Instructions for use AfluGrip powder for oral solution sachet No. 10
Composition
active ingredients: 1 sachet contains: paracetamol 500 mg, guaifenesin 200 mg, phenylephrine hydrochloride 10 mg;
excipients: sucrose, citric acid anhydrous (E 330), tartaric acid (E 334), sodium cyclamate (E 952), sodium citrate (E 331), aspartame (E 951), acesulfame potassium (E 950), lemon flavor 8476 (flavor, flavoring of natural origin, corn maltodextrin, gum arabic (E 414), sodium citrate (E 331), citric acid (E 330), butylhydroxyanisole (E 320) (0.01 %)), lemon flavor PHS-163671 (flavor, flavors, flavoring of natural origin, maltodextrin, modified starch (E 1450), butylhydroxyanisole (E 320) (0.03 %)), menthol powder flavor (menthol of natural origin) origin, corn maltodextrin, gum arabic), quinoline yellow (E 104).
Dosage form
Powder for oral solution.
Main physical and chemical properties: Almost white free-flowing powder without large lumps and foreign particles. Has a characteristic citrus/menthol odor.
Reconstituted solution: yellow opalescent solution. Has a characteristic citrus/menthol odor.
Pharmacotherapeutic group
Paracetamol, combinations without psycholeptics.
ATX code N02B E51.
Pharmacological properties
Pharmacodynamics.
Paracetamol has analgesic and antipyretic effects, which are believed to be mainly due to inhibition of prostaglandin synthesis in the central nervous system (CNS).
Guaifenesin is an expectorant. It works by increasing the volume and reducing the viscosity of secretions in the trachea and bronchi, which makes it easier to cough up phlegm.
Phenylephrine hydrochloride is a sympathomimetic that primarily stimulates α-adrenergic receptors. It is an anti-edematous agent and acts by vasoconstriction, reducing swelling, particularly of the nasal mucosa and paranasal sinuses.
The active ingredients do not have a sedative effect.
Pharmacokinetics.
Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract, crosses the placental barrier, and a small amount is excreted in breast milk. After administration of paracetamol dissolved in a hot drink, absorption of paracetamol was significantly faster and significant during the first 60 minutes after administration compared to conventional tablets, as evidenced by the faster appearance of paracetamol in the blood plasma (the average time to reach a concentration of 0.25 μg/ml was 4.6 min after administration of the hot drink and 23.1 min after administration of conventional tablets). In addition, the time to reach maximum concentration (tmax) was significantly shorter after administration of the hot drink compared to conventional tablets. This difference can be explained by faster gastric emptying after administration of the hot drink. Maximum concentration (Cmax) in blood plasma is reached 10-60 minutes after oral administration. Paracetamol is mainly metabolized in the liver by three pathways: glucuronidation, sulfation and oxidation. It is excreted in the urine, mainly as glucuronide and sulfate conjugates. The half-life (t1/2) is 1 to 3 hours.
Guaifenesin is rapidly absorbed from the gastrointestinal tract after oral administration, with Cmax in the blood being reached within 15 minutes after administration. It is rapidly metabolized in the kidneys by oxidation to β-(2-methoxy-phenoxy)-lactic acid, which is excreted in the urine. The half-life is one hour.
Phenylephrine hydrochloride is unevenly absorbed from the gastrointestinal tract and undergoes presystemic metabolism by monoamine oxidase in the intestine and liver; oral administration of phenylephrine leads to a decrease in its bioavailability. It is excreted from the body with urine almost completely as a sulfate conjugate. Cmax in blood plasma is achieved within 1-2 hours, and t1/2 is from 2 to 3 hours.
Indication
For short-term relief of cold and flu symptoms (body aches and pains, headache, nasal congestion, sore throat, chills, fever, productive cough with difficulty in expectorating sputum).
Contraindication
Hypersensitivity to the active or excipients of the drug. Liver dysfunction, severe renal dysfunction. Heart disease and cardiovascular disorders. Hypertension. Hyperthyroidism. Diabetes. Pheochromocytoma. Patients taking tricyclic antidepressants, β-blockers.
