the drug in this group of patients is not recommended.

Breastfeeding period

It is unknown whether the active substances of the drug pass into breast milk. The use of the drug Orvis^® Flu during breastfeeding is not recommended. If use is necessary, breastfeeding should be discontinued.

Fertility

Data are not available.

Use in Hepatic Impairment

Contraindicated in patients with hepatic insufficiency.

Use with caution in patients with congenital hyperbilirubinemias (Gilbert’s, Dubin-Johnson and Rotor syndromes), viral hepatitis, alcoholic hepatitis.

Use in Renal Impairment

In patients with renal insufficiency (CrCl <10 ml/min), use with caution, the interval between doses of the drug should be at least 8 hours.

Pediatric Use

The drug is contraindicated for use in children aged 0 to 15 years.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

The drug should not be used simultaneously with other medicines containing Paracetamol.

To avoid toxic liver damage, Paracetamol should not be combined with the intake of alcoholic beverages, and should not be taken by patients prone to alcohol abuse.

The risk of liver damage increases in patients with alcoholic hepatitis. It should not be used simultaneously with drugs that have hypnotic and anxiolytic effects, and in case of impaired renal function – without consulting a doctor. With long-term use, monitoring of the peripheral blood picture, blood and urine glucose levels, bilirubin, plasma uric acid, activity of hepatic transaminases and lactate dehydrogenase is necessary.

If the recommended doses are exceeded and with prolonged use, mental dependence on the drug may occur.

To avoid an overdose of paracetamol, it should be ensured that the total daily dose of paracetamol contained in all drugs taken by the patient does not exceed 4 g.

Excipients

Note for patients with diabetes the drug does not contain sugar and can be used by patients with diabetes.

The drug contains a source of phenylalanine – aspartame in the amount of 24.75 mg in 1 sachet. It may be harmful to people with phenylketonuria.

The drug contains 58.07 mg of sodium in 1 sachet, this should be taken into account by patients on a sodium-restricted diet.

Influence on the ability to drive vehicles and mechanisms

Considering the possibility of developing such adverse effects as drowsiness and dizziness, during treatment with the drug it is recommended to refrain from performing potentially hazardous activities that require increased concentration and speed of psychomotor reactions (driving a car and other vehicles, working with moving mechanisms, work of a dispatcher, operator, etc.).

Overdose

Symptoms due to paracetamol

In case of overdose, intoxication is possible, especially in elderly patients, children, patients with liver diseases (caused by chronic alcoholism), in patients with malnutrition, as well as in patients taking inducers of liver microsomal enzymes, in which fulminant hepatitis, liver failure, cholestatic hepatitis may develop, in the above cases – sometimes with a fatal outcome. The overdose threshold in these categories of patients may be lower. The clinical picture of acute overdose develops within 24 hours after taking paracetamol.

Symptoms gastrointestinal disorders (nausea, vomiting, loss of appetite, discomfort in the abdominal cavity and (or) abdominal pain), pallor of the skin. With a single administration of 7.5 g or more to adults or more than 140 mg/kg to children, cytolysis of hepatocytes occurs with complete irreversible liver necrosis, development of liver failure, metabolic acidosis and encephalopathy, which can lead to coma and death. 12-48 hours after the administration of paracetamol, an increase in the activity of liver microsomal enzymes, lactate dehydrogenase, bilirubin concentration and a decrease in prothrombin concentration are noted. Clinical symptoms of liver damage appear 12-48 hours after drug overdose and reach a maximum on the 4-6th day.

Treatment immediate hospitalization. Gastric lavage within the first hours of poisoning, intake of enterosorbents (activated charcoal, hydrolytic lignin). Determination of the quantitative content of paracetamol in blood plasma before starting treatment as soon as possible after overdose. Administration of SH-group donors and precursors of glutathione synthesis – methionine and acetylcysteine – is most effective within the first 8 hours. The need for additional therapeutic measures (further administration of methionine, intravenous administration of acetylcysteine) is determined depending on the concentration of paracetamol in the blood, as well as the time elapsed after its administration.

