dosoflu 4g powder N10

• The contents of the sachet should be dissolved in a glass of hot (but not boiling) water (150 ml), stir well to obtain a homogeneous solution.

• When the solution reaches a suitable temperature, take orally.

• The duration of treatment should not exceed 5 days unless prescribed by a doctor.

Contraindications:

- Hypersensitivity to paracetamol, guaifenesin, phenylephrine, or any of the excipients listed in section 6.1

- Severe liver or kidney impairment

- Heart disease and cardiovascular system disorders, including severe hemolytic anemia

- Arterial hypertension

- Hyperthyroidism

- Diabetes mellitus

- Pheochromocytoma

- Narrow-angle glaucoma

- Urinary retention

- Use of tricyclic antidepressants or beta-blockers 

- Patients who are taking or have taken MAO inhibitors within the last 14 days

- Patients taking other sympathomimetics (decongestants, appetite suppressants, and amphetamine-like psychostimulants).

Special warnings and precautions for use:

• Use of this medicinal product is recommended only in patients with confirmed clinical symptoms (muscle and joint pain, fever, nasal congestion, and cough).

• Before use, it is necessary to verify (by a doctor or pharmacist) whether it is possible to take other medicines containing sympathomimetics, regardless of their route of administration (oral or topical, including eye or nasal drops, inhalers).

• Medicinal products from the sympathomimetic group should be used with caution in patients with ischemic heart disease (IHD).

  
  

In the following groups of patients, this medicinal product should be used after consultation with a doctor:

- Prostatic hyperplasia or other conditions causing urinary disturbances

- Occlusive vascular diseases (e.g. Raynaud’s disease)

- Cardiovascular diseases

- Myasthenia gravis

- Severe diseases of the gastrointestinal tract

Concomitant use with other products containing paracetamol should be avoided in order to reduce the risk of overdose. The maximum daily dose of paracetamol should not exceed 3 g.

The use of paracetamol should be restricted in patients with severe renal or hepatic impairment. Paracetamol overdose is particularly dangerous in subjects with liver disease associated with alcohol abuse.

In patients with chronic cough and asthma, the product should be used after consultation with a doctor. Consultation is also required if the cough lasts more than 5 days, if cough recurs after discontinuation of treatment, or if the cough is accompanied by significant fever, rash, or persistent headache.

This medicinal product contains:

- Sucrose; therefore, it should not be used in patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltase deficiency.

- A source of phenylalanine/aspartame (E951). It may be harmful to patients with phenylketonuria.

- 49.1 mg sodium per dose. This should be taken into consideration by patients on a low-sodium diet.

Interaction with other medicinal products and other forms of interaction:

Paracetamol

• Regular long-term use of paracetamol may increase the anticoagulant effect of warfarin and other coumarin anticoagulants, which may increase the risk of bleeding, although usual doses have no significant effect.

• The hepatotoxic effect of paracetamol may be enhanced by the consumption of large amounts of alcohol. Barbiturates, MAO inhibitors, and tricyclic antidepressants may increase the hepatotoxicity of paracetamol, especially in cases of overdose.

• The rate of absorption of paracetamol is increased when taken with metoclopramide or domperidone and reduced when taken with cholestyramine.

• Regular use of paracetamol may reduce the metabolism of zidovudine (increased risk of neutropenia).

• Use of salicylates/aspirin may prolong the plasma half-life of paracetamol.

• Concomitant use of paracetamol and NSAIDs increases the risk of renal impairment.

• Paracetamol may affect the results of certain laboratory tests for blood glucose and uric acid.

Phenylephrine
Products containing phenylephrine should be used with caution due to possible reactions with the following medicinal products:

• MAO inhibitors (including moclobemide): hypertensive reactions may occur with concomitant use of sympathomimetic amines (e.g. phenylephrine) and MAO inhibitors

• Sympathomimetic amines: concomitant use of phenylephrine and other sympathomimetic amines may increase the risk of cardiovascular adverse reactions

• Beta-blockers and other antihypertensive agents (debrisoquine, guanethidine, reserpine, methyldopa): phenylephrine may reduce the effectiveness of beta-blockers and antihypertensive agents. The risk of hypertension and other cardiovascular adverse reactions may be increased.

• Tricyclic antidepressants (e.g. amitriptyline): concomitant use with phenylephrine may increase the risk of cardiovascular adverse reactions

• Ergot alkaloids (ergotamine and methysergide): increased risk of ergotism

• Digoxin and other cardiac glycosides: increased risk of arrhythmias and myocardial infarction

• Phenothiazines used as sedatives: CNS effects may be enhanced

• Halogenated general anesthetics (cyclopropane, halothane, enflurane, isoflurane): possible provocation or worsening of ventricular arrhythmias

Guaifenesin

• It enhances the effects of sedatives and muscle relaxants.

• During 24-hour urine collection after administration of this product, its metabolites may affect the colorimetric determination of 5-hydroxyindoleacetic acid (5-HIAA) and vanillylmandelic acid (VMA).

  
  

Fertility: there are no data on the effects of the active substances on fertility.

Pregnancy
According to epidemiological study data, no adverse effects of paracetamol on pregnancy or on the health of the fetus and newborn have been identified in humans when the product is used at recommended doses and duration. There are no data on fetotoxic or teratogenic effects.
The safety of the use of guaifenesin and phenylephrine during pregnancy in humans has not been established.

Lactation
Paracetamol and phenylephrine are excreted in breast milk in clinically insignificant amounts.
This medicinal product should not be used during pregnancy and breastfeeding unless prescribed by a doctor.

Effects on ability to drive and use machines: Patients should be advised not to drive or use machines if dizziness occurs after taking the product.

Adverse reactions:

Paracetamol

- Blood and lymphatic system disorders: thrombocytopenia; agranulocytosis; these adverse reactions were not necessarily causally related to paracetamol.

- Immune system disorders: anaphylaxis; skin hypersensitivity reactions: skin rash, angioedema, Stevens–Johnson syndrome; toxic epidermal necrolysis

- Respiratory, thoracic, and mediastinal disorders: bronchospasm*

- Hepatobiliary disorders: liver function impairment

- Gastrointestinal disorders: acute pancreatitis

*More likely in asthmatic patients who are sensitive to aspirin or other NSAIDs.

Guaifenesin

- Immune system disorders: allergic reactions, angioedema, anaphylactic reactions

- Respiratory, thoracic, and mediastinal disorders: dyspnea

- Gastrointestinal disorders: nausea, vomiting, abdominal discomfort, diarrhea

- Skin and subcutaneous tissue disorders: rash, urticaria

Phenylephrine
Most commonly reported:

- Psychiatric disorders: restlessness, irritability, anxiety, excitability

- Nervous system disorders: headache, dizziness, insomnia

- Cardiac disorders: increased blood pressure

- Gastrointestinal disorders: nausea, vomiting, diarrhea

Rare:

- Eye disorders: mydriasis, acute narrow-angle glaucoma, more frequently observed in patients with narrow-angle glaucoma

- Cardiac disorders: tachycardia, palpitations

- Skin and subcutaneous tissue disorders: allergic reactions (rash, urticaria, allergic dermatitis), hypersensitivity reactions, including cross-sensitivity reactions with other sympathomimetics

- Renal and urinary disorders: dysuria, urinary retention, most commonly observed in patients with urinary tract obstruction, e.g. prostatic hypertrophy

Overdose

Paracetamol
In adults, liver function impairment may occur after ingestion of 10 g or more of paracetamol.
Ingestion of 5 g may cause liver function impairment in high-risk patients, such as:

• Long-term treatment with liver enzyme inducers (carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John’s wort-containing products);

• Regular consumption of alcohol in amounts exceeding recommended levels;

• Diseases and conditions leading to reduced glutathione levels, e.g. eating disorders, starvation, cachexia, cystic fibrosis, HIV infection.

Symptoms

- Symptoms of overdose within the first 24 hours include pallor, nausea, vomiting, loss of appetite, anorexia, and abdominal pain.

- Liver function impairment usually manifests 12–48 hours after ingestion, with disturbances of glucose metabolism and metabolic acidosis.

- In severe cases, progression may occur with encephalopathy, hemorrhages, hypoglycemia, cerebral edema, and death.

- Acute renal failure with acute tubular necrosis, manifested by flank pain, hematuria, and proteinuria, may develop even in the absence of liver function impairment.

- There have been reports of cardiac arrhythmias and pancreatitis.

Treatment
- Paracetamol overdose requires urgent treatment.  Regardless of the absence of early symptoms, patients should be hospitalized and symptomatic treatment should be initiated.

- Treatment with activated charcoal is appropriate within the first hour after ingestion.

- Plasma paracetamol concentration should be measured 4 hours or later after ingestion.
- Treatment with N-acetylcysteine, which can also be administered parenterally, is appropriate within 24 hours after ingestion, although maximum protective effect is observed within 8 hours. The effectiveness of N-acetylcysteine decreases when administered after this period.

Phenylephrine
Symptoms: overdose of phenylephrine usually manifests with symptoms similar to the described adverse reactions.
Hypertension and bradycardia may also occur; in severe cases, confusion, hallucinations, seizures, and arrhythmias.
Treatment: treatment is symptomatic. Severe hypertension sometimes requires the use of alpha-blockers such as phentolamine.

Guaifenesin
Symptoms: ingestion of very high doses may cause nausea and vomiting.
Treatment: in cases of vomiting, replacement rehydration with fluids and electrolytes may sometimes be necessary.

Pharmacodynamic properties: Pharmacotherapeutic group: Paracetamol combinations, excluding psycholeptics

Paracetamol has analgesic and antipyretic properties due to inhibition of prostaglandin synthesis in the CNS and, to a lesser extent, peripheral mechanisms associated with blocking pain impulses. Paracetamol exerts an antipyretic effect by acting on the thermoregulatory center, causing peripheral vasodilation, which leads to increased blood flow in the skin, resulting in sweating and heat loss.

Guaifenesin is believed to relieve and facilitate expectoration by increasing the volume and reducing the viscosity of bronchial secretions; it increases mucociliary clearance.

Phenylephrine is a sympathomimetic decongestant that acts on alpha-adrenergic receptors in the respiratory system, causing vasoconstriction and reducing inflammation and swelling of the nasal and sinus mucosa.
By the same mechanism, it reduces mucus production, thereby preventing accumulation of secretions in the nasal cavity and reducing pressure and pain associated with secretion retention.

Pharmacokinetic properties

Paracetamol is rapidly absorbed from the gastrointestinal tract. Maximum plasma concentrations are reached 10–60 minutes after oral administration. It is metabolized in the liver and excreted in the urine mainly as glucuronide and sulfate conjugates. Its plasma half-life is 1–3 hours.

Guaifenesin is rapidly absorbed after oral administration, with maximum plasma concentration reached after approximately 15 minutes. It is rapidly metabolized by oxidation to β-(2-methoxyphenoxy) lactic acid, which is excreted in the urine. The elimination half-life is approximately 1 hour.

Phenylephrine is irregularly absorbed from the gastrointestinal tract and undergoes first-pass metabolism by monoamine oxidase in the intestinal wall and liver. Phenylephrine has low oral bioavailability. Maximum plasma concentration is reached 1–2 hours after administration. It is excreted in the urine as sulfate conjugates. The plasma half-life is 2–3 hours.

Preclinical safety data:
Based on standard studies of safety pharmacology, repeated-dose toxicity, genotoxicity, carcinogenic potential, and reproductive toxicity, non-clinical data reveal no special hazard for humans.

Shelf life: 3 years

Special precautions for storage: store at a temperature not exceeding 25°C.

Dispensing status: Pharmaceutical product group III, supplied without prescription.

Marketing authorization holder
Adipharm EAD
130 Simeonovsko Shose Blvd.,
Sofia 1700, Bulgaria