Patients taking monoamine oxidase inhibitors (MAOIs) (or within two weeks of stopping such treatment).
Patients with angle-closure glaucoma. Patients with urinary retention and prostatic hyperplasia.
Patients currently taking other sympathomimetic drugs (decongestants, appetite suppressants, amphetamine-like psychostimulants).
Pregnancy.
Interaction with other medicinal products and other types of interactions
Paracetamol.
In case of therapy with simultaneous use of probenecid, the dose of paracetamol should be reduced, since probenecid prevents the binding of paracetamol with glucuronic acid and thus reduces the clearance of paracetamol by 50%.
Metoclopramide or domperidone may increase the rate of absorption of paracetamol, while cholestyramine may decrease it.
With prolonged regular use of paracetamol, the anticoagulant effect of warfarin and other coumarins may be enhanced, with an increased risk of bleeding; infrequent use does not have a similar effect. Before using the drug, it is necessary to consult a doctor if the patient is using warfarin or similar drugs that have an anticoagulant effect.
The hepatotoxicity of paracetamol may be increased by excessive alcohol consumption.
Concomitant use of high doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome.
Drugs that stimulate the activity of liver microsomal enzymes, such as ethanol, barbiturates, MAO inhibitors and tricyclic antidepressants, may enhance the toxic effect of paracetamol on the liver, especially after overdose. Paracetamol is contraindicated in patients taking MAO inhibitors or who have stopped taking them two weeks before treatment with AfluGrip, due to the risk of developing hypertensive crisis.
Concomitant use of paracetamol and zidovudine may reduce the metabolism of zidovudine, which increases the risk of neutropenia. Therefore, concomitant use of paracetamol and zidovudine should be carried out under medical supervision.
Salicylates (acetylsalicylic acid) may prolong the t1/2 of paracetamol.
Concomitant use of paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk of developing renal dysfunction.
Paracetamol reduces the effectiveness of diuretics.
Paracetamol may affect the results of laboratory tests using the phosphorus-tungsten reagent for the content of uric acid and glucose in the blood.
There is limited evidence that paracetamol may affect the pharmacokinetics of chloramphenicol, but its reliability has been criticized and evidence of a clinically significant interaction is insufficient. Although routine monitoring is not necessary, it is important to be aware of the potential for interaction when these two drugs are used concomitantly, especially in malnourished patients.
Caution should be exercised when using paracetamol and flucloxacillin simultaneously, as concomitant administration is associated with metabolic acidosis with a high anion gap, especially in patients at risk (see "Special warnings and precautions for use").
Guaifenesin.
Guaifenesin enhances the effects of sedatives and muscle relaxants.
When urine is collected within 24 hours of a dose of this drug, the metabolite may cause color interference with laboratory determinations of 5-hydroxyindoleacetic acid (5-HIAC) and vanillylmandelic acid (VMA).
Phenylephrine hydrochloride.
Phenylephrine hydrochloride should be used with caution in combination with the following drugs, as interactions have been reported:
MAO inhibitors (including moclobemide) - hypertensive interaction occurs with sympathomimetic amines such as phenylephrine and MAO inhibitors.
Sympathomimetic amines – concomitant use of phenylephrine with other sympathomimetic amines may increase the risk of cardiovascular side effects.
β-blockers and other antihypertensive drugs (including debrisoquine, guanethidine, reserpine, methyldopa) - phenylephrine may reduce the effectiveness of β-blockers and antihypertensive drugs. The risk of hypertension and other cardiovascular adverse reactions may be increased.
Tricyclic antidepressants (e.g. amitriptyline) – Concomitant use of phenylephrine with tricyclic antidepressants may increase the risk of cardiovascular adverse reactions.
Phenothiazide drugs used as sedatives - when used simultaneously with phenylephrine, the effect of these drugs on the CNS may be enhanced.
Ergot alkaloids (ergotamine and methylsergide) – when used simultaneously with phenylephrine, the risk of ergot poisoning may increase.
Cardiac glycosides (e.g., digitalis preparations) – may increase the risk of arrhythmia or heart attack.
