INSTRUCTION

or medical use of the preparation

GRIPPFLU

General characteristic:

Main chemical and physical properties: white or almost white color, round shape, flat tablets with break line and canton on one side;

Composition: 1 tablet contains: paracetamol - 500 mg, chlorpheniamine maleate - 2 mg, phenylephrine hydrochloride - 10 mg, and caffeine - 30 mg;

Auxiliary substances: starch, sodium methylparaben, sodium propylparaben, colloidal silicon dioxide, magnesium stearate, purified talc.

Medicinal form. Tablets.

Pharmacotherapeutical group. Analgetics and antipyretics. Paracetamol in combination with other preparations (without psycholeptics). АТС code N02ВЕ51.

Pharmacological properties.

Pharmacodynamics. Paracetamol has analgetic, antipyretic and mild anti-inflammatory activity due to inhibition of prostaglandin synthesis in the central nervous synthesis (CNS).

Chlorpheniamine maleate is a histamine receptor-blocking agent, which suppresses biological effects of histamine. It has anti-allergic action, promotes decreased manifestation of local exudative reactions of nose and paranasal sinus mucous membranes. It suppresses the symptoms of rhinitis, rhinorrhea, itchy eyes, unpleasant feelings in nasopharynx and larynx.

Mechanism of action of caffeine is conditioned by inhibition of phosphodiesterase enzyme, which leads to intracellular accumulation of cyclic adenosine monophosphate. The letter increases glycogenolysis and stimulates metabolism in organs and tissues, including those in the CNS and in muscles. Caffeine enhances and regulates excitative process in the cerebral cortex.

Neurochemical mechanism of caffeine’s stimulating action lies in its ability to block specific Р1 "purine" (or adenosine) receptors of the brain, the endogenous ligand of which is adenosine, which decreases excitative processes in the brain. Caffeine stimulates CNS, enhances mental and physical activity, decreases the feeling of tiredness, increases the power and rate of heart contractions, excites respiratory and vasomotor centers, increases the tone of brain vessels, dilates vessels of skeletal muscles, heart, kidneys, and decreases thrombocyte aggregation.

Phenylephrine hydrochloride as for its mechanism is a direct α-adrenoceptor agonist. By influencing α-adrenoceptors, it causes narrowing of arterioles in the nose mucous membrane, promotes decrease of edema and hyperemia of the mucous membrane of upper respiratory tract and paranasal sinuses.

Pharmacokinetics. Paracetamol is readily and nearly entirely absorbed by gastrointestinal tract. Its maximal plasma concentration is achieved in 30-60 min. It is metabolized in the liver and excreted with urine as glucuronid, sulfate and cysteine compounds. Its half-life is about 2 hours.

Caffeine is well absorbed from gastrointestinal system. It distributes evenly in the organism. It crosses easily blood-brain barrier. Biotransformation: demethylation and oxidation. It is excreted with urine as metabolites, about 8% in unchanged state. Its half-life is 3.9-5.3 hours; it is fully excreted in 24 hours.

Chlorpheniamine maleate is well absorbed by gastrointestinal tract; its action starts in 30 min after administration and lasts for 3-6 hours. It undergoes metabolism at “first-pass” through the liver and intrahepatic recirculation. Intake of chlorpheniamine with food decreases its bioavailability significantly. Insignificant amount of the preparation is excreted with urine in unchanged state. Most of it is excreted from the organism as metabolism products.

Phenylephrine is readily absorbed after oral intake; its peak plasma concentrations are achieved in 1-2 hours; its half-life is 2-3 hours. Phenylephrine is metabolized in the organism and excreted mostly with urine.

Indications. Symptomatic treatment of the infections of upper respiratory ways accompanied with stuffy nose, increased body temperature and headache, muscle pain.

Way of introduction and doses. Adults and children over 12 years old are indicated 1 tablet 3-4 times a day, but not more than 4 tablets during the day. The course of treatment should not exceed 3 days.

Side effects. 

From the side of the nervous system: sleepiness, sleeping disorders, increased anxiety.

From the side of the digestive tract: loss of appetite, nausea, dyspeptic phenomena, unpleasant feeling in epigastrium.

Allergic reactions: seldom there can be observed dermatological reactions such as rash and itch.

From the side of the hematopoietic system: anemia, thrombocytopenia, agranulocytosis.

Sometimes there can occur dry mouth, complicated urination, accommodation disorder, increased intraocular pressure.

Contraindications. Pregnancy and lactation. Children under 12 years old. Hypersensitivity to any component of the preparation. Dysfunction of liver and kidneys. Alcoholism.

Overdose. Due to significant overdose of the preparation there can be observed gastrointestinal disorders (diarrhea, decreased appetite, nausea, vomiting, abdominal pain), increased sweetening. Long-term use of high doses of the preparation can cause hepatotoxic effect with disturbed liver function, long-term use of high doses of caffeine ‒ irritation, permanent tremor, hyperflexion. Caution should be exercised at the use of phenylephrine in patients with arterial hypertension, hyperthyroidism, cardiovascular pathology, diabetes mellitus, and glaucoma.

Treatment: gastric lavage, intake of activated coal, symptomatic therapy. The antidote for paracetamol is acetylcysteine and methionine.

Precautions at use. The preparation should be indicated with caution to the patients with diseases of liver and kidneys, severe form of arterial hypertension, chronic heart failure, hyperthyroidism, diabetes mellitus, and prostate gland adenoma. During the period of treatment with the preparation one should abstain from driving, operating mechanisms and other dangerous types of activity. Do not take alcohol. 

Discontinue breast-feeding during treatment.

Interaction with other drugs. Grippflu should not be indicated concomitantly with other preparations, containing paracetamol, to avoid overdose. At concomitant use of paracetamol with barbiturates, tricyclic antidepressants, rifampicin there is a significantly increased risk of hepatotoxic action of paracetamol. Long-term use of anticonvulsants can cause decreased therapeutic action of paracetamol.Concomitant use of the preparation with hypnotics, tranquilizers, neuroleptics, sedatives and alcohol-containing preparations promote increased action of chlorpheniamine on the central nervous system.

Concomitant use with phenothiazine, alpha-adrenergic blocking agents (phentolamine), furosemide and other diuretics can lead to hypertensic crisis. Guanethidine enhances mydriatic effect of phenylephrine. monoamine oxidase inhibitors, oxytocin, tricyclic antidepressants, furazolidon, procarbatine, selegiline, adrenostimulators increase the risk of development of ventricular arrhythmia.

Caffeine is able to enhance analgetic effect of acetylsalicylic acid and ibuprofen, as well as ergotamine at migraine treatment. In combination with amantadine there can occur excitant action on the central nervous system. At concomitant use with cimetidine the enhancement of side effects of caffeine due to its decreased inactivation in the liver is possible.

Storage conditions and shelf life. Store at room temperature (15-25°С), in protected from light place. Keep out of the reach of children.

Shelf life. 3 years.

Terms of dispensing. Without prescription – tablets No 4.On prescription – tablets No 200.   

Packing. 4 tablets in a strip, 1 strip in the envelope labeled in Ukrainian; 50 envelopes in a carton labeled in Ukrainian.  

Name and Address of the Manufacturer. Ananta Medicare Ltd.

Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, London, Great Britain.