Patient information leaflet

GROSTUDIN

Trade name: Grostudin

Pharmaceutical form: powder for oral solution (with lemon flavour or honey and lemon flavour).

Composition: one sachet contains:

Active substances: paracetamol – 0.325 g, caffeine – 0.030 g, pheniramine maleate – 0.020 g; phenylephrine hydrochloride – 0.010 g.

Excipients: anhydrous citric acid, sodium saccharin, sodium citrate, sucrose;

quinoline yellow (E-104), lemon flavour – for lemon-flavoured powder;

quinoline yellow (E-104), honey flavour, lemon flavour – for lemon and honey-flavoured powder.

Description

Grostudin with lemon flavour, with lemon and honey flavour is a light yellow to yellow powder with white, yellow and/or dark yellow inclusions with characteristic odour, corresponding to the drug flavour. During storage, lumps formation is acceptable, which are destroyed upon slight pushing.

Solution description

Grostudin with lemon flavour, with lemon and honey flavour is a yellow opalescent solution with few suspended particles.

Pharmacotherapeutic group: paracetamol in combination with other drugs, excluding psycholeptics.

ATC code: NO2BE51.

Pharmacological action

A combined drug, the action of which is defined by its components.

Paracetamol produces analgesic and antipyretic effects predominantly by inhibiting prostaglandins synthesis in the CNS, as well as influencing pain and thermoregulation centres.

Caffeine has a stimulating effect on the central nervous system and on the mental activity centres in particular, which leads to reduction of fatigue and somnolence, increase in mental capacity. Caffeine influences the respiratory centre, resulting in respiration rate and depth increase. It stimulates muscular activity, leading to increase in physical capacity. Additionally, caffeine produces slight bronchodilatory and diuretic effects.

Pheniramine produces antiallergic effect. It eradicates eye, nose and throat itching, oedema and hyperemia of nasal mucosa, nasopharynx and paranasal sinuses, reduces exudative signs.

Phenylephrine is a sympathomimetic drug, producing moderate vasoconstrictor effect – decreases the oedema and hyperemia of the upper respiratory tract and paranasal sinuses mucosae.

Indications for use

Short-term treatment of catarrhal diseases, rhinitis, rhinopharyngitis and flu-like conditions in adults and children over the age of 15 years, which are accompanied by:

-          Transparent nasal discharge and tearing;

-          Sneezing;

-          Headache and/or fever.

Method of administration and posology

Pour the contents of one sachet into a glass, fill the latter with hot water, mix to achieve a solution with few suspended particles and drink (sugar or honey may be added, if desired). The drug should be taken with large amount of liquid 1-2 hours after meal. Adults and children over the age of 15 years: one sachet 3-4 times per day with 4-6 hours intervals (not more than 4 sachets per day). Maximum treatment duration without medical consultation should not exceed 3 days (if taken as an antipyretic drug) and 5 days (if taken as an analgesic drug).

Side effects

The incidence of possible side effects indicated below is determined as follows:

ü  Very common (≥1/10)

ü  Common (≥1/100 to <1/10)

ü  Uncommon (≥1/1,000 to <1/100)

ü  Rare (≥1/10,000 to <1/1,000)

ü  Very rare (<1/10,000)

ü  Unknown (can not be estimated based on available data)

Paracetamol

Incidence of these reactions is not determined, but usually they rarely occur.

Pheniramine

* - children and elderly patients are more sensitive to neurological cholinergic effects and paradoxical excitement (for example, surge of energy, anxiety, nervousness).

Phenylephrine

The following side effects were observed during clinical trials with phenylephrine, and therefore they are the most widespread ones.

The side effects, which were revealed during the post-marketing period, are submitted below. The incidence of these reactions is unknown, but possibly, they will rarely occur.

Caffeine

In case of any side effects mentioned above or not stated in this leaflet, it is recommended to seek for medical advice.