Halogenated anesthetics (such as cyclopropane, halothane, enflurane, isoflurane) - concomitant use with phenylephrine may cause or worsen ventricular arrhythmia.
Application features
Concomitant use of the drug with other drugs containing paracetamol may lead to overdose. Paracetamol overdose may cause liver failure, which may require liver transplantation or be fatal.
The doctor or pharmacist should check that sympathomimetic drugs are not being administered simultaneously by multiple routes, i.e. orally and topically (nasal, ear, and eye medications).
Sympathomimetic drugs should be used very cautiously in patients with angina.
Before using the drug, patients with the following diseases should consult a doctor:
× Prostatic hypertrophy (may cause problems with urination).
× Occlusive vascular disease, such as Raynaud's phenomenon.
× Cardiovascular diseases.
× Myasthenia gravis is an autoimmune disorder.
× Severe gastrointestinal diseases.
× Glucose-6-phosphate dehydrogenase deficiency.
× Hemolytic anemia.
× Glutathione deficiency.
× Chronic cough, which occurs, for example, with smoking, asthma, chronic bronchitis or emphysema.
× Chronic alcoholism.
× Gilbert's syndrome (familial nonhemolytic jaundice).
The drug should be used with extreme caution in the following conditions:
× Chronic malnutrition.
× Dehydration.
× Elderly patients, adults and adolescents weighing less than 50 kg
Use with caution in patients taking the following medications:
⋅ vasoconstrictor drugs (e.g., ergotamine and methylsergide);
⋅ digoxin and cardiac glycosides;
× medications that affect liver function.
This medicine should only be recommended if all symptoms are present (pain and/or fever, nasal congestion and chesty cough).
Patients with chronic cough or asthma should consult a doctor before using this medication. Patients should stop using the medication and consult a doctor if cough persists for more than 3 days or returns, or is accompanied by fever, rash, or persistent headache.
Caution should be exercised in patients with asthma sensitive to acetylsalicylic acid, as moderate cases of bronchospasm have been reported due to the presence of paracetamol in the preparation (cross-reaction).
Do not take with cough medicines.
A history of liver disease increases the risk of liver damage associated with the use of paracetamol. Patients who have been diagnosed with liver or kidney failure should seek medical advice before using this drug. The risk of overdose is increased in patients with alcoholic liver disease without signs of cirrhosis.
Concomitant use with alcohol should be avoided.
It is not recommended to take other medicines containing paracetamol at the same time. Immediate medical attention should be sought in case of overdose, even if the patient feels well, as there is a risk of irreversible liver damage (see section "Overdose").
Prolonged use of any type of headache medication may worsen the headache. If this occurs or is suspected, treatment should be discontinued and a doctor should be consulted. The diagnosis of medication overuse headache should be suspected in patients who have frequent or daily headaches despite (or because of) regular use of headache medication.
Hepatotoxicity at therapeutic doses of paracetamol
Cases of paracetamol-induced hepatotoxicity, including fatalities, have been reported in patients taking paracetamol at therapeutic doses. These cases have been reported in patients with one or more risk factors for hepatotoxicity, including low body weight (< 50 kg), renal and hepatic insufficiency, chronic alcoholism, concomitant use of hepatotoxic drugs and acute and chronic malnutrition (low hepatic glutathione stores). Paracetamol should be administered with caution to patients with these risk factors. Caution is also recommended in patients receiving concomitant treatment with hepatic enzyme-inducing drugs and in conditions that may cause glutathione deficiency (see sections 4.5 and 4.8). Paracetamol doses should be reviewed at clinically appropriate intervals and patients should be monitored for the emergence of new risk factors for hepatotoxicity that may require dose adjustment.
Caution is advised when using paracetamol and flucloxacillin concomitantly due to the increased risk of developing metabolic acidosis with a high anion gap, especially in patients with severe renal insufficiency, sepsis, malnutrition and other sources of glutathione deficiency (e.g. chronic alcoholism), as well as in those taking maximum daily doses of paracetamol. Close monitoring, including measurement of urinary 5-oxoproline, is recommended.
Contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Contains aspartame (E 951), a source of phenylalanine. May be harmful for patients with phenylketonuria.
This medicinal product contains 129 mg sodium per dose, equivalent to 6.5% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
Use during pregnancy or breastfeeding
Pregnancy.
Paracetamol. A large amount of data on use in pregnant women indicate the absence of malformations and neonatal/fetal toxicity after the use of paracetamol. Epidemiological studies of neurodevelopment in children exposed to paracetamol in utero have shown mixed results. Paracetamol may be used during pregnancy if clinically necessary, at the lowest effective dose for the shortest duration and as infrequently as possible.
Guaifenesin: There are no data on the use of guaifenesin in pregnant women. The safety of guaifenesin during pregnancy has not been established.
Phenylephrine hydrochloride. Based on human experience, phenylephrine hydrochloride causes birth defects when administered during pregnancy. In addition, its use may be associated with fetal hypoxia. Phenylephrine should not be used during pregnancy.
Breastfeeding period.
It is not recommended to use this drug during breastfeeding without consulting a doctor due to insufficient data.
Paracetamol: Paracetamol/metabolites are excreted in breast milk, but at therapeutic doses of the drug have no effect on newborns/infants during breastfeeding.
Guaifenesin/phenylephrine hydrochloride: There is insufficient information on the excretion of guaifenesin/phenylephrine hydrochloride/metabolites in human milk.
Fertility.
There are no or limited data on the use of paracetamol, guaifenesin or phenylephrine hydrochloride and their effects on fertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
You should avoid driving or operating machinery if you feel dizzy after using the drug.
Method of administration and doses
For oral use.
Dissolve the contents of 1 sachet in a standard cup (250 ml) of hot, but not boiling, water. Consume warm. Drink the entire solution within 1.5 hours.
Adults, elderly patients and children over 12 years of age: 1 sachet every 4-6 hours, depending on the need, but not more than four doses (4 sachets) per day.
If symptoms of the disease persist for more than 3 days, you should seek medical advice.
Children.
Do not use in children under 12 years of age.
Overdose
Paracetamol.
An overdose of paracetamol can cause liver damage, which can be fatal.
Signs and symptoms: Symptoms usually appear within the first 24 hours and may include nausea, vomiting, anorexia, pallor, abdominal pain, or symptoms may be absent.
Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. Elevated levels of hepatic transaminases (AST, ALT), lactate dehydrogenase and bilirubin may be present, as may elevations in prothrombin time. Paracetamol overdose may cause necrosis of liver cells, and in severe poisoning, liver failure may progress, with encephalopathy, hemorrhage, hypoglycemia, cerebral edema, and death.
Acute renal failure with acute tubular necrosis may develop, as clearly indicated by low back pain, hematuria, and proteinuria, even in the absence of severe liver damage.
There is also data on the occurrence of cardiac arrhythmia and pancreatitis.
Liver damage is possible in adults who have taken 10 g or more of paracetamol. Taking 5 g or more of paracetamol may cause liver damage if the patient has risk factors (see below).
Risk factors:
- Patients with liver disease.
- Elderly patients.
- Small children.
- Patients who are receiving carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort or other drugs that induce liver enzymes for a long time.
- Patients who regularly consume excessive amounts of alcohol.
- Patients with glutathione deficiency, for example due to nutritional deficiencies, cystic fibrosis, HIV infection, starvation, and cachexia.
Immediate treatment is essential in the management of paracetamol overdose. Despite the lack of clear early symptoms, patients should be referred to hospital for emergency medical treatment. Symptoms may be limited to nausea or vomiting and may not be commensurate with the severity of the overdose or the risk of organ damage. Treatment. Should be carried out according to established guidelines.
The effectiveness of the antidote decreases sharply at the end of this period. If necessary, the patient can be given intravenous N-acetylcysteine, according to the established dosage regimen. If vomiting is not a problem, oral methionine may be a suitable alternative for locations far from a hospital. Treatment of individuals who develop severe hepatic dysfunction within 24 hours of ingestion should be discussed with a poison control center or liver disease specialist.
Guaifenesin.
Signs and symptoms: Very large doses of guaifenesin may cause nausea and vomiting.
Treatment: Vomiting should be treated with fluid replacement and electrolyte monitoring, if indicated.
Phenylephrine hydrochloride.
Signs and symptoms. Overdose of phenylephrine may produce effects similar to those listed as adverse reactions. Additional symptoms may include hypertension and possibly associated reflex bradycardia. In severe cases, confusion, hallucinations, convulsions and arrhythmia may occur, but the amount of phenylephrine required to cause serious intoxication would exceed that required to cause toxicity from paracetamol.
Treatment: Clinically appropriate treatment should be instituted and may include gastric lavage and symptomatic treatment. Hypertensive effects may be treated with an alpha-blocker (e.g. phentolamine mesylate 6-10 mg) administered intravenously, and bradycardia may be treated with atropine, preferably only after adequate blood pressure control.
Side effects
The frequency of adverse reactions is usually classified as follows:
very common (≥1/10);
common (≥1/100 to <1/10);
uncommon (≥1/1000 to <1/100);
rare (≥1/10,000 to <1/1,000);
very rare (<1/10,000);
frequency unknown (cannot be estimated from the available data).
Paracetamol.
Due to limited clinical trial data, the frequency of adverse reactions is unknown (cannot be estimated from the available data). Post-marketing experience shows that adverse reactions to paracetamol are rare and serious adverse reactions are very rare.
From the side of the circulatory and lymphatic systems: thrombocytopenia, agranulocytosis. They do not necessarily have a causal relationship with paracetamol.
Immune system disorders: anaphylaxis.
Respiratory system: bronchospasm in patients with asthma sensitive to acetylsalicylic acid and other NSAIDs.
Hepatobiliary system: liver dysfunction.
From the digestive system: acute pancreatitis.
On the part of the immune system: rarely - allergy (not including angioedema).
Skin and subcutaneous tissue disorders: very rarely - cutaneous hypersensitivity reactions, including skin rashes and angioedema, itching, sweating, purpura and urticaria, toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug dermatitis, acute generalized exanthematous pustulosis (AGEP).
Very rare cases of serious skin reactions have been reported.
On the part of the kidneys and urinary tract: very rarely - sterile pyuria (cloudy urine).
Guaifenesin.
The frequency of adverse reactions is unknown, but is considered to be probably rare.
On the part of the immune system: allergic reactions, angioedema, anaphylactic reactions.
From the respiratory system: dyspnea.
On the part of the digestive system: nausea, vomiting, feeling of discomfort in the gastrointestinal tract, diarrhea.
Skin and subcutaneous tissue disorders: rash, urticaria.
Phenylephrine hydrochloride.
In clinical trials with phenylephrine, the following adverse reactions were observed, which may be common.
Mental disorders: nervousness, irritability, restlessness and excitability.
From the nervous system: headache, dizziness, insomnia.
Cardiovascular system: increased blood pressure.
On the part of the digestive system: nausea, vomiting, diarrhea.
The following adverse reactions have been identified during post-marketing use. The frequency of these reactions is unknown, but they are likely to be rare.
On the part of the organs of vision: mydriasis, acute angle-closure glaucoma, most likely in patients with angle-closure glaucoma.
Cardiovascular system: tachycardia, palpitations.
Skin and subcutaneous tissue disorders: allergic reactions (e.g. rash, urticaria, allergic dermatitis). Hypersensitivity reactions, including cross-sensitivity, which may occur with other sympathomimetics.
Urinary system: dysuria, urinary retention. This most often occurs in patients with bladder outlet obstruction, for example, with prostatic hypertrophy.
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua/.
Expiration date
3 years.
The shelf life after reconstitution is 1.5 hours.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 sachets in a cardboard box.
Vacation category
Without a prescription.
Producer
Rafton Laboratories Limited.
Location of the manufacturer and address of its place of business.
Exeter Road, Rafton, Braunton, EX3 2DL, United Kingdom.