Symptomatic treatment laboratory tests of liver microsomal enzyme activity should be performed at the beginning of treatment and then every 24 hours. In most cases, the activity of liver microsomal enzymes normalizes within 1-2 weeks. In very severe cases, a liver transplant may be required.

Symptoms due to pheniramine

Symptoms convulsions, impaired consciousness, coma.

Treatment if symptoms of poisoning appear, the use of the drug should be stopped immediately and a doctor should be consulted. Gastric lavage, intake of enterosorbents (activated charcoal, hydrolytic lignin), intravenous or oral administration of the antidote acetylcysteine (if possible, within the first 10 hours after overdose), symptomatic treatment are recommended.

Drug Interactions

Ethanol enhances the sedative effect of antihistamines (pheniramine), so its intake should be avoided during treatment. In addition, ethanol when used simultaneously with pheniramine contributes to the development of acute pancreatitis.

Pheniramine enhances the effect of sedative drugs: morphine derivatives, barbiturates, benzodiazepine derivatives and other tranquilizers, neuroleptics (meprobamate, phenothiazine derivatives), antidepressants (amitriptyline, mirtazapine, mianserin), centrally acting antihypertensive drugs, sedatives belonging to the group of H₁-histamine blockers, baclofen; this not only increases the sedative effect, but also increases the risk of developing adverse effects of the drug (urinary retention, dry oral mucosa, constipation).

The possibility of enhancing central atropine-like effects when used in combination with other substances that have anticholinergic properties (other antihistamines, imipramine group antidepressants, phenothiazine neuroleptics, m-cholinoblocking antiparkinsonian agents, atropine-like antispasmodic agents, disopyramide) should be taken into account.

When using the drug together with inducers of microsomal oxidation: barbiturates, tricyclic antidepressants, anticonvulsants (phenytoin), flumecinol, phenylbutazone, rifampicin and ethanol, the risk of hepatotoxic effects (due to the paracetamol included in the composition) is significantly increased.

Concomitant use of glucocorticosteroids increases the risk of developing glaucoma.

Concomitant use with salicylates increases the risk of nephrotoxic effects.

Concomitant use with chloramphenicol increases the toxicity of the latter.

Paracetamol, contained in the preparation, enhances the effect of indirect anticoagulants and reduces the effectiveness of uricosuric drugs.

Ascorbic acid increases the blood concentration of benzylpenicillin and tetracyclines; at a dose of 1 g/day, it increases the bioavailability of ethinylestradiol (including that which is part of oral contraceptives).

It improves the intestinal absorption of iron preparations (converts ferric iron to ferrous iron); may increase iron excretion when used concomitantly with deferoxamine.

It reduces the effectiveness of heparin and indirect anticoagulants.

Concomitant use with acetylsalicylic acid (ASA) increases the urinary excretion of ascorbic acid and decreases the excretion of ASA. ASA reduces the absorption of ascorbic acid by approximately 30%.

It increases the risk of crystalluria during treatment with salicylates and short-acting sulfonamides, slows the renal excretion of acids, increases the excretion of drugs with an alkaline reaction (including alkaloids), and reduces the blood concentration of oral contraceptives.

It increases the total clearance of ethanol, which, in turn, reduces the concentration of ascorbic acid in the body.

Drugs of the quinoline series, calcium chloride, salicylates, and glucocorticosteroid drugs, with long-term use, deplete the reserves of ascorbic acid.

Concomitant use of Ascorbic acid reduces the chronotropic effect of isoprenaline.

With long-term use or use in high doses, it may interfere with the interaction between disulfiram and ethanol.

In high doses, it increases the renal excretion of mexiletine.

Barbiturates and primidone increase the urinary excretion of ascorbic acid.

It reduces the therapeutic effect of antipsychotics – phenothiazine derivatives, the tubular reabsorption of amphetamine and tricyclic antidepressants.

Storage Conditions

The drug should be stored at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life is 3 years.

Dispensing Status

The drug is available without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.