Contraindications

Hypersensitivity to the drug components, cardiovascular diseases (severe forms of ischemic heart disease, myocardium infarction, unstable angina, aortic valve stenosis, expressed atherosclerosis, heart rhythm disorder, decompensated cardiac insufficiency, uncontrolled arterial hypertension), pulmonary and arterial hypertension, asthma, chronic obstructive pulmonary diseases, active erosive-ulcerative lesions in the gastrointestinal tract, acute pancreatitis, pheochromocytoma, tendency to vasospasm, vasospastic syndromes (Raynaud's disease), metabolic acidosis, hypovolemia, hypercapnia, hypoxia, angle-closure glaucoma, hyperexcitability, sleep disorder, psychomotor agitation, epilepsy and tendency to convulsive seizures, alcoholism, porphyria, diabetes mellitus, thyrotoxicosis, severe forms of liver and/or renal impairment, congenital hyperbilirubinemia (Gilbert's syndrome, Dubin-Johnson syndrome, Rotor syndrome), prostate hypertrophy with urinary retention, blood system diseases, expressed leucopenia, anemia, congenital glucose-6-phosphate dehydrogenase deficit, children under 15 years old, pregnancy and lactation.

The drug should not be taken concomitantly with tricyclic antidepressants, beta-blockers, sympathomimetics, monoaminoxidase (MAO) inhibitors and during 2 weeks after their withdrawal, other paracetamol-containing medicinal products, decongestants, catarrhal diseases and flu symptoms treatment drugs.

Use with caution: elderly patients, concomitant use of antihypertensive agents.

Overdose

Symptoms, caused by paracetamol

Hepatic injury is possible in adult patients, who took 10 g and more of paracetamol. Intake of 5 g and more  of paracetamol can result in hepatic injury, if the patient has the following risk factors:

a)      The patient is on long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort and other drugs, inducing hepatic enzymes;

b)      The patient regularly drinks ethanol, exceeding the recommended amount;

c)      The patient is debilitated, for example, due to mucoviscidosis, HIV, starving.

Symptoms

Paracetamol overdose symptoms during the first 24 hours include the following: paleness, nausea, vomiting, appetite loss and abdominal pain. Hepatic injury can manifest during 12-48 hours after paracetamol intake. Glucose metabolism failure and metabolic acidosis are possible. In cases of severe poisoning, liver insufficiency can progress to encephalopathy, haemorrhage, hypoglycemia, brain oedema and death. Acute renal insufficiency with acute necrosis, back pain, hematuria and proteinuria may develop even in absence of serious hepatic injury. Several reports of cardiac arrhythmia and pancreatitis were received.

Treatment

Immediate measures are of great importance in paracetamol overdose treatment. Although there are no significant early overdose symptoms, the patient must be immediately brought to in-patient facility. The symptoms can be limited to vomiting and not correspond to overdose severity or organs injury risk. Medical help should be provided according to the established treatment standards. Treatment using activated charcoal should be considered if the overdose was diagnosed within 1 hour after the drug product intake. Paracetamol plasma concentrations should be measured every 4 hours after drug intake. Treatment with N-acetylcysteine can be used during 24 hours after paracetamol intake, but maximal protective effect is achieved during 8 hours after the drug administration. Subsequently, the antidote efficiency abruptly decreases. If necessary, N-acetylcysteine can be injected intravenously. In case the patient is not hypersensitive to methionine, the latter can be an appropriate alternative for urgent medical help.

Caused by potentiation of antihistamine component (pheniramine) parasympathic action

Pheniramine overdose can lead to the effects, which are similar to the ones mentioned in the “Side effects” section for pheniramine. Additional symptoms can include paradoxical excitement, toxic psychosis, seizures, apnea, dystonic reactions and cardiovascular insufficiency (including arrhythmia), somnolence, which can be followed by excitement (especially in children); depression, oral mucosa ulceration, visual disturbances, headache, dizziness, insomnia, coma, seizures, behaviour alteration, arterial hypertension, bradycardia, atropine-like “psychosis”.

Caffeine overdose symptoms

CNS stimulation, nervousness, anxiety, insomnia, muscle cramps, confused consciousness.

Cardiovascular disorders: tachycardia, arrhythmia.

Gastrointestinal disorders: abdominal pain.

Others: diuresis, face reddening.

Treatment of caffeine overdose is primarily symptomatic and maintaining. Due to increased diuresis, it is necessary to maintain water-electrolytic balance. CNS symptoms can be relieved using intravenous diazepam.

Phenylephrine

Overdose symptoms include arterial pressure increase and reflex bradycardia and arrhythmia, associated with hypertension.

Treatment

Increased arterial pressure should be corrected using alpha-receptors antagonist, for example, by intravenous phentolamine. Arterial pressure decrease leads to reflex increase in heart rate, therefore if necessary this condition can be corrected by atropine injection.

Precautions

In such cases when fever persists for more than 3 days and pain syndrome – for more than 5 days, along with drug intake, the patient should seek for medical advice.

The patient should consult the doctor if the symptoms:

-          Do not resolve during 5 days;

-          Are accompanied by fever persisting for more than 3 days;

-          Include sore throat, which does not resolve for more than 3 days, is accompanied by fever, headache, rash, nausea or vomiting.

It is recommended to avoid simultaneous use of other medicinal products, containing paracetamol.

During treatment period, it is not recommended to drink alcohol, since ethyl alcohol can result in liver dysfunction in case of simultaneous use with paracetamol.

Patients with the following conditions should consult the doctor before using this drug:

·         Hypertension;

·         Cardiovascular diseases;

·         Diabetes mellitus;

·         Hyperthyreosis;

·         Intraocular pressure increase (glaucoma);

·         Pheochromocytoma;

·         Prostate enlargement;

·         Obliterating vascular endarteritis (for example, Raynaud's phenomenon);

·         Epilepsy;

·         Bronchitis;

·         Bronchiectasis;

·         Asthma;

·         Hepatic and renal diseases. It is necessary to exercise caution with respect to patients with renal function impairment and/or liver insufficiency due to the fact that this drug contains paracetamol and pheniramine, which elevate risk of paracetamol-associated hepatic injury.

Patients with diagnosed liver and/or renal insufficiency should apply to the doctor before taking this drug.

Pheniramine can enhance alcohol effect, therefore patients should avoid their simultaneous use.

Concomitant use with drugs producing sedative effect, such as tranquilizers and sleeping drugs, can lead to sedative effect enhancement, therefore the patients should consult the doctor before using pheniramine simultaneously with these medicinal products.

Grostudin should not be used concomitantly with other antihistamine agents.

Elderly patients are more likely to demonstrate anticholinergic effects and paradoxical excitement (for example, surge of energy, anxiety, nervousness).

When using pheniramine in the evening, gastroesophageal reflux disease symptoms may aggravate.

Caution should be exercised during pheniramine use in combination with drugs, which can cause ototoxic effect, since ototoxic symptoms masking may occur.

If symptoms persist, the patient should seek for medical advice.

Phenylephrine can contribute to false-positive doping control results of sportsmen.

Keep out of reach of children.

Use of alcohol drinks and sedating agents (barbiturates, in particular) enhances pheniramine sedative effect, therefore patients should avoid simultaneous use of these substances during treatment.

Somnolence risk is increased in case of concomitant use of alcohol drinks, alcohol-containing drugs or sedating agents.

Drug dependence occurs only in case of doses, exceeding the recommended ones or in case of long-term treatment.

In order to prevent overdose risks, patients should be sure that other drugs used by them do not contain paracetamol.

For adult patients with body weight of more than 50 kg, total paracetamol dose should not exceed 4 g per day.

Recommended drug dose contains approximately the same amount of caffeine as a coffee cup.

During the treatment period, it is necessary to limit the usage of drugs, drinks and meals, containing caffeine, because excessive caffeine intake can cause nervousness, irritability, insomnia and sometimes tachycardia.

Use in children

For children under 15 years old the drug is contraindicated.

Children are more likely to demonstrate neurologic anticholinergic effects and paradoxical excitement (for example, surge of energy, anxiety, nervousness).

Use in pregnancy and lactation

The drug is contraindicated during pregnancy.

Paracetamol and pheniramine – category A (according to FDA classification): drug agents, which were taken by many pregnant women and women of reproductive age, and did not demonstrate any proved increase of congenital abnormality incidence or other direct or indirect harmful influence on the fetus.

Paracetamol crosses the placental barrier. Paracetamol studies on animals did not reveal any risks for gestation course and embryo or fetus development.

There are no adequate and well-controlled studies in pheniramine with participation of pregnant women, though it was stated that retrolental fibroplasia (RLF) occurred in newborns, whose mothers received antihistamine drugs during the last two weeks of gestation.

Pregnant women should limit caffeine consumption.

Use during lactation period

Paracetamol is excreted into human milk. It is not recommended to use the drug during breast-feeding period. The studies in paracetamol influence on human did not reveal any risks for breast-feeding mothers.

Pheniramine and other antihistamine drugs can inhibit lactation and be excreted into human milk. Caffeine is excreted into human milk and can result in excitement and sleep disorder, since it is slowly eliminated from infants’ organisms. Phenylephrine is excreted into human milk and is strongly contraindicated for breast-feeding mothers.

Effects on ability to drive and use other potentially dangerous mechanisms.

During the treatment period, it is not recommended to drive and work with complicated mechanisms, requiring increased attention and psychomotor abilities quick response rate. Due to cholinergic properties, pheniramine can cause somnolence, dizziness, blurred vision and psychomotor disorders in some patients and it may seriously influence the ability to drive and use technical equipment. Somnolence may be enhanced during concomitant use of sedating agents, tranquilizers or alcohol.

Interaction with other medicinal products

Paracetamol

Paracetamol drug interactions usually are insignificant, but they intensify when the concomitant drugs are anticoagulants (warfarin and coumarin) and anticonvulsants with low therapeutic index. Simultaneous use of paracetamol and NSAID can increase nephrotoxicity. Pharmacological interactions can occur upon using other analgesic agents, such as caffeine, opiates. Barbiturates decrease antipyretic effect. In case of paracetamol and chloramphenicol concomitant use, extension of elimination half-life of the latter is observed. Probenecid, cholestyramine inhibit paracetamol metabolism. Simultaneous treatment of tuberculosis with rifampicin and isoniazid increases paracetamol hepatotoxicity. Antiepileptic drugs (phenobarbital, phenytoin, carbamazepine) do not increase paracetamol hepatotoxic action risk.

Pheniramine

Pheniramine potentiates the action of the medicinal products, inhibiting the ce-ntral nervous system (for example, antiparkinson and antipsychotic drugs), and alcohol, inhibits action of anticoagulants and interacts with progesterone, reserpine, thiazide diuretics. Oral contraceptives may lead to decrease in antihistamine agents efficacy.

Phenylephrine should be used with caution in cases of concomitant use with the following drugs:

Storage conditions

Store in protected from light and moisture place at temperature below 25 °С. Keep out of reach of children.

Shelf life

2 years. The drug should not be used after expiration date.

Prescription status

No prescription.

Packaging

5 or 10 sachets made of combination paper and cardboard based material (paper/polyethylene) or packaging material (polypropylene/polypropylene) in a boxboard pack.

Manufacturer:

Belmedpreparaty RUE

30 Fabritsius Str., 220007 Minsk, Republic of Belarus,

Tel./fax: (+375 17) 220 37 16,

e-mail: medic@belmedpreparaty.com,

http://www.belmedpreparaty